Patent Publication Number: US-2022228130-A1

Title: Optimized cannabinoid synthase polypeptides

Description:
DESCRIPTION OF THE TEXT FILE SUBMITTED ELECTRONICALLY 
     The contents of the text file submitted electronically herewith are incorporated herein by reference in their entirety: a computer readable format copy of the sequence listing (filename: DEMT-004_03WO_SeqList_ST25.txt, date recorded: May 19, 2020, file size 924 kilobytes). 
     BACKGROUND 
     Plants from the genus  Cannabis  have been used by humans for their medicinal properties for thousands of years. In modern times, the bioactive effects of  Cannabis  are attributed to a class of compounds termed “cannabinoids,” of which there are hundreds of structural analogs including tetrahydrocannabinol (THC) and cannabidiol (CBD). These molecules and preparations of  Cannabis  material have recently found application as therapeutics for chronic pain, multiple sclerosis, cancer-associated nausea and vomiting, weight loss, appetite loss, spasticity, seizures, and other conditions. 
     
       
         
         
             
             
         
       
     
     The physiological effects of certain cannabinoids are thought to be mediated by their interaction with two cellular receptors found in humans and other animals. Cannabinoid receptor type 1 (CB1) is common in the brain, the reproductive system, and the eye. Cannabinoid receptor type 2 (CB2) is common in the immune system and mediates therapeutic effects related to inflammation in animal models. The discovery of cannabinoid receptors and their interactions with plant-derived cannabinoids predated the identification of endogenous ligands. 
     Besides THC and CBD, hundreds of other cannabinoids have been identified in  Cannabis . However, many of these compounds exist at low levels and alongside more abundant cannabinoids, making it difficult to obtain pure samples from plants to study their therapeutic potential. Similarly, methods of chemically synthesizing these types of products have been cumbersome and costly, and tend to produce insufficient yield. Accordingly, additional methods of making pure cannabinoids or cannabinoid derivatives are needed. 
     One possible method is production via fermentation of engineered microbes, such as yeast. By engineering production of the relevant plant enzymes in microbes, it may be possible to achieve conversion of various feedstocks into a range of cannabinoids, potentially at much lower cost and with much higher purity than what is available from the plant. A key challenge to this effort is the difficulty of expressing plant enzymes in the microbe, particularly secreted enzymes such as the cannabinoid synthases, which must successfully traverse the microbe&#39;s secretory pathway to fold and function properly. Engineered variants of cannabinoid synthases, modified host cells, and new methods are needed to address these challenges. 
     SUMMARY 
     The present disclosure provides engineered variants of a cannabidiolic acid synthase (CBDAS) polypeptide comprising an amino acid sequence of SEQ ID NO:3 with one or more amino acid substitutions, nucleic acids comprising nucleotide sequences encoding said engineered variants, methods of making modified host cells comprising said nucleic acids, modified host cells for producing cannabinoids or cannabinoid derivatives, methods of producing cannabinoids or cannabinoid derivatives, and methods of screening engineered variants of the cannabidiolic acid synthase (CBDAS) polypeptide. The engineered variants of the disclosure may be useful for producing cannabinoids or cannabinoid derivatives (e.g., non-naturally occurring cannabinoids). The modified host cells of the disclosure may be useful for producing cannabinoids or cannabinoid derivatives (e.g., non-naturally occurring cannabinoids) and/or for expressing engineered variants of the disclosure. The disclosure also provides for modified host cells for expressing the engineered variants of the disclosure. Additionally, the disclosure provides for preparation of engineered variants of the disclosure. 
     An aspect of the disclosure relates to an engineered variant of a cannabidiolic acid synthase (CBDAS) polypeptide comprising an amino acid sequence of SEQ ID NO:3 with one or more amino acid substitutions. In some embodiments, the engineered variant comprises an amino acid sequence with at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO:3. In some embodiments, the engineered variant comprises an amino acid sequence with 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to SEQ ID NO:3. In some embodiments, the engineered variant comprises at least one amino acid substitution in a signal polypeptide, a flavin adenine dinucleotide (FAD) binding domain, a berberine bridge enzyme (BBE) domain, or a combination of the foregoing. In some embodiments, the engineered variant comprises substitution of at least one surface exposed amino acid. 
     In some embodiments, the engineered variant comprises at least one amino acid substitution at an amino acid selected from the group consisting of C12, F17, F18, S20, R31, N33, P43, L49, K50, L51, Q55, N56, N57, L59, M61, S62, V63, S66, L71, S75, I97, L98, S100, V103, T109, Q124, V125, I129, L132, S137, H143, V149, W161, K165, E167, N168, S170, L171, A172, Y175, C180, A181, N196, H208, A235, A250, M256, K260, L268, H309, T310, F316, L326, G378, K389, E406, S428, L439, N466, K474, Y499, N527, P538, R541, H542, R543, and H544. In some embodiments, the engineered variant comprises at least one amino acid substitution at an amino acid selected from the group consisting of C12, F17, F18, S20, R31, N33, P43, L49, K50, L51, Q55, N56, N57, L59, M61, S62, V63, S66, L71, S75, I97, L98, S100, V103, T109, Q124, V125, I129, L132, S137, H143, V149, W161, K165, E167, N168, S170, L171, A172, Y175, C180, A181, N196, H208, A235, A250, M256, K260, L268, H309, T310, F316, L326, G378, K389, E406, M412, L415, S428, L439, I445, N466, K474, Y499, N527, P538, R541, H542, R543, and H544. In some embodiments, the engineered variant comprises at least one amino acid substitution at an amino acid selected from the group consisting of R31, P43, L49, K50, L51, Q55, N56, N57, M61, S62, L71, I97, S100, V103, T109, Q124, V125, I129, L132, S137, H143, V149, W161, K165, E167, N168, S170, L171, A172, Y175, C180, A181, N196, H208, A235, A250, M256, K260, L268, H309, T310, F316, L326, G378, K389, S428, L439, N466, K474, Y499, N527, P538, R541, H542, R543, and H544. In some embodiments, the engineered variant comprises at least one amino acid substitution at an amino acid selected from the group consisting of L49, K50, N56, N57, V125, L132, V149, W161, K165, S170, L171, A172, N196, A235, K260, L268, T310, F316, L326, G378, S428, Y499, N527, H543, and H544. In some embodiments, the engineered variant comprises at least one amino acid substitution at an amino acid selected from the group consisting of R541, H542, R543, and H544. In some embodiments, the engineered variant comprises at least one amino acid substitution at an amino acid selected from the group consisting of R31, N57, M61, L71, S170, A172, Y175, N196, H208, A235, K260, G378, K389, and R543. In some embodiments, the engineered variant comprises at least one amino acid substitution at an amino acid selected from the group consisting of N57, S170, A172, N196, A235, K260, and G378. In some embodiments, the engineered variant comprises at least one amino acid substitution at an amino acid selected from the group consisting of M412, L415, and I445. In some embodiments, the engineered variant comprises an amino acid substitution at amino acid I445. In some embodiments, the engineered variant comprises at least one amino acid substitution at an amino acid selected from the group consisting of M61, G378, and K389. In some embodiments, the engineered variant comprises amino acid substitutions at amino acids M61 and G378. In some embodiments, the engineered variant comprises amino acid substitutions at amino acids M61 and K389. In some embodiments, the engineered variant comprises amino acid substitutions at amino acids G378 and K389. In some embodiments, the engineered variant comprises amino acid substitutions at amino acids M61, G378, and K389. 
     In some embodiments, the engineered variant comprises at least one amino acid substitution selected from the group consisting of C12F, F17M, F18T, F18W, S20G, R31Q, N33K, P43E, L49E, L49K, L49Q, K50T, L51I, Q55E, Q55P, N56E, N57D, N57E, L59E, M61H, M61S, M61W, S62N, S62Q, V63M, S66D, L71A, L71H, L71Q, S75D, S75E, I97V, L98V, S100A, V103A, V103F, T109V, Q124D, Q124E, Q124N, V125E, V125Q, I129V, L132M, S137G, H143D, V149I, W161K, W161R, W161Y, K165A, E167P, N168S, S170T, L171I, A172V, Y175F, C180A, A181V, N196Q, N196T, N196V, H208T, A235P, A250T, M256V, K260C, K260W, L268I, H309V, T310A, T310C, F316Y, L326I, G378T, G378S, K389E, E406K, S428L, L439M, N466D, K474S, Y499M, Y499V, N527E, P538T, R541E, R541V, H542V, R543A, R543E, H544E, and H544D. In some embodiments, the engineered variant comprises at least one amino acid substitution selected from the group consisting of C12F, F17M, F18T, F18W, S20G, R31Q, N33K, P43E, L49E, L49K, L49Q, K50T, L51I, Q55E, Q55P, N56E, N57D, N57E, L59E, M61H, M61S, M61W, S62N, S62Q, V63M, S66D, L71A, L71H, L71Q, S75D, S75E, I97V, L98V, S100A, V103A, V103F, T109V, Q124D, Q124E, Q124N, V125E, V125Q, I129V, L132M, S137G, H143D, V149I, W161K, W161R, W161Y, K165A, E167P, N168S, S170T, L171I, A172V, Y175F, C180A, A181V, N196Q, N196T, N196V, H208T, A235P, A250T, M256V, K260C, K260W, L268I, H309V, T310A, T310C, F316Y, L326I, G378T, G378S, K389E, E406K, M412Q, L415M, S428L, L439M, I445M, N466D, K474S, Y499M, Y499V, N527E, P538T, R541E, R541V, H542V, R543A, R543E, H544E, and H544D. In some embodiments, the engineered variant comprises at least one amino acid substitution selected from the group consisting of R31Q, P43E, L49E, L49K, L49Q, K50T, L51I, Q55E, Q55P, N56E, N57D, M61H, M61S, M61W, S62Q, L71A, L71Q, I97V, S100A, V103A, V103F, T109V, Q124D, Q124E, Q124N, V125E, V125Q, I129V, L132M, S137G, H143D, V149I, W161K, W161R, W161Y, K165A, E167P, N168S, S170T, L171I, A172V, Y175F, C180A, A181V, N196Q, N196T, N196V, H208T, A235P, A250T, M256V, K260C, K260W, L268I, H309V, T310A, T310C, F316Y, L326I, G378T, G378S, K389E, S428L, L439M, N466D, K474S, Y499M, Y499V, N527E, P538T, R541E, R541V, H542V, R543A, R543E, H544E, and H544D. In some embodiments, the engineered variant comprises at least one amino acid substitution selected from the group consisting of L49E, L49Q, K50T, N56E, N57D, V125E, L132M, V149I, W161R, K165A, S170T, L171I, A172V, N196Q, N196T, N196V, A235P, K260W, K260C, L268I, T310A, T310C, F316Y, L326I, G378T, S428L, Y499M, Y499V, N527E, H543E, and H544E. In some embodiments, the engineered variant comprises at least one amino acid substitution selected from the group consisting of R541E, R541V, H542V, R543A, R543E, H544E, and H544D. In some embodiments, the engineered variant comprises at least one amino acid substitution selected from the group consisting of R31Q, N57D, M61W, L71H, S170T, A172V, Y175F, N196V, H208T, A235P, K260W, G378T, K389E, and R543E. In some embodiments, the engineered variant comprises at least one amino acid substitution selected from the group consisting of N57D, S170T, A172V, N196V, A235P, K260W, and G378T. In some embodiments, the engineered variant comprises at least one amino acid substitution selected from the group consisting of M412Q, L415M, and I445M. In some embodiments, the engineered variant comprises amino acid substitution I445M. In some embodiments, the engineered variant comprises at least one amino acid substitution selected from the group consisting of M61W, G378T, and K389E. In some embodiments, the engineered variant comprises amino acid substitutions M61W and G378T. In some embodiments, the engineered variant comprises amino acid substitutions M61W and K389E. In some embodiments, the engineered variant comprises amino acid substitutions G378T and K389E. In some embodiments, the engineered variant comprises amino acid substitutions M61W, G378T, and K389E. 
     In some embodiments, the engineered variant comprises an amino acid sequence selected from the group consisting of SEQ ID NO:50, SEQ ID NO:52, SEQ ID NO:54, SEQ ID NO:56, SEQ ID NO:58, SEQ ID NO:60, SEQ ID NO:62, SEQ ID NO:64, SEQ ID NO:66, SEQ ID NO:68, SEQ ID NO:70, SEQ ID NO:72, SEQ ID NO:74, SEQ ID NO:76, SEQ ID NO:78, SEQ ID NO:80, SEQ ID NO:82, SEQ ID NO:84, SEQ ID NO:86, SEQ ID NO:88, SEQ ID NO:90, SEQ ID NO:92, SEQ ID NO:94, SEQ ID NO:96, SEQ ID NO:98, SEQ ID NO:100, SEQ ID NO:102, SEQ ID NO:104, SEQ ID NO:106, SEQ ID NO:108, SEQ ID NO:110, SEQ ID NO:112, SEQ ID NO:114, SEQ ID NO:116, SEQ ID NO:118, SEQ ID NO:120, SEQ ID NO:122, SEQ ID NO:124, SEQ ID NO:126, SEQ ID NO:128, SEQ ID NO:130, SEQ ID NO:132, SEQ ID NO:134, SEQ ID NO:136, SEQ ID NO:138, SEQ ID NO:140, SEQ ID NO:142, SEQ ID NO:144, SEQ ID NO:146, SEQ ID NO:148, SEQ ID NO:150, SEQ ID NO:152, SEQ ID NO:154, SEQ ID NO:156, SEQ ID NO:158, SEQ ID NO:160, SEQ ID NO:162, SEQ ID NO:164, SEQ ID NO:166, SEQ ID NO:168, SEQ ID NO:170, SEQ ID NO:172, SEQ ID NO:174, SEQ ID NO:176, SEQ ID NO:178, SEQ ID NO:180, SEQ ID NO:182, SEQ ID NO:184, SEQ ID NO:186, SEQ ID NO:188, SEQ ID NO:190, SEQ ID NO:192, SEQ ID NO:194, SEQ ID NO:196, SEQ ID NO:198, SEQ ID NO:200, SEQ ID NO:202, SEQ ID NO:204, SEQ ID NO:206, SEQ ID NO:208, SEQ ID NO:210, SEQ ID NO:212, SEQ ID NO:214, SEQ ID NO:216, SEQ ID NO:218, SEQ ID NO:220, SEQ ID NO:222, SEQ ID NO:224, SEQ ID NO:226, SEQ ID NO:228, SEQ ID NO:230, SEQ ID NO:232, and SEQ ID NO:234. 
     In some embodiments, the engineered variant comprises an amino acid sequence selected from the group consisting of SEQ ID NO:50, SEQ ID NO:52, SEQ ID NO:54, SEQ ID NO:56, SEQ ID NO:58, SEQ ID NO:60, SEQ ID NO:62, SEQ ID NO:64, SEQ ID NO:66, SEQ ID NO:68, SEQ ID NO:70, SEQ ID NO:72, SEQ ID NO:74, SEQ ID NO:76, SEQ ID NO:78, SEQ ID NO:80, SEQ ID NO:82, SEQ ID NO:84, SEQ ID NO:86, SEQ ID NO:88, SEQ ID NO:90, SEQ ID NO:92, SEQ ID NO:94, SEQ ID NO:96, SEQ ID NO:98, SEQ ID NO:100, SEQ ID NO:102, SEQ ID NO:104, SEQ ID NO:106, SEQ ID NO:108, SEQ ID NO:110, SEQ ID NO:112, SEQ ID NO:114, SEQ ID NO:116, SEQ ID NO:118, SEQ ID NO:120, SEQ ID NO:122, SEQ ID NO:124, SEQ ID NO:126, SEQ ID NO:128, SEQ ID NO:130, SEQ ID NO:132, SEQ ID NO:134, SEQ ID NO:136, SEQ ID NO:138, SEQ ID NO:140, SEQ ID NO:142, SEQ ID NO:144, SEQ ID NO:146, SEQ ID NO:148, SEQ ID NO:150, SEQ ID NO:152, SEQ ID NO:154, SEQ ID NO:156, SEQ ID NO:158, SEQ ID NO:160, SEQ ID NO:162, SEQ ID NO:164, SEQ ID NO:166, SEQ ID NO:168, SEQ ID NO:170, SEQ ID NO:172, SEQ ID NO:174, SEQ ID NO:176, SEQ ID NO:178, SEQ ID NO:180, SEQ ID NO:182, SEQ ID NO:184, SEQ ID NO:186, SEQ ID NO:188, SEQ ID NO:190, SEQ ID NO:192, SEQ ID NO:194, SEQ ID NO:196, SEQ ID NO:198, SEQ ID NO:200, SEQ ID NO:202, SEQ ID NO:204, SEQ ID NO:206, SEQ ID NO:208, SEQ ID NO:210, SEQ ID NO:212, SEQ ID NO:214, SEQ ID NO:216, SEQ ID NO:218, SEQ ID NO:220, SEQ ID NO:222, SEQ ID NO:224, SEQ ID NO:226, SEQ ID NO:228, SEQ ID NO:230, SEQ ID NO:232, SEQ ID NO:234, SEQ ID NO:300, SEQ ID NO:302, and SEQ ID NO:304. 
     In some embodiments, the engineered variant comprises an amino acid sequence selected from the group consisting of SEQ ID NO:60, SEQ ID NO:64, SEQ ID NO:66, SEQ ID NO:68, SEQ ID NO:70, SEQ ID NO:72, SEQ ID NO:74, SEQ ID NO:76, SEQ ID NO:78, SEQ ID NO:80, SEQ ID NO:82, SEQ ID NO:88, SEQ ID NO:90, SEQ ID NO:92, SEQ ID NO:96, SEQ ID NO:102, SEQ ID NO:106, SEQ ID NO:112, SEQ ID NO:116, SEQ ID NO:118, SEQ ID NO:120, SEQ ID NO:122, SEQ ID NO:124, SEQ ID NO:126, SEQ ID NO:128, SEQ ID NO:130, SEQ ID NO:132, SEQ ID NO:134, SEQ ID NO:136, SEQ ID NO:138, SEQ ID NO:140, SEQ ID NO:142, SEQ ID NO:144, SEQ ID NO:146, SEQ ID NO:148, SEQ ID NO:150, SEQ ID NO:152, SEQ ID NO:154, SEQ ID NO:156, SEQ ID NO:158, SEQ ID NO:160, SEQ ID NO:162, SEQ ID NO:164, SEQ ID NO:166, SEQ ID NO:168, SEQ ID NO:170, SEQ ID NO:172, SEQ ID NO:174, SEQ ID NO:176, SEQ ID NO:178, SEQ ID NO:180, SEQ ID NO:182, SEQ ID NO:184, SEQ ID NO:186, SEQ ID NO:188, SEQ ID NO:190, SEQ ID NO:192, SEQ ID NO:194, SEQ ID NO:196, SEQ ID NO:198, SEQ ID NO:200, SEQ ID NO:202, SEQ ID NO:206, SEQ ID NO:208, SEQ ID NO:210, SEQ ID NO:212, SEQ ID NO:214, SEQ ID NO:216, SEQ ID NO:218, SEQ ID NO:220, SEQ ID NO:222, SEQ ID NO:224, SEQ ID NO:226, SEQ ID NO:228, SEQ ID NO:230, SEQ ID NO:232, and SEQ ID NO:234. 
     In some embodiments, the engineered variant comprises an amino acid sequence selected from the group consisting of SEQ ID NO:66, SEQ ID NO:70, SEQ ID NO:72, SEQ ID NO:80, SEQ ID NO:82, SEQ ID NO:130, SEQ ID NO:136, SEQ ID NO:142, SEQ ID NO:146, SEQ ID NO:150, SEQ ID NO:156, SEQ ID NO:158, SEQ ID NO:160, SEQ ID NO:168, SEQ ID NO:170, SEQ ID NO:172, SEQ ID NO:176, SEQ ID NO:182, SEQ ID NO:184, SEQ ID NO:186, SEQ ID NO:190, SEQ ID NO:192, SEQ ID NO:194, SEQ ID NO:196, SEQ ID NO:198, SEQ ID NO:206, SEQ ID NO:214, SEQ ID NO:216, SEQ ID NO:218, SEQ ID NO:230, and SEQ ID NO:232. 
     In some embodiments, the engineered variant comprises an amino acid sequence selected from the group consisting of SEQ ID NO:222, SEQ ID NO:224, SEQ ID NO:226, SEQ ID NO:228, SEQ ID NO:230, SEQ ID NO:232, and SEQ ID NO:234. 
     In some embodiments, the engineered variant comprises an amino acid sequence selected from the group consisting of SEQ ID NO:60, SEQ ID NO:82, SEQ ID NO:92, SEQ ID NO:104, SEQ ID NO:156, SEQ ID NO:160, SEQ ID NO:162, SEQ ID NO:172, SEQ ID NO:174, SEQ ID NO:176, SEQ ID NO:184, SEQ ID NO:198, SEQ ID NO:202, and SEQ ID NO:230. 
     In some embodiments, the engineered variant comprises an amino acid sequence selected from the group consisting of SEQ ID NO:82, SEQ ID NO:156, SEQ ID NO:160, SEQ ID NO:172, SEQ ID NO:176, SEQ ID NO:184, and SEQ ID NO:198. 
     In some embodiments, the engineered variant comprises an amino acid sequence selected from the group consisting of SEQ ID NO:300, SEQ ID NO:302, and SEQ ID NO:304. In some embodiments, the engineered variant comprises an amino acid sequence of SEQ ID NO:300. 
     In some embodiments, the engineered variant comprises an amino acid sequence selected from the group consisting of SEQ ID NO:314, SEQ ID NO:316, SEQ ID NO:318, and SEQ ID NO:320. In some embodiments, the engineered variant comprises an amino acid sequence of SEQ ID NO:314. In some embodiments, the engineered variant comprises an amino acid sequence of SEQ ID NO:316. In some embodiments, the engineered variant comprises an amino acid sequence of SEQ ID NO:318. In some embodiments, the engineered variant comprises an amino acid sequence of SEQ ID NO:320. 
     In some embodiments, the engineered variant comprises an amino acid sequence of SEQ ID NO:3 with at least 1, at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 21, at least 22, at least 23, at least 24, at least 25, at least 26, at least 27, at least 28, at least 29, or at least 30 amino acid substitutions. In some embodiments, the engineered variant comprises an amino acid sequence of SEQ ID NO:3 with 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 amino acid substitutions. 
     In some embodiments, the engineered variant comprises at least one immutable amino acid in a flavin adenine dinucleotide (FAD) binding domain, a berberine bridge enzyme (BBE) domain, or a combination of the foregoing. In some embodiments, the engineered variant comprises at least 1, at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, or at least 15 immutable amino acids in the FAD binding domain. In some embodiments, the engineered variant comprises at least 1, at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, or at least 15 immutable amino acids in the BBE domain. 
     In some embodiments, the engineered variant comprises at least one immutable amino acid selected from the group consisting of A28, F34, L35, C37, L64, N70, P87, I93, C99, R108, R110, G112, E117, G118, 5120, P126, F127, D131, D141, W148, G152, A153, L155, G156, E157, Y159, Y160, N163, A173, G174, C176, P177, T178, V179, G182, G183, H184, F185, G187, G188, G189, Y190, G191, P192, L193, R195, A201, D202, I205, D206, V210, G214, G223, D225, L226, F227, W228, R231, G234, 5237, F238, G239, K245, I246, L248, V251, V259, Q276, F312, 5313, L323, C341, F352, 5354, F380, K381, I382, K383, D385, Y386, I391, G419, M422, I425, I430, P431, P433, H434, R435, G437, Y440, W443, Y444, I464, Y465, M468, T469, Y471, V472, P476, R484, N498, A502, N513, F514, K521, N528, F529, E533, Q534, and S535. In some embodiments, the engineered variant comprises at least one immutable amino acid selected from the group consisting of C37, N70, I93, C99, E117, 5120, F127, D131, G156, E157, Y159, G174, C176, G182, G183, F185, G187, G188, G189, Y190, G191, P192, R195, D202, D206, G214, W228, G234, F238, L248, Q276, 5313, L323, S354, K381, K383, D385, G419, M422, R435, Y440, W443, Y444, Y471, P476, N513, F514, N528, and Q534. In some embodiments, the engineered variant comprises at least one immutable amino acid selected from the group consisting of A28, F34, L35, C37, L64, N70, P87, I93, C99, R108, R110, G112, E117, G118, 5120, P126, F127, D131, D141, W148, G152, A153, L155, G156, E157, Y159, Y160, N163, A173, G174, C176, P177, T178, V179, G182, G183, H184, F185, G187, G188, G189, Y190, G191, P192, L193, R195, A201, D202, I205, D206, V210, G214, G223, D225, L226, F227, W228, R231, G234, 5237, F238, G239, K245, I246, L248, V251, V259, Q276, F312, 5313, L323, C341, F352, S354, F380, K381, I382, K383, D385, Y386, 1391, M412, L415, G419, M422, I425, I430, P431, P433, H434, R435, G437, Y440, W443, Y444, I445, I464, Y465, M468, T469, Y471, V472, P476, R484, N498, A502, N513, F514, K521, N528, F529, E533, Q534, and S535. 
     In some embodiments, the engineered variant comprises at least 1, at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 21, at least 22, at least 23, at least 24, or at least 25 immutable amino acids. 
     In some embodiments, the engineered variant produces cannabidiolic acid (CBDA) from cannabigerolic acid (CBGA) in a greater amount, as measured in mg/L or mM, than an amount of CBDA produced from CBGA by a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3 under similar conditions for the same length of time. In some embodiments, the engineered variant produces cannabidiolic acid (CBDA) from cannabigerolic acid (CBGA) in an amount, as measured in mg/L or mM, at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 100%, at least 150% at least 200%, at least 500%, or at least 1000% greater than an amount of CBDA produced from CBGA by a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3 under similar conditions for the same length of time. 
     In some embodiments, the engineered variant produces cannabidiolic acid (CBDA) from cannabigerolic acid (CBGA) in an increased ratio of CBDA over tetrahydrocannabinolic acid (THCA) compared to that produced by a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3 under similar conditions for the same length of time. In some embodiments, the engineered variant produces CBDA from CBGA in a ratio of CBDA over THCA of about 11:1, about 11.5:1, about 12:1, about 12.5:1, about 13:1, about 13.5:1, about 14:1, about 14.5:1, about 15:1, about 15.5:1, about 16:1, about 16.5:1, about 17:1, about 17.5:1, about 18:1, about 18.5:1, about 19:1, about 19.5:1, about 20:1, about 25:1, about 30:1, about 35:1, about 40:1, about 45:1, about 50:1, about 60:1, about 70:1, about 80:1, about 90:1, about 100:1, about 150:1, about 200:1, about 500:1, or greater than about 500:1. 
     In some embodiments, the engineered variant produces cannabidiolic acid (CBDA) from cannabigerolic acid (CBGA) in an increased ratio of CBDA over cannabichromenic acid (CBCA) compared to that produced by a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3 under similar conditions for the same length of time. In some embodiments, the engineered variant produces CBDA from CBGA in a ratio of CBDA over CBCA of about 11:1, about 11.5:1, about 12:1, about 12.5:1, about 13:1, about 13.5:1, about 14:1, about 14.5:1, about 15:1, about 15.5:1, about 16:1, about 16.5:1, about 17:1, about 17.5:1, about 18:1, about 18.5:1, about 19:1, about 19.5:1, about 20:1, about 25:1, about 30:1, about 35:1, about 40:1, about 45:1, about 50:1, about 60:1, about 70:1, about 80:1, about 90:1, about 100:1, about 150:1, about 200:1, about 500:1, or greater than about 500:1. 
     In some embodiments, the engineered variant comprises a truncation at an N-terminus, at a C-terminus, or at both the N- and C-termini. In some embodiments, the truncated engineered variant comprises a signal polypeptide or a membrane anchor. In some embodiments, the engineered variant lacks a native signal polypeptide. In some embodiments, the engineered variant comprises a truncation of at least 1, at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, or at least 10 amino acids at the C-terminus. In some embodiments, the engineered variant comprises a truncation of 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acids at the C-terminus. 
     Another aspect of the disclosure relates to a nucleic acid comprising a nucleotide sequence encoding an engineered variant of the disclosure. In some embodiments, the nucleotide sequence encoding the engineered variant of the disclosure is selected from the group consisting of SEQ ID NO:49, SEQ ID NO:51, SEQ ID NO:53, SEQ ID NO:55, SEQ ID NO:57, SEQ ID NO:59, SEQ ID NO:61, SEQ ID NO:63, SEQ ID NO:65, SEQ ID NO:67, SEQ ID NO:69, SEQ ID NO:71, SEQ ID NO:73, SEQ ID NO:75, SEQ ID NO:77, SEQ ID NO:79, SEQ ID NO:81, SEQ ID NO:83, SEQ ID NO:85, SEQ ID NO:87, SEQ ID NO:89, SEQ ID NO:91, SEQ ID NO:93, SEQ ID NO:95, SEQ ID NO:97, SEQ ID NO:99, SEQ ID NO:101, SEQ ID NO:103, SEQ ID NO:105, SEQ ID NO:107, SEQ ID NO:109, SEQ ID NO:111, SEQ ID NO:113, SEQ ID NO:115, SEQ ID NO:117, SEQ ID NO:119, SEQ ID NO:121, SEQ ID NO:123, SEQ ID NO:125, SEQ ID NO:127, SEQ ID NO:129, SEQ ID NO:131, SEQ ID NO:133, SEQ ID NO:135, SEQ ID NO:137, SEQ ID NO:139, SEQ ID NO:141, SEQ ID NO:143, SEQ ID NO:145, SEQ ID NO:147, SEQ ID NO:149, SEQ ID NO:151, SEQ ID NO:153, SEQ ID NO:155, SEQ ID NO:157, SEQ ID NO:159, SEQ ID NO:161, SEQ ID NO:163, SEQ ID NO:165, SEQ ID NO:167, SEQ ID NO:169, SEQ ID NO:171, SEQ ID NO:173, SEQ ID NO:175, SEQ ID NO:177, SEQ ID NO:179, SEQ ID NO:181, SEQ ID NO:183, SEQ ID NO:185, SEQ ID NO:187, SEQ ID NO:189, SEQ ID NO:191, SEQ ID NO:193, SEQ ID NO:195, SEQ ID NO:197, SEQ ID NO:199, SEQ ID NO:201, SEQ ID NO:203, SEQ ID NO:205, SEQ ID NO:207, SEQ ID NO:209, SEQ ID NO:211, SEQ ID NO:213, SEQ ID NO:215, SEQ ID NO:217, SEQ ID NO:219, SEQ ID NO:221, SEQ ID NO:223, SEQ ID NO:225, SEQ ID NO:227, SEQ ID NO:229, SEQ ID NO:231, and SEQ ID NO:233. In some embodiments of the nucleic acids of the disclosure, the nucleotide sequence is codon-optimized. 
     In some embodiments, the nucleotide sequence encoding the engineered variant of the disclosure is selected from the group consisting of SEQ ID NO:49, SEQ ID NO:51, SEQ ID NO:53, SEQ ID NO:55, SEQ ID NO:57, SEQ ID NO:59, SEQ ID NO:61, SEQ ID NO:63, SEQ ID NO:65, SEQ ID NO:67, SEQ ID NO:69, SEQ ID NO:71, SEQ ID NO:73, SEQ ID NO:75, SEQ ID NO:77, SEQ ID NO:79, SEQ ID NO:81, SEQ ID NO:83, SEQ ID NO:85, SEQ ID NO:87, SEQ ID NO:89, SEQ ID NO:91, SEQ ID NO:93, SEQ ID NO:95, SEQ ID NO:97, SEQ ID NO:99, SEQ ID NO:101, SEQ ID NO:103, SEQ ID NO:105, SEQ ID NO:107, SEQ ID NO:109, SEQ ID NO:111, SEQ ID NO:113, SEQ ID NO:115, SEQ ID NO:117, SEQ ID NO:119, SEQ ID NO:121, SEQ ID NO:123, SEQ ID NO:125, SEQ ID NO:127, SEQ ID NO:129, SEQ ID NO:131, SEQ ID NO:133, SEQ ID NO:135, SEQ ID NO:137, SEQ ID NO:139, SEQ ID NO:141, SEQ ID NO:143, SEQ ID NO:145, SEQ ID NO:147, SEQ ID NO:149, SEQ ID NO:151, SEQ ID NO:153, SEQ ID NO:155, SEQ ID NO:157, SEQ ID NO:159, SEQ ID NO:161, SEQ ID NO:163, SEQ ID NO:165, SEQ ID NO:167, SEQ ID NO:169, SEQ ID NO:171, SEQ ID NO:173, SEQ ID NO:175, SEQ ID NO:177, SEQ ID NO:179, SEQ ID NO:181, SEQ ID NO:183, SEQ ID NO:185, SEQ ID NO:187, SEQ ID NO:189, SEQ ID NO:191, SEQ ID NO:193, SEQ ID NO:195, SEQ ID NO:197, SEQ ID NO:199, SEQ ID NO:201, SEQ ID NO:203, SEQ ID NO:205, SEQ ID NO:207, SEQ ID NO:209, SEQ ID NO:211, SEQ ID NO:213, SEQ ID NO:215, SEQ ID NO:217, SEQ ID NO:219, SEQ ID NO:221, SEQ ID NO:223, SEQ ID NO:225, SEQ ID NO:227, SEQ ID NO:229, SEQ ID NO:231, SEQ ID NO:233, SEQ ID NO:299, SEQ ID NO:301, and SEQ ID NO:303. In some embodiments of the nucleic acids of the disclosure, the nucleotide sequence is codon-optimized. 
     In some embodiments, the nucleotide sequence encoding the engineered variant of the disclosure is selected from the group consisting of SEQ ID NO:313, SEQ ID NO:315, SEQ ID NO:317, and SEQ ID NO:319. In some embodiments of the nucleic acids of the disclosure, the nucleotide sequence is codon-optimized. 
     An aspect of the disclosure relates to a method of making a modified host cell for producing a cannabinoid or a cannabinoid derivative, the method comprising introducing one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure into a host cell. 
     Another aspect of the disclosure relates to a vector comprising one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure. 
     An aspect of the disclosure relates to a method of making a modified host cell for producing a cannabinoid or a cannabinoid derivative, the method comprising introducing one or more vectors comprising one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure into a host cell. 
     Another aspect of the disclosure relates to a modified host cell for producing a cannabinoid or a cannabinoid derivative, wherein the modified host cell comprises one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure. 
     In some embodiments of the disclosure, the modified host cell comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a geranyl pyrophosphate:olivetolic acid geranyltransferase (GOT) polypeptide. In certain such embodiments, the GOT polypeptide comprises an amino acid sequence having at least 85% sequence identity to SEQ ID NO:17. In some embodiments, the modified host cell comprises two or more heterologous nucleic acids comprising the nucleotide sequence encoding the GOT polypeptide. 
     In some embodiments of the disclosure, the modified host cell comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a NphB polypeptide. In certain such embodiments, the NphB polypeptide comprises an amino acid sequence having at least 85% sequence identity to SEQ ID NO:294. 
     In some embodiments of the disclosure, the modified host cell comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a tetraketide synthase (TKS) polypeptide and one or more heterologous nucleic acids comprising a nucleotide sequence encoding an olivetolic acid cyclase (OAC) polypeptide. In certain such embodiments, the TKS polypeptide comprises an amino acid sequence having at least 85% sequence identity to SEQ ID NO:19. In some embodiments, the modified host cell comprises three or more heterologous nucleic acids comprising a nucleotide sequence encoding a TKS polypeptide. In some embodiments, the OAC polypeptide comprises an amino acid sequence having at least 85% sequence identity to SEQ ID NO:21 or SEQ ID NO:48. In some embodiments, the modified host cell comprises three or more heterologous nucleic acids comprising a nucleotide sequence encoding an OAC polypeptide. 
     In some embodiments of the disclosure, the modified host cell comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding an acyl-activating enzyme (AAE) polypeptide. In certain such embodiments, the AAE polypeptide comprises an amino acid sequence having at least 85% sequence identity to SEQ ID NO:23. In some embodiments, the modified host cell comprises two or more heterologous nucleic acids comprising a nucleotide sequence encoding an AAE polypeptide. 
     In some embodiments of the disclosure, the modified host cell comprises one or more of the following: a) one or more heterologous nucleic acids comprising a nucleotide sequence encoding a HMG-CoA synthase (HMGS) polypeptide; b) one or more heterologous nucleic acids comprising a nucleotide sequence encoding a truncated 3-hydroxy-3-methyl-glutaryl-CoA reductase (tHMGR) polypeptide; c) one or more heterologous nucleic acids comprising a nucleotide sequence encoding a mevalonate kinase (MK) polypeptide; d) one or more heterologous nucleic acids comprising a nucleotide sequence encoding a phosphomevalonate kinase (PMK) polypeptide; e) one or more heterologous nucleic acids comprising a nucleotide sequence encoding a mevalonate pyrophosphate decarboxylase (MVD1) polypeptide; or f) one or more heterologous nucleic acids comprising a nucleotide sequence encoding a isopentenyl diphosphate isomerase (IDI1) polypeptide. In some embodiments, the IDI1 polypeptide comprises an amino acid sequence having at least 85% sequence identity to SEQ ID NO:25. In some embodiments, the tHMGR polypeptide comprises an amino acid sequence having at least 85% sequence identity to SEQ ID NO:27. In some embodiments, the HMGS polypeptide comprises an amino acid sequence having at least 85% sequence identity to SEQ ID NO:29. In some embodiments, the MK polypeptide comprises an amino acid sequence having at least 85% sequence identity to SEQ ID NO:39. In some embodiments, the PMK polypeptide comprises an amino acid sequence having at least 85% sequence identity to SEQ ID NO:37. In some embodiments, the MVD1 polypeptide comprises an amino acid sequence having at least 85% sequence identity to SEQ ID NO:33. 
     In some embodiments of the disclosure, the modified host cell comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding an acetoacetyl-CoA thiolase polypeptide. In certain such embodiments, the acetoacetyl-CoA thiolase polypeptide comprises an amino acid sequence having at least 85% sequence identity to SEQ ID NO:31. 
     In some embodiments of the disclosure, the modified host cell comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a pyruvate decarboxylase (PDC) polypeptide. In certain such embodiments, the PDC polypeptide comprises an amino acid sequence having at least 85% sequence identity to SEQ ID NO:35. 
     In some embodiments of the disclosure, the modified host cell comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a geranyl pyrophosphate synthetase (GPPS) polypeptide. In certain such embodiments, the GPPS polypeptide comprises an amino acid sequence having at least 85% sequence identity to SEQ ID NO:41. 
     In some embodiments of the disclosure, the modified host cell comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a KAR2 polypeptide. In certain such embodiments, the KAR2 polypeptide comprises an amino acid sequence having at least 85% sequence identity to SEQ ID NO:5. In some embodiments, the modified host cell comprises two or more heterologous nucleic acids comprising a nucleotide sequence encoding a KAR2 polypeptide. 
     In some embodiments of the disclosure, the modified host cell comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a PDI1 polypeptide. In certain such embodiments, the PDI1 polypeptide comprises an amino acid sequence having at least 85% sequence identity to SEQ ID NO:9. 
     In some embodiments of the disclosure, the modified host cell comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding an IRE1 polypeptide. In certain such embodiments, the IRE1 polypeptide comprises an amino acid sequence having at least 85% sequence identity to SEQ ID NO:11 or SEQ ID NO:296. 
     In some embodiments of the disclosure, the modified host cell comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding an ERO1 polypeptide. In certain such embodiments, the ERO1 polypeptide comprises an amino acid sequence having at least 85% sequence identity to SEQ ID NO:7. 
     In some embodiments of the disclosure, the modified host cell comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a FAD1 polypeptide. In certain such embodiments, the FAD1 polypeptide comprises an amino acid sequence having at least 85% sequence identity to SEQ ID NO:298. 
     In some embodiments of the disclosure, the modified host cell comprises a deletion or downregulation of one or more genes encoding a PEP4 polypeptide. In certain such embodiments, the PEP4 polypeptide comprises an amino acid sequence having at least 85% sequence identity to SEQ ID NO:15. 
     In some embodiments of the disclosure, the modified host cell comprises a deletion or downregulation of one or more genes encoding a ROT2 polypeptide. In certain such embodiments, the ROT2 polypeptide comprises an amino acid sequence having at least 85% sequence identity to SEQ ID NO:13. 
     In some embodiments of the disclosure, the modified host cell is a eukaryotic cell. In certain such embodiments, the eukaryotic cell is a yeast cell. In certain such embodiments, the yeast cell is  Saccharomyces cerevisiae . In certain such embodiments, the  Saccharomyces cerevisiae  is a protease-deficient strain of  Saccharomyces cerevisiae.    
     In some embodiments of the disclosure, at least one of the one or more nucleic acids are integrated into the chromosome of the modified host cell. In some embodiments of the disclosure, at least one of the one or more nucleic acids are maintained extrachromosomally (e.g., on a plasmid or artificial chromosome). In some embodiments of the disclosure, at least one of the one or more nucleic acids are operably-linked to an inducible promoter. In some embodiments of the disclosure, at least one of the one or more nucleic acids are operably-linked to a constitutive promoter. 
     In some embodiments of the disclosure, the modified host cell produces a cannabinoid or a cannabinoid derivative in an amount, as measured in mg/L or mM, greater than an amount of the cannabinoid or the cannabinoid derivative produced by a modified host cell comprising one or more nucleic acids comprising a nucleotide sequence encoding a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3, wherein the modified host cell comprising one or more nucleic acids comprising the nucleotide sequence encoding the cannabidiolic acid synthase polypeptide having the amino acid sequence of SEQ ID NO:3 lacks a nucleic acid comprising a nucleotide sequence encoding an engineered variant of the disclosure, grown under similar culture conditions for the same length of time. 
     In some embodiments of the disclosure, the modified host cell produces a cannabinoid or a cannabinoid derivative in an amount, as measured in mg/L or mM, at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 100%, at least 150% at least 200%, at least 500%, or at least 1000% greater than an amount of the cannabinoid or the cannabinoid derivative produced by a modified host cell comprising one or more nucleic acids comprising a nucleotide sequence encoding a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3, wherein the modified host cell comprising one or more nucleic acids comprising the nucleotide sequence encoding the cannabidiolic acid synthase polypeptide having the amino acid sequence of SEQ ID NO:3 lacks a nucleic acid comprising a nucleotide sequence encoding an engineered variant of the disclosure, grown under similar culture conditions for the same length of time. 
     In some embodiments of the disclosure, the modified host cell has a faster growth rate and/or higher biomass yield compared to a growth rate and/or higher biomass yield of a modified host cell comprising one or more nucleic acids comprising a nucleotide sequence encoding a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3, wherein the modified host cell comprising one or more nucleic acids comprising the nucleotide sequence encoding the cannabidiolic acid synthase polypeptide having the amino acid sequence of SEQ ID NO:3 lacks a nucleic acid comprising a nucleotide sequence encoding an engineered variant of the disclosure, grown under similar culture conditions for the same length of time. 
     In some embodiments of the disclosure, the modified host cell has a growth rate and/or higher biomass yield at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 100%, at least 150% at least 200%, at least 500%, or at least 1000% faster than a growth rate and/or higher biomass yield of a modified host cell comprising one or more nucleic acids comprising a nucleotide sequence encoding a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3, wherein the modified host cell comprising one or more nucleic acids comprising the nucleotide sequence encoding the cannabidiolic acid synthase polypeptide having the amino acid sequence of SEQ ID NO:3 lacks a nucleic acid comprising a nucleotide sequence encoding an engineered variant of the disclosure, grown under similar culture conditions for the same length of time. 
     In some embodiments of the disclosure, the modified host cell produces cannabidiolic acid (CBDA) from cannabigerolic acid (CBGA) in an increased ratio of CBDA over tetrahydrocannabinolic acid (THCA) compared to that produced by a modified host cell comprising one or more nucleic acids comprising a nucleotide sequence encoding a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3, wherein the modified host cell comprising one or more nucleic acids comprising the nucleotide sequence encoding the cannabidiolic acid synthase polypeptide having the amino acid sequence of SEQ ID NO:3 lacks a nucleic acid comprising a nucleotide sequence encoding an engineered variant of the disclosure, grown under similar culture conditions for the same length of time. 
     In some embodiments of the disclosure, the modified host cell produces CBDA from CBGA in a ratio of CBDA over THCA of about 11:1, about 11.5:1, about 12:1, about 12.5:1, about 13:1, about 13.5:1, about 14:1, about 14.5:1, about 15:1, about 15.5:1, about 16:1, about 16.5:1, about 17:1, about 17.5:1, about 18:1, about 18.5:1, about 19:1, about 19.5:1, about 20:1, about 25:1, about 30:1, about 35:1, about 40:1, about 45:1, about 50:1, about 60:1, about 70:1, about 80:1, about 90:1, about 100:1, about 150:1, about 200:1, about 500:1, or greater than about 500:1. 
     In some embodiments of the disclosure, the modified host cell produces cannabidiolic acid (CBDA) from cannabigerolic acid (CBGA) in an increased ratio of CBDA over cannabichromenic acid (CBCA) compared to that produced by a modified host cell comprising one or more nucleic acids comprising a nucleotide sequence encoding a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3, wherein the modified host cell comprising one or more nucleic acids comprising the nucleotide sequence encoding the cannabidiolic acid synthase polypeptide having the amino acid sequence of SEQ ID NO:3 lacks a nucleic acid comprising a nucleotide sequence encoding an engineered variant of the disclosure, grown under similar culture conditions for the same length of time. 
     In some embodiments of the disclosure, the modified host cell produces CBDA from CBGA in a ratio of CBDA over CBCA of about 11:1, about 11.5:1, about 12:1, about 12.5:1, about 13:1, about 13.5:1, about 14:1, about 14.5:1, about 15:1, about 15.5:1, about 16:1, about 16.5:1, about 17:1, about 17.5:1, about 18:1, about 18.5:1, about 19:1, about 19.5:1, about 20:1, about 25:1, about 30:1, about 35:1, about 40:1, about 45:1, about 50:1, about 60:1, about 70:1, about 80:1, about 90:1, about 100:1, about 150:1, about 200:1, about 500:1, or greater than about 500:1. 
     Another aspect of the disclosure relates to a method of producing a cannabinoid or a cannabinoid derivative, the method comprising: a) culturing a modified host cell of the disclosure in a culture medium. In certain such embodiments, the method comprises: b) recovering the produced cannabinoid or cannabinoid derivative. In some embodiments, the culture medium comprises a carboxylic acid. In certain such embodiments, the carboxylic acid is an unsubstituted or substituted C 3 -C 18  carboxylic acid. In certain such embodiments, the unsubstituted or substituted C 3 -C 18  carboxylic acid is an unsubstituted or substituted hexanoic acid. In some embodiments, the culture medium comprises olivetolic acid or an olivetolic acid derivative. In some embodiments, the cannabinoid is cannabidiolic acid, cannabidiol, cannabidivarinic acid, or cannabidivarin. In some embodiments, the culture medium comprises a fermentable sugar. In some embodiments, the culture medium comprises a pretreated cellulosic feedstock. In some embodiments, the culture medium comprises a non-fermentable carbon source. In certain such embodiments, the non-fermentable carbon source comprises ethanol. In some embodiments, the cannabinoid or the cannabinoid derivative is produced in an amount of more than 100 mg/L culture medium. 
     In some embodiments of the methods of the disclosure, the cannabinoid or the cannabinoid derivative is produced in an amount, as measured in mg/L or mM, greater than an amount of the cannabinoid or the cannabinoid derivative produced in a method comprising culturing a modified host cell comprising one or more nucleic acids comprising a nucleotide sequence encoding a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3 instead of the modified host cell of the disclosure, wherein the modified host cell comprising one or more nucleic acids comprising the nucleotide sequence encoding the cannabidiolic acid synthase polypeptide having the amino acid sequence of SEQ ID NO:3 lacks a nucleic acid comprising a nucleotide sequence encoding an engineered variant of the disclosure, and wherein the modified host cell of the disclosure and the modified host cell comprising one or more nucleic acids comprising the nucleotide sequence encoding the cannabidiolic acid synthase polypeptide having the amino acid sequence of SEQ ID NO:3, but lacking a nucleic acid comprising a nucleotide sequence encoding an engineered variant of the disclosure, are cultured under similar culture conditions for the same length of time. 
     In some embodiments of the methods of the disclosure, the cannabinoid or the cannabinoid derivative is produced in an amount, as measured in mg/L or mM, at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 100%, at least 150% at least 200%, at least 500%, or at least 1000% greater than an amount of the cannabinoid or the cannabinoid derivative produced in a method comprising culturing a modified host cell comprising one or more nucleic acids comprising a nucleotide sequence encoding a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3 instead of the modified host cell of the disclosure, wherein the modified host cell comprising one or more nucleic acids comprising the nucleotide sequence encoding the cannabidiolic acid synthase polypeptide having the amino acid sequence of SEQ ID NO:3 lacks a nucleic acid comprising a nucleotide sequence encoding an engineered variant of the disclosure, and wherein the modified host cell of the disclosure and the modified host cell comprising one or more nucleic acids comprising the nucleotide sequence encoding the cannabidiolic acid synthase polypeptide having the amino acid sequence of SEQ ID NO:3, but lacking a nucleic acid comprising a nucleotide sequence encoding an engineered variant of the disclosure, are cultured under similar culture conditions for the same length of time. 
     In some embodiments of the methods of the disclosure, the cannabinoid is cannabidiolic acid (CBDA), and wherein the method produces CBDA in an increased ratio of CBDA over tetrahydrocannabinolic acid (THCA) compared to that produced in a method comprising culturing a modified host cell comprising one or more nucleic acids comprising a nucleotide sequence encoding a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3 instead of the modified host cell of the disclosure, wherein the modified host cell comprising one or more nucleic acids comprising the nucleotide sequence encoding the cannabidiolic acid synthase polypeptide having the amino acid sequence of SEQ ID NO:3 lacks a nucleic acid comprising a nucleotide sequence encoding an engineered variant of the disclosure, grown under similar culture conditions for the same length of time. 
     In some embodiments of the methods of the disclosure, the cannabinoid is cannabidiolic acid (CBDA), and wherein the method produces CBDA in an increased ratio of CBDA over cannabichromenic acid (CBCA) compared to that produced in a method comprising culturing a modified host cell comprising one or more nucleic acids comprising a nucleotide sequence encoding a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3 instead of the modified host cell of the disclosure, wherein the modified host cell comprising one or more nucleic acids comprising the nucleotide sequence encoding the cannabidiolic acid synthase polypeptide having the amino acid sequence of SEQ ID NO:3 lacks a nucleic acid comprising a nucleotide sequence encoding an engineered variant of the disclosure, grown under similar culture conditions for the same length of time. 
     An aspect of the disclosure relates to a method of producing a cannabinoid or a cannabinoid derivative, the method comprising use of an engineered variant of the disclosure. In certain such embodiments, the method comprises recovering the produced cannabinoid or cannabinoid derivative. In some embodiments of the methods of the disclosure, the cannabinoid is cannabidiolic acid, cannabidiol, cannabidivarinic acid, or cannabidivarin. 
     In some embodiments of the methods of the disclosure, the cannabinoid or the cannabinoid derivative is produced in an amount, as measured in mg/L or mM, greater than an amount of the cannabinoid or the cannabinoid derivative produced in a method comprising use of a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3 instead of the engineered variant of the disclosure, wherein the engineered variant of the disclosure and the cannabidiolic acid synthase polypeptide having the amino acid sequence of SEQ ID NO:3 are used under similar conditions for the same length of time. 
     In some embodiments of the methods of the disclosure, the cannabinoid or the cannabinoid derivative is produced in an amount, as measured in mg/L or mM, at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 100%, at least 150% at least 200%, at least 500%, or at least 1000% greater than an amount of the cannabinoid or the cannabinoid derivative produced in a method comprising use of a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3 instead of the engineered variant of the disclosure, wherein the engineered variant of the disclosure and the cannabidiolic acid synthase polypeptide having the amino acid sequence of SEQ ID NO:3 are used under similar conditions for the same length of time. 
     In some embodiments of the methods of the disclosure, the cannabinoid is cannabidiolic acid (CBDA), and wherein the method produces CBDA in an increased ratio of CBDA over tetrahydrocannabinolic acid (THCA) compared to that produced in a method comprising use of a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3 instead of the engineered variant of the disclosure, wherein the engineered variant of the disclosure and the cannabidiolic acid synthase polypeptide having the amino acid sequence of SEQ ID NO:3 are used under similar conditions for the same length of time. 
     In some embodiments of the methods of the disclosure, the method produces CBDA from CBGA in a ratio of CBDA over THCA of about 11:1, about 11.5:1, about 12:1, about 12.5:1, about 13:1, about 13.5:1, about 14:1, about 14.5:1, about 15:1, about 15.5:1, about 16:1, about 16.5:1, about 17:1, about 17.5:1, about 18:1, about 18.5:1, about 19:1, about 19.5:1, about 20:1, about 25:1, about 30:1, about 35:1, about 40:1, about 45:1, about 50:1, about 60:1, about 70:1, about 80:1, about 90:1, about 100:1, about 150:1, about 200:1, about 500:1, or greater than about 500:1. 
     In some embodiments of the methods of the disclosure, the cannabinoid is cannabidiolic acid (CBDA), and wherein the method produces CBDA in an increased ratio of CBDA over cannabichromenic acid (CBCA) compared to that produced in a method comprising use of a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3 instead of the engineered variant of the disclosure, wherein the engineered variant of the disclosure and the cannabidiolic acid synthase polypeptide having the amino acid sequence of SEQ ID NO:3 are used under similar conditions for the same length of time. 
     In some embodiments of the methods of the disclosure, the method produces CBDA from CBGA in a ratio of CBDA over CBCA of about 11:1, about 11.5:1, about 12:1, about 12.5:1, about 13:1, about 13.5:1, about 14:1, about 14.5:1, about 15:1, about 15.5:1, about 16:1, about 16.5:1, about 17:1, about 17.5:1, about 18:1, about 18.5:1, about 19:1, about 19.5:1, about 20:1, about 25:1, about 30:1, about 35:1, about 40:1, about 45:1, about 50:1, about 60:1, about 70:1, about 80:1, about 90:1, about 100:1, about 150:1, about 200:1, about 500:1, or greater than about 500:1. 
     Another aspect of the disclosure relates to a method of screening an engineered variant of a cannabidiolic acid synthase (CBDAS) polypeptide comprising an amino acid sequence of SEQ ID NO:3 with one or more amino acid substitutions, the method comprising: a) dividing a population of host cells into a control population and a test population; b) co-expressing in the control population a CBDAS polypeptide having an amino acid sequence of SEQ ID NO:3 and a comparison cannabinoid synthase polypeptide, wherein the CBDAS polypeptide having an amino acid sequence of SEQ ID NO:3 can convert cannabigerolic acid (CBGA) to a first cannabinoid, cannabidiolic acid (CBDA), and the comparison cannabinoid synthase polypeptide can convert the same CBGA to a different second cannabinoid; c) co-expressing in the test population the engineered variant and the comparison cannabinoid synthase polypeptide, wherein the engineered variant may convert CBGA to the same first cannabinoid, cannabidiolic acid (CBDA), as the CBDAS polypeptide having an amino acid sequence of SEQ ID NO:3, and wherein the comparison cannabinoid synthase polypeptide can convert the same CBGA to the second cannabinoid and is expressed at similar levels in the test population and in the control population; d) measuring a ratio of the first cannabinoid, cannabidiolic acid (CBDA), over the second cannabinoid produced by both the test population and the control population; and e) measuring an amount, in mg/L or mM, of the first cannabinoid produced by both the test population and the control population. In certain such embodiments, the test population is identified as comprising an engineered variant having improved in vivo performance compared to the cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3, wherein improved in vivo performance is demonstrated by an increase in the ratio of the first cannabinoid over the second cannabinoid produced by the test population compared to that produced by the control population under similar culture conditions for the same length of time. In some embodiments of the method of screening the engineered variant of a CBDAS polypeptide, the test population is identified as comprising an engineered variant having improved in vivo performance compared to the cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3 by producing the first cannabinoid in a greater amount, as measured in mg/L or mM, by the test population compared to the amount produced by the control population under similar culture conditions for the same length of time. 
     In some embodiments of the method of screening the engineered variant of a CBDAS polypeptide, the cannabinoid synthase polypeptide is a tetrahydrocannabinolic acid synthase polypeptide. In certain such embodiments, the tetrahydrocannabinolic acid synthase polypeptide comprises an amino acid sequence having at least 85% sequence identity to SEQ ID NO:44. In some embodiments of the method of screening the engineered variant of a CBDAS polypeptide, the second cannabinoid is tetrahydrocannabinolic acid (THCA). 
     In some embodiments of the method of screening the engineered variant of a CBDAS polypeptide, the engineered variant is an engineered variant of the disclosure. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIGS. 1A, 1B, and 1C  depict expression constructs used in the production of the S29 strain. The expression constructs depicted in  FIGS. 1A, 1B, and 1C  were also used in the production of the following strains: S61, S122, S171, S181, S206, S220, S241, S270, S478, S487, S510, S562, S579, S606-S791, S1100-S1120, S935, S938, S940-S946, and S1205-S1208. Throughout the figures, in addition to the specified coding sequences from Table 1, construct maps depict regulatory, non-coding and genomic cassette sequences described in Table 6. Construct maps also depict genes denoted with a preceding “m” (e.g., mERG13), which specify open reading frames from Table 1 with 200-250 base pairs (bp) of downstream regulatory (terminator) sequence. Arrows in construct maps indicate the directionality of certain DNA parts. The “!” preceding a part name is an output of the DNA design software used, is redundant with the arrow directionality, and can be ignored. 
         FIG. 2  depicts an expression construct used in the production of the S181 strain. The expression construct depicted in  FIG. 2  was also used in the production of following strains: S220, S241, S270, S478, S487, S562, S579, S606-S791, S935, S938, S940-S946, and S1205-S1208. 
         FIG. 3  depicts an expression construct used in the production of the S220 strain. The expression construct depicted in  FIG. 3  was also used in the production of following strains: S241, S270, S478, S487, S562, S579, S606-S791, S935, S938, S940-S946, and S1205-S1208. 
         FIG. 4  depicts expression constructs used in the production of the S241 strain. The expression constructs depicted in  FIG. 4  were also used in the production of following strains: S270, S478, S487, S562, S579, S606-S791, S935, S938, S940-S946, and S1205-51208. 
         FIG. 5  depicts a landing pad construct used in the production of the S61 strain. The construct depicted in  FIG. 5  was also used in the production of the following strains: S122, S171, S181, S220, S241, S270, S478, S487, S562, S579, S606-S791, S935, S938, S940-S946, and S1205-S1208. 
         FIG. 6  depicts expression constructs used in the production of the S122 strain. The expression constructs depicted in  FIG. 6  were also used in the production of the following strains: S171, S181, S220, S241, S270, S478, S487, S562, S579, S606-S791, S935, S938, S940-S946, and S1205-S1208. 
         FIG. 7  depicts an expression construct used in the production of the S171 strain. The expression construct depicted in  FIG. 7  was also used in the production of the following strains: S181, S220, S241, S270, S478, S487, S562, S579, S606-S791, S935, S938, S940-S946, and S1205-S1208. 
         FIG. 8  depicts expression constructs used in the production of the S270 strain. The expression constructs depicted in  FIG. 8  were also used in the production of the following strains: S478, S487, S562, S579, S606-S791, S935, S938, S940-S946, and S1205-S1208. 
         FIG. 9  depicts expression constructs used in the production of the S478 strain. The expression constructs depicted in  FIG. 9  were also used in the production of the following strains: S562 and S606-S698. 
         FIG. 10  depicts expression constructs used in the production of the S487 strain. The expression constructs depicted in  FIG. 10  were also used in the production of the following strains: S579, S699-S791, S935, S938, S940-S946, and S1205-S1208. 
         FIG. 11  depicts an expression construct used in the production of the S562, S579, and S1100 strains. 
         FIG. 12  depicts an expression construct used in the production of the S606-S791, S935, S938, S940-S946, S1101-S1120, and S1205-S1208 strains. 
         FIGS. 13A and 13B  depict expression constructs used in the production of S206. The expression constructs depicted in  FIGS. 13A and 13B  were also used in the production of following strains: S510 and S1100-S1120. 
         FIG. 14  depicts an expression construct used in the production of the S510 strain. The expression construct depicted in  FIG. 14  was also used in the production of the following strains: S1100-S1120. 
     
    
    
     DETAILED DESCRIPTION 
     Synthetic biology allows for the engineering of industrial host organisms—e.g., microbes—to convert simple sugar feedstocks into medicines. This approach includes identifying genes that produce the target molecules and optimizing their activities in the industrial host. Microbial production can be significantly cost-advantaged over agriculture and chemical synthesis, less variable, and allow tailoring of the target molecule. However, reconstituting or creating a pathway to produce a target molecule in an industrial host organism can require significant engineering of both the pathway genes and the host. The present disclosure provides engineered variants of a cannabidiolic acid synthase (CBDAS) polypeptide comprising an amino acid sequence of SEQ ID NO:3 with one or more amino acid substitutions, nucleic acids comprising nucleotide sequences encoding said engineered variants, methods of making modified host cells comprising said nucleic acids, modified host cells for producing cannabinoids or cannabinoid derivatives, methods of producing cannabinoids or cannabinoid derivatives, and methods of screening engineered variants of the CBDAS polypeptide. The engineered variants of the disclosure may be useful for producing cannabinoids or cannabinoid derivatives (e.g., non-naturally occurring cannabinoids). The modified host cells of the disclosure may be useful for producing cannabinoids or cannabinoid derivatives (e.g., non-naturally occurring cannabinoids) and/or for expressing engineered variants of the disclosure. The disclosure also provides for modified host cells for expressing the engineered variants of the disclosure. Additionally, the disclosure provides for preparation of engineered variants of the disclosure. 
     Cannabinoid synthase polypeptides, such as tetrahydrocannabinolic acid synthase, cannabichromenic acid synthase, or cannabidiolic acid synthase polypeptides, play an important role in the biosynthesis of cannabinoids. However, reconstituting their activity in a modified host cell has proven challenging, hampering progress in the production of cannabinoids or cannabinoid derivatives. Cannabinoid synthases must successfully traverse the secretory pathway to fold and function properly. These secreted plant enzymes have not evolved to be expressed in a yeast cell, and as a result have poor activity, with limited conversion of their substrate cannabigerolic acid (CBGA) into cannabidiolic acid (CBDA), cannabichromenic acid (CBCA), or tetrahydrocannabinolic acid (THCA). A simple method to increase activity of an enzyme is to increase its copy number (expression). However, expression of cannabinoid synthase genes, such as CBDAS and tetrahydrocannabinolic acid synthase (THCAS) genes, in yeast is toxic (likely owing to misfolding of the protein), frustrating straightforward attempts to boost activity by integrating multiple copies of the genes. Product profile presents another problem. While the primary product of the natural CBDAS enzyme is CBDA, the enzyme also makes significant amounts of THCA and CBCA, undesired byproducts, which would require expensive additional downstream purification steps to separate in an industrial process. 
     For these reasons, the natural cannabinoid synthase enzymes, such as CBDAS or THCAS enzymes, are not optimal for industrial purposes, and improved enzymes are required. Parameters of interest include catalytic activity, product profile, enzyme stability, and pH and temperature optima. Enzyme improvement is typically accomplished by coupling the generation of diversity (a library of engineered variants) to a screen or selection for the properties of interest. DNA libraries encoding engineered variants can be generated in a variety of ways. For example, libraries can be generated using error prone PCR using the wild type gene sequence as a template. The resulting library can be quite large, consisting of genes with variable numbers of mutations at random positions. Error prone PCR is inexpensive and convenient but has several drawbacks. First, instead of a precise number of mutations per construct, a distribution is obtained. This presents an unfortunate trade-off. A distribution centered around a low number of mutations will include a significant amount of zero-mutation wild-type constructs that waste screening capacity. A distribution centered around a higher number of mutations is likely to generate constructs that have accumulated loss of function mutations that would prevent identification of the desired gain of function mutations. Second, error prone PCR introduces mutational bias (an intrinsic property of the low fidelity polymerases used) which means that the library underrepresents certain types of mutation. A powerful alternative to error prone PCR is saturation mutagenesis, which involves synthesis of a library containing every possible amino acid at every position in the protein. Recent advances in DNA synthesis technologies have improved the quality of these libraries significantly. 
     Once a library encoding engineered variants is generated, it is necessary to select or screen for engineered variants with the properties of interest. This can be accomplished by using a protein production host to express and purify the engineered variants, followed by testing in vitro. Such an approach allows careful measurement of the engineered variants&#39; kinetic parameters and assessment of performance under carefully controlled conditions. However, for application in an engineered microbial strain, in vitro data can be highly misleading as no in vitro system can represent the cellular milieu accurately. In this case, the best option is to test the engineered variants in the exact context they must eventually perform—inside an engineered production strain. In the case of the cannabinoid synthases, such a production strain would be engineered to produce the substrate CBGA in excess. One challenge with this in vivo system is that variability is higher. When testing a large library, this variability can make it difficult to distinguish clones with more subtle improvements over the wild type enzyme activity. To address this issue, competition approaches can be valuable. In a competition system, the library engineered variant is expressed alongside a related enzyme (e.g., a library CBDAS construct alongside a THCAS construct). By calculating the ratio of the library enzyme product titer and the invariant competition enzyme titer, it is possible to reduce the variability in data significantly. This is because biological variables tend to affect both of the enzymes in the same way, allowing normalization of the effect. Unlike a kinetic parameter, the competition ratio reports on both changes in both enzyme catalytic parameters such as K m  and K cat  as well as changes in the steady state levels of functional engineered variant (expression and stability). 
     Through use of the above methods, the present disclosure provides engineered variants of a cannabidiolic acid synthase (CBDAS) polypeptide. Herein, over 6500 engineered variants were screened for improvement of titer. CBDA titers were improved (outside standard deviation of wild type) in 68 distinct variants covering 52 positions (nearly 10% of all residues). In a second effort, more intensive screening of 75 active site residues (defined by ˜11 angstrom proximity to the active site tyrosine at position 483) was conducted to identify mutations that reduce THCA (and in some cases CBCA production) by the CBDA synthase polypeptide. These active site residues included: 69, 70, 72, 113, 114, 115, 116, 117, 118, 119, 155, 173, 174, 175, 176, 177, 179, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 232, 234, 236, 289, 291, 353, 380, 381, 382, 383, 384, 385, 386, 412, 413, 414, 415, 416, 418, 432, 434, 441, 442, 443, 444, 445, 446, 461, 465, 477, 478, 479, 480, 481, 482, 483, 484, 485, 486, 487, 488, 489, 505, 508, 509, 510, 532, and 534 of the CBDAS polypeptide of SEQ ID NO:3 from  Cannabis sativa . Engineered variants of the disclosure may be useful for producing cannabinoids or cannabinoid derivatives (e.g., non-naturally occurring cannabinoids). The engineered variants of the disclosure may produce cannabidiolic acid (CBDA) from cannabigerolic acid (CBGA) in a greater amount, as measured in mg/L or mM, than an amount of CBDA produced from CBGA by a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3 under similar conditions for the same length of time. Additionally, the engineered variants of the disclosure may produce CBDA from CBGA in an increased ratio of CBDA over THCA compared to that produced by a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3 under similar conditions for the same length of time. In some embodiments, the engineered variants of the disclosure may produce CBDA from CBGA in an increased ratio of CBDA over CBCA compared to that produced by a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3 under similar conditions for the same length of time. Similar conditions may include the same temperature, pH, buffer, and/or fermentation conditions and in the same culture medium and/or reaction solvent. 
     The methods of the disclosure may include using engineered microorganisms (e.g., modified host cells) or engineered variants of a CBDAS polypeptide of the disclosure to produce naturally-occurring and non-naturally occurring cannabinoids. Naturally-occurring cannabinoids and non-naturally occurring cannabinoids (e.g., cannabinoid derivatives) are challenging to produce using chemical synthesis due to their complex structures. The methods of the disclosure enable the construction of metabolic pathways inside living cells to produce bespoke cannabinoids or cannabinoid derivatives from simple precursors such as sugars and carboxylic acids. One or more nucleic acids (e.g., heterologous nucleic acids) disclosed herein comprising nucleotide sequences encoding one or more polypeptides or engineered variants disclosed herein can be introduced into host microorganisms allowing for the stepwise conversion of inexpensive feedstocks, e.g., sugar, into final products: cannabinoids or cannabinoid derivatives. These products can be specified by the choice and construction of expression constructs or vectors comprising one or more nucleic acids (e.g., heterologous nucleic acids) disclosed herein, allowing for the efficient bioproduction of chosen cannabinoids, such as CBD and CBDA and less common cannabinoid species found at low levels in  Cannabis ; or cannabinoid derivatives. Bioproduction also enables synthesis of cannabinoids or cannabinoid derivatives with defined stereochemistries, which is challenging to do using chemical synthesis. To produce cannabinoids or cannabinoid derivatives and create biosynthetic pathways within modified host cells, modified host cells comprising one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of a CBDAS polypeptide of the disclosure may express or overexpress combinations of heterologous nucleic acids comprising nucleotide sequences encoding one or more polypeptides involved in cannabinoid or cannabinoid precursor (e.g., geranylpyrophosphate (GPP), prenyl phosphates, olivetolic acid, or hexanoyl-CoA) biosynthesis. In some embodiments, the nucleotide sequences encoding the polypeptides involved in cannabinoid or cannabinoid precursor (e.g., geranylpyrophosphate (GPP), prenyl phosphates, olivetolic acid, or hexanoyl-CoA) biosynthesis are codon-optimized. 
     The disclosure also provides for modification of the secretory pathway of a host cell modified with one or more nucleic acids (e.g., heterologous nucleic acids) comprising a nucleotide sequence encoding an engineered variant of a CBDAS polypeptide of the disclosure. In some embodiments, the nucleotide sequence encoding the engineered variant of a CBDAS polypeptide is codon-optimized. Modification of the secretory pathway in the host cell may improve expression and solubilization of the engineered variants of the disclosure, as these variants are processed through the secretory pathway. Reconstituting the activity of polypeptides processed through the secretory pathway, such as the engineered variants of the disclosure, in a modified host cell, such as a modified yeast cell, can be challenging and unreliable. Often the expressed engineered variants may be misfolded or mislocalized, resulting in low expression, expressed engineered variants lacking activity, engineered variant aggregation, reduced host cell viability, and/or cell death. Additionally, a backlog of misfolded or mislocalized expressed engineered variants can induce metabolic stress within the modified host cell, harming the modified host cell. The expressed engineered variants may lack necessary posttranslational modifications for folding and activity, such as disulfide bonds, glycosylation and trimming, and cofactors, affording inactive polypeptides or polypeptides with reduced enzymatic activity. 
     The modified host cell of the disclosure may be a modified yeast cell. Yeast cells may be cultured using known conditions, grow rapidly, and are generally regarded as safe. Yeast cells contain the secretory pathway common to all eukaryotes. As disclosed herein, manipulation of that secretory pathway in yeast host cells modified with one or more nucleic acids (e.g., heterologous nucleic acids) comprising a nucleotide sequence encoding an engineered variant of a CBDAS polypeptide of the disclosure may improve expression, folding, and enzymatic activity of the engineered variant as well as viability of the modified yeast host cell, such as modified  Saccharomyces cerevisiae . Further, use of codon-optimized nucleotide sequences encoding engineered variants of the disclosure may improve expression and activity of the engineered variant and viability of modified yeast host cells, such as modified  Saccharomyces cerevisiae.    
     Besides allowing for the production of desired cannabinoids or cannabinoid derivatives, the present disclosure provides a more reliable and economical process than agriculture-based production. Microbial fermentations can be completed in days versus the months necessary for an agricultural crop, are not affected by climate variation or soil contamination (e.g., by heavy metals), and can produce pure products at high titer. 
     The present disclosure also provides a platform for the economical production of high-value cannabinoids, including CBD, as well as derivatives thereof. It also provides for the production of different cannabinoids or cannabinoid derivatives for which no viable method of production exists. Using the engineered variants, methods, and modified host cells disclosed herein, cannabinoids and cannabinoid derivatives may be produced in an amount of over 100 mg per liter of culture medium, over 1 g per liter of culture medium, over 10 g per liter of culture medium, or over 100 g per liter of culture medium. 
     Additionally, the disclosure provides engineered variants of a CBDAS polypeptide, methods, modified host cells, and nucleic acids to produce cannabinoids or cannabinoid derivatives in vivo or in vitro from simple precursors. Nucleic acids (e.g., heterologous nucleic acids) disclosed herein can be introduced into microorganisms (e.g., modified host cells), resulting in expression or overexpression of one or more polypeptides, such as the engineered variants of the disclosure, which can then be utilized in vitro or in vivo for the production of cannabinoids or cannabinoid derivatives. In some embodiments, the in vitro methods are cell-free. 
     Cannabinoid Biosynthesis 
     In addition to one or more nucleic acids (e.g., heterologous nucleic acids) encoding an engineered variant of a CBDAS polypeptide, one or more nucleic acids (e.g., heterologous nucleic acids) encoding one or more polypeptides having at least one activity of a polypeptide present in the cannabinoid or cannabinoid precursor biosynthetic pathway may be useful in the methods and modified host cells for the synthesis of cannabinoids or cannabinoid derivatives. Cannabinoid precursors may include, for example, geranylpyrophosphate (GPP), prenyl phosphates, olivetolic acid, or hexanoyl-CoA. 
     In  Cannabis , cannabinoids are produced from the common metabolite precursors geranylpyrophosphate (GPP) and hexanoyl-CoA by the action of three polypeptides. Hexanoyl-CoA and malonyl-CoA are combined to afford a 12-carbon tetraketide intermediate by a tetraketide synthase (TKS) polypeptide. This tetraketide intermediate is then cyclized by an olivetolic acid cyclase (OAC) polypeptide to produce olivetolic acid. Olivetolic acid is then prenylated with the common isoprenoid precursor GPP by a geranyl pyrophosphate:olivetolic acid geranyltransferase (GOT) polypeptide (e.g., a CsPT4 polypeptide) to produce CBGA, the cannabinoid also known as the “mother cannabinoid.” The engineered variants of a CBDAS polypeptide of the disclosure then convert CBGA into other cannabinoids, e.g., CBDA, etc. In the presence of heat or light, the acidic cannabinoids can undergo decarboxylation, e.g., CBDA producing CBD. 
     GPP and hexanoyl-CoA can be generated through several pathways. One or more nucleic acids (e.g., heterologous nucleic acids) encoding one or more polypeptides having at least one activity of a polypeptide present in these pathways can be useful in the methods and modified host cells for the synthesis of cannabinoids or cannabinoid derivatives. 
     Polypeptides that generate GPP or are part of a biosynthetic pathway that generates GPP may be one or more polypeptides having at least one activity of a polypeptide present in the mevalonate (MEV) pathway (e.g., one or more MEV pathway polypeptides). The term “mevalonate pathway” or “MEV pathway,” as used herein, may refer to the biosynthetic pathway that converts acetyl-CoA to isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP). The mevalonate pathway comprises polypeptides that catalyze the following steps: (a) condensing two molecules of acetyl-CoA to generate acetoacetyl-CoA (e.g., by action of an acetoacetyl-CoA thiolase polypeptide); (b) condensing acetoacetyl-CoA with acetyl-CoA to form hydroxymethylglutaryl-CoA (HMG-CoA) (e.g., by action of a HMG-CoA synthase (HMGS) polypeptide); (c) converting HMG-CoA to mevalonate (e.g., by action of a HMG-CoA reductase (HMGR) polypeptide); (d) phosphorylating mevalonate to mevalonate 5-phosphate (e.g., by action of a mevalonate kinase (MK) polypeptide); (e) converting mevalonate 5-phosphate to mevalonate 5-pyrophosphate (e.g., by action of a phosphomevalonate kinase (PMK) polypeptide); (f) converting mevalonate 5-pyrophosphate to isopentenyl pyrophosphate (e.g., by action of a mevalonate pyrophosphate decarboxylase (MVD1) polypeptide); and (g) converting isopentenyl pyrophosphate (IPP) to dimethylallyl pyrophosphate (DMAPP) (e.g., by action of an isopentenyl pyrophosphate isomerase (IDI1) polypeptide). A geranyl pyrophosphate synthetase (GPPS) polypeptide then acts on IPP and/or DMAPP to generate GPP. 
     Polypeptides that generate hexanoyl-CoA may include polypeptides that generate acyl-CoA compounds or acyl-CoA compound derivatives (e.g., an acyl-activating enzyme polypeptide, a fatty acyl-CoA synthetase polypeptide, or a fatty acyl-CoA ligase polypeptide). Hexanoyl CoA derivatives, acyl-CoA compounds, or acyl-CoA compound derivatives may also be formed via such polypeptides. 
     
       
         
         
             
             
         
       
     
     GPP and hexanoyl-CoA may also be generated through pathways comprising polypeptides that condense two molecules of acetyl-CoA to generate acetoacetyl-CoA and pyruvate decarboxylase polypeptides that generate acetyl-CoA from pyruvate via acetaldehyde. Hexanoyl CoA derivatives, acyl-CoA compounds, or acyl-CoA compound derivatives may also be formed via such pathways. 
     General Information 
     In certain aspects, the practice of the present disclosure will employ, unless otherwise indicated, conventional techniques of molecular biology (including recombinant techniques), microbiology, cell biology, biochemistry, and immunology, which are within the skill of the art. Such techniques are explained fully in the literature: “ Molecular Cloning: A Laboratory Manual ,” second edition (Sambrook et al., 1989); “ Oligonucleotide Synthesis ” (M. J. Gait, ed., 1984); “ Animal Cell Culture ” (R. I. Freshney, ed., 1987); “ Methods in Enzymology ” (Academic Press, Inc.); “ Current Protocols in Molecular Biology ” (F. M. Ausubel et al., eds., 1987, and periodic updates); “ PCR: The Polymerase Chain Reaction ,” (Mullis et al., eds., 1994). Singleton et al.,  Dictionary of Microbiology and Molecular Biology  2nd ed., J. Wiley &amp; Sons (New York, N.Y. 1994), and March,  Advanced Organic Chemistry Reactions, Mechanisms and Structure  4th ed., John Wiley &amp; Sons (New York, N.Y. 1992), provide one skilled in the art with a general guide to many of the terms used in the present application. 
     “Cannabinoid” or “cannabinoid compound” as used herein may refer to a member of a class of unique meroterpenoids found until now only in  Cannabis sativa . Cannabinoids may include, but are not limited to, cannabichromene (CBC) type (e.g., cannabichromenic acid), cannabigerol (CBG) type (e.g., cannabigerolic acid), cannabidiol (CBD) type (e.g., cannabidiolic acid), Δ 9 -trans-tetrahydrocannabinol (Δ 9 -THC) type (e.g., Δ 9 -tetrahydrocannabinolic acid), Δ 8 -trans-tetrahydrocannabinol (Δ 8 -THC) type, cannabicyclol (CBL) type, cannabielsoin (CBE) type, cannabinol (CBN) type, cannabinodiol (CBND) type, cannabitriol (CBT) type, cannabigerolic acid (CBGA), cannabigerolic acid monomethylether (CBGAM), cannabigerol (CBG), cannabigerol monomethylether (CBGM), cannabigerovarinic acid (CBGVA), cannabigerovarin (CBGV), cannabichromenic acid (CBCA), cannabichromene (CBC), cannabichromevarinic acid (CBCVA), cannabichromevarin (CBCV), cannabidiolic acid (CBDA), cannabidiol (CBD), cannabidiol monomethylether (CBDM), cannabidiol-C 4  (CBD-C 4 ), cannabidivarinic acid (CBDVA), cannabidivarin (CBDV), cannabidiorcol (CBD-C 1 ), Δ 9 -tetrahydrocannabinolic acid A (THCA-A), Δ 9 -tetrahydrocannabinolic acid B (THCA-B), Δ 9 -tetrahydrocannabinol (THC), Δ 9 -tetrahydrocannabinolic acid-C4 (THCA-C4), Δ 9 -tetrahydrocannabinol-C4 (THC-C4), Δ 9 -tetrahydrocannabivarinic acid (THCVA), Δ 9 -tetrahydrocannabivarin (THCV), Δ 9 -tetrahydrocannabiorcolic acid (THCA-C 1 ), Δ 9 -tetrahydrocannabiorcol (THC-C 1 ), Δ 7 -cis-iso-tetrahydrocannabivarin, Δ 8 -tetrahydrocannabinolic acid (Δ 8 -THCA), Δ 8 -tetrahydrocannabinol (Δ 8 -THC), cannabicyclolic acid (CBLA), cannabicyclol (CBL), cannabicyclovarin (CBLV), cannabielsoic acid A (CBEA-A), cannabielsoic acid B (CBEA-B), cannabielsoin (CBE), cannabielsoinic acid, cannabicitranic acid, cannabinolic acid (CBNA), cannabinol (CBN), cannabinol methylether (CBNM), cannabinol-C 4 , (CBN-C 4 ), cannabivarin (CBV), cannabinol-C 2  (CNB-C 2 ), cannabiorcol (CBN-C 1 ), cannabinodiol (CBND), cannabinodivarin (CBVD), cannabitriol (CBT), 10-ethyoxy-9-hydroxy-delta-6a-tetrahydrocannabinol, 8,9-dihydroxyl-delta-6a-tetrahydrocannabinol, cannabitriolvarin (CBTVE), dehydrocannabifuran (DCBF), cannabifuran (CBF), cannabichromanon (CBCN), cannabicitran (CBT), 10-oxo-delta-6a-tetrahydrocannabinol (OTHC), delta-9-cis-tetrahydrocannabinol (cis-THC), 3,4,5,6-tetrahydro-7-hydroxy-alpha-alpha-2-trimethyl-9-n-propyl-2,6-methano-2H-1-benzoxocin-5-methanol (OH-iso-HHCV), cannabiripsol (CBR), and trihydroxy-delta-9-tetrahydrocannabinol (triOH-THC). 
     An acyl-CoA compound as detailed herein may include compounds with the following structure: 
     
       
         
         
             
             
         
       
     
     wherein R may be an unsubstituted fatty acid side chain or a fatty acid side chain substituted with or comprising one or more functional and/or reactive groups as disclosed herein (i.e., an acyl-CoA compound derivative). 
     As used herein, a hexanoyl CoA derivative, an acyl-CoA compound derivative, a cannabinoid derivative, or an olivetolic acid derivative may refer to hexanoyl CoA, an acyl-CoA compound, a cannabinoid, or olivetolic acid substituted with or comprising one or more functional and/or reactive groups. Functional groups may include, but are not limited to, azido, halo (e.g., chloride, bromide, iodide, fluorine), methyl, alkyl (including branched and straight chain alkyl groups), alkynyl, alkenyl, methoxy, alkoxy, acetyl, amino, carboxyl, carbonyl, oxo, ester, hydroxyl, thio (e.g., thiol), cyano, aryl, heteroaryl, cycloalkyl, cycloalkenyl, cycloalkylalkenyl, cycloalkylalkynyl, cycloalkenylalkyl, cycloalkenylalkenyl, cycloalkenylalkynyl, heterocyclylalkenyl, heterocyclylalkynyl, heteroarylalkenyl, heteroarylalkynyl, arylalkenyl, arylalkynyl, heterocyclyl, spirocyclyl, heterospirocyclyl, thioalkyl (or alkylthio), arylthio, heteroarylthio, sulfone, sulfonyl, sulfoxide, amido, alkylamino, dialkylamino, arylamino, alkylarylamino, diarylamino, N-oxide, imide, enamine, imine, oxime, hydrazone, nitrile, aralkyl, cycloalkylalkyl, haloalkyl, heterocyclylalkyl, heteroarylalkyl, nitro, thioxo, and the like. Suitable reactive groups may include, but are not necessarily limited to, azide, carboxyl, carbonyl, amine (e.g., alkyl amine (e.g., lower alkyl amine), aryl amine), halide, ester (e.g., alkyl ester (e.g., lower alkyl ester, benzyl ester), aryl ester, substituted aryl ester), cyano, thioester, thioether, sulfonyl halide, alcohol, thiol, succinimidyl ester, isothiocyanate, iodoacetamide, maleimide, hydrazine, alkynyl, alkenyl, and the like. A reactive group may facilitate covalent attachment of a molecule of interest. Suitable molecules of interest may include, but are not limited to, a detectable label; imaging agents; a toxin (including cytotoxins); a linker; a peptide; a drug (e.g., small molecule drugs); a member of a specific binding pair; an epitope tag; ligands for binding by a target receptor; tags to aid in purification; molecules that increase solubility; molecules that enhance bioavailability; molecules that increase in vivo half-life; molecules that target to a particular cell type; molecules that target to a particular tissue; molecules that provide for crossing the blood-brain barrier; molecules to facilitate selective attachment to a surface; and the like. Functional and reactive groups may be unsubstituted or substituted with one or more functional or reactive groups. 
     A cannabinoid derivative or olivetolic acid derivative may also refer to a compound lacking one or more chemical moieties found in naturally-occurring cannabinoids or olivetolic acid, yet retains the core structural features (e.g., cyclic core) of a naturally-occurring cannabinoid or olivetolic acid. Such chemical moieties may include, but are not limited to, methyl, alkyl, alkenyl, methoxy, alkoxy, acetyl, carboxyl, carbonyl, oxo, ester, hydroxyl, and the like. In some embodiments, a cannabinoid derivative or olivetolic acid derivative may also comprise one or more of any of the functional and/or reactive groups described herein. Functional and reactive groups may be unsubstituted or substituted with one or more functional or reactive groups. 
     The term “nucleic acid” or “nucleic acids” used herein, may refer to a polymeric form of nucleotides of any length, either ribonucleotides or deoxynucleotides. Thus, this term may include, but is not limited to, single-, double-, or multi-stranded DNA or RNA, genomic DNA, cDNA, genes, synthetic DNA or RNA, DNA-RNA hybrids, or a polymer comprising purine and pyrimidine bases or other naturally-occurring, chemically or biochemically modified, non-naturally-occurring, or derivatized nucleotide bases. 
     The terms “peptide,” “polypeptide,” and “protein” may be used interchangeably herein, and may refer to a polymeric form of amino acids of any length, which can include coded and non-coded amino acids and chemically or biochemically modified or derivatized amino acids. The polypeptides disclosed herein may include full-length polypeptides, fragments of polypeptides, truncated polypeptides, fusion polypeptides, or polypeptides having modified peptide backbones. The polypeptides disclosed herein may also be variants differing from a specifically recited “reference” polypeptide (e.g., a wild-type polypeptide) by amino acid insertions, deletions, mutations, and/or substitutions. 
     An “engineered variant of a cannabidiolic acid synthase polypeptide” or “engineered variant of the disclosure” may indicate a non-wild type polypeptide having cannabidiolic acid synthase activity. One skilled in the art can measure the cannabidiolic acid synthase activity of the engineered variants using known methods. For example, by GC-MS or LC-MS or as described in the examples provided herein. Engineered variants may have amino acid substitutions compared to a wild type cannabidiolic acid synthase sequence, such as the cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3. In addition to substitutions, engineered variants may comprise truncations, additions, and/or deletions, and/or other mutations compared to a wild type cannabidiolic acid synthase sequence, such as the cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3. Engineered variants may have substitutions compared a non-wild type cannabidiolic acid synthase sequence. In addition to substitutions, engineered variants may comprise truncations, additions, and/or deletions and/or other mutations compared to a non-wild type cannabidiolic acid synthase sequence. The engineered variants described herein contain at least one amino acid residue substitution from a parent cannabidiolic acid synthase polypeptide. In some embodiments, the parent cannabidiolic acid synthase polypeptide is a wild type sequence. In some embodiments, the parent cannabidiolic acid synthase polypeptide is a non-wild type sequence. 
     As used herein, the term “heterologous” may refer to what is not normally found in nature. The term “heterologous nucleotide sequence” or the term “heterologous nucleic acid” may refer to a nucleic acid or nucleotide sequence not normally found in a given cell in nature. A heterologous nucleotide sequence may be: (a) foreign to its host cell (i.e., is “exogenous” to the cell); (b) naturally found in the host cell (i.e., “endogenous”) but present at an unnatural quantity in the cell (i.e., greater or lesser quantity than naturally found in the host cell); (c) be naturally found in the host cell but positioned outside of its natural locus; or (d) be naturally found in the host cell, but with introns removed or added. A heterologous nucleic acid may be: (a) foreign to its host cell (i.e., is “exogenous” to the cell); (b) naturally found in the host cell (i.e., “endogenous”) but present at an unnatural quantity in the cell (i.e., greater or lesser quantity than naturally found in the host cell); or (c) be naturally found in the host cell but positioned outside of its natural locus. In some embodiments, a heterologous nucleic acid may comprise a codon-optimized nucleotide sequence. A codon-optimized nucleotide sequence may be an example of a heterologous nucleotide sequence. In some embodiments, the heterologous nucleic acids disclosed herein may comprise nucleotide sequences that encode a polypeptide disclosed herein, such as an engineered variant of the disclosure, but do not comprise nucleotide sequences that do not encode the polypeptide disclosed herein (e.g., vector sequences, promoters, enhancers, upstream or downstream elements). In some embodiments, the heterologous nucleic acids disclosed herein may comprise nucleotide sequences encoding a polypeptide disclosed herein, such as an engineered variant of the disclosure, along with nucleotide sequences that do not encode the polypeptide disclosed herein (e.g., vector sequences, promoters, enhancers, upstream or downstream elements). 
     The term “heterologous enzyme” or “heterologous polypeptide” may refer to an enzyme or polypeptide that is not normally found in a given cell in nature. The term encompasses an enzyme or polypeptide that is: (a) exogenous to a given cell (i.e., encoded by a nucleic acid that is not naturally present in the host cell or not naturally present in a given context in the host cell); or (b) naturally found in the host cell (e.g., the enzyme or polypeptide is encoded by a nucleic acid that is endogenous to the cell) but that is produced in an unnatural amount (e.g., greater or lesser than that naturally found) in the host cell. For example, a heterologous polypeptide may include a mutated version of a polypeptide naturally occurring in a host cell. 
     As used herein, the term “one or more heterologous nucleic acids” or “one or more heterologous nucleotide sequences” may refer to heterologous nucleic acids comprising one or more nucleotide sequences encoding one or more polypeptides. In some embodiments, the one or more heterologous nucleic acids may comprise a nucleotide sequence encoding one polypeptide. In other embodiments, the one or more heterologous nucleic acids may comprise nucleotide sequences encoding more than one polypeptide. In certain such embodiments, the nucleotide sequences encoding the more than one polypeptide may be present on the same heterologous nucleic acid or on different heterologous nucleic acids, or combinations thereof. In some embodiments, the one or more heterologous nucleic acids may comprise nucleotide sequences encoding multiple copies of the same polypeptide. In certain such embodiments, the nucleotide sequences encoding the multiple copies of the same polypeptide may be present on the same heterologous nucleic acid or on different heterologous nucleic acids, or combinations thereof. In some embodiments, the one or more heterologous nucleic acids may comprise nucleotide sequences encoding multiple copies of different polypeptides. In certain such embodiments, the nucleotide sequences encoding the multiple copies of the different polypeptides may be present on the same heterologous nucleic acid or on different heterologous nucleic acids, or combinations thereof. 
     As used herein, “increased ratio” may refer to an increase in the molar ratio, an increase in the mass (or weight) ratio, an increase in the molarity ratio, or an increase in the mass concentration (e.g., mg/L or mg/mL) ratio between two products produced by a polypeptide, engineered variant, method, and/or modified host cell disclosed herein compared to the molar ratio, mass (or weight) ratio, molarity ratio, or mass concentration ratio between the same two products produced by another polypeptide, engineered variant, method, and/or modified host cell disclosed herein (e.g., a comparative polypeptide, engineered variant, method, and/or modified host cell disclosed herein). For example, a 100:1 ratio of CBDA over THCA produced by an engineered variant disclosed herein would be an increased ratio of CBDA over THCA compared to an 11:1 ratio of CBDA over THCA produced by a different engineered variant disclosed herein. 
     As used herein, a ratio of products produced by a polypeptide, engineered variant, method, and/or modified host cell disclosed herein, such as the ratio of CBDA over THCA, may refer to a molar ratio, a mass (or weight) ratio, molarity ratio, or a mass concentration (e.g., mg/L or mg/mL) ratio. For example, if a modified host cell disclosed herein produced 4 mM CBDA and 1 mM THCA, the ratio of CBDA over THCA would be 4:1. 
     “Operably linked” may refer to an arrangement of elements wherein the components so described are configured so as to perform their usual function. Thus, control sequences operably linked to a coding sequence are capable of effecting the expression of the coding sequence. The control sequences need not be contiguous with the coding sequence, so long as they function to direct the expression thereof. Thus, for example, intervening untranslated yet transcribed sequences can be present between a promoter sequence and the coding sequence and the promoter sequence can still be considered “operably linked” to the coding sequence. 
     “Isolated” may refer to polypeptides or nucleic acids that are substantially or essentially free from components that normally accompany them in their natural state. An isolated polypeptide or nucleic acid may be other than in the form or setting in which it is found in nature. Isolated polypeptides and nucleic acids therefore may be distinguished from the polypeptides and nucleic acids as they exist in natural cells. An isolated nucleic acid or polypeptide may further be purified from one or more other components in a mixture with the isolated nucleic acid or polypeptide, if such components are present. 
     A “modified host cell” (also may be referred to as a “recombinant host cell”) may refer to a host cell into which has been introduced a nucleic acid (e.g., a heterologous nucleic acid), e.g., an expression vector or construct. For example, a modified eukaryotic host cell may be produced through introduction into a suitable eukaryotic host cell of a nucleic acid (e.g., a heterologous nucleic acid). 
     As used herein, a “cell-free system” may refer to a cell lysate, cell extract or other preparation in which substantially all of the cells in the preparation have been disrupted or otherwise processed so that all or selected cellular components, e.g., organelles, proteins, nucleic acids, the cell membrane itself (or fragments or components thereof), or the like, are released from the cell or resuspended into an appropriate medium and/or purified from the cellular milieu. Cell-free systems can include reaction mixtures prepared from purified and/or isolated polypeptides and suitable reagents and buffers. 
     In some embodiments, conservative substitutions may be made in the amino acid sequence of a polypeptide without disrupting the three-dimensional structure or function of the polypeptide. Conservative substitutions may be accomplished by the skilled artisan by substituting amino acids with similar hydrophobicity, polarity, and R-chain length for one another. Additionally, by comparing aligned sequences of homologous proteins from different species, conservative substitutions may be identified by locating amino acid residues that have been mutated between species without altering the basic functions of the encoded proteins. The term “conservative amino acid substitution” may refer to the interchangeability in proteins of amino acid residues having similar side chains. For example, a group of amino acids having aliphatic side chains may consist of glycine, alanine, valine, leucine, and isoleucine; a group of amino acids having aliphatic-hydroxyl side chains may consist of serine and threonine; a group of amino acids having amide containing side chains may consist of asparagine and glutamine; a group of amino acids having aromatic side chains may consist of phenylalanine, tyrosine, and tryptophan; a group of amino acids having basic side chains may consist of lysine, arginine, and histidine; a group of amino acids having acidic side chains may consist of glutamate and aspartate; and a group of amino acids having sulfur containing side chains may consist of cysteine and methionine. Exemplary conservative amino acid substitution groups are: valine-leucine-isoleucine, phenylalanine-tyrosine, lysine-arginine, alanine-valine, and asparagine-glutamine. 
     A polynucleotide or polypeptide has a certain percent “sequence identity” to another polynucleotide or polypeptide, meaning that, when aligned, that percentage of bases or amino acids are the same, and in the same relative position, when comparing the two sequences. Sequence identity can be determined in a number of different manners. To determine sequence identity, sequences can be aligned using various methods and computer programs (e.g., BLAST, T-COFFEE, MUSCLE, MAFFT, etc.), available over the world wide web at sites including ncbi.nlm.nili.gov/BLAST,ebi.ac.uk/Tools/msa/tcoffee/ebi.ac.uk/Tools/msa/muscle/mafft.cbrc.jp/alignment/software/. See, e.g., Altschul et al. (1990), J. Mol. Biol. 215:403-10. 
     Before the present disclosure is further described, it is to be understood that this disclosure is not limited to particular embodiments described, as such may, of course, vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to be limiting. 
     Where a range of values is provided, it is understood that each intervening value, to the tenth of the unit of the lower limit unless the context clearly dictates otherwise, between the upper and lower limit of that range and any other stated or intervening value in that stated range, is encompassed within the disclosure. The upper and lower limits of these smaller ranges may independently be included in the smaller ranges, and are also encompassed within the disclosure, subject to any specifically excluded limit in the stated range. Where the stated range includes one or both of the limits, ranges excluding either or both of those included limits are also included in the disclosure. 
     Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. Although any methods and materials similar or equivalent to those described herein can also be used in the practice or testing of the present disclosure, the preferred methods and materials are now described. All publications mentioned herein are incorporated herein by reference to disclose and describe the methods and/or materials in connection with which the publications are cited. 
     It must be noted that as used herein and in the appended claims, the singular forms “a,” “an,” and “the” may include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to “a cannabinoid compound” or “cannabinoid” may include a plurality of such compounds and reference to “the modified host cell” may include reference to one or more modified host cells and equivalents thereof known to those skilled in the art, and so forth. It is further noted that the claims may be drafted to exclude any optional element. As such, this statement is intended to serve as antecedent basis for use of such exclusive terminology as “solely,” “only” and the like in connection with the recitation of claim elements, or use of a “negative” limitation. 
     It is appreciated that certain features of the disclosure, which are, for clarity, described in the context of separate embodiments, may also be provided in combination in a single embodiment. Conversely, various features of the disclosure, which are, for brevity, described in the context of a single embodiment, may also be provided separately or in any suitable sub-combination. All combinations of the embodiments pertaining to the disclosure are specifically embraced by the present disclosure and are disclosed herein just as if each and every combination was individually and explicitly disclosed. In addition, all sub-combinations of the various embodiments and elements thereof are also specifically embraced by the present disclosure and are disclosed herein just as if each and every such sub-combination was individually and explicitly disclosed herein. 
     Engineered Variants of the Cannabidiolic Acid Synthase (CBDAS) Polypeptide 
     Disclosed herein are engineered variants of a cannabidiolic acid synthase (CBDAS) polypeptide comprising an amino acid sequence of SEQ ID NO:3 with one or more amino acid substitutions. The inventors have identified amino acid locations of the CBDAS polypeptide comprising an amino acid sequence of SEQ ID NO:3 that when substituted, may result in one or more improved properties of the engineered variant. In one aspect of the disclosure, the substitution is at a location corresponding to the position in the CBDAS polypeptide of SEQ ID NO:3 from  Cannabis sativa . The CBDAS polypeptide of SEQ ID NO:3 from  Cannabis sativa  comprises the following domains: 
     1. Signal polypeptide: amino acids 1-28. 
     2. FAD binding domain: amino acids 77-251. 
     3. BBE domain: amino acids 479-537. 
     The CBDAS polypeptide of SEQ ID NO:3 from  Cannabis sativa  also comprises the following domains surface exposed amino acids: 28-33, 35, 36, 39-45, 47-50, 52, 55-59, 61, 62, 65, 66, 69, 71-77, 79, 80, 82, 88, 89, 90, 94, 98, 101, 102, 104, 109, 114, 115, 124, 125, 126, 133, 134, 136-139, 141-145, 148, 150, 161, 164-168, 176, 183, 197, 202, 205, 208, 213, 215-221, 223, 224, 225, 231, 236, 245, 247, 250, 252, 253, 258, 260, 261-267, 270, 273, 274, 277, 278, 280, 281, 283, 284, 285, 291, 293, 295-305, 311, 317, 320, 321, 322, 325, 326, 328, 329, 330, 332, 333, 335, 337-340, 342, 343, 348, 355, 357-367, 370-373, 376, 377, 388, 389, 390, 392, 393, 394, 398, 401, 402, 404, 405, 407, 408, 409, 412, 421, 423-429, 436, 437, 443, 445, 447, 449, 450-453, 455, 456, 459, 462, 463, 466, 467, 469, 470, 471, 474-477, 482, 483, 486, 487, 490, 492-501, 503, 504, 507, 508, 512, 515, 516, 519, 523, 524, 526, 527, 529, 531, and 539-544. 
     Residue positions in the engineered variants discussed herein are identified with respect to a reference amino acid sequence, the CBDAS polypeptide of SEQ ID NO:3 from  Cannabis sativa  (shown herein in Table 1; UniProtKB/Swiss-Prot: A6P6V9.1). Accordingly, a reference to “K165” identifies an amino acid that, in the CBDAS polypeptide of SEQ ID NO:3 from  Cannabis sativa , is the 165 th  amino acid from the N-terminus, wherein the methionine is the first amino acid. The 165 th  amino acid is a lysine (K) in the CBDAS polypeptide of SEQ ID NO:3 from  Cannabis sativa . Those of skill in the art appreciate that the K165 amino acid may have a different position in the CBDAS polypeptides from different species or in different isoforms. These engineered variants are intended to be encompassed by this disclosure. 
     The polypeptide sequence position at which a particular amino acid or amino acid change (“residue difference”) is present is sometimes described herein as “Xn”, or “position n”, where n refers to the amino acid position with respect to the reference sequence. Accordingly, a reference to “X165” identifies an amino acid that, in the CBDAS polypeptide of SEQ ID NO:3 from  Cannabis sativa , is the 165 th  amino acid from the N-terminus. 
     A specific substitution mutation, which is a replacement of the specific amino acid in a reference sequence with a different specified residue may be denoted by the conventional notation “X (number)Y”, where X is the single letter identifier of the amino in the reference sequence, “number” is the amino acid position in the reference sequence, and Y is the single letter identifier of the amino acid substitution in the engineered sequence. Accordingly, a reference to “K165A” identifies a substitution that, in the CBDAS polypeptide of SEQ ID NO:3 from  Cannabis sativa , is the 165 th  amino acid from the N-terminus, lysine, being replaced by alanine. 
     Cannabinoid synthase polypeptides, secreted polypeptides, have structural features that may hinder expression in modified host cells, such as modified yeast cells. Cannabinoid synthase polypeptides comprise disulfide bonds, numerous glycosylation sites, including N-glycosylation sites, and a bicovalently attached flavin adenine dinucleotide (FAD) cofactor moiety. Accordingly, reconstituting the activity of or expressing cannabinoid synthase polypeptides in a modified host cell, such as a modified yeast cell, can be challenging and unreliable. Often these secreted polypeptides are misfolded or mislocalized, resulting in low expression, polypeptides lacking activity, reduced host cell viability, and/or cell death. As disclosed herein, engineered variants may have improved expression, folding, and enzymatic activity compared to the CBDAS polypeptide comprising an amino acid sequence of SEQ ID NO:3. Additionally, expression of the engineered variants of the disclosure may enhance viability of the modified host cells disclosed herein compared to modified host cells expressing a CBDAS polypeptide comprising an amino acid sequence of SEQ ID NO:3. 
     The disclosure provides for an engineered variant of a cannabidiolic acid synthase (CBDAS) polypeptide comprising an amino acid sequence of SEQ ID NO:3 with one or more amino acid substitutions. In certain such embodiments, the engineered variant comprises an amino acid sequence with at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO:3. In some embodiments, the engineered variant comprises an amino acid sequence with at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, or at least 84% sequence identity to SEQ ID NO:3. 
     The disclosure provides for an engineered variant of a cannabidiolic acid synthase (CBDAS) polypeptide comprising an amino acid sequence of SEQ ID NO:3 with one or more amino acid substitutions, wherein the engineered variant comprises at least one amino acid substitution in a signal polypeptide, a flavin adenine dinucleotide (FAD) binding domain, a berberine bridge enzyme (BBE) domain, or a combination of the foregoing. In some embodiments, at least one amino acid substitution is present in the signal polypeptide. In certain such embodiments, the engineered variant comprises at least 1, at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, or at least 15 amino acid substitutions in the signal polypeptide. In some embodiments, the engineered variant comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 amino acid substitutions in the signal polypeptide. In some embodiments, wherein at least one amino acid substitution is present in the signal polypeptide, the engineered variant comprises at least one amino acid substitution at an amino acid selected from the group consisting of X12, X17, X18, and X20. In some embodiments, wherein at least one amino acid substitution is present in the signal polypeptide, the engineered variant comprises at least one amino acid substitution at an amino acid selected from the group consisting of C12, F17, F18, and S20. In some embodiments, wherein at least one amino acid substitution is present in the signal polypeptide, the engineered variant comprises at least one amino acid substitution selected from the group consisting of C12F, F17M, F18T, F18W, and S20G. In some embodiments, at least one amino acid substitution is present in the FAD binding domain. In certain such embodiments, the engineered variant comprises at least 1, at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, or at least 15 amino acid substitutions in the FAD binding domain. In some embodiments, the engineered variant comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 amino acid substitutions in the FAD binding domain. In some embodiments, wherein at least one amino acid substitution is present in the FAD domain, the engineered variant comprises at least one amino acid substitution at an amino acid selected from the group consisting of X97, X98, X100, X103, X109, X124, X125, X129, X132, X137, X143, X149, X161, X165, X167, X168, X170, X171, X172, X175, X180, X181, X196, X208, X235, and X250. In some embodiments, wherein at least one amino acid substitution is present in the FAD domain, the engineered variant comprises at least one amino acid substitution at an amino acid selected from the group consisting of 197, L98, S100, V103, T109, Q124, V125, I129, L132, S137, H143, V149, W161, K165, E167, N168, S170, L171, A172, Y175, C180, A181, N196, H208, A235, and A250. In some embodiments, wherein at least one amino acid substitution is present in the FAD domain, the engineered variant comprises at least one amino acid substitution selected from the group consisting of I97V, L98V, S100A, V103A, V103F, T109V, Q124D, Q124E, Q124N, V125E, V125Q, I129V, L132M, S137G, H143D, V149I, W161K, W161R, W161Y, K165A, E167P, N168S, S170T, L171I, A172V, Y175F, C180A, A181V, N196Q, N196T, N196V, H208T, A235P, and A250T. In some embodiments, at least one amino acid substitution is present in the BBE domain. In certain such embodiments, the engineered variant comprises at least 1, at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, or at least 15 amino acid substitutions in the BBE domain. In some embodiments, the engineered variant comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 amino acid substitutions in the BBE domain. In some embodiments, wherein at least one amino acid substitution is present in the BBE domain, the engineered variant comprises at least one amino acid substitution at an amino acid selected from the group consisting of X499 and X527. In some embodiments, wherein at least one amino acid substitution is present in the BBE domain, the engineered variant comprises at least one amino acid substitution at an amino acid selected from the group consisting of Y499 and N527. In some embodiments, wherein at least one amino acid substitution is present in the BBE domain, the engineered variant comprises at least one amino acid substitution selected from the group consisting of Y499M, Y499V, and N527E. 
     The disclosure provides for an engineered variant of a cannabidiolic acid synthase (CBDAS) polypeptide comprising an amino acid sequence of SEQ ID NO:3 with one or more amino acid substitutions, wherein the engineered variant comprises substitution of at least one surface exposed amino acid. In certain such embodiments, at least one hydrophobic surface exposed amino acid is substituted with a hydrophilic amino acid. In some embodiments, at least one hydrophilic surface exposed amino acid is substituted with a hydrophobic amino acid. In some embodiments, the engineered variant comprises substitution of at least 1, at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, or at least 15 surface exposed amino acids. In some embodiments, the engineered variant comprises substitution of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 surface exposed amino acids. In some embodiments, wherein the engineered variant comprises substitution of at least one surface exposed amino acid, the engineered variant comprises at least one amino acid substitution selected from the group consisting of X31, X43, X49, X50, X55, X56, X57, X61, X62, X71, X109, X124, X125, X137, X143, X161, X165, X167, X168, X208, X250, X260, X326, X389, X428, X466, X499, X527, X541, X542, X543, and X544. In some embodiments, wherein the engineered variant comprises substitution of at least one surface exposed amino acid, the engineered variant comprises at least one amino acid substitution selected from the group consisting of X31, X43, X49, X50, X55, X56, X57, X61, X62, X71, X109, X124, X125, X137, X143, X161, X165, X167, X168, X208, X250, X260, X326, X389, X412, X428, X445, X466, X499, X527, X541, X542, X543, and X544. In some embodiments, wherein the engineered variant comprises substitution of at least one surface exposed amino acid, the engineered variant comprises at least one amino acid substitution selected from the group consisting of R31, P43, L49, K50, Q55, N56, N57, M61, S62, L71, T109, Q124, V125, S137, H143, W161, K165, E167, N168, H208, A250, K260, L326, K389, S428, N466, Y499, N527, R541, H542, R543, and H544. In some embodiments, wherein the engineered variant comprises substitution of at least one surface exposed amino acid, the engineered variant comprises at least one amino acid substitution selected from the group consisting of R31, P43, L49, K50, Q55, N56, N57, M61, S62, L71, T109, Q124, V125, S137, H143, W161, K165, E167, N168, H208, A250, K260, L326, K389, M412, S428, I445, N466, Y499, N527, R541, H542, R543, and H544. In some embodiments, wherein the engineered variant comprises substitution of at least one surface exposed amino acid, the engineered variant comprises at least one amino acid substitution selected from the group consisting of R31Q, P43E, L49E, L49K, L49Q, K50T, Q55E, Q55P, N56E, N57D, N57E, M61H, M61S, M61W, S62N, S62Q, L71A, L71H, L71Q, T109V, Q124D, Q124E, Q124N, V125E, V125Q, S137G, H143D, W161K, W161R, W161Y, K165A, E167P, N168S, H208T, A250T, K260C, K260W, L326I, K389E, S428L, N466D, Y499M, Y499V, N527E, R541E, R541V, H542V, R543A, R543E, H544E, and H544D. In some embodiments, wherein the engineered variant comprises substitution of at least one surface exposed amino acid, the engineered variant comprises at least one amino acid substitution selected from the group consisting of R31Q, P43E, L49E, L49K, L49Q, K50T, Q55E, Q55P, N56E, N57D, N57E, M61H, M61S, M61W, S62N, S62Q, L71A, L71H, L71Q, T109V, Q124D, Q124E, Q124N, V125E, V125Q, S137G, H143D, W161K, W161R, W161Y, K165A, E167P, N168S, H208T, A250T, K260C, K260W, L326I, K389E, M412Q, S428L, I445M, N466D, Y499M, Y499V, N527E, R541E, R541V, H542V, R543A, R543E, H544E, and H544D. Substitution of hydrophobic surface exposed amino acids with hydrophilic amino acids may increase the hydrophilicity of solvent-exposed amino acids, which may improve solubility of the engineered variants of the disclosure in an aqueous (non-trichome) environment. 
     The disclosure provides for an engineered variant, wherein the engineered variant comprises at least one amino acid substitution at an amino acid selected from the group consisting of X12, X17, X18, X20, X31, X33, X43, X49, X50, X51, X55, X56, X57, X59, X61, X62, X63, X66, X71, X75, X97, X98, X100, X103, X109, X124, X125, X129, X132, X137, X143, X149, X161, X165, X167, X168, X170, X171, X172, X175, X180, X181, X196, X208, X235, X250, X256, X260, X268, X309, X310, X316, X326, X378, X389, X406, X428, X439, X466, X474, X499, X527, X538, X541, X542, X543, and X544. In some embodiments, the engineered variant comprises at least one amino acid substitution at an amino acid selected from the group consisting of X12, X17, X18, X20, X31, X33, X43, X49, X50, X51, X55, X56, X57, X59, X61, X62, X63, X66, X71, X75, X97, X98, X100, X103, X109, X124, X125, X129, X132, X137, X143, X149, X161, X165, X167, X168, X170, X171, X172, X175, X180, X181, X196, X208, X235, X250, X256, X260, X268, X309, X310, X316, X326, X378, X389, X406, X412, X415, X428, X439, X445, X466, X474, X499, X527, X538, X541, X542, X543, and X544. In some embodiments, the engineered variant comprises at least one amino acid substitution at an amino acid selected from the group consisting of X31, X43, X49, X50, X51, X55, X56, X57, X61, X62, X71, X97, X100, X103, X109, X124, X125, X129, X132, X137, X143, X149, X161, X165, X167, X168, X170, X171, X172, X175, X180, X181, X196, X208, X235, X250, X256, X260, X268, X309, X310, X316, X326, X378, X389, X428, X439, X466, X474, X499, X527, X538, X541, X542, X543, and X544. In certain such embodiments, the engineered variant comprises at least one amino acid substitution at an amino acid selected from the group consisting of X49, X50, X56, X57, X125, X132, X149, X161, X165, X170, X171, X172, X196, X235, X260, X268, X310, X316, X326, X378, X428, X499, X527, X543, and X544. In some embodiments, the engineered variant comprises at least one amino acid substitution at an amino acid selected from the group consisting of X31, X43, X49, X50, X56, X57, X71, X100, X103, X109, X124, X125, X129, X132, X137, X143, X161, X165, X167, X168, X170, X171, X172, X175, X180, X181, X196, X208, X235, X250, X256, X260, X268, X309, X310, X316, X326, X378, X389, X406, X428, X439, X466, X474, X499, X527, X541, X542, X543, and X544. Such engineered variants may produce CBDA from CBGA in a greater amount, as measured in mg/L or mM, than an amount of CBDA produced from CBGA by a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3 under similar conditions for the same length of time. 
     The disclosure provides for an engineered variant, wherein the engineered variant comprises at least one amino acid substitution at an amino acid selected from the group consisting of X31, X57, X61, X71, X170, X172, X175, X196, X208, X235, X260, X378, X389, and X543. In certain such embodiments, the engineered variant comprises at least one amino acid substitution at an amino acid selected from the group consisting of X57, X170, X172, X196, X235, X260, and X378. In some embodiments, the engineered variant comprises at least one amino acid substitution at an amino acid selected from the group consisting of X412, X415, and X445. In some embodiments, the engineered variant comprises an amino acid substitution at amino acid X445. Such engineered variants may produce CBDA from CBGA in a greater amount, as measured in mg/L or mM, than an amount of CBDA produced from CBGA by a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3 under similar conditions for the same length of time and/or may produce CBDA from CBGA in an increased ratio of CBDA over THCA compared to that produced by a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3 under similar conditions for the same length of time. In some embodiments, such engineered variants may produce CBDA from CBGA in an increased ratio of CBDA over CBCA compared to that produced by a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3 under similar conditions for the same length of time. 
     The disclosure provides for an engineered variant, wherein the engineered variant comprises at least one amino acid substitution at an amino acid selected from the group consisting of C12, F17, F18, S20, R31, N33, P43, L49, K50, L51, Q55, N56, N57, L59, M61, S62, V63, S66, L71, S75, I97, L98, S100, V103, T109, Q124, V125, I129, L132, S137, H143, V149, W161, K165, E167, N168, S170, L171, A172, Y175, C180, A181, N196, H208, A235, A250, M256, K260, L268, H309, T310, F316, L326, G378, K389, E406, S428, L439, N466, K474, Y499, N527, P538, R541, H542, R543, and H544. In some embodiments, the engineered variant comprises at least one amino acid substitution at an amino acid selected from the group consisting of C12, F17, F18, S20, R31, N33, P43, L49, K50, L51, Q55, N56, N57, L59, M61, S62, V63, S66, L71, S75, I97, L98, S100, V103, T109, Q124, V125, I129, L132, S137, H143, V149, W161, K165, E167, N168, S170, L171, A172, Y175, C180, A181, N196, H208, A235, A250, M256, K260, L268, H309, T310, F316, L326, G378, K389, E406, M412, L415, S428, L439, I445, N466, K474, Y499, N527, P538, R541, H542, R543, and H544. In some embodiments, the engineered variant comprises at least one amino acid substitution at an amino acid selected from the group consisting of R31, P43, L49, K50, L51, Q55, N56, N57, M61, S62, L71, I97, S100, V103, T109, Q124, V125, I129, L132, S137, H143, V149, W161, K165, E167, N168, S170, L171, A172, Y175, C180, A181, N196, H208, A235, A250, M256, K260, L268, H309, T310, F316, L326, G378, K389, S428, L439, N466, K474, Y499, N527, P538, R541, H542, R543, and H544. In certain such embodiments, the engineered variant comprises at least one amino acid substitution at an amino acid selected from the group consisting of L49, K50, N56, N57, V125, L132, V149, W161, K165, S170, L171, A172, N196, A235, K260, L268, T310, F316, L326, G378, S428, Y499, N527, H543, and H544. In some embodiments, the engineered variant comprises at least one amino acid substitution at an amino acid selected from the group consisting of R31, P43, L49, K50, N56, N57, L71, S100, V103, T109, Q124, V125, 1129, L132, S137, H143, W161, K165, E167, N168, S170, L171, A172, Y175, C180, A181, N196, H208, A235, A250, M256, K260, L268, H309, T310, F316, L326, G378, K389, E406, S428, L439, N466, K474, Y499, N527, R541, H542, R543, and H544. Such engineered variants may produce CBDA from CBGA in a greater amount, as measured in mg/L or mM, than an amount of CBDA produced from CBGA by a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3 under similar conditions for the same length of time. 
     The disclosure provides for an engineered variant, wherein the engineered variant comprises at least one amino acid substitution at an amino acid selected from the group consisting of R31, N57, M61, L71, S170, A172, Y175, N196, H208, A235, K260, G378, K389, and R543. In certain such embodiments, the engineered variant comprises at least one amino acid substitution at an amino acid selected from the group consisting of N57, S170, A172, N196, A235, K260, and G378. In some embodiments, the engineered variant comprises at least one amino acid substitution at an amino acid selected from the group consisting of M412, L415, and I445. In some embodiments, the engineered variant comprises an amino acid substitution at amino acid I445. Such engineered variants may produce CBDA from CBGA in a greater amount, as measured in mg/L or mM, than an amount of CBDA produced from CBGA by a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3 under similar conditions for the same length of time and/or may produce CBDA from CBGA in an increased ratio of CBDA over THCA compared to that produced by a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3 under similar conditions for the same length of time. In some embodiments, such engineered variants may produce CBDA from CBGA in an increased ratio of CBDA over CBCA compared to that produced by a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3 under similar conditions for the same length of time. 
     The disclosure provides for an engineered variant, wherein the engineered variant comprises at least one amino acid substitution selected from the group consisting of C12F, F17M, F18T, F18W, 520G, R31Q, N33K, P43E, L49E, L49K, L49Q, K50T, L51I, Q55E, Q55P, N56E, N57D, N57E, L59E, M61H, M61S, M61W, S62N, S62Q, V63M, S66D, L71A, L71H, L71Q, S75D, S75E, I97V, L98V, S100A, V103A, V103F, T109V, Q124D, Q124E, Q124N, V125E, V125Q, I129V, L132M, S137G, H143D, V149I, W161K, W161R, W161Y, K165A, E167P, N168S, S170T, L171I, A172V, Y175F, C180A, A181V, N196Q, N196T, N196V, H208T, A235P, A250T, M256V, K260C, K260W, L268I, H309V, T310A, T310C, F316Y, L326I, G378T, G3785, K389E, E406K, S428L, L439M, N466D, K474S, Y499M, Y499V, N527E, P538T, R541E, R541V, H542V, R543A, R543E, H544E, and H544D. In some embodiments, the engineered variant comprises at least one amino acid substitution selected from the group consisting of C12F, F17M, F18T, F18W, 520G, R31Q, N33K, P43E, L49E, L49K, L49Q, K50T, L51I, Q55E, Q55P, N56E, N57D, N57E, L59E, M61H, M61S, M61W, S62N, S62Q, V63M, S66D, L71A, L71H, L71Q, S75D, S75E, I97V, L98V, S100A, V103A, V103F, T109V, Q124D, Q124E, Q124N, V125E, V125Q, I129V, L132M, S137G, H143D, V149I, W161K, W161R, W161Y, K165A, E167P, N168S, S170T, L171I, A172V, Y175F, C180A, A181V, N196Q, N196T, N196V, H208T, A235P, A250T, M256V, K260C, K260W, L268I, H309V, T310A, T310C, F316Y, L326I, G378T, G378S, K389E, E406K, M412Q, L415M, S428L, L439M, I445M, N466D, K474S, Y499M, Y499V, N527E, P538T, R541E, R541V, H542V, R543A, R543E, H544E, and H544D. In some embodiments, the engineered variant comprises at least one amino acid substitution selected from the group consisting of R31Q, P43E, L49E, L49K, L49Q, K50T, L51I, Q55E, Q55P, N56E, N57D, M61H, M61S, M61W, S62Q, L71A, L71Q, I97V, S100A, V103A, V103F, T109V, Q124D, Q124E, Q124N, V125E, V125Q, I129V, L132M, S137G, H143D, V149I, W161K, W161R, W161Y, K165A, E167P, N168S, S170T, L171I, A172V, Y175F, C180A, A181V, N196Q, N196T, N196V, H208T, A235P, A250T, M256V, K260C, K260W, L268I, H309V, T310A, T310C, F316Y, L326I, G378T, G378S, K389E, S428L, L439M, N466D, K474S, Y499M, Y499V, N527E, P538T, R541E, R541V, H542V, R543A, R543E, H544E, and H544D. In certain such embodiments, the engineered variant comprises at least one amino acid substitution selected from the group consisting of L49E, L49Q, K50T, N56E, N57D, V125E, L132M, V149I, W161R, K165A, S170T, L171I, A172V, N196Q, N196T, N196V, A235P, K260W, K260C, L268I, T310A, T310C, F316Y, L326I, G378T, S428L, Y499M, Y499V, N527E, H543E, and H544E. In some embodiments, the engineered variant comprises at least one amino acid substitution selected from the group consisting of R31Q, P43E, L49E, L49Q, L49K, K50T, N56E, N57D, L71Q, L71H, L71A, S100A, V103F, V103A, T109V, Q124D, V125E, V125Q, I129V, L132M, S137G, H143D, W161R, W161K, W161Y, K165A, E167P, N168S, S170T, L171I, A172V, Y175F, C180A, A181V, N196Q, N196T, N196V, H208T, A235P, A250T, M256V, K260W, K260C, L268I, H309V, T310A, T310C, F316Y, L326I, G378T, G378S, K389E, E406K, S428L, L439M, N466D, K474S, Y499V, Y499M, N527E, R541V, H542V, R543E, R543A, H544D, and H544E. Such engineered variants may produce CBDA from CBGA in a greater amount, as measured in mg/L or mM, than an amount of CBDA produced from CBGA by a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3 under similar conditions for the same length of time. 
     The disclosure provides for an engineered variant, wherein the engineered variant comprises at least one amino acid substitution selected from the group consisting of R31Q, N57D, M61W, L71H, S170T, A172V, Y175F, N196V, H208T, A235P, K260W, G378T, K389E, and R543E. In certain such embodiments, the engineered variant comprises at least one amino acid substitution selected from the group consisting of N57D, S170T, A172V, N196V, A235P, K260W, and G378T. In some embodiments, the engineered variant comprises at least one amino acid substitution selected from the group consisting of M412Q, L415M, and I445M. In some embodiments, the engineered variant comprises amino acid substitution I445M. Such engineered variants may produce CBDA from CBGA in a greater amount, as measured in mg/L or mM, than an amount of CBDA produced from CBGA by a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3 under similar conditions for the same length of time and/or may produce CBDA from CBGA in an increased ratio of CBDA over THCA compared to that produced by a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3 under similar conditions for the same length of time. In some embodiments, such engineered variants may produce CBDA from CBGA in an increased ratio of CBDA over CBCA compared to that produced by a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3 under similar conditions for the same length of time. 
     The disclosure provides for an engineered variant, wherein the engineered variant comprises an amino acid sequence selected from the group consisting of SEQ ID NO:50, SEQ ID NO:52, SEQ ID NO:54, SEQ ID NO:56, SEQ ID NO:58, SEQ ID NO:60, SEQ ID NO:62, SEQ ID NO:64, SEQ ID NO:66, SEQ ID NO:68, SEQ ID NO:70, SEQ ID NO:72, SEQ ID NO:74, SEQ ID NO:76, SEQ ID NO:78, SEQ ID NO:80, SEQ ID NO:82, SEQ ID NO:84, SEQ ID NO:86, SEQ ID NO:88, SEQ ID NO:90, SEQ ID NO:92, SEQ ID NO:94, SEQ ID NO:96, SEQ ID NO:98, SEQ ID NO:100, SEQ ID NO:102, SEQ ID NO:104, SEQ ID NO:106, SEQ ID NO:108, SEQ ID NO:110, SEQ ID NO:112, SEQ ID NO:114, SEQ ID NO:116, SEQ ID NO:118, SEQ ID NO:120, SEQ ID NO:122, SEQ ID NO:124, SEQ ID NO:126, SEQ ID NO:128, SEQ ID NO:130, SEQ ID NO:132, SEQ ID NO:134, SEQ ID NO:136, SEQ ID NO:138, SEQ ID NO:140, SEQ ID NO:142, SEQ ID NO:144, SEQ ID NO:146, SEQ ID NO:148, SEQ ID NO:150, SEQ ID NO:152, SEQ ID NO:154, SEQ ID NO:156, SEQ ID NO:158, SEQ ID NO:160, SEQ ID NO:162, SEQ ID NO:164, SEQ ID NO:166, SEQ ID NO:168, SEQ ID NO:170, SEQ ID NO:172, SEQ ID NO:174, SEQ ID NO:176, SEQ ID NO:178, SEQ ID NO:180, SEQ ID NO:182, SEQ ID NO:184, SEQ ID NO:186, SEQ ID NO:188, SEQ ID NO:190, SEQ ID NO:192, SEQ ID NO:194, SEQ ID NO:196, SEQ ID NO:198, SEQ ID NO:200, SEQ ID NO:202, SEQ ID NO:204, SEQ ID NO:206, SEQ ID NO:208, SEQ ID NO:210, SEQ ID NO:212, SEQ ID NO:214, SEQ ID NO:216, SEQ ID NO:218, SEQ ID NO:220, SEQ ID NO:222, SEQ ID NO:224, SEQ ID NO:226, SEQ ID NO:228, SEQ ID NO:230, SEQ ID NO:232, and SEQ ID NO:234. In some embodiments, the engineered variant comprises an amino acid sequence selected from the group consisting of SEQ ID NO:50, SEQ ID NO:52, SEQ ID NO:54, SEQ ID NO:56, SEQ ID NO:58, SEQ ID NO:60, SEQ ID NO:62, SEQ ID NO:64, SEQ ID NO:66, SEQ ID NO:68, SEQ ID NO:70, SEQ ID NO:72, SEQ ID NO:74, SEQ ID NO:76, SEQ ID NO:78, SEQ ID NO:80, SEQ ID NO:82, SEQ ID NO:84, SEQ ID NO:86, SEQ ID NO:88, SEQ ID NO:90, SEQ ID NO:92, SEQ ID NO:94, SEQ ID NO:96, SEQ ID NO:98, SEQ ID NO:100, SEQ ID NO:102, SEQ ID NO:104, SEQ ID NO:106, SEQ ID NO:108, SEQ ID NO:110, SEQ ID NO:112, SEQ ID NO:114, SEQ ID NO:116, SEQ ID NO:118, SEQ ID NO:120, SEQ ID NO:122, SEQ ID NO:124, SEQ ID NO:126, SEQ ID NO:128, SEQ ID NO:130, SEQ ID NO:132, SEQ ID NO:134, SEQ ID NO:136, SEQ ID NO:138, SEQ ID NO:140, SEQ ID NO:142, SEQ ID NO:144, SEQ ID NO:146, SEQ ID NO:148, SEQ ID NO:150, SEQ ID NO:152, SEQ ID NO:154, SEQ ID NO:156, SEQ ID NO:158, SEQ ID NO:160, SEQ ID NO:162, SEQ ID NO:164, SEQ ID NO:166, SEQ ID NO:168, SEQ ID NO:170, SEQ ID NO:172, SEQ ID NO:174, SEQ ID NO:176, SEQ ID NO:178, SEQ ID NO:180, SEQ ID NO:182, SEQ ID NO:184, SEQ ID NO:186, SEQ ID NO:188, SEQ ID NO:190, SEQ ID NO:192, SEQ ID NO:194, SEQ ID NO:196, SEQ ID NO:198, SEQ ID NO:200, SEQ ID NO:202, SEQ ID NO:204, SEQ ID NO:206, SEQ ID NO:208, SEQ ID NO:210, SEQ ID NO:212, SEQ ID NO:214, SEQ ID NO:216, SEQ ID NO:218, SEQ ID NO:220, SEQ ID NO:222, SEQ ID NO:224, SEQ ID NO:226, SEQ ID NO:228, SEQ ID NO:230, SEQ ID NO:232, SEQ ID NO:234, SEQ ID NO:300, SEQ ID NO:302, and SEQ ID NO:304. In some embodiments, the engineered variant comprises an amino acid sequence selected from the group consisting of SEQ ID NO:60, SEQ ID NO:64, SEQ ID NO:66, SEQ ID NO:68, SEQ ID NO:70, SEQ ID NO:72, SEQ ID NO:74, SEQ ID NO:76, SEQ ID NO:78, SEQ ID NO:80, SEQ ID NO:82, SEQ ID NO:88, SEQ ID NO:90, SEQ ID NO:92, SEQ ID NO:96, SEQ ID NO:102, SEQ ID NO:106, SEQ ID NO:112, SEQ ID NO: 116, SEQ ID NO: 118, SEQ ID NO:120, SEQ ID NO:122, SEQ ID NO: 124, SEQ ID NO:126, SEQ ID NO:128, SEQ ID NO:130, SEQ ID NO:132, SEQ ID NO: 134, SEQ ID NO:136, SEQ ID NO:138, SEQ ID NO:140, SEQ ID NO:142, SEQ ID NO: 144, SEQ ID NO:146, SEQ ID NO:148, SEQ ID NO:150, SEQ ID NO:152, SEQ ID NO:154, SEQ ID NO:156, SEQ ID NO:158, SEQ ID NO:160, SEQ ID NO:162, SEQ ID NO: 164, SEQ ID NO:166, SEQ ID NO:168, SEQ ID NO:170, SEQ ID NO:172, SEQ ID NO: 174, SEQ ID NO:176, SEQ ID NO:178, SEQ ID NO:180, SEQ ID NO:182, SEQ ID NO: 184, SEQ ID NO:186, SEQ ID NO:188, SEQ ID NO:190, SEQ ID NO:192, SEQ ID NO: 194, SEQ ID NO:196, SEQ ID NO:198, SEQ ID NO:200, SEQ ID NO:202, SEQ ID NO:206, SEQ ID NO:208, SEQ ID NO:210, SEQ ID NO:212, SEQ ID NO:214, SEQ ID NO:216, SEQ ID NO:218, SEQ ID NO:220, SEQ ID NO:222, SEQ ID NO:224, SEQ ID NO:226, SEQ ID NO:228, SEQ ID NO:230, SEQ ID NO:232, and SEQ ID NO:234. In certain such embodiments, the engineered variant comprises an amino acid sequence selected from the group consisting of SEQ ID NO:66, SEQ ID NO:70, SEQ ID NO:72, SEQ ID NO:80, SEQ ID NO:82, SEQ ID NO:130, SEQ ID NO:136, SEQ ID NO:142, SEQ ID NO:146, SEQ ID NO:150, SEQ ID NO:156, SEQ ID NO:158, SEQ ID NO:160, SEQ ID NO:168, SEQ ID NO:170, SEQ ID NO:172, SEQ ID NO:176, SEQ ID NO:182, SEQ ID NO:184, SEQ ID NO:186, SEQ ID NO:190, SEQ ID NO:192, SEQ ID NO:194, SEQ ID NO:196, SEQ ID NO:198, SEQ ID NO:206, SEQ ID NO:214, SEQ ID NO:216, SEQ ID NO:218, SEQ ID NO:230, and SEQ ID NO:232. In some embodiments, the engineered variant comprises an amino acid sequence selected from the group consisting of SEQ ID NO:60, SEQ ID NO:64, SEQ ID NO:66, SEQ ID NO:68, SEQ ID NO:70, SEQ ID NO:72, SEQ ID NO:80, SEQ ID NO:82, SEQ ID NO:102, SEQ ID NO:104, SEQ ID NO:106, SEQ ID NO:116, SEQ ID NO:118, SEQ ID NO:120, SEQ ID NO:122, SEQ ID NO:124, SEQ ID NO:130, SEQ ID NO:132, SEQ ID NO:134, SEQ ID NO:136, SEQ ID NO:138, SEQ ID NO:140, SEQ ID NO:144, SEQ ID NO:146, SEQ ID NO:148, SEQ ID NO:150, SEQ ID NO:152, SEQ ID NO:154, SEQ ID NO:156, SEQ ID NO:158, SEQ ID NO:160, SEQ ID NO:162, SEQ ID NO:164, SEQ ID NO:166, SEQ ID NO:168, SEQ ID NO:170, SEQ ID NO:172, SEQ ID NO:174, SEQ ID NO:176, SEQ ID NO:178, SEQ ID NO:180, SEQ ID NO:182, SEQ ID NO:184, SEQ ID NO:186, SEQ ID NO:188, SEQ ID NO:190, SEQ ID NO:192, SEQ ID NO:194, SEQ ID NO:196, SEQ ID NO:198, SEQ ID NO:200, SEQ ID NO:202, SEQ ID NO:204, SEQ ID NO:206, SEQ ID NO:208, SEQ ID NO:210, SEQ ID NO:212, SEQ ID NO:214, SEQ ID NO:216, SEQ ID NO:218, SEQ ID NO:224, SEQ ID NO:226, SEQ ID NO:228, SEQ ID NO:230, SEQ ID NO:232, and SEQ ID NO:234. Such engineered variants may produce CBDA from CBGA in a greater amount, as measured in mg/L or mM, than an amount of CBDA produced from CBGA by a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3 under similar conditions for the same length of time. 
     The disclosure provides for an engineered variant, wherein the engineered variant comprises an amino acid sequence selected from the group consisting of SEQ ID NO:60, SEQ ID NO:82, SEQ ID NO:92, SEQ ID NO:104, SEQ ID NO:156, SEQ ID NO:160, SEQ ID NO:162, SEQ ID NO:172, SEQ ID NO:174, SEQ ID NO:176, SEQ ID NO:184, SEQ ID NO:198, SEQ ID NO:202, and SEQ ID NO:230. In certain such embodiments, the engineered variant comprises an amino acid sequence selected from the group consisting of SEQ ID NO:82, SEQ ID NO:156, SEQ ID NO:160, SEQ ID NO:172, SEQ ID NO:176, SEQ ID NO:184, and SEQ ID NO:198. In some embodiments, the engineered variant comprises an amino acid sequence selected from the group consisting of SEQ ID NO:300, SEQ ID NO:302, and SEQ ID NO:304. In some embodiments, the engineered variant comprises an amino acid sequence of SEQ ID NO:300. Such engineered variants may produce CBDA from CBGA in a greater amount, as measured in mg/L or mM, than an amount of CBDA produced from CBGA by a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3 under similar conditions for the same length of time and/or may produce CBDA from CBGA in an increased ratio of CBDA over THCA compared to that produced by a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3 under similar conditions for the same length of time. In some embodiments, such engineered variants may produce CBDA from CBGA in an increased ratio of CBDA over CBCA compared to that produced by a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3 under similar conditions for the same length of time. 
     The disclosure provides for an engineered variant, wherein the engineered variant comprises an amino acid sequence of SEQ ID NO:3 with at least 1, at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 21, at least 22, at least 23, at least 24, at least 25, at least 26, at least 27, at least 28, at least 29, or at least 30 amino acid substitutions. The disclosure provides for an engineered variant, wherein the engineered variant comprises an amino acid sequence of SEQ ID NO:3 with 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 amino acid substitutions. Combinations of the amino acid substitutions described herein can be made and the resulting engineered variants screened for improved cannabidiolic acid synthase (CBDAS) properties. Engineered variants comprising combinations of all of the substitutions described herein are intended to be encompassed by this disclosure. In some embodiments, the engineered variant comprises at least 1, at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 21, at least 22, at least 23, at least 24, at least 25, at least 26, at least 27, at least 28, at least 29, or at least 30 of the amino acid substitutions described herein. In some embodiments, the engineered variant comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 of the amino acid substitutions described herein (e.g., 1-30 of the amino acid substitutions described herein). In some embodiments, the engineered variant comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 of the amino acid substitutions described herein (e.g., 1-15 of the amino acid substitutions described herein). In some embodiments, the engineered variant comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 of the amino acid substitutions described herein (e.g., 1-10 of the amino acid substitutions described herein). In some embodiments, the engineered variant comprises 1, 2, 3, 4, or 5 of the amino acid substitutions described herein (e.g., 1-5 of the amino acid substitutions described herein). In some embodiments, the engineered variant comprises 1, 2, 3, or 4 of the amino acid substitutions described herein (e.g., 1-4 of the amino acid substitutions described herein). In some embodiments, the engineered variant comprises 1, 2, or 3 of the amino acid substitutions described herein (e.g., 1-3 of the amino acid substitutions described herein). In some embodiments, the engineered variant comprises 1 or 2 of the amino acid substitutions described herein (e.g., 1-2 of the amino acid substitutions described herein). In some embodiments, the engineered variant comprises 1 of the amino acid substitutions described herein. In some embodiments, the engineered variant comprises 2 of the amino acid substitutions described herein. In some embodiments, the engineered variant comprises 3 of the amino acid substitutions described herein. In some embodiments, the engineered variant comprises 4 of the amino acid substitutions described herein. In some embodiments, the engineered variant comprises 5 of the amino acid substitutions described herein. 
     The disclosure provides for an engineered variant, wherein the engineered variant comprises at least one amino acid substitution at an amino acid selected from the group consisting of X61, X378, and X389. In some embodiments, the engineered variant comprises amino acid substitutions at amino acids X61 and X378. In some embodiments, the engineered variant comprises amino acid substitutions at amino acids X61 and X389. In some embodiments, the engineered variant comprises amino acid substitutions at amino acids X378 and X389. In some embodiments, the engineered variant comprises amino acid substitutions at amino acids X61, X378, and X389. The disclosure provides for an engineered variant, wherein the engineered variant comprises at least one amino acid substitution at an amino acid selected from the group consisting of M61, G378, and K389. In some embodiments, the engineered variant comprises amino acid substitutions at amino acids M61 and G378. In some embodiments, the engineered variant comprises amino acid substitutions at amino acids M61 and K389. In some embodiments, the engineered variant comprises amino acid substitutions at amino acids G378 and K389. In some embodiments, the engineered variant comprises amino acid substitutions at amino acids M61, G378, and K389. The disclosure provides for an engineered variant, wherein the engineered variant comprises at least one amino acid substitution selected from the group consisting of M61W, G378T, and K389E. In some embodiments, the engineered variant comprises amino acid substitutions M61W and G378T. In some embodiments, the engineered variant comprises amino acid substitutions M61W and K389E. In some embodiments, the engineered variant comprises amino acid substitutions G378T and K389E. In some embodiments, the engineered variant comprises amino acid substitutions M61W, G378T, and K389E. The disclosure provides for an engineered variant, wherein the engineered variant comprises an amino acid sequence selected from the group consisting of SEQ ID NO:314, SEQ ID NO:316, SEQ ID NO:318, and SEQ ID NO:320. In some embodiments, the engineered variant comprises an amino acid sequence of SEQ ID NO:314. In some embodiments, the engineered variant comprises an amino acid sequence of SEQ ID NO:316. In some embodiments, the engineered variant comprises an amino acid sequence of SEQ ID NO:318. In some embodiments, the engineered variant comprises an amino acid sequence of SEQ ID NO:320. Such engineered variants may produce CBDA from CBGA in a greater amount, as measured in mg/L or mM, than an amount of CBDA produced from CBGA by a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3 under similar conditions for the same length of time and/or may produce CBDA from CBGA in an increased ratio of CBDA over THCA compared to that produced by a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3 under similar conditions for the same length of time. In some embodiments, such engineered variants may produce CBDA from CBGA in an increased ratio of CBCA over CBDA compared to that produced by a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3 under similar conditions for the same length of time. 
     The disclosure provides for an engineered variant, wherein the engineered variant comprises at least one immutable amino acid. The disclosure provides for an engineered variant, wherein the engineered variant comprises at least one immutable amino acid in a flavin adenine dinucleotide (FAD) binding domain, a berberine bridge enzyme (BBE) domain, or a combination of the foregoing. 
     In some embodiments, the engineered variant comprises at least one immutable amino acid in the FAD binding domain. In certain such embodiments, the engineered variant comprises at least 1, at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, or at least 15 immutable amino acids in the FAD binding domain. In some embodiments, wherein the engineered variant comprises at least one immutable amino acid in the FAD binding domain, the at least one immutable amino acid is selected from the group consisting of X87, X93, X99, X108, X110, X112, X117, X118, X120, X126, X127, X131, X141, X148, X152, X153, X155, X156, X157, X159, X160, X163, X173, X174, X176, X177, X178, X179, X182, X183, X184, X185, X187, X188, X189, X190, X191, X192, X193, X195, X201, X202, X205, X206, X210, X214, X223, X225, X226, X227, X228, X231, X234, X237, X238, X239, X245, X246, X248, and X251. In some embodiments, wherein the engineered variant comprises at least one immutable amino acid in the FAD binding domain, the at least one immutable amino acid is selected from the group consisting of P87, I93, C99, R108, R110, G112, E117, G118, 5120, P126, F127, D131, D141, W148, G152, A153, L155, G156, E157, Y159, Y160, N163, A173, G174, C176, P177, T178, V179, G182, G183, H184, F185, G187, G188, G189, Y190, G191, P192, L193, R195, A201, D202, I205, D206, V210, G214, G223, D225, L226, F227, W228, R231, G234, 5237, F238, G239, K245, I246, L248, and V251. 
     Engineered variants comprising a substitution at amino acid D115, such as D115N (SEQ ID NO:306), present in the FAD binding domain, may produce THCA from CBGA in an increased ratio of THCA over CBDA compared to that produced by a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3 under similar conditions for the same length of time. 
     In some embodiments, the engineered variant comprises at least one immutable amino acid in the BBE domain. In certain such embodiments, the engineered variant comprises at least 1, at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, or at least 15 immutable amino acids in the BBE domain. In some embodiments, wherein the engineered variant comprises at least one immutable amino acid in the BBE domain, the at least one immutable amino acid selected from the group consisting of X484, X498, X502, X513, X514, X521, X528, X529, X533, X534, and X535. In some embodiments, wherein the engineered variant comprises at least one immutable amino acid in the BBE domain, the at least one immutable amino acid selected from the group consisting of R484, N498, A502, N513, F514, K521, N528, F529, E533, Q534, and S535. 
     The disclosure provides for an engineered variant, wherein the engineered variant comprises at least one immutable amino acid selected from the group consisting of X28, X34, X35, X37, X64, X70, X87, X93, X99, X108, X110, X112, X117, X118, X120, X126, X127, X131, X141, X148, X152, X153, X155, X156, X157, X159, X160, X163, X173, X174, X176, X177, X178, X179, X182, X183, X184, X185, X187, X188, X189, X190, X191, X192, X193, X195, X201, X202, X205, X206, X210, X214, X223, X225, X226, X227, X228, X231, X234, X237, X238, X239, X245, X246, X248, X251, X259, X276, X312, X313, X323, X341, X352, X354, X380, X381, X382, X383, X385, X386, X391, X419, X422, X425, X430, X431, X433, X434, X435, X437, X440, X443, X444, X464, X465, X468, X469, X471, X472, X476, X484, X498, X502, X513, X514, X521, X528, X529, X533, X534, and X535. In certain such embodiments, the engineered variant comprises at least one immutable amino acid selected from the group consisting of X37, X70, X93, X99, X117, X120, X127, X131, X156, X157, X159, X174, X176, X182, X183, X185, X187, X188, X189, X190, X191, X192, X195, X202, X206, X214, X228, X234, X238, X248, X276, X313, X323, X354, X381, X383, X385, X419, X422, X435, X440, X443, X444, X471, X476, X513, X514, X528, and X534. The disclosure provides for an engineered variant, wherein the engineered variant comprises at least one immutable amino acid selected from the group consisting of A28, F34, L35, C37, L64, N70, P87, I93, C99, R108, R110, G112, E117, G118, 5120, P126, F127, D131, D141, W148, G152, A153, L155, G156, E157, Y159, Y160, N163, A173, G174, C176, P177, T178, V179, G182, G183, H184, F185, G187, G188, G189, Y190, G191, P192, L193, R195, A201, D202, I205, D206, V210, G214, G223, D225, L226, F227, W228, R231, G234, 5237, F238, G239, K245, I246, L248, V251, V259, Q276, F312, 5313, L323, C341, F352, 5354, F380, K381, I382, K383, D385, Y386, I391, G419, M422, I425, I430, P431, P433, H434, R435, G437, Y440, W443, Y444, I464, Y465, M468, T469, Y471, V472, P476, R484, N498, A502, N513, F514, K521, N528, F529, E533, Q534, and S535. In certain such embodiments, the engineered variant comprises at least one immutable amino acid selected from the group consisting of C37, N70, I93, C99, E117, 5120, F127, D131, G156, E157, Y159, G174, C176, G182, G183, F185, G187, G188, G189, Y190, G191, P192, R195, D202, D206, G214, W228, G234, F238, L248, Q276, 5313, L323, S354, K381, K383, D385, G419, M422, R435, Y440, W443, Y444, Y471, P476, N513, F514, N528, and Q534. The disclosure provides for an engineered variant, wherein the engineered variant comprises at least one immutable amino acid selected from the group consisting of A28, F34, L35, C37, L64, N70, P87, I93, C99, R108, R110, G112, E117, G118, 5120, P126, F127, D131, D141, W148, G152, A153, L155, G156, E157, Y159, Y160, N163, A173, G174, C176, P177, T178, V179, G182, G183, H184, F185, G187, G188, G189, Y190, G191, P192, L193, R195, A201, D202, I205, D206, V210, G214, G223, D225, L226, F227, W228, R231, G234, S237, F238, G239, K245, I246, L248, V251, V259, Q276, F312, 5313, L323, C341, F352, S354, F380, K381, I382, K383, D385, Y386, I391, M412, L415, G419, M422, I425, I430, P431, P433, H434, R435, G437, Y440, W443, Y444, I445, I464, Y465, M468, T469, Y471, V472, P476, R484, N498, A502, N513, F514, K521, N528, F529, E533, Q534, and S535. 
     The disclosure provides for an engineered variant, wherein the engineered variant comprises at least 1, at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 21, at least 22, at least 23, at least 24, or at least 25 immutable amino acids, provided that the engineered variant has at least one amino acid substitution compared to SEQ ID NO:3. Engineered variants with combinations of the immutable amino acids and substitutions described herein can be made and the resulting engineered variants screened for improved cannabidiolic acid synthase (CBDAS) properties. Engineered variants comprising combinations of all of the substitutions and immutable amino acids described herein are intended to be encompassed by this disclosure. 
     Engineered variants comprising a substitution at amino acid D115, such as D115N (SEQ ID NO:306), or A414, such as A414T (SEQ ID NO:308), A414V (SEQ ID NO:310), and A414M (SEQ ID NO:312), may produce THCA from CBGA in an increased ratio of THCA over CBDA compared to that produced by a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3 under similar conditions for the same length of time. 
     The disclosure provides for an engineered variant, wherein the engineered variant comprises at least one amino acid substitution at the C-terminus. In certain such embodiments, a hydrophilic amino acid is replaced with a hydrophobic amino acid. In some embodiments, wherein the engineered variant comprises at least one amino acid substitution at the C-terminus, a hydrophobic amino acid is replaced with a hydrophilic amino acid. In some embodiments, the engineered variant comprises at least one amino acid substitution at an amino acid selected from the group consisting of X541, X542, X543, and X544. In some embodiments, the engineered variant comprises at least one amino acid substitution at an amino acid selected from the group consisting of R541, H542, R543, and H544. In some embodiments, the engineered variant comprises at least one amino acid substitution selected from the group consisting of R541E, R541V, H542V, R543A, R543E, H544E, and H544D. The disclosure provides for an engineered variant, wherein the engineered variant comprises an amino acid sequence selected from the group consisting of SEQ ID NO:222, SEQ ID NO:224, SEQ ID NO:226, SEQ ID NO:228, SEQ ID NO:230, SEQ ID NO:232, and SEQ ID NO:234. Such engineered variants may produce CBDA from CBGA in a greater amount, as measured in mg/L or mM, than an amount of CBDA produced from CBGA by a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3 under similar conditions for the same length of time. 
     The disclosure provides for an engineered variant, wherein the engineered variant comprises a truncation at the N-terminus, at the C-terminus, or at both the N- and C-termini. In some embodiments, the engineered variant comprises a truncation at the N-terminus. In some embodiments, the engineered variant comprises a truncation at the C-terminus. In some embodiments, the engineered variant comprises a truncation at both the N- and C-termini. In some embodiments, the engineered variant lacks a native signal polypeptide (i.e., amino acids 1-28 of SEQ ID NO:3). 
     In some embodiments, the engineered variant comprises a truncation at the N-terminus, at the C-terminus, or at both the N- and C-termini, and comprises an amino acid sequence with at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO:3. In some embodiments, the engineered variant comprises a truncation at the N-terminus, at the C-terminus, or at both the N- and C-termini, and comprises an amino acid sequence with at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, or at least 84% sequence identity to SEQ ID NO:3. 
     In some embodiments, the engineered variant comprises a truncation of at least 1, at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, or at least 10 amino acids at the N-terminus. In some embodiments, the engineered variant comprises a truncation of at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, or at least 20 amino acids at the N-terminus. In some embodiments, the engineered variant comprises a truncation of at least 21, at least 22, at least 23, at least 24, at least 25, at least 26, at least 27, at least 28, at least 29, or at least 30 amino acids at the N-terminus. In some embodiments, the engineered variant comprises a truncation of 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acids at the N-terminus (e.g., 1-10 amino acids at the N-terminus). In some embodiments, the engineered variant comprises a truncation of 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acids at the N-terminus (e.g., 11-20 amino acids at the N-terminus). In some embodiments, the engineered variant comprises a truncation of 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 amino acids at the N-terminus (e.g., 21-30 amino acids at the N-terminus). 
     In some embodiments, the engineered variant comprises a truncation of at least 1, at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, or at least 10 amino acids at the C-terminus. In some embodiments, the engineered variant comprises a truncation of at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, or at least 20 amino acids at the C-terminus. In some embodiments, the engineered variant comprises a truncation of at least 21, at least 22, at least 23, at least 24, at least 25, at least 26, at least 27, at least 28, at least 29, or at least 30 amino acids at the C-terminus. In some embodiments, the engineered variant comprises a truncation of 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acids at the C-terminus (e.g., 1-10 amino acids at the C-terminus). In some embodiments, the engineered variant comprises a truncation of 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acids at the C-terminus (e.g., 11-20 amino acids at the C-terminus). In some embodiments, the engineered variant comprises a truncation of 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 amino acids at the C-terminus (e.g., 21-30 amino acids at the C-terminus). 
     In some embodiments, a truncated engineered variant of the disclosure may comprise a signal polypeptide. In certain such embodiments, the truncated engineered variant lacks a native signal polypeptide. In some embodiments, the signal polypeptide is a secretory signal polypeptide. In some embodiments, the secretory signal polypeptide is a native secretory signal polypeptide. In some embodiments, the secretory signal polypeptide is a synthetic secretory signal polypeptide. In some embodiments, the secretory signal polypeptide is an endoplasmic reticulum retention signal polypeptide. In certain such embodiments, the endoplasmic reticulum retention signal polypeptide is a HDEL polypeptide or a KDEL polypeptide. In some embodiments, the secretory signal polypeptide is a mitochondrial targeting signal polypeptide. In some embodiments, the secretory signal polypeptide is a Golgi targeting signal polypeptide. In some embodiments, the secretory signal polypeptide is a vacuolar localization signal polypeptide. In certain such embodiments, the vacuolar localization signal polypeptide is a PEP4t polypeptide or a PRC1t polypeptide. In certain such embodiments, the vacuolar localization signal polypeptide is a PEP4t polypeptide. In some embodiments, the secretory signal polypeptide is a plasma membrane localization signal polypeptide. In some embodiments, the secretory signal polypeptide is a peroxisome targeting signal polypeptide. In some embodiments, the peroxisome targeting signal polypeptide is a PEX8 polypeptide. In some embodiments, the secretory signal polypeptide is a mating factor secretory signal polypeptide (e.g., a MF polypeptide or an evolved MF polypeptide (MFev)). In some embodiments, the signal polypeptide is linked to the N-terminus of the engineered variant. 
     In some embodiments, a truncated engineered variant of the disclosure may comprise a membrane anchor. A membrane anchor may be a sequence that inserts into a membrane in the cell and anchor an attached polypeptide there. A membrane anchor may be present in a membrane external to the cell (e.g., GPI polypeptides) or internal to the cell (e.g., tail anchors, ER anchoring). Examples of membrane anchors include, but are not limited to, glycosylphosphatidylinositol membrane anchors (GPI polypeptides, e.g., AGA1), CAAX box polypeptides (get prenylated, e.g., RAS1), or tail anchored polypeptides with a hydrophobic C-terminus (e.g., phosphatidylinositol 4,5-bisphosphate 5-phosphatase (INP54) has a hydrophobic tail anchor in ER membrane or synaptobrevin 2 (VAMP2) has a hydrophobic poly-I tail anchor in vesicle membranes). 
     The disclosure provides for an engineered variant, wherein the engineered variant comprises an addition and/or deletion of one or more amino acids. 
     Engineered variants of a CBDAS polypeptide can be made and screened for improved properties, such as, production of CBDA from CBGA in a greater amount, as measured in mg/L or mM, than an amount of CBDA produced from CBGA by a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3 under similar conditions for the same length of time. Additionally, engineered variants of a CBDAS polypeptide can be made and screened for improved properties, such as, production of CBDA from CBGA in an increased ratio of CBDA over THCA compared to that produced by a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3 under similar conditions for the same length of time. In some embodiments, engineered variants of the disclosure may produce CBDA from CBGA in an increased ratio of CBDA over CBCA compared to that produced by a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3 under similar conditions for the same length of time. Similar conditions may refer to reaction conditions at the same temperature, pH, buffer, and/or fermentation conditions and in the same culture medium and/or reaction solvent. 
     In some embodiments of the disclosure, the engineered variant produces cannabidiolic acid (CBDA) from cannabigerolic acid (CBGA) in an amount, as measured in mg/L or mM, at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 100%, at least 150% at least 200%, at least 500%, or at least 1000% greater than an amount of CBDA produced from CBGA by a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3 under similar conditions for the same length of time. 
     In some embodiments of the disclosure, the engineered variant produces CBDA from CBGA in a ratio of CBDA over THCA of about 11:1, about 11.5:1, about 12:1, about 12.5:1, about 13:1, about 13.5:1, about 14:1, about 14.5:1, about 15:1, about 15.5:1, about 16:1, about 16.5:1, about 17:1, about 17.5:1, about 18:1, about 18.5:1, about 19:1, about 19.5:1, about 20:1, about 25:1, about 30:1, about 35:1, about 40:1, about 45:1, about 50:1, about 60:1, about 70:1, about 80:1, about 90:1, about 100:1, about 150:1, about 200:1, about 500:1, or greater than about 500:1. 
     In some embodiments of the disclosure, the engineered variant produces CBDA from CBGA in a ratio of CBDA over CBCA of about 11:1, about 11.5:1, about 12:1, about 12.5:1, about 13:1, about 13.5:1, about 14:1, about 14.5:1, about 15:1, about 15.5:1, about 16:1, about 16.5:1, about 17:1, about 17.5:1, about 18:1, about 18.5:1, about 19:1, about 19.5:1, about 20:1, about 25:1, about 30:1, about 35:1, about 40:1, about 45:1, about 50:1, about 60:1, about 70:1, about 80:1, about 90:1, about 100:1, about 150:1, about 200:1, about 500:1, or greater than about 500:1. 
     These improved properties may be assessed by the conversion of CBGA to CBDA, or alternatively the conversion of another starting material to a desired cannabinoid or cannabinoid derivative, in vitro with isolated and/or purified engineered variants of the disclosure or in vivo in the context of a modified host cell expressing the engineered variant. In some embodiments, the modified host cell expresses polypeptides involved in the MEV pathway and/or polypeptides involved in cannabinoid biosynthesis and/or comprises modifications to the secretory pathway. It is contemplated that engineered variants of the disclosure having various degrees of stability, solubility, activity, and/or expression level in one or more of the test conditions will find use in the present disclosure for the production of cannabinoids or cannabinoid derivatives in a diversity of host cells. 
     Additionally, engineered variants of a CBDAS polypeptide can be made and screened for improved properties, such as, production of cannabinoids or cannabinoid derivatives by modified host cells comprising one or more nucleic acids comprising a nucleotide sequence encoding the engineered variant in an amount, as measured in mg/L or mM, greater than an amount of the cannabinoid or the cannabinoid derivative produced by modified host cells comprising one or more nucleic acids comprising a nucleotide sequence encoding a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3, but lacking a nucleic acid comprising a nucleotide sequence encoding an engineered variant, grown under similar culture conditions for the same length of time. 
     Additionally, engineered variants of a CBDAS polypeptide can be made and screened for improved properties, such as, modified host cells comprising one or more nucleic acids comprising a nucleotide sequence encoding the engineered variant have a faster growth rate and/or higher biomass yield compared to a growth rate and/or higher biomass yield of modified host cells comprising one or more nucleic acids comprising a nucleotide sequence encoding a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3, but lacking a nucleic acid comprising a nucleotide sequence encoding an engineered variant, grown under similar culture conditions for the same length of time. Additionally, engineered variants of a CBDAS polypeptide can be made and screened for improved properties, such as, modified host cells comprising one or more nucleic acids comprising a nucleotide sequence encoding the engineered variant produce CBDA from CBGA in an increased ratio of CBDA over THCA compared to that produced by modified host cells comprising one or more nucleic acids comprising a nucleotide sequence encoding a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3, but lacking a nucleic acid comprising a nucleotide sequence encoding an engineered variant, grown under similar culture conditions for the same length of time. Moreover, engineered variants of a CBDAS polypeptide can be made and screened for improved properties, such as, modified host cells comprising one or more nucleic acids comprising a nucleotide sequence encoding the engineered variant produce CBDA from CBGA in an increased ratio of CBDA over CBCA compared to that produced by modified host cells comprising one or more nucleic acids comprising a nucleotide sequence encoding a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3, but lacking a nucleic acid comprising a nucleotide sequence encoding an engineered variant, grown under similar culture conditions for the same length of time. Similar culture conditions may refer to host cells grown in the same culture medium at the same temperature, pH, and/or fermentation conditions. 
     Moreover, engineered variants of a CBDAS polypeptide can be made and screened for improved properties, such as, modified host cells comprising one or more nucleic acids comprising a nucleotide sequence encoding the engineered variant do not have significantly decreased growth or viability compared to modified host cells comprising one or more nucleic acids comprising a nucleotide sequence encoding a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3, but lacking a nucleic acid comprising a nucleotide sequence encoding an engineered variant, grown under similar culture conditions for the same length of time. Additionally, engineered variants of a CBDAS polypeptide can be made and screened for improved properties, such as, modified host cells comprising one or more nucleic acids comprising a nucleotide sequence encoding the engineered variant do not have significantly decreased growth or viability compared to an unmodified host cell. 
     Nucleic Acids Comprising Nucleotide Sequences Encoding Engineered Variants of the Cannabidiolic Acid Synthase (CBDAS) Polypeptide and Expression Vectors and Constructs 
     The disclosure provides for nucleic acids comprising nucleotide sequences encoding engineered variants of the cannabidiolic acid synthase (CBDAS) polypeptide disclosed herein and expression vectors and constructs comprising said nucleic acids. 
     The disclosure provides nucleic acids comprising nucleotide sequences encoding engineered variants of the disclosure. Some embodiments of the disclosure relate to a nucleic acid comprising a nucleotide sequence encoding an engineered variant of the disclosure comprising an amino acid sequence set forth in SEQ ID NO:50, SEQ ID NO:52, SEQ ID NO:54, SEQ ID NO:56, SEQ ID NO:58, SEQ ID NO:60, SEQ ID NO:62, SEQ ID NO:64, SEQ ID NO:66, SEQ ID NO:68, SEQ ID NO:70, SEQ ID NO:72, SEQ ID NO:74, SEQ ID NO:76, SEQ ID NO:78, SEQ ID NO:80, SEQ ID NO:82, SEQ ID NO:84, SEQ ID NO:86, SEQ ID NO:88, SEQ ID NO:90, SEQ ID NO:92, SEQ ID NO:94, SEQ ID NO:96, SEQ ID NO:98, SEQ ID NO:100, SEQ ID NO:102, SEQ ID NO:104, SEQ ID NO:106, SEQ ID NO:108, SEQ ID NO:110, SEQ ID NO:112, SEQ ID NO:114, SEQ ID NO:116, SEQ ID NO:118, SEQ ID NO:120, SEQ ID NO:122, SEQ ID NO:124, SEQ ID NO:126, SEQ ID NO:128, SEQ ID NO:130, SEQ ID NO:132, SEQ ID NO:134, SEQ ID NO:136, SEQ ID NO:138, SEQ ID NO:140, SEQ ID NO:142, SEQ ID NO:144, SEQ ID NO:146, SEQ ID NO:148, SEQ ID NO:150, SEQ ID NO:152, SEQ ID NO:154, SEQ ID NO:156, SEQ ID NO:158, SEQ ID NO:160, SEQ ID NO:162, SEQ ID NO:164, SEQ ID NO:166, SEQ ID NO:168, SEQ ID NO:170, SEQ ID NO:172, SEQ ID NO:174, SEQ ID NO:176, SEQ ID NO:178, SEQ ID NO:180, SEQ ID NO:182, SEQ ID NO:184, SEQ ID NO:186, SEQ ID NO:188, SEQ ID NO:190, SEQ ID NO:192, SEQ ID NO:194, SEQ ID NO:196, SEQ ID NO:198, SEQ ID NO:200, SEQ ID NO:202, SEQ ID NO:204, SEQ ID NO:206, SEQ ID NO:208, SEQ ID NO:210, SEQ ID NO:212, SEQ ID NO:214, SEQ ID NO:216, SEQ ID NO:218, SEQ ID NO:220, SEQ ID NO:222, SEQ ID NO:224, SEQ ID NO:226, SEQ ID NO:228, SEQ ID NO:230, SEQ ID NO:232, or SEQ ID NO:234. In some embodiments, the nucleotide sequence is codon-optimized. 
     The disclosure provides nucleic acids comprising nucleotide sequences encoding engineered variants of the disclosure. Some embodiments of the disclosure relate to a nucleic acid comprising a nucleotide sequence encoding an engineered variant of the disclosure comprising an amino acid sequence set forth in SEQ ID NO:50, SEQ ID NO:52, SEQ ID NO:54, SEQ ID NO:56, SEQ ID NO:58, SEQ ID NO:60, SEQ ID NO:62, SEQ ID NO:64, SEQ ID NO:66, SEQ ID NO:68, SEQ ID NO:70, SEQ ID NO:72, SEQ ID NO:74, SEQ ID NO:76, SEQ ID NO:78, SEQ ID NO:80, SEQ ID NO:82, SEQ ID NO:84, SEQ ID NO:86, SEQ ID NO:88, SEQ ID NO:90, SEQ ID NO:92, SEQ ID NO:94, SEQ ID NO:96, SEQ ID NO:98, SEQ ID NO:100, SEQ ID NO:102, SEQ ID NO:104, SEQ ID NO:106, SEQ ID NO:108, SEQ ID NO:110, SEQ ID NO:112, SEQ ID NO:114, SEQ ID NO:116, SEQ ID NO:118, SEQ ID NO:120, SEQ ID NO:122, SEQ ID NO:124, SEQ ID NO:126, SEQ ID NO:128, SEQ ID NO:130, SEQ ID NO:132, SEQ ID NO:134, SEQ ID NO:136, SEQ ID NO:138, SEQ ID NO:140, SEQ ID NO:142, SEQ ID NO:144, SEQ ID NO:146, SEQ ID NO:148, SEQ ID NO:150, SEQ ID NO:152, SEQ ID NO:154, SEQ ID NO:156, SEQ ID NO:158, SEQ ID NO:160, SEQ ID NO:162, SEQ ID NO:164, SEQ ID NO:166, SEQ ID NO:168, SEQ ID NO:170, SEQ ID NO:172, SEQ ID NO:174, SEQ ID NO:176, SEQ ID NO:178, SEQ ID NO:180, SEQ ID NO:182, SEQ ID NO:184, SEQ ID NO:186, SEQ ID NO:188, SEQ ID NO:190, SEQ ID NO:192, SEQ ID NO:194, SEQ ID NO:196, SEQ ID NO:198, SEQ ID NO:200, SEQ ID NO:202, SEQ ID NO:204, SEQ ID NO:206, SEQ ID NO:208, SEQ ID NO:210, SEQ ID NO:212, SEQ ID NO:214, SEQ ID NO:216, SEQ ID NO:218, SEQ ID NO:220, SEQ ID NO:222, SEQ ID NO:224, SEQ ID NO:226, SEQ ID NO:228, SEQ ID NO:230, SEQ ID NO:232, SEQ ID NO:234, SEQ ID NO:300, SEQ ID NO:302, or SEQ ID NO:304. In some embodiments, the nucleotide sequence is codon-optimized. 
     Some embodiments of the disclosure relate to a nucleic acid comprising a nucleotide sequence encoding an engineered variant of the disclosure comprising an amino acid sequence set forth in SEQ ID NO:60, SEQ ID NO:64, SEQ ID NO:66, SEQ ID NO:68, SEQ ID NO:70, SEQ ID NO:72, SEQ ID NO:74, SEQ ID NO:76, SEQ ID NO:78, SEQ ID NO:80, SEQ ID NO:82, SEQ ID NO:88, SEQ ID NO:90, SEQ ID NO:92, SEQ ID NO:96, SEQ ID NO:102, SEQ ID NO:106, SEQ ID NO:112, SEQ ID NO:116, SEQ ID NO:118, SEQ ID NO:120, SEQ ID NO:122, SEQ ID NO:124, SEQ ID NO:126, SEQ ID NO:128, SEQ ID NO:130, SEQ ID NO:132, SEQ ID NO:134, SEQ ID NO:136, SEQ ID NO:138, SEQ ID NO:140, SEQ ID NO:142, SEQ ID NO:144, SEQ ID NO:146, SEQ ID NO:148, SEQ ID NO:150, SEQ ID NO:152, SEQ ID NO:154, SEQ ID NO:156, SEQ ID NO:158, SEQ ID NO:160, SEQ ID NO:162, SEQ ID NO:164, SEQ ID NO:166, SEQ ID NO:168, SEQ ID NO:170, SEQ ID NO:172, SEQ ID NO:174, SEQ ID NO:176, SEQ ID NO:178, SEQ ID NO:180, SEQ ID NO:182, SEQ ID NO:184, SEQ ID NO:186, SEQ ID NO:188, SEQ ID NO:190, SEQ ID NO:192, SEQ ID NO:194, SEQ ID NO:196, SEQ ID NO:198, SEQ ID NO:200, SEQ ID NO:202, SEQ ID NO:206, SEQ ID NO:208, SEQ ID NO:210, SEQ ID NO:212, SEQ ID NO:214, SEQ ID NO:216, SEQ ID NO:218, SEQ ID NO:220, SEQ ID NO:222, SEQ ID NO:224, SEQ ID NO:226, SEQ ID NO:228, SEQ ID NO:230, SEQ ID NO:232, or SEQ ID NO:234. In some embodiments, the nucleotide sequence is codon-optimized. 
     Some embodiments of the disclosure relate to a nucleic acid comprising a nucleotide sequence encoding an engineered variant of the disclosure comprising an amino acid sequence set forth in SEQ ID NO:66, SEQ ID NO:70, SEQ ID NO:72, SEQ ID NO:80, SEQ ID NO:82, SEQ ID NO:130, SEQ ID NO:136, SEQ ID NO:142, SEQ ID NO:146, SEQ ID NO:150, SEQ ID NO:156, SEQ ID NO:158, SEQ ID NO:160, SEQ ID NO:168, SEQ ID NO:170, SEQ ID NO:172, SEQ ID NO:176, SEQ ID NO:182, SEQ ID NO:184, SEQ ID NO:186, SEQ ID NO:190, SEQ ID NO:192, SEQ ID NO:194, SEQ ID NO:196, SEQ ID NO:198, SEQ ID NO:206, SEQ ID NO:214, SEQ ID NO:216, SEQ ID NO:218, SEQ ID NO:230, or SEQ ID NO:232. In some embodiments, the nucleotide sequence is codon-optimized. 
     Some embodiments of the disclosure relate to a nucleic acid comprising a nucleotide sequence encoding an engineered variant of the disclosure comprising an amino acid sequence set forth in SEQ ID NO:60, SEQ ID NO:64, SEQ ID NO:66, SEQ ID NO:68, SEQ ID NO:70, SEQ ID NO:72, SEQ ID NO:80, SEQ ID NO:82, SEQ ID NO:102, SEQ ID NO:104, SEQ ID NO:106, SEQ ID NO:116, SEQ ID NO:118, SEQ ID NO:120, SEQ ID NO:122, SEQ ID NO:124, SEQ ID NO:130, SEQ ID NO:132, SEQ ID NO:134, SEQ ID NO:136, SEQ ID NO:138, SEQ ID NO:140, SEQ ID NO:144, SEQ ID NO:146, SEQ ID NO:148, SEQ ID NO:150, SEQ ID NO:152, SEQ ID NO:154, SEQ ID NO:156, SEQ ID NO:158, SEQ ID NO:160, SEQ ID NO:162, SEQ ID NO:164, SEQ ID NO:166, SEQ ID NO:168, SEQ ID NO:170, SEQ ID NO:172, SEQ ID NO:174, SEQ ID NO:176, SEQ ID NO:178, SEQ ID NO:180, SEQ ID NO:182, SEQ ID NO:184, SEQ ID NO:186, SEQ ID NO:188, SEQ ID NO:190, SEQ ID NO:192, SEQ ID NO:194, SEQ ID NO:196, SEQ ID NO:198, SEQ ID NO:200, SEQ ID NO:202, SEQ ID NO:204, SEQ ID NO:206, SEQ ID NO:208, SEQ ID NO:210, SEQ ID NO:212, SEQ ID NO:214, SEQ ID NO:216, SEQ ID NO:218, SEQ ID NO:224, SEQ ID NO:226, SEQ ID NO:228, SEQ ID NO:230, SEQ ID NO:232, or SEQ ID NO:234. In some embodiments, the nucleotide sequence is codon-optimized. 
     Some embodiments of the disclosure relate to a nucleic acid comprising a nucleotide sequence encoding an engineered variant of the disclosure comprising an amino acid sequence set forth in SEQ ID NO:222, SEQ ID NO:224, SEQ ID NO:226, SEQ ID NO:228, SEQ ID NO:230, SEQ ID NO:232, or SEQ ID NO:234. In some embodiments, the nucleotide sequence is codon-optimized. 
     Some embodiments of the disclosure relate to a nucleic acid comprising a nucleotide sequence encoding an engineered variant of the disclosure comprising an amino acid sequence set forth in SEQ ID NO:60, SEQ ID NO:82, SEQ ID NO:92, SEQ ID NO:104, SEQ ID NO:156, SEQ ID NO:160, SEQ ID NO:162, SEQ ID NO:172, SEQ ID NO:174, SEQ ID NO:176, SEQ ID NO:184, SEQ ID NO:198, SEQ ID NO:202, or SEQ ID NO:230. In some embodiments, the nucleotide sequence is codon-optimized. 
     Some embodiments of the disclosure relate to a nucleic acid comprising a nucleotide sequence encoding an engineered variant of the disclosure comprising an amino acid sequence set forth in SEQ ID NO:82, SEQ ID NO:156, SEQ ID NO:160, SEQ ID NO:172, SEQ ID NO:176, SEQ ID NO:184, or SEQ ID NO:198. In some embodiments, the nucleotide sequence is codon-optimized. 
     Some embodiments of the disclosure relate to a nucleic acid comprising a nucleotide sequence encoding an engineered variant of the disclosure comprising an amino acid sequence set forth in SEQ ID NO:300, SEQ ID NO:302, or SEQ ID NO:304. Some embodiments of the disclosure relate to a nucleic acid comprising a nucleotide sequence encoding an engineered variant of the disclosure comprising an amino acid sequence set forth in SEQ ID NO:300. In some embodiments, the nucleotide sequence is codon-optimized. 
     Some embodiments of the disclosure relate to a nucleic acid comprising a nucleotide sequence encoding an engineered variant of the disclosure comprising an amino acid sequence set forth in SEQ ID NO:314, SEQ ID NO:316, SEQ ID NO:318, or SEQ ID NO:320. Some embodiments of the disclosure relate to a nucleic acid comprising a nucleotide sequence encoding an engineered variant of the disclosure comprising an amino acid sequence set forth in SEQ ID NO:314. Some embodiments of the disclosure relate to a nucleic acid comprising a nucleotide sequence encoding an engineered variant of the disclosure comprising an amino acid sequence set forth in SEQ ID NO:316. Some embodiments of the disclosure relate to a nucleic acid comprising a nucleotide sequence encoding an engineered variant of the disclosure comprising an amino acid sequence set forth in SEQ ID NO:318. Some embodiments of the disclosure relate to a nucleic acid comprising a nucleotide sequence encoding an engineered variant of the disclosure comprising an amino acid sequence set forth in SEQ ID NO:320. In some embodiments, the nucleotide sequence is codon-optimized. 
     The disclosure also provides a nucleic acid comprising a nucleotide sequence encoding an engineered variant, wherein the nucleotide sequence is that set forth in SEQ ID NO:49, SEQ ID NO:51, SEQ ID NO:53, SEQ ID NO:55, SEQ ID NO:57, SEQ ID NO:59, SEQ ID NO:61, SEQ ID NO:63, SEQ ID NO:65, SEQ ID NO:67, SEQ ID NO:69, SEQ ID NO:71, SEQ ID NO:73, SEQ ID NO:75, SEQ ID NO:77, SEQ ID NO:79, SEQ ID NO:81, SEQ ID NO:83, SEQ ID NO:85, SEQ ID NO:87, SEQ ID NO:89, SEQ ID NO:91, SEQ ID NO:93, SEQ ID NO:95, SEQ ID NO:97, SEQ ID NO:99, SEQ ID NO:101, SEQ ID NO:103, SEQ ID NO:105, SEQ ID NO:107, SEQ ID NO:109, SEQ ID NO:111, SEQ ID NO:113, SEQ ID NO:115, SEQ ID NO:117, SEQ ID NO:119, SEQ ID NO:121, SEQ ID NO:123, SEQ ID NO:125, SEQ ID NO:127, SEQ ID NO:129, SEQ ID NO:131, SEQ ID NO:133, SEQ ID NO:135, SEQ ID NO:137, SEQ ID NO:139, SEQ ID NO:141, SEQ ID NO:143, SEQ ID NO:145, SEQ ID NO:147, SEQ ID NO:149, SEQ ID NO:151, SEQ ID NO:153, SEQ ID NO:155, SEQ ID NO:157, SEQ ID NO:159, SEQ ID NO:161, SEQ ID NO:163, SEQ ID NO:165, SEQ ID NO:167, SEQ ID NO:169, SEQ ID NO:171, SEQ ID NO:173, SEQ ID NO:175, SEQ ID NO:177, SEQ ID NO:179, SEQ ID NO:181, SEQ ID NO:183, SEQ ID NO:185, SEQ ID NO:187, SEQ ID NO:189, SEQ ID NO:191, SEQ ID NO:193, SEQ ID NO:195, SEQ ID NO:197, SEQ ID NO:199, SEQ ID NO:201, SEQ ID NO:203, SEQ ID NO:205, SEQ ID NO:207, SEQ ID NO:209, SEQ ID NO:211, SEQ ID NO:213, SEQ ID NO:215, SEQ ID NO:217, SEQ ID NO:219, SEQ ID NO:221, SEQ ID NO:223, SEQ ID NO:225, SEQ ID NO:227, SEQ ID NO:229, SEQ ID NO:231, or SEQ ID NO:233. In some embodiments, the nucleotide sequence is codon-optimized. 
     The disclosure provides a nucleic acid comprising a nucleotide sequence encoding an engineered variant, wherein the nucleotide sequence is that set forth in SEQ ID NO:49, SEQ ID NO:51, SEQ ID NO:53, SEQ ID NO:55, SEQ ID NO:57, SEQ ID NO:59, SEQ ID NO:61, SEQ ID NO:63, SEQ ID NO:65, SEQ ID NO:67, SEQ ID NO:69, SEQ ID NO:71, SEQ ID NO:73, SEQ ID NO:75, SEQ ID NO:77, SEQ ID NO:79, SEQ ID NO:81, SEQ ID NO:83, SEQ ID NO:85, SEQ ID NO:87, SEQ ID NO:89, SEQ ID NO:91, SEQ ID NO:93, SEQ ID NO:95, SEQ ID NO:97, SEQ ID NO:99, SEQ ID NO:101, SEQ ID NO:103, SEQ ID NO:105, SEQ ID NO:107, SEQ ID NO:109, SEQ ID NO:111, SEQ ID NO:113, SEQ ID NO:115, SEQ ID NO:117, SEQ ID NO:119, SEQ ID NO:121, SEQ ID NO:123, SEQ ID NO:125, SEQ ID NO:127, SEQ ID NO:129, SEQ ID NO:131, SEQ ID NO:133, SEQ ID NO:135, SEQ ID NO:137, SEQ ID NO:139, SEQ ID NO:141, SEQ ID NO:143, SEQ ID NO:145, SEQ ID NO:147, SEQ ID NO:149, SEQ ID NO:151, SEQ ID NO:153, SEQ ID NO:155, SEQ ID NO:157, SEQ ID NO:159, SEQ ID NO:161, SEQ ID NO:163, SEQ ID NO:165, SEQ ID NO:167, SEQ ID NO:169, SEQ ID NO:171, SEQ ID NO:173, SEQ ID NO:175, SEQ ID NO:177, SEQ ID NO:179, SEQ ID NO:181, SEQ ID NO:183, SEQ ID NO:185, SEQ ID NO:187, SEQ ID NO:189, SEQ ID NO:191, SEQ ID NO:193, SEQ ID NO:195, SEQ ID NO:197, SEQ ID NO:199, SEQ ID NO:201, SEQ ID NO:203, SEQ ID NO:205, SEQ ID NO:207, SEQ ID NO:209, SEQ ID NO:211, SEQ ID NO:213, SEQ ID NO:215, SEQ ID NO:217, SEQ ID NO:219, SEQ ID NO:221, SEQ ID NO:223, SEQ ID NO:225, SEQ ID NO:227, SEQ ID NO:229, SEQ ID NO:231, or SEQ ID NO:233, or a codon degenerate sequence of any of the foregoing. In some embodiments, the nucleotide sequence is codon-optimized. 
     The disclosure also provides a nucleic acid comprising a nucleotide sequence encoding an engineered variant, wherein the nucleotide sequence is that set forth in SEQ ID NO:49, SEQ ID NO:51, SEQ ID NO:53, SEQ ID NO:55, SEQ ID NO:57, SEQ ID NO:59, SEQ ID NO:61, SEQ ID NO:63, SEQ ID NO:65, SEQ ID NO:67, SEQ ID NO:69, SEQ ID NO:71, SEQ ID NO:73, SEQ ID NO:75, SEQ ID NO:77, SEQ ID NO:79, SEQ ID NO:81, SEQ ID NO:83, SEQ ID NO:85, SEQ ID NO:87, SEQ ID NO:89, SEQ ID NO:91, SEQ ID NO:93, SEQ ID NO:95, SEQ ID NO:97, SEQ ID NO:99, SEQ ID NO:101, SEQ ID NO:103, SEQ ID NO:105, SEQ ID NO:107, SEQ ID NO:109, SEQ ID NO:111, SEQ ID NO:113, SEQ ID NO:115, SEQ ID NO:117, SEQ ID NO:119, SEQ ID NO:121, SEQ ID NO:123, SEQ ID NO:125, SEQ ID NO:127, SEQ ID NO:129, SEQ ID NO:131, SEQ ID NO:133, SEQ ID NO:135, SEQ ID NO:137, SEQ ID NO:139, SEQ ID NO:141, SEQ ID NO:143, SEQ ID NO:145, SEQ ID NO:147, SEQ ID NO:149, SEQ ID NO:151, SEQ ID NO:153, SEQ ID NO:155, SEQ ID NO:157, SEQ ID NO:159, SEQ ID NO:161, SEQ ID NO:163, SEQ ID NO:165, SEQ ID NO:167, SEQ ID NO:169, SEQ ID NO:171, SEQ ID NO:173, SEQ ID NO:175, SEQ ID NO:177, SEQ ID NO:179, SEQ ID NO:181, SEQ ID NO:183, SEQ ID NO:185, SEQ ID NO:187, SEQ ID NO:189, SEQ ID NO:191, SEQ ID NO:193, SEQ ID NO:195, SEQ ID NO:197, SEQ ID NO:199, SEQ ID NO:201, SEQ ID NO:203, SEQ ID NO:205, SEQ ID NO:207, SEQ ID NO:209, SEQ ID NO:211, SEQ ID NO:213, SEQ ID NO:215, SEQ ID NO:217, SEQ ID NO:219, SEQ ID NO:221, SEQ ID NO:223, SEQ ID NO:225, SEQ ID NO:227, SEQ ID NO:229, SEQ ID NO:231, SEQ ID NO:233, SEQ ID NO:299, SEQ ID NO:301, or SEQ ID NO:303. In some embodiments, the nucleotide sequence is codon-optimized. 
     The disclosure provides a nucleic acid comprising a nucleotide sequence encoding an engineered variant, wherein the nucleotide sequence is that set forth in SEQ ID NO:49, SEQ ID NO:51, SEQ ID NO:53, SEQ ID NO:55, SEQ ID NO:57, SEQ ID NO:59, SEQ ID NO:61, SEQ ID NO:63, SEQ ID NO:65, SEQ ID NO:67, SEQ ID NO:69, SEQ ID NO:71, SEQ ID NO:73, SEQ ID NO:75, SEQ ID NO:77, SEQ ID NO:79, SEQ ID NO:81, SEQ ID NO:83, SEQ ID NO:85, SEQ ID NO:87, SEQ ID NO:89, SEQ ID NO:91, SEQ ID NO:93, SEQ ID NO:95, SEQ ID NO:97, SEQ ID NO:99, SEQ ID NO:101, SEQ ID NO:103, SEQ ID NO:105, SEQ ID NO:107, SEQ ID NO:109, SEQ ID NO:111, SEQ ID NO:113, SEQ ID NO:115, SEQ ID NO:117, SEQ ID NO:119, SEQ ID NO:121, SEQ ID NO:123, SEQ ID NO:125, SEQ ID NO:127, SEQ ID NO:129, SEQ ID NO:131, SEQ ID NO:133, SEQ ID NO:135, SEQ ID NO:137, SEQ ID NO:139, SEQ ID NO:141, SEQ ID NO:143, SEQ ID NO:145, SEQ ID NO:147, SEQ ID NO:149, SEQ ID NO:151, SEQ ID NO:153, SEQ ID NO:155, SEQ ID NO:157, SEQ ID NO:159, SEQ ID NO:161, SEQ ID NO:163, SEQ ID NO:165, SEQ ID NO:167, SEQ ID NO:169, SEQ ID NO:171, SEQ ID NO:173, SEQ ID NO:175, SEQ ID NO:177, SEQ ID NO:179, SEQ ID NO:181, SEQ ID NO:183, SEQ ID NO:185, SEQ ID NO:187, SEQ ID NO:189, SEQ ID NO:191, SEQ ID NO:193, SEQ ID NO:195, SEQ ID NO:197, SEQ ID NO:199, SEQ ID NO:201, SEQ ID NO:203, SEQ ID NO:205, SEQ ID NO:207, SEQ ID NO:209, SEQ ID NO:211, SEQ ID NO:213, SEQ ID NO:215, SEQ ID NO:217, SEQ ID NO:219, SEQ ID NO:221, SEQ ID NO:223, SEQ ID NO:225, SEQ ID NO:227, SEQ ID NO:229, SEQ ID NO:231, SEQ ID NO:233, SEQ ID NO:299, SEQ ID NO:301, or SEQ ID NO:303, or a codon degenerate sequence of any of the foregoing. In some embodiments, the nucleotide sequence is codon-optimized. 
     The disclosure provides a nucleic acid comprising a nucleotide sequence encoding an engineered variant, wherein the nucleotide sequence is that set forth in SEQ ID NO:59, SEQ ID NO:63, SEQ ID NO:65, SEQ ID NO:67, SEQ ID NO:69, SEQ ID NO:71, SEQ ID NO:73, SEQ ID NO:75, SEQ ID NO:77, SEQ ID NO:79, SEQ ID NO:81, SEQ ID NO:87, SEQ ID NO:89, SEQ ID NO:91, SEQ ID NO:95, SEQ ID NO:101, SEQ ID NO:105, SEQ ID NO:111, SEQ ID NO:115, SEQ ID NO:117, SEQ ID NO:119, SEQ ID NO:121, SEQ ID NO:123, SEQ ID NO:125, SEQ ID NO:127, SEQ ID NO:129, SEQ ID NO:131, SEQ ID NO:133, SEQ ID NO:135, SEQ ID NO:137, SEQ ID NO:139, SEQ ID NO:141, SEQ ID NO:143, SEQ ID NO:145, SEQ ID NO:147, SEQ ID NO:149, SEQ ID NO:151, SEQ ID NO:153, SEQ ID NO:155, SEQ ID NO:157, SEQ ID NO:159, SEQ ID NO:161, SEQ ID NO:163, SEQ ID NO:165, SEQ ID NO:167, SEQ ID NO:169, SEQ ID NO:171, SEQ ID NO:173, SEQ ID NO:175, SEQ ID NO:177, SEQ ID NO:179, SEQ ID NO:181, SEQ ID NO:183, SEQ ID NO:185, SEQ ID NO:187, SEQ ID NO:189, SEQ ID NO:191, SEQ ID NO:193, SEQ ID NO:195, SEQ ID NO:197, SEQ ID NO:199, SEQ ID NO:201, SEQ ID NO:205, SEQ ID NO:207, SEQ ID NO:209, SEQ ID NO:211, SEQ ID NO:213, SEQ ID NO:215, SEQ ID NO:217, SEQ ID NO:219, SEQ ID NO:221, SEQ ID NO:223, SEQ ID NO:225, SEQ ID NO:227, SEQ ID NO:229, SEQ ID NO:231, or SEQ ID NO:233. In some embodiments, the nucleotide sequence is codon-optimized. 
     The disclosure provides a nucleic acid comprising a nucleotide sequence encoding an engineered variant, wherein the nucleotide sequence is that set forth in SEQ ID NO:59, SEQ ID NO:63, SEQ ID NO:65, SEQ ID NO:67, SEQ ID NO:69, SEQ ID NO:71, SEQ ID NO:73, SEQ ID NO:75, SEQ ID NO:77, SEQ ID NO:79, SEQ ID NO:81, SEQ ID NO:87, SEQ ID NO:89, SEQ ID NO:91, SEQ ID NO:95, SEQ ID NO:101, SEQ ID NO:105, SEQ ID NO:111, SEQ ID NO:115, SEQ ID NO:117, SEQ ID NO:119, SEQ ID NO:121, SEQ ID NO:123, SEQ ID NO:125, SEQ ID NO:127, SEQ ID NO:129, SEQ ID NO:131, SEQ ID NO:133, SEQ ID NO:135, SEQ ID NO:137, SEQ ID NO:139, SEQ ID NO:141, SEQ ID NO:143, SEQ ID NO:145, SEQ ID NO:147, SEQ ID NO:149, SEQ ID NO:151, SEQ ID NO:153, SEQ ID NO:155, SEQ ID NO:157, SEQ ID NO:159, SEQ ID NO:161, SEQ ID NO:163, SEQ ID NO:165, SEQ ID NO:167, SEQ ID NO:169, SEQ ID NO:171, SEQ ID NO:173, SEQ ID NO:175, SEQ ID NO:177, SEQ ID NO:179, SEQ ID NO:181, SEQ ID NO:183, SEQ ID NO:185, SEQ ID NO:187, SEQ ID NO:189, SEQ ID NO:191, SEQ ID NO:193, SEQ ID NO:195, SEQ ID NO:197, SEQ ID NO:199, SEQ ID NO:201, SEQ ID NO:205, SEQ ID NO:207, SEQ ID NO:209, SEQ ID NO:211, SEQ ID NO:213, SEQ ID NO:215, SEQ ID NO:217, SEQ ID NO:219, SEQ ID NO:221, SEQ ID NO:223, SEQ ID NO:225, SEQ ID NO:227, SEQ ID NO:229, SEQ ID NO:231, or SEQ ID NO:233, or a codon degenerate sequence of any of the foregoing. In some embodiments, the nucleotide sequence is codon-optimized. 
     The disclosure also provides a nucleic acid comprising a nucleotide sequence encoding an engineered variant, wherein the nucleotide sequence is that set forth in SEQ ID NO:221, SEQ ID NO:223, SEQ ID NO:225, SEQ ID NO:227, SEQ ID NO:229, SEQ ID NO:231, or SEQ ID NO:233. In some embodiments, the nucleotide sequence is codon-optimized. 
     The disclosure also provides a nucleic acid comprising a nucleotide sequence encoding an engineered variant, wherein the nucleotide sequence is that set forth in SEQ ID NO:221, SEQ ID NO:223, SEQ ID NO:225, SEQ ID NO:227, SEQ ID NO:229, SEQ ID NO:231, or SEQ ID NO:233, or a codon degenerate sequence of any of the foregoing. In some embodiments, the nucleotide sequence is codon-optimized. 
     The disclosure provides a nucleic acid comprising a nucleotide sequence encoding an engineered variant, wherein the nucleotide sequence is that set forth in SEQ ID NO:65, SEQ ID NO:69, SEQ ID NO:71, SEQ ID NO:79, SEQ ID NO:81, SEQ ID NO:129, SEQ ID NO:135, SEQ ID NO:141, SEQ ID NO:145, SEQ ID NO:149, SEQ ID NO:155, SEQ ID NO:157, SEQ ID NO:159, SEQ ID NO:167, SEQ ID NO:169, SEQ ID NO:171, SEQ ID NO:175, SEQ ID NO:181, SEQ ID NO:183, SEQ ID NO:185, SEQ ID NO:189, SEQ ID NO:191, SEQ ID NO:193, SEQ ID NO:195, SEQ ID NO:197, SEQ ID NO:205, SEQ ID NO:213, SEQ ID NO:215, SEQ ID NO:217, SEQ ID NO:229, or SEQ ID NO:231. In some embodiments, the nucleotide sequence is codon-optimized. 
     The disclosure provides a nucleic acid comprising a nucleotide sequence encoding an engineered variant, wherein the nucleotide sequence is that set forth in SEQ ID NO:65, SEQ ID NO:69, SEQ ID NO:71, SEQ ID NO:79, SEQ ID NO:81, SEQ ID NO:129, SEQ ID NO:135, SEQ ID NO:141, SEQ ID NO:145, SEQ ID NO:149, SEQ ID NO:155, SEQ ID NO:157, SEQ ID NO:159, SEQ ID NO:167, SEQ ID NO:169, SEQ ID NO:171, SEQ ID NO:175, SEQ ID NO:181, SEQ ID NO:183, SEQ ID NO:185, SEQ ID NO:189, SEQ ID NO:191, SEQ ID NO:193, SEQ ID NO:195, SEQ ID NO:197, SEQ ID NO:205, SEQ ID NO:213, SEQ ID NO:215, SEQ ID NO:217, SEQ ID NO:229, or SEQ ID NO:231, or a codon degenerate sequence of any of the foregoing. In some embodiments, the nucleotide sequence is codon-optimized. 
     The disclosure provides a nucleic acid comprising a nucleotide sequence encoding an engineered variant, wherein the nucleotide sequence is that set forth in SEQ ID NO:59, SEQ ID NO:63, SEQ ID NO:65, SEQ ID NO:67, SEQ ID NO:69, SEQ ID NO:71, SEQ ID NO:79, SEQ ID NO:81, SEQ ID NO:101, SEQ ID NO:103, SEQ ID NO:105, SEQ ID NO:115, SEQ ID NO:117, SEQ ID NO:119, SEQ ID NO:121, SEQ ID NO:123, SEQ ID NO:129, SEQ ID NO:131, SEQ ID NO:133, SEQ ID NO:135, SEQ ID NO:137, SEQ ID NO:139, SEQ ID NO:143, SEQ ID NO:145, SEQ ID NO:147, SEQ ID NO:149, SEQ ID NO:151, SEQ ID NO:153, SEQ ID NO:155, SEQ ID NO:157, SEQ ID NO:159, SEQ ID NO:161, SEQ ID NO:163, SEQ ID NO:165, SEQ ID NO:167, SEQ ID NO:169, SEQ ID NO:171, SEQ ID NO:173, SEQ ID NO:175, SEQ ID NO:177, SEQ ID NO:179, SEQ ID NO:181, SEQ ID NO:183, SEQ ID NO:185, SEQ ID NO:187, SEQ ID NO:189, SEQ ID NO:191, SEQ ID NO:193, SEQ ID NO:195, SEQ ID NO:197, SEQ ID NO:199, SEQ ID NO:201, SEQ ID NO:203, SEQ ID NO:205, SEQ ID NO:207, SEQ ID NO:209, SEQ ID NO:211, SEQ ID NO:213, SEQ ID NO:215, SEQ ID NO:217, SEQ ID NO:223, SEQ ID NO:225, SEQ ID NO:227, SEQ ID NO:229, SEQ ID NO:231, or SEQ ID NO:233. In some embodiments, the nucleotide sequence is codon-optimized. 
     The disclosure provides a nucleic acid comprising a nucleotide sequence encoding an engineered variant, wherein the nucleotide sequence is that set forth in SEQ ID NO:59, SEQ ID NO:63, SEQ ID NO:65, SEQ ID NO:67, SEQ ID NO:69, SEQ ID NO:71, SEQ ID NO:79, SEQ ID NO:81, SEQ ID NO:101, SEQ ID NO:103, SEQ ID NO:105, SEQ ID NO:115, SEQ ID NO:117, SEQ ID NO:119, SEQ ID NO:121, SEQ ID NO:123, SEQ ID NO:129, SEQ ID NO:131, SEQ ID NO:133, SEQ ID NO:135, SEQ ID NO:137, SEQ ID NO:139, SEQ ID NO:143, SEQ ID NO:145, SEQ ID NO:147, SEQ ID NO:149, SEQ ID NO:151, SEQ ID NO:153, SEQ ID NO:155, SEQ ID NO:157, SEQ ID NO:159, SEQ ID NO:161, SEQ ID NO:163, SEQ ID NO:165, SEQ ID NO:167, SEQ ID NO:169, SEQ ID NO:171, SEQ ID NO:173, SEQ ID NO:175, SEQ ID NO:177, SEQ ID NO:179, SEQ ID NO:181, SEQ ID NO:183, SEQ ID NO:185, SEQ ID NO:187, SEQ ID NO:189, SEQ ID NO:191, SEQ ID NO:193, SEQ ID NO:195, SEQ ID NO:197, SEQ ID NO:199, SEQ ID NO:201, SEQ ID NO:203, SEQ ID NO:205, SEQ ID NO:207, SEQ ID NO:209, SEQ ID NO:211, SEQ ID NO:213, SEQ ID NO:215, SEQ ID NO:217, SEQ ID NO:223, SEQ ID NO:225, SEQ ID NO:227, SEQ ID NO:229, SEQ ID NO:231, or SEQ ID NO:233, or a codon degenerate sequence of any of the foregoing. In some embodiments, the nucleotide sequence is codon-optimized. 
     The disclosure provides a nucleic acid comprising a nucleotide sequence encoding an engineered variant, wherein the nucleotide sequence is that set forth in SEQ ID NO:59, SEQ ID NO:81, SEQ ID NO:91, SEQ ID NO:103, SEQ ID NO:155, SEQ ID NO:159, SEQ ID NO:161, SEQ ID NO:171, SEQ ID NO:173, SEQ ID NO:175, SEQ ID NO:183, SEQ ID NO:197, SEQ ID NO:201, or SEQ ID NO:229. In some embodiments, the nucleotide sequence is codon-optimized. 
     The disclosure provides a nucleic acid comprising a nucleotide sequence encoding an engineered variant, wherein the nucleotide sequence is that set forth in SEQ ID NO:59, SEQ ID NO:81, SEQ ID NO:91, SEQ ID NO:103, SEQ ID NO:155, SEQ ID NO:159, SEQ ID NO:161, SEQ ID NO:171, SEQ ID NO:173, SEQ ID NO:175, SEQ ID NO:183, SEQ ID NO:197, SEQ ID NO:201, or SEQ ID NO:229, or a codon degenerate sequence of any of the foregoing. In some embodiments, the nucleotide sequence is codon-optimized. 
     The disclosure provides a nucleic acid comprising a nucleotide sequence encoding an engineered variant, wherein the nucleotide sequence is that set forth in SEQ ID NO:81, SEQ ID NO:155, SEQ ID NO:159, SEQ ID NO:171, SEQ ID NO:175, SEQ ID NO:183, or SEQ ID NO:197. In some embodiments, the nucleotide sequence is codon-optimized. 
     The disclosure provides a nucleic acid comprising a nucleotide sequence encoding an engineered variant, wherein the nucleotide sequence is that set forth in SEQ ID NO:81, SEQ ID NO:155, SEQ ID NO:159, SEQ ID NO:171, SEQ ID NO:175, SEQ ID NO:183, or SEQ ID NO:197, or a codon degenerate sequence of any of the foregoing. In some embodiments, the nucleotide sequence is codon-optimized. 
     The disclosure provides a nucleic acid comprising a nucleotide sequence encoding an engineered variant, wherein the nucleotide sequence is that set forth in SEQ ID NO:299, SEQ ID NO:301, or SEQ ID NO:303. In some embodiments, the nucleotide sequence is codon-optimized. 
     The disclosure provides a nucleic acid comprising a nucleotide sequence encoding an engineered variant, wherein the nucleotide sequence is that set forth in SEQ ID NO:299, SEQ ID NO:301, or SEQ ID NO:303, or a codon degenerate sequence of any of the foregoing. In some embodiments, the nucleotide sequence is codon-optimized. 
     The disclosure provides a nucleic acid comprising a nucleotide sequence encoding an engineered variant, wherein the nucleotide sequence is that set forth in SEQ ID NO:299. In some embodiments, the nucleotide sequence is codon-optimized. 
     The disclosure provides a nucleic acid comprising a nucleotide sequence encoding an engineered variant, wherein the nucleotide sequence is that set forth in SEQ ID NO:299, or a codon degenerate sequence of any of the foregoing. In some embodiments, the nucleotide sequence is codon-optimized. 
     The disclosure provides a nucleic acid comprising a nucleotide sequence encoding an engineered variant, wherein the nucleotide sequence is that set forth in SEQ ID NO:313, SEQ ID NO:315, SEQ ID NO:317, or SEQ ID NO:319. In some embodiments, the nucleotide sequence is codon-optimized. 
     The disclosure provides a nucleic acid comprising a nucleotide sequence encoding an engineered variant, wherein the nucleotide sequence is that set forth in SEQ ID NO:313, SEQ ID NO:315, SEQ ID NO:317, or SEQ ID NO:319, or a codon degenerate sequence of any of the foregoing. In some embodiments, the nucleotide sequence is codon-optimized. 
     The disclosure provides a nucleic acid comprising a nucleotide sequence encoding an engineered variant, wherein the nucleotide sequence is that set forth in SEQ ID NO:313. In some embodiments, the nucleotide sequence is codon-optimized. 
     The disclosure provides a nucleic acid comprising a nucleotide sequence encoding an engineered variant, wherein the nucleotide sequence is that set forth in SEQ ID NO:313, or a codon degenerate sequence of any of the foregoing. In some embodiments, the nucleotide sequence is codon-optimized. 
     The disclosure provides a nucleic acid comprising a nucleotide sequence encoding an engineered variant, wherein the nucleotide sequence is that set forth in SEQ ID NO:315. In some embodiments, the nucleotide sequence is codon-optimized. 
     The disclosure provides a nucleic acid comprising a nucleotide sequence encoding an engineered variant, wherein the nucleotide sequence is that set forth in SEQ ID NO:315, or a codon degenerate sequence of any of the foregoing. In some embodiments, the nucleotide sequence is codon-optimized. 
     The disclosure provides a nucleic acid comprising a nucleotide sequence encoding an engineered variant, wherein the nucleotide sequence is that set forth in SEQ ID NO:317. In some embodiments, the nucleotide sequence is codon-optimized. 
     The disclosure provides a nucleic acid comprising a nucleotide sequence encoding an engineered variant, wherein the nucleotide sequence is that set forth in SEQ ID NO:317, or a codon degenerate sequence of any of the foregoing. In some embodiments, the nucleotide sequence is codon-optimized. 
     The disclosure provides a nucleic acid comprising a nucleotide sequence encoding an engineered variant, wherein the nucleotide sequence is that set forth in SEQ ID NO:319. In some embodiments, the nucleotide sequence is codon-optimized. 
     The disclosure provides a nucleic acid comprising a nucleotide sequence encoding an engineered variant, wherein the nucleotide sequence is that set forth in SEQ ID NO:319, or a codon degenerate sequence of any of the foregoing. In some embodiments, the nucleotide sequence is codon-optimized. 
     Further included are nucleic acids that hybridize to the nucleic acids disclosed herein. Hybridization conditions may be stringent in that hybridization will occur if there is at least a 90%, at least a 95%, or at least a 97% sequence identity with the nucleotide sequence present in the nucleic acid encoding the polypeptides disclosed herein. The stringent conditions may include those used for known Southern hybridizations such as, for example, incubation overnight at 42° C. in a solution having 50% formamide, 5×SSC (150 mM NaCl, 15 mM trisodium citrate), 50 mM sodium phosphate (pH 7.6), 5×Denhardt&#39;s solution, 10% dextran sulfate, and 20 micrograms/milliliter denatured, sheared salmon sperm DNA, following by washing the hybridization support in 0.1×SSC at about 65° C. Other known hybridization conditions are well known and are described in Sambrook et al., Molecular Cloning: A Laboratory Manual, Third Edition, Cold Spring Harbor, N.Y. (2001). 
     The length of the nucleic acids disclosed herein may depend on the intended use. For example, if the intended use is as a primer or probe, for example for PCR amplification or for screening a library, the length of the nucleic acid will be less than the full length sequence, for example, 15-50 nucleotides. In certain such embodiments, the primers or probes may be substantially identical to a highly conserved region of the nucleotide sequence or may be substantially identical to either the 5′ or 3′ end of the nucleotide sequence. In some cases, these primers or probes may use universal bases in some positions so as to be “substantially identical” but still provide flexibility in sequence recognition. It is of note that suitable primer and probe hybridization conditions are well known in the art. 
     Some embodiments of the disclosure relate to a vector comprising one or more nucleic acids disclosed herein. Some embodiments of the disclosure relate to an expression construct comprising one or more nucleic acids disclosed herein. Some embodiments of the disclosure relate to nucleic acids comprising codon-optimized nucleotide sequences encoding the engineered variants of the disclosure. In some embodiments, the nucleic acids disclosed herein are heterologous. 
     Methods of Screening Engineered Variants of the Cannabidiolic Acid Synthase (CBDAS) Polypeptide 
     The disclosure provides a method of screening an engineered variant of a cannabidiolic acid synthase (CBDAS) polypeptide comprising an amino acid sequence of SEQ ID NO:3 with one or more amino acid substitutions. In certain such embodiments, the method involves a competition assay wherein the engineered variant of the disclosure is expressed in a modified host cells alongside a related enzyme. 
     Some embodiments of the disclosure relate to a method of screening an engineered variant of a cannabidiolic acid synthase (CBDAS) polypeptide comprising an amino acid sequence of SEQ ID NO:3 with one or more amino acid substitutions, the method comprising: 
     a) dividing a population of host cells into a control population and a test population; 
     b) co-expressing in the control population a CBDAS polypeptide having an amino acid sequence of SEQ ID NO:3 and a comparison cannabinoid synthase polypeptide, wherein the CBDAS polypeptide having an amino acid sequence of SEQ ID NO:3 can convert CBGA to a first cannabinoid, CBDA, and the comparison cannabinoid synthase polypeptide can convert the same CBGA to a different second cannabinoid; 
     c) co-expressing in the test population the engineered variant and the comparison cannabinoid synthase polypeptide, wherein the engineered variant may convert CBGA to the same first cannabinoid, CBDA, as the CBDAS polypeptide having an amino acid sequence of SEQ ID NO:3, and wherein the comparison cannabinoid synthase polypeptide can convert the same CBGA to the second cannabinoid and is expressed at similar levels in the test population and in the control population; 
     d) measuring a ratio of the first cannabinoid, CBDA, over the second cannabinoid produced by both the test population and the control population; and 
     e) measuring an amount, in mg/L or mM, of the first cannabinoid produced by both the test population and the control population. In certain such embodiments, the engineered variant is an engineered variant of the disclosure. 
     In some embodiments, the test population is identified as comprising an engineered variant having improved in vivo performance compared to the cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3 by producing the first cannabinoid in a greater amount, as measured in mg/L or mM, by the test population compared to the amount produced by the control population under similar culture conditions for the same length of time. In some embodiments, the test population is identified as comprising an engineered variant having improved in vivo performance compared to the cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3, wherein improved in vivo performance is demonstrated by an increase in the ratio of the first cannabinoid over the second cannabinoid produced by the test population compared to that produced by the control population under similar culture conditions for the same length of time. 
     In some embodiments, the cannabinoid synthase polypeptide is a tetrahydrocannabinolic acid synthase (THCAS) polypeptide. In certain such embodiments, the THCAS polypeptide comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, at least 99.6%, at least 99.7%, at least 99.8%, at least 99.9%, or 100% sequence identity to SEQ ID NO:44. In some embodiments, a nucleotide sequence encoding the THCAS polypeptide is the nucleotide sequence set forth in SEQ ID NO:45. In some embodiments, a nucleotide sequence encoding the THCAS polypeptide is the nucleotide sequence set forth in SEQ ID NO:45, or a codon degenerate nucleotide sequence thereof. In some embodiments, a nucleotide sequence encoding the THCAS polypeptide has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, at least 99.6%, at least 99.7%, at least 99.8%, at least 99.9%, or 100% sequence identity to SEQ ID NO:45. In some embodiments, the second cannabinoid is THCA. 
     Modified Host Cells for Expressing Engineered Variants of the Cannabidiolic Acid Synthase (CBDAS) Polypeptide and for Producing Cannabinoids and Cannabinoid Derivatives 
     The present disclosure provides modified host cells comprising one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure. In certain such embodiments, the modified host cells of the disclosure are for expressing an engineered variant and/or for producing a cannabinoid or a cannabinoid derivative. In some embodiments, the nucleotide sequence encoding the engineered variant is codon-optimized. 
     The disclosure also provides nucleic acids (e.g., heterologous nucleic acids), which can be introduced into microorganisms (e.g., modified host cells), resulting in expression or overexpression of the engineered variants of the disclosure, which can then be utilized in vitro (e.g., cell-free) or in vivo for the production of cannabinoids or cannabinoid derivatives. In some embodiments, these nucleic acids comprise a codon-optimized nucleotide sequence encoding the engineered variant. 
     Cannabinoid synthase polypeptides, secreted polypeptides, such as the engineered variants of the disclosure, have structural features that may hinder expression in modified host cells, such as modified yeast cells. Cannabinoid synthase polypeptides, including the engineered variants of the disclosure, comprise disulfide bonds, numerous glycosylation sites, including N-glycosylation sites, and a bicovalently attached flavin adenine dinucleotide (FAD) cofactor moiety. Often these secreted polypeptides are misfolded or mislocalized, resulting in low expression, polypeptides lacking activity, reduced host cell viability, and/or cell death. As disclosed herein, manipulation of secretory pathway in host cells modified with one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure may improve expression, folding, and enzymatic activity of the engineered variant of the disclosure as well as viability of the modified host cell. In certain such embodiments, the nucleotide sequence encoding the engineered variant is codon-optimized. 
     To produce cannabinoids or cannabinoid derivatives and create biosynthetic pathways within modified host cells, modified host cells comprising one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure may express or overexpress combinations of heterologous nucleic acids comprising nucleotide sequences encoding polypeptides involved in cannabinoid or cannabinoid precursor (e.g., geranylpyrophosphate (GPP), prenyl phosphates, olivetolic acid, or hexanoyl-CoA) biosynthesis. In some embodiments, the nucleotide sequences encoding the polypeptides involved in cannabinoid or cannabinoid precursor (e.g., geranylpyrophosphate (GPP), prenyl phosphates, olivetolic acid, or hexanoyl-CoA) biosynthesis are codon-optimized. In some embodiments, the modified host cells of the disclosure for producing cannabinoid or cannabinoid derivatives comprising one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure comprise one or more modifications to modulate the expression of one or more secretory pathway polypeptides. The one or more modifications to modulate the expression of one or more secretory pathway polypeptides may include introducing into a host cell one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more secretory pathway polypeptides and/or deletion or downregulation of one or more genes encoding one or more secretory pathway polypeptides in a host cell. In some embodiments, a modified host cell of the present disclosure for producing cannabinoids or cannabinoid derivatives comprising one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure comprises one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more secretory pathway polypeptides, resulting in expression or overexpression of the one or more secretory pathway polypeptides. In some embodiments, the nucleotide sequences encoding the one or more secretory pathway polypeptides are codon-optimized. In some embodiments, the modified host cell for producing cannabinoids or cannabinoid derivatives comprising one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure comprises a deletion or downregulation of one or more genes encoding one or more secretory pathway polypeptides, reducing or eliminating the expression of the one or more secretory pathway polypeptides. In certain such embodiments, the modified host cells comprise a deletion of one or more genes encoding one or more secretory pathway polypeptides. In some embodiments, the modified host cells comprise a downregulation of one or more genes encoding one or more secretory pathway polypeptides. 
     In some embodiments, culturing of a modified host cell for producing cannabinoids or cannabinoid derivatives in a culture medium provides for synthesis of the cannabinoid or the cannabinoid derivative. 
     To express an engineered variant of the disclosure, the modified host cells may express or overexpress one or more nucleic acids comprising a nucleotide sequence encoding the engineered variant. In some embodiments, the nucleotide sequences encoding the engineered variants are codon-optimized. In some embodiments, the modified host cells of the disclosure for expressing an engineered variant of the disclosure comprising one or more nucleic acids comprising a nucleotide sequence encoding the engineered variant comprise one or more modifications to modulate the expression of one or more secretory pathway polypeptides. The one or more modifications to modulate the expression of one or more secretory pathway polypeptides may include introducing into a host cell one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more secretory pathway polypeptides and/or deletion or downregulation of one or more genes encoding one or more secretory pathway polypeptides in a host cell. In some embodiments, a modified host cell of the present disclosure for expressing an engineered variant of the disclosure comprising one or more nucleic acids comprising a nucleotide sequence encoding the engineered variant comprises one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more secretory pathway polypeptides, resulting in expression or overexpression of the one or more secretory pathway polypeptides. In some embodiments, the nucleotide sequences encoding the one or more secretory pathway polypeptides are codon-optimized. In some embodiments, the modified host cell for expressing an engineered variant of the disclosure comprising one or more nucleic acids comprising a nucleotide sequence encoding the engineered variant comprises a deletion or downregulation of one or more genes encoding one or more secretory pathway polypeptides, reducing or eliminating the expression of the one or more secretory pathway polypeptides. In certain such embodiments, the modified host cells comprise a deletion of one or more genes encoding one or more secretory pathway polypeptides. In some embodiments, the modified host cells comprise a downregulation of one or more genes encoding one or more secretory pathway polypeptides. In some embodiments of the modified host cell for expressing an engineered variant of the disclosure, the modified host cell comprises one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more polypeptides involved in cannabinoid or cannabinoid precursor biosynthesis. In some embodiments, the nucleotide sequences encoding the one or more polypeptides involved in cannabinoid or cannabinoid precursor biosynthesis are codon-optimized. 
     Secretory Pathway Modifications 
     Secretory pathway polypeptides with modulated expression in the modified host cells of the disclosure may include, but are not limited to: a KAR2 polypeptide, a ROT2 polypeptide, a PIM polypeptide, an ERO1 polypeptide, a FAD1 polypeptide, a PEP4 polypeptide, and an IRE1 polypeptide. Expression of secretory pathway polypeptides may be modulated by introducing into a host cell one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more secretory pathway polypeptides and/or deletion or downregulation of one or more genes encoding one or more secretory pathway polypeptides in a host cell. In some embodiments, the nucleotide sequences encoding the one or more secretory pathway polypeptides are codon-optimized. 
     In some embodiments, the modified host cells of the disclosure comprise a deletion or downregulation of one or more of the following genes: a ROT2 gene or a PEP4 gene. In some embodiments, the modified host cells of the disclosure comprise a deletion of one or more of the following genes: a ROT2 gene or a PEP4 gene. In some embodiments, the modified host cells of the disclosure comprise a downregulation of one or more of the following genes: a ROT2 gene or a PEP4 gene. 
     The secretory pathway polypeptides and the nucleotide sequences encoding the secretory pathway polypeptides may be derived from any suitable source, for example, bacteria, yeast, fungi, algae, human, plant, or mouse. In some embodiments, the secretory pathway polypeptides and the nucleotide sequences encoding the secretory pathway polypeptides may be derived from  Pichia pastoris  (now known as  Komagataella phaffii ),  Pichia finlandica, Pichia trehalophila, Pichia koclamae, Pichia membranaefaciens, Pichia opuntiae, Pichia thermotolerans, Pichia salictaria, Pichia guercuum, Pichia pijperi, Pichia stiptis, Pichia methanolica, Pichia  sp.,  Saccharomyces cerevisiae, Saccharomyces  sp.,  Hansenula polymorpha  (now known as  Pichia angusta ),  Yarrowia lipolytica, Kluyveromyces  sp.,  Kluyveromyces lactis, Kluyveromyces marxianus, Schizosaccharomyces pombe, Scheffersomyces stipites, Dekkera bruxellensis, Blastobotrys adeninivorans  (formerly  Arxula adeninivorans ),  Candida albicans, Aspergillus nidulans, Aspergillus niger, Aspergillus oryzae, Trichoderma reesei, Chrysosporium lucknowense, Fusarium  sp.,  Fusarium gramineum, Fusarium venenatum, Neurospora crassa , and the like. In some embodiments, the disclosure also encompasses orthologous genes encoding the secretory pathway polypeptides disclosed herein. Exemplary secretory pathway polypeptides disclosed herein may also include a full-length secretory pathway polypeptide, a fragment of a secretory pathway polypeptide, a variant of a secretory pathway polypeptide, a truncated secretory pathway polypeptide, or a fusion polypeptide that has at least one activity of a secretory pathway polypeptide. The disclosure also provides for nucleotide sequences encoding secretory pathway polypeptides, such as, a full-length secretory pathway polypeptide, a fragment of a secretory pathway polypeptide, a variant of a secretory pathway polypeptide, a truncated secretory pathway polypeptide, or a fusion polypeptide that has at least one activity of a secretory pathway polypeptide. In some embodiments, the nucleotide sequences encoding the secretory pathway polypeptides are codon-optimized. 
     Exemplary KAR2 polypeptides disclosed herein may include a full-length KAR2 polypeptide, a fragment of a KAR2 polypeptide, a variant of a KAR2 polypeptide, a truncated KAR2 polypeptide, or a fusion polypeptide that has at least one activity of a KAR2 polypeptide. 
     Exemplary ROT2 polypeptides disclosed herein may include a full-length ROT2 polypeptide, a fragment of a ROT2 polypeptide, a variant of a ROT2 polypeptide, a truncated ROT2 polypeptide, or a fusion polypeptide that has at least one activity of a ROT2 polypeptide. 
     Exemplary PDI1 polypeptides disclosed herein may include a full-length PDI1 polypeptide, a fragment of a PDI1 polypeptide, a variant of a PDI1 polypeptide, a truncated PDI1 polypeptide, or a fusion polypeptide that has at least one activity of a PDI1 polypeptide. 
     Exemplary ERO1 polypeptides disclosed herein may include a full-length ERO1 polypeptide, a fragment of an ERO1 polypeptide, a variant of an ERO1 polypeptide, a truncated ERO1 polypeptide, or a fusion polypeptide that has at least one activity of an ERO1 polypeptide. 
     Exemplary FAD1 polypeptides disclosed herein may include a full-length FAD1 polypeptide, a fragment of a FAD1 polypeptide, a variant of a FAD1 polypeptide, a truncated FAD1 polypeptide, or a fusion polypeptide that has at least one activity of a FAD1 polypeptide. 
     Exemplary PEP4 polypeptides disclosed herein may include a full-length PEP4 polypeptide, a fragment of a PEP4 polypeptide, a variant of a PEP4 polypeptide, a truncated PEP1 polypeptide, or a fusion polypeptide that has at least one activity of a PEP4 polypeptide. 
     Exemplary IRE1 polypeptides disclosed herein may include a full-length IRE1 polypeptide, a fragment of an IRE1 polypeptide (e.g., missing the first 7 amino acids), a variant of an IRE1 polypeptide, a truncated IRE1 polypeptide, or a fusion polypeptide that has at least one activity of an IRE1 polypeptide. 
     Modified host cells of the disclosure may comprise one or more modifications to modulate the expression of one or more of a KAR2 polypeptide, a ROT2 polypeptide, a PDI1 polypeptide, an ERO1 polypeptide, a FAD1 polypeptide, a PEP4 polypeptide, or an IRE1 polypeptide. The one or more modifications to modulate the expression of one or more of a KAR2 polypeptide, a ROT2 polypeptide, a PDI1 polypeptide, an ERO1 polypeptide, a FAD1 polypeptide, a PEP4 polypeptide, or an IRE1 polypeptide may include introducing into a host cell one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more of the KAR2 polypeptide, the PDI1 polypeptide, the ERO1 polypeptide, the FAD1 polypeptide, or the IRE1 polypeptide and/or deletion or downregulation of one or more genes encoding one or more of the ROT2 polypeptide or the PEP4 polypeptide in a host cell. In some embodiments, a modified host cell of the present disclosure comprises one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more of a KAR2 polypeptide, a PDI1 polypeptide, an ERO1 polypeptide, a FAD1 polypeptide, or an IRE1 polypeptide resulting in expression or overexpression of the KAR2 polypeptide, the PDI1 polypeptide, the ERO1 polypeptide, the FAD1 polypeptide, or the IRE1 polypeptide. In some embodiments, the modified host cells of the disclosure comprise a deletion or downregulation of one or more genes encoding one or more of a ROT2 polypeptide or a PEP4 polypeptide, reducing or eliminating the expression of the ROT2 polypeptide or the PEP4 polypeptide. 
     In some embodiments, the one or more modifications to modulate the expression of one or more secretory pathway polypeptides may improve modified host cell viability. Improving modified host cell viability may improve the industrial fermentation process. The ERO1 polypeptide may serve as a partner to the PDI1 polypeptide, a protein disulfide isomerase polypeptide. Modulating the expression of an IRE1 polypeptide may prevent degradation of expressed engineered variants of the disclosure. 
     In some embodiments, the modified host cells of the disclosure comprise one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more of a KAR2 polypeptide, a PDI1 polypeptide, an ERO1 polypeptide, a FAD1 polypeptide, or an IRE1 polypeptide. 
     In some embodiments, the modified host cells of the disclosure comprise one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more secretory pathway polypeptides comprising the amino acid sequences set forth in SEQ ID NO:5 (a KAR2 polypeptide), SEQ ID NO:9 (a PDI1 polypeptide), SEQ ID NO:7 (an ERO1 polypeptide), SEQ ID NO:298 (a FAD1 polypeptide), SEQ ID NO:11 (an IRE1 polypeptide), or SEQ ID NO:296 (an IRE1 polypeptide fragment). 
     In some embodiments, the modified host cells of the disclosure comprise one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more secretory pathway polypeptides comprising the amino acid sequences set forth in SEQ ID NO:5 (a KAR2 polypeptide), SEQ ID NO:9 (a PDI1 polypeptide), SEQ ID NO:7 (an ERO1 polypeptide), SEQ ID NO:298 (a FAD1 polypeptide), SEQ ID NO:11 (an IRE1 polypeptide), or SEQ ID NO:296 (an IRE1 polypeptide fragment), or a conservatively substituted amino acid sequence of any of the foregoing. 
     In some embodiments, the modified host cells of the disclosure comprise one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more secretory pathway polypeptides comprising amino acid sequences having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, at least 99.6%, at least 99.7%, at least 99.8%, at least 99.9%, or 100% amino acid sequence identity to SEQ ID NO:5 (a KAR2 polypeptide), SEQ ID NO:9 (a PDI1 polypeptide), SEQ ID NO:7 (an ERO1 polypeptide), SEQ ID NO:298 (a FAD1 polypeptide), SEQ ID NO:11 (an IRE1 polypeptide), or SEQ ID NO:296 (an IRE1 polypeptide fragment). 
     In some embodiments, the modified host cells of the disclosure comprise a deletion or downregulation of one or more genes encoding encoding one or more of a ROT2 polypeptide or a PEP4 polypeptide. 
     In some embodiments, the modified host cells of the disclosure comprise a deletion or downregulation of one or more genes encoding one or more secretory pathway polypeptides comprising the amino acid sequences set forth in SEQ ID NO:13 (a ROT2 polypeptide) or SEQ ID NO:15 (a PEP4 polypeptide). 
     In some embodiments, a modified host cell of the present disclosure comprises one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more of a KAR2 polypeptide, a PDI1 polypeptide, an ERO1 polypeptide, or an IRE1 polypeptide. In some embodiments, a modified host cell of the present disclosure comprises one or more heterologous nucleic acids comprising nucleotide sequences encoding two or more of a KAR2 polypeptide, a PDI1 polypeptide, an ERO1 polypeptide, or an IRE1 polypeptide. In some embodiments, a modified host cell of the present disclosure comprises one or more heterologous nucleic acids comprising nucleotide sequences encoding three or more of a KAR2 polypeptide, a PDI1 polypeptide, an ERO1 polypeptide, or an IRE1 polypeptide. In some embodiments, a modified host cell of the present disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a KAR2 polypeptide, one or more heterologous nucleic acids comprising a nucleotide sequence encoding a PDI1 polypeptide, one or more heterologous nucleic acids comprising a nucleotide sequence encoding an ERO1 polypeptide, and one or more heterologous nucleic acids comprising a nucleotide sequence encoding an IRE1 polypeptide. 
     In some embodiments, a modified host cell of the present disclosure comprises one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more of a KAR2 polypeptide, a PDI1 polypeptide, an ERO1 polypeptide, or a FAD1 polypeptide. In some embodiments, a modified host cell of the present disclosure comprises one or more heterologous nucleic acids comprising nucleotide sequences encoding two or more of a KAR2 polypeptide, a PDI1 polypeptide, an ERO1 polypeptide, or a FAD1 polypeptide. In some embodiments, a modified host cell of the present disclosure comprises one or more heterologous nucleic acids comprising nucleotide sequences encoding three or more of a KAR2 polypeptide, a PDI1 polypeptide, an ERO1 polypeptide, or a FAD1 polypeptide. In some embodiments, a modified host cell of the present disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a KAR2 polypeptide, one or more heterologous nucleic acids comprising a nucleotide sequence encoding a PDI1 polypeptide, one or more heterologous nucleic acids comprising a nucleotide sequence encoding an ERO1 polypeptide, and one or more heterologous nucleic acids comprising a nucleotide sequence encoding a FAD1 polypeptide. 
     In some embodiments, the nucleotide sequences encoding the one or more of a KAR2 polypeptide, a PDI1 polypeptide, an ERO1 polypeptide, a FAD1 polypeptide, or an IRE1 polypeptide are codon-optimized. 
     In some embodiments, the modified host cells of the disclosure comprise a deletion or downregulation of one or more genes encoding one or more of a ROT2 polypeptide or a PEP4 polypeptide. In some embodiments, the modified host cells of the disclosure comprise a deletion or downregulation of genes encoding a ROT2 polypeptide and a PEP4 polypeptide. 
     Exemplary heterologous nucleic acids disclosed herein may include nucleic acids comprising a nucleotide sequence that encodes a secretory pathway polypeptide, such as, a full-length secretory pathway polypeptide, a fragment of a secretory pathway polypeptide, a variant of a secretory pathway polypeptide, a truncated secretory pathway polypeptide, or a fusion polypeptide that has at least one activity of a secretory pathway polypeptide. In some embodiments, the nucleotide sequence is codon-optimized. 
     Exemplary heterologous nucleic acids disclosed herein may include nucleic acids comprising a nucleotide sequence that encodes a KAR2 polypeptide, such as, a full-length KAR2 polypeptide, a fragment of a KAR2 polypeptide, a variant of a KAR2 polypeptide, a truncated KAR2 polypeptide, or a fusion polypeptide that has at least one activity of a KAR2 polypeptide. In some embodiments, the nucleotide sequence is codon-optimized. 
     Exemplary heterologous nucleic acids disclosed herein may include nucleic acids comprising a nucleotide sequence that encodes a ROT2 polypeptide, such as, a full-length ROT2 polypeptide, a fragment of a ROT2 polypeptide, a variant of a ROT2 polypeptide, a truncated ROT2 polypeptide, or a fusion polypeptide that has at least one activity of a ROT2 polypeptide. In some embodiments, the nucleotide sequence is codon-optimized. 
     Exemplary heterologous nucleic acids disclosed herein may include nucleic acids comprising a nucleotide sequence that encodes a PDI1 polypeptide, such as, a full-length PDI1 polypeptide, a fragment of a PDI1 polypeptide, a variant of a PDI1 polypeptide, a truncated PDI1 polypeptide, or a fusion polypeptide that has at least one activity of a PDI1 polypeptide. In some embodiments, the nucleotide sequence is codon-optimized. 
     Exemplary heterologous nucleic acids disclosed herein may include nucleic acids comprising a nucleotide sequence that encodes an ERO1 polypeptide, such as, a full-length ERO1 polypeptide, a fragment of an ERO1 polypeptide, a variant of an ERO1 polypeptide, a truncated ERO1 polypeptide, or a fusion polypeptide that has at least one activity of an ERO1 polypeptide. In some embodiments, the nucleotide sequence is codon-optimized. 
     Exemplary heterologous nucleic acids disclosed herein may include nucleic acids comprising a nucleotide sequence that encodes a FAD1 polypeptide, such as, a full-length FAD1 polypeptide, a fragment of a FAD1 polypeptide, a variant of a FAD1 polypeptide, a truncated FAD1 polypeptide, or a fusion polypeptide that has at least one activity of a FAD1 polypeptide. In some embodiments, the nucleotide sequence is codon-optimized. 
     Exemplary heterologous nucleic acids disclosed herein may include nucleic acids comprising a nucleotide sequence that encodes a PEP4 polypeptide, such as, a full-length PEP4 polypeptide, a fragment of a PEP4 polypeptide, a variant of a PEP4 polypeptide, a truncated PEP1 polypeptide, or a fusion polypeptide that has at least one activity of a PEP4 polypeptide. In some embodiments, the nucleotide sequence is codon-optimized. 
     Exemplary heterologous nucleic acids disclosed herein may include nucleic acids comprising a nucleotide sequence that encodes an IRE1 polypeptide, such as, a full-length IRE1 polypeptide, a fragment of an IRE1 polypeptide (e.g., missing the first 7 amino acids), a variant of an IRE1 polypeptide, a truncated IRE1 polypeptide, or a fusion polypeptide that has at least one activity of an IRE1 polypeptide. In some embodiments, the nucleotide sequence is codon-optimized. 
     In some embodiments, one or more secretory pathway polypeptides, such as a KAR2 polypeptide, a PDI1 polypeptide, an ERO1 polypeptide, a FAD1 polypeptide, or an IRE1 polypeptide, are overexpressed in the modified host cell. Overexpression may be achieved by increasing the copy number of the one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more secretory pathway polypeptides, such as a KAR2 polypeptide, a PDI1 polypeptide, an ERO1 polypeptide, a FAD1 polypeptide, or an IRE1 polypeptide, e.g., through use of a high copy number expression vector (e.g., a plasmid that exists at 10-40 copies or about 100 copies per cell) and/or by operably linking the nucleotide sequences encoding the one or more secretory pathway polypeptides, such as a KAR2 polypeptide, a PDI1 polypeptide, an ERO1 polypeptide, a FAD1 polypeptide, or an IRE1 polypeptide, to a strong promoter. In some embodiments, the modified host cell has one copy of a heterologous nucleic acid comprising a nucleotide sequence encoding a secretory pathway polypeptide, such as a KAR2 polypeptide, a PDI1 polypeptide, an ERO1 polypeptide, a FAD1 polypeptide, or an IRE1 polypeptide. In some embodiments, the modified host cell has two copies of a heterologous nucleic acid comprising a nucleotide sequence encoding a secretory pathway polypeptide, such as a KAR2 polypeptide, a PDI1 polypeptide, an ERO1 polypeptide, a FAD1 polypeptide, or an IRE1 polypeptide. In some embodiments, the modified host cell has three copies of a heterologous nucleic acid comprising a nucleotide sequence encoding a secretory pathway polypeptide, such as a KAR2 polypeptide, a PDI1 polypeptide, an ERO1 polypeptide, a FAD1 polypeptide, or an IRE1 polypeptide. In some embodiments, the modified host cell has four copies of a heterologous nucleic acid comprising a nucleotide sequence encoding a secretory pathway polypeptide, such as a KAR2 polypeptide, a PDI1 polypeptide, an ERO1 polypeptide, a FAD1 polypeptide, or an IRE1 polypeptide. In some embodiments, the modified host cell has five copies of a heterologous nucleic acid comprising a nucleotide sequence encoding a secretory pathway polypeptide, such as a KAR2 polypeptide, a PDI1 polypeptide, an ERO1 polypeptide, a FAD1 polypeptide, or an IRE1 polypeptide. In some embodiments, the modified host cell has five or more copies of a heterologous nucleic acid comprising a nucleotide sequence encoding a secretory pathway polypeptide, such as a KAR2 polypeptide, a PDI1 polypeptide, an ERO1 polypeptide, a FAD1 polypeptide, or an IRE1 polypeptide. Increased copy number of the heterologous nucleic acid and/or codon optimization of the nucleotide sequence may result in an increase in the desired polypeptide activity in the modified host cell. 
     In some embodiments, the modified host cells of the disclosure comprise one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more secretory pathway polypeptides selected from the group consisting of nucleotide sequences set forth in SEQ ID NO:4 (encodes a KAR2 polypeptide), SEQ ID NO:8 (encodes a PDI1 polypeptide), SEQ ID NO:6 (encodes an ERO1 polypeptide), SEQ ID NO:297 (encodes a FAD1 polypeptide), SEQ ID NO:10 (encodes an IRE1 polypeptide), and SEQ ID NO:295 (encodes an IRE1 polypeptide fragment). 
     In some embodiments, the modified host cells of the disclosure comprise one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more secretory pathway polypeptides selected from the group consisting of nucleotide sequences set forth in SEQ ID NO:4 (encodes a KAR2 polypeptide), SEQ ID NO:8 (encodes a PDI1 polypeptide), SEQ ID NO:6 (encodes an ERO1 polypeptide), SEQ ID NO:297 (encodes a FAD1 polypeptide), SEQ ID NO:10 (encodes an IRE1 polypeptide), and SEQ ID NO:295 (an IRE1 polypeptide fragment), or a codon degenerate nucleotide sequence of any of the foregoing. 
     In some embodiments, the modified host cells of the disclosure comprise one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more secretory pathway polypeptides selected from the group consisting of nucleotide sequences having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, at least 99.6%, at least 99.7%, at least 99.8%, at least 99.9%, or 100% sequence identity to SEQ ID NO:4 (encodes a KAR2 polypeptide), SEQ ID NO:8 (encodes a PDI1 polypeptide), SEQ ID NO:6 (encodes an ERO1 polypeptide), SEQ ID NO:297 (encodes a FAD1 polypeptide), SEQ ID NO:10 (encodes an IRE1 polypeptide), and SEQ ID NO:295 (an IRE1 polypeptide fragment). 
     In some embodiments, the modified host cells of the disclosure comprise a deletion or downregulation of one or more genes encoding one or more secretory pathway polypeptides encoded by nucleotide sequences selected from the group consisting of nucleotide sequences set forth in SEQ ID NO:12 (encodes a ROT2 polypeptide) and SEQ ID NO:14 (encodes a PEP4 polypeptide). 
     In some embodiments, the modified host cells of the disclosure comprise a deletion or downregulation of a ROT2 gene. In some embodiments, the modified host cells of the disclosure comprise a deletion of a ROT2 gene. In some embodiments, the modified host cells of the disclosure comprise a downregulation of a ROT2 gene. 
     In some embodiments, the modified host cells of the disclosure comprise a deletion or downregulation of a PEP4 gene. In some embodiments, the modified host cells of the disclosure comprise a deletion of a PEP4 gene. In some embodiments, the modified host cells of the disclosure comprise a downregulation of a PEP4 gene. 
     In some embodiments, the modified host cells of the disclosure comprise a deletion or downregulation of a PEP4 gene and a ROT2 gene. In some embodiments, the modified host cells of the disclosure comprise a deletion of a PEP4 gene and a ROT2 gene. In some embodiments, the modified host cells of the disclosure comprise a downregulation of a PEP4 gene and a ROT2 gene. 
     Cannabinoid and Cannabinoid Precursor Biosynthetic Pathway Modifications 
     A modified host cell of the present disclosure comprising one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure may also comprise one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more polypeptides involved in cannabinoid or cannabinoid precursor (e.g., geranylpyrophosphate (GPP), prenyl phosphates, olivetolic acid, or hexanoyl-CoA) biosynthesis. In addition to engineered variants of the disclosure, such polypeptides may include, but are not limited to: a geranyl pyrophosphate:olivetolic acid geranyltransferase (GOT) polypeptide, a tetraketide synthase (TKS) polypeptide, an olivetolic acid cyclase (OAC) polypeptide, one or more polypeptides having at least one activity of a polypeptide present in the mevalonate (MEV) pathway (e.g., one or more MEV pathway polypeptides), an acyl-activating enzyme (AAE) polypeptide, a polypeptide that generates GPP (e.g., a geranyl pyrophosphate synthetase (GPPS) polypeptide), a polypeptide that condenses two molecules of acetyl-CoA to generate acetoacetyl-CoA (e.g., an acetoacetyl-CoA thiolase polypeptide), and a pyruvate decarboxylase polypeptide. In some embodiments, the nucleotide sequences encoding the one or more polypeptides involved in cannabinoid or cannabinoid precursor (e.g., geranylpyrophosphate (GPP), prenyl phosphates, olivetolic acid, or hexanoyl-CoA) biosynthesis are codon-optimized. 
     The polypeptides involved in cannabinoid or cannabinoid precursor biosynthesis and the nucleotide sequences encoding the polypeptides involved in cannabinoid or cannabinoid precursor biosynthesis may be derived from any suitable source, for example, bacteria, yeast, fungi, algae, human, plant (e.g.,  Cannabis ), or mouse. In some embodiments, the disclosure also encompasses orthologous genes encoding the polypeptides involved in cannabinoid or cannabinoid precursor biosynthesis disclosed herein. Exemplary polypeptides involved in cannabinoid or cannabinoid precursor biosynthesis disclosed herein may also include a full-length polypeptide involved in cannabinoid or cannabinoid precursor biosynthesis, a fragment of a polypeptide involved in cannabinoid or cannabinoid precursor biosynthesis, a variant of a polypeptide involved in cannabinoid or cannabinoid precursor biosynthesis, a truncated polypeptide involved in cannabinoid or cannabinoid precursor biosynthesis, or a fusion polypeptide that has at least one activity of a polypeptide involved in cannabinoid or cannabinoid precursor biosynthesis. The disclosure also provides for nucleotide sequences encoding polypeptides involved in cannabinoid or cannabinoid precursor biosynthesis, such as, a full-length polypeptide involved in cannabinoid or cannabinoid precursor biosynthesis, a fragment of a polypeptide involved in cannabinoid or cannabinoid precursor biosynthesis, a variant of a polypeptide involved in cannabinoid or cannabinoid precursor biosynthesis, a truncated polypeptide involved in cannabinoid or cannabinoid precursor biosynthesis, or a fusion polypeptide that has at least one activity of a polypeptide involved in cannabinoid or cannabinoid precursor biosynthesis. In some embodiments, the nucleotide sequences encoding the polypeptides involved in cannabinoid or cannabinoid precursor biosynthesis are codon-optimized. 
     Engineered Variants of the Cannabidiolic Acid Synthase (CBDAS) Polypeptide 
     A modified host cell of the present disclosure may comprise one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the cannabidiolic acid synthase (CBDAS) polypeptide disclosed herein. In certain such embodiments, the cannabidiolic acid synthase polypeptide has an amino acid sequence of SEQ ID NO:3. 
     In some embodiments, a modified host cell of the disclosure comprises one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure, wherein the engineered variant comprises the amino acid sequence set forth in SEQ ID NO:50, SEQ ID NO:52, SEQ ID NO:54, SEQ ID NO:56, SEQ ID NO:58, SEQ ID NO:60, SEQ ID NO:62, SEQ ID NO:64, SEQ ID NO:66, SEQ ID NO:68, SEQ ID NO:70, SEQ ID NO:72, SEQ ID NO:74, SEQ ID NO:76, SEQ ID NO:78, SEQ ID NO:80, SEQ ID NO:82, SEQ ID NO:84, SEQ ID NO:86, SEQ ID NO:88, SEQ ID NO:90, SEQ ID NO:92, SEQ ID NO:94, SEQ ID NO:96, SEQ ID NO:98, SEQ ID NO:100, SEQ ID NO:102, SEQ ID NO:104, SEQ ID NO:106, SEQ ID NO:108, SEQ ID NO:110, SEQ ID NO:112, SEQ ID NO:114, SEQ ID NO:116, SEQ ID NO:118, SEQ ID NO:120, SEQ ID NO:122, SEQ ID NO:124, SEQ ID NO:126, SEQ ID NO:128, SEQ ID NO:130, SEQ ID NO:132, SEQ ID NO:134, SEQ ID NO:136, SEQ ID NO:138, SEQ ID NO:140, SEQ ID NO:142, SEQ ID NO:144, SEQ ID NO:146, SEQ ID NO:148, SEQ ID NO:150, SEQ ID NO:152, SEQ ID NO:154, SEQ ID NO:156, SEQ ID NO:158, SEQ ID NO:160, SEQ ID NO:162, SEQ ID NO:164, SEQ ID NO:166, SEQ ID NO:168, SEQ ID NO:170, SEQ ID NO:172, SEQ ID NO:174, SEQ ID NO:176, SEQ ID NO:178, SEQ ID NO:180, SEQ ID NO:182, SEQ ID NO:184, SEQ ID NO:186, SEQ ID NO:188, SEQ ID NO:190, SEQ ID NO:192, SEQ ID NO:194, SEQ ID NO:196, SEQ ID NO:198, SEQ ID NO:200, SEQ ID NO:202, SEQ ID NO:204, SEQ ID NO:206, SEQ ID NO:208, SEQ ID NO:210, SEQ ID NO:212, SEQ ID NO:214, SEQ ID NO:216, SEQ ID NO:218, SEQ ID NO:220, SEQ ID NO:222, SEQ ID NO:224, SEQ ID NO:226, SEQ ID NO:228, SEQ ID NO:230, SEQ ID NO:232, or SEQ ID NO:234. In some embodiments, the nucleotide sequence is codon-optimized. 
     In some embodiments, a modified host cell of the disclosure comprises one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure, wherein the engineered variant comprises the amino acid sequence set forth in SEQ ID NO:50, SEQ ID NO:52, SEQ ID NO:54, SEQ ID NO:56, SEQ ID NO:58, SEQ ID NO:60, SEQ ID NO:62, SEQ ID NO:64, SEQ ID NO:66, SEQ ID NO:68, SEQ ID NO:70, SEQ ID NO:72, SEQ ID NO:74, SEQ ID NO:76, SEQ ID NO:78, SEQ ID NO:80, SEQ ID NO:82, SEQ ID NO:84, SEQ ID NO:86, SEQ ID NO:88, SEQ ID NO:90, SEQ ID NO:92, SEQ ID NO:94, SEQ ID NO:96, SEQ ID NO:98, SEQ ID NO:100, SEQ ID NO:102, SEQ ID NO:104, SEQ ID NO:106, SEQ ID NO:108, SEQ ID NO:110, SEQ ID NO:112, SEQ ID NO:114, SEQ ID NO:116, SEQ ID NO:118, SEQ ID NO:120, SEQ ID NO:122, SEQ ID NO:124, SEQ ID NO:126, SEQ ID NO:128, SEQ ID NO:130, SEQ ID NO:132, SEQ ID NO:134, SEQ ID NO:136, SEQ ID NO:138, SEQ ID NO:140, SEQ ID NO:142, SEQ ID NO:144, SEQ ID NO:146, SEQ ID NO:148, SEQ ID NO:150, SEQ ID NO:152, SEQ ID NO:154, SEQ ID NO:156, SEQ ID NO:158, SEQ ID NO:160, SEQ ID NO:162, SEQ ID NO:164, SEQ ID NO:166, SEQ ID NO:168, SEQ ID NO:170, SEQ ID NO:172, SEQ ID NO:174, SEQ ID NO:176, SEQ ID NO:178, SEQ ID NO:180, SEQ ID NO:182, SEQ ID NO:184, SEQ ID NO:186, SEQ ID NO:188, SEQ ID NO:190, SEQ ID NO:192, SEQ ID NO:194, SEQ ID NO:196, SEQ ID NO:198, SEQ ID NO:200, SEQ ID NO:202, SEQ ID NO:204, SEQ ID NO:206, SEQ ID NO:208, SEQ ID NO:210, SEQ ID NO:212, SEQ ID NO:214, SEQ ID NO:216, SEQ ID NO:218, SEQ ID NO:220, SEQ ID NO:222, SEQ ID NO:224, SEQ ID NO:226, SEQ ID NO:228, SEQ ID NO:230, SEQ ID NO:232, SEQ ID NO:234, SEQ ID NO:300, SEQ ID NO:302, or SEQ ID NO:304. In some embodiments, the nucleotide sequence is codon-optimized. 
     In some embodiments, a modified host cell of the disclosure comprises one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure, wherein the engineered variant comprises the amino acid sequence set forth in SEQ ID NO:60, SEQ ID NO:64, SEQ ID NO:66, SEQ ID NO:68, SEQ ID NO:70, SEQ ID NO:72, SEQ ID NO:74, SEQ ID NO:76, SEQ ID NO:78, SEQ ID NO:80, SEQ ID NO:82, SEQ ID NO:88, SEQ ID NO:90, SEQ ID NO:92, SEQ ID NO:96, SEQ ID NO:102, SEQ ID NO:106, SEQ ID NO:112, SEQ ID NO:116, SEQ ID NO:118, SEQ ID NO:120, SEQ ID NO:122, SEQ ID NO:124, SEQ ID NO:126, SEQ ID NO:128, SEQ ID NO:130, SEQ ID NO:132, SEQ ID NO:134, SEQ ID NO:136, SEQ ID NO:138, SEQ ID NO:140, SEQ ID NO:142, SEQ ID NO:144, SEQ ID NO:146, SEQ ID NO:148, SEQ ID NO:150, SEQ ID NO:152, SEQ ID NO:154, SEQ ID NO:156, SEQ ID NO:158, SEQ ID NO:160, SEQ ID NO:162, SEQ ID NO:164, SEQ ID NO:166, SEQ ID NO:168, SEQ ID NO:170, SEQ ID NO:172, SEQ ID NO:174, SEQ ID NO:176, SEQ ID NO:178, SEQ ID NO:180, SEQ ID NO:182, SEQ ID NO:184, SEQ ID NO:186, SEQ ID NO:188, SEQ ID NO:190, SEQ ID NO:192, SEQ ID NO:194, SEQ ID NO:196, SEQ ID NO:198, SEQ ID NO:200, SEQ ID NO:202, SEQ ID NO:206, SEQ ID NO:208, SEQ ID NO:210, SEQ ID NO:212, SEQ ID NO:214, SEQ ID NO:216, SEQ ID NO:218, SEQ ID NO:220, SEQ ID NO:222, SEQ ID NO:224, SEQ ID NO:226, SEQ ID NO:228, SEQ ID NO:230, SEQ ID NO:232, or SEQ ID NO:234. In some embodiments, the nucleotide sequence is codon-optimized. 
     In some embodiments, a modified host cell of the disclosure comprises one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure, wherein the engineered variant comprises the amino acid sequence set forth in SEQ ID NO:66, SEQ ID NO:70, SEQ ID NO:72, SEQ ID NO:80, SEQ ID NO:82, SEQ ID NO:130, SEQ ID NO:136, SEQ ID NO:142, SEQ ID NO:146, SEQ ID NO:150, SEQ ID NO:156, SEQ ID NO:158, SEQ ID NO:160, SEQ ID NO:168, SEQ ID NO:170, SEQ ID NO:172, SEQ ID NO:176, SEQ ID NO:182, SEQ ID NO:184, SEQ ID NO:186, SEQ ID NO:190, SEQ ID NO:192, SEQ ID NO:194, SEQ ID NO:196, SEQ ID NO:198, SEQ ID NO:206, SEQ ID NO:214, SEQ ID NO:216, SEQ ID NO:218, SEQ ID NO:230, or SEQ ID NO:232. In some embodiments, the nucleotide sequence is codon-optimized. 
     In some embodiments, a modified host cell of the disclosure comprises one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure, wherein the engineered variant comprises the amino acid sequence set forth in SEQ ID NO:60, SEQ ID NO:64, SEQ ID NO:66, SEQ ID NO:68, SEQ ID NO:70, SEQ ID NO:72, SEQ ID NO:80, SEQ ID NO:82, SEQ ID NO:102, SEQ ID NO:104, SEQ ID NO:106, SEQ ID NO:116, SEQ ID NO:118, SEQ ID NO:120, SEQ ID NO:122, SEQ ID NO:124, SEQ ID NO:130, SEQ ID NO:132, SEQ ID NO:134, SEQ ID NO:136, SEQ ID NO:138, SEQ ID NO:140, SEQ ID NO:144, SEQ ID NO:146, SEQ ID NO:148, SEQ ID NO:150, SEQ ID NO:152, SEQ ID NO:154, SEQ ID NO:156, SEQ ID NO:158, SEQ ID NO:160, SEQ ID NO:162, SEQ ID NO:164, SEQ ID NO:166, SEQ ID NO:168, SEQ ID NO:170, SEQ ID NO:172, SEQ ID NO:174, SEQ ID NO:176, SEQ ID NO:178, SEQ ID NO:180, SEQ ID NO:182, SEQ ID NO:184, SEQ ID NO:186, SEQ ID NO:188, SEQ ID NO:190, SEQ ID NO:192, SEQ ID NO:194, SEQ ID NO:196, SEQ ID NO:198, SEQ ID NO:200, SEQ ID NO:202, SEQ ID NO:204, SEQ ID NO:206, SEQ ID NO:208, SEQ ID NO:210, SEQ ID NO:212, SEQ ID NO:214, SEQ ID NO:216, SEQ ID NO:218, SEQ ID NO:224, SEQ ID NO:226, SEQ ID NO:228, SEQ ID NO:230, SEQ ID NO:232, or SEQ ID NO:234. In some embodiments, the nucleotide sequence is codon-optimized. 
     In some embodiments, a modified host cell of the disclosure comprises one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure, wherein the engineered variant comprises the amino acid sequence set forth in SEQ ID NO:222, SEQ ID NO:224, SEQ ID NO:226, SEQ ID NO:228, SEQ ID NO:230, SEQ ID NO:232, or SEQ ID NO:234. In some embodiments, the nucleotide sequence is codon-optimized. 
     In some embodiments, a modified host cell of the disclosure comprises one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure, wherein the engineered variant comprises the amino acid sequence set forth in SEQ ID NO:60, SEQ ID NO:82, SEQ ID NO:92, SEQ ID NO:104, SEQ ID NO:156, SEQ ID NO:160, SEQ ID NO:162, SEQ ID NO:172, SEQ ID NO:174, SEQ ID NO:176, SEQ ID NO:184, SEQ ID NO:198, SEQ ID NO:202, or SEQ ID NO:230. In some embodiments, the nucleotide sequence is codon-optimized. 
     In some embodiments, a modified host cell of the disclosure comprises one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure, wherein the engineered variant comprises the amino acid sequence set forth in SEQ ID NO:82, SEQ ID NO:156, SEQ ID NO:160, SEQ ID NO:172, SEQ ID NO:176, SEQ ID NO:184, or SEQ ID NO:198. In some embodiments, the nucleotide sequence is codon-optimized. 
     In some embodiments, a modified host cell of the disclosure comprises one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure, wherein the engineered variant comprises the amino acid sequence set forth in SEQ ID NO:300, SEQ ID NO:302, or SEQ ID NO:304. In some embodiments, a modified host cell of the disclosure comprises one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure, wherein the engineered variant comprises the amino acid sequence set forth in SEQ ID NO:300. In some embodiments, the nucleotide sequence is codon-optimized. 
     In some embodiments, a modified host cell of the disclosure comprises one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure, wherein the engineered variant comprises the amino acid sequence set forth in SEQ ID NO:314, SEQ ID NO:316, SEQ ID NO:318, or SEQ ID NO:320. In some embodiments, a modified host cell of the disclosure comprises one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure, wherein the engineered variant comprises the amino acid sequence set forth in SEQ ID NO:314. In some embodiments, a modified host cell of the disclosure comprises one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure, wherein the engineered variant comprises the amino acid sequence set forth in SEQ ID NO:316. In some embodiments, a modified host cell of the disclosure comprises one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure, wherein the engineered variant comprises the amino acid sequence set forth in SEQ ID NO:318. In some embodiments, a modified host cell of the disclosure comprises one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure, wherein the engineered variant comprises the amino acid sequence set forth in SEQ ID NO:320. In some embodiments, the nucleotide sequence is codon-optimized. 
     In some embodiments, the engineered variant of the disclosure is overexpressed in the modified host cell. Overexpression may be achieved by increasing the copy number of the one or more nucleic acids comprising a nucleotide sequence encoding the engineered variant of the disclosure, e.g., through use of a high copy number expression vector (e.g., a plasmid that exists at 10-40 copies or about 100 copies per cell) and/or by operably linking the nucleotide sequence encoding the engineered variant of the disclosure to a strong promoter. In some embodiments, the modified host cell has one copy of a nucleic acid comprising a nucleotide sequence encoding the engineered variant of the disclosure. In some embodiments, the modified host cell has two copies of a nucleic acid comprising a nucleotide sequence encoding the engineered variant of the disclosure. In some embodiments, the modified host cell has three copies of a nucleic acid comprising a nucleotide sequence encoding the engineered variant of the disclosure. In some embodiments, the modified host cell has four copies of a nucleic acid comprising a nucleotide sequence encoding the engineered variant of the disclosure. In some embodiments, the modified host cell has five copies of a nucleic acid comprising a nucleotide sequence encoding the engineered variant of the disclosure. In some embodiments, the modified host cell has six copies of a nucleic acid comprising a nucleotide sequence encoding the engineered variant of the disclosure. In some embodiments, the modified host cell has seven copies of a nucleic acid comprising a nucleotide sequence encoding the engineered variant of the disclosure. In some embodiments, the modified host cell has eight copies of a nucleic acid comprising a nucleotide sequence encoding the engineered variant of the disclosure. In some embodiments, the modified host cell has eight or more copies of a nucleic acid comprising a nucleotide sequence encoding the engineered variant of the disclosure. Increased copy number of the nucleic acid and/or codon optimization of the nucleotide sequence may result in an increase in the desired enzyme catalytic activity in the modified host cell. 
     In some embodiments, a modified host cell of the disclosure comprises one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the cannabidiolic acid synthase (CBDAS) polypeptide disclosed herein, wherein the nucleotide sequence is that set forth in SEQ ID NO:49, SEQ ID NO:51, SEQ ID NO:53, SEQ ID NO:55, SEQ ID NO:57, SEQ ID NO:59, SEQ ID NO:61, SEQ ID NO:63, SEQ ID NO:65, SEQ ID NO:67, SEQ ID NO:69, SEQ ID NO:71, SEQ ID NO:73, SEQ ID NO:75, SEQ ID NO:77, SEQ ID NO:79, SEQ ID NO:81, SEQ ID NO:83, SEQ ID NO:85, SEQ ID NO:87, SEQ ID NO:89, SEQ ID NO:91, SEQ ID NO:93, SEQ ID NO:95, SEQ ID NO:97, SEQ ID NO:99, SEQ ID NO:101, SEQ ID NO:103, SEQ ID NO:105, SEQ ID NO:107, SEQ ID NO:109, SEQ ID NO:111, SEQ ID NO:113, SEQ ID NO:115, SEQ ID NO:117, SEQ ID NO:119, SEQ ID NO:121, SEQ ID NO:123, SEQ ID NO:125, SEQ ID NO:127, SEQ ID NO:129, SEQ ID NO:131, SEQ ID NO:133, SEQ ID NO:135, SEQ ID NO:137, SEQ ID NO:139, SEQ ID NO:141, SEQ ID NO:143, SEQ ID NO:145, SEQ ID NO:147, SEQ ID NO:149, SEQ ID NO:151, SEQ ID NO:153, SEQ ID NO:155, SEQ ID NO:157, SEQ ID NO:159, SEQ ID NO:161, SEQ ID NO:163, SEQ ID NO:165, SEQ ID NO:167, SEQ ID NO:169, SEQ ID NO:171, SEQ ID NO:173, SEQ ID NO:175, SEQ ID NO:177, SEQ ID NO:179, SEQ ID NO:181, SEQ ID NO:183, SEQ ID NO:185, SEQ ID NO:187, SEQ ID NO:189, SEQ ID NO:191, SEQ ID NO:193, SEQ ID NO:195, SEQ ID NO:197, SEQ ID NO:199, SEQ ID NO:201, SEQ ID NO:203, SEQ ID NO:205, SEQ ID NO:207, SEQ ID NO:209, SEQ ID NO:211, SEQ ID NO:213, SEQ ID NO:215, SEQ ID NO:217, SEQ ID NO:219, SEQ ID NO:221, SEQ ID NO:223, SEQ ID NO:225, SEQ ID NO:227, SEQ ID NO:229, SEQ ID NO:231, or SEQ ID NO:233. In some embodiments, the nucleotide sequence is codon-optimized. 
     In some embodiments, a modified host cell of the disclosure comprises one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the cannabidiolic acid synthase (CBDAS) polypeptide disclosed herein, wherein the nucleotide sequence is that set forth in SEQ ID NO:49, SEQ ID NO:51, SEQ ID NO:53, SEQ ID NO:55, SEQ ID NO:57, SEQ ID NO:59, SEQ ID NO:61, SEQ ID NO:63, SEQ ID NO:65, SEQ ID NO:67, SEQ ID NO:69, SEQ ID NO:71, SEQ ID NO:73, SEQ ID NO:75, SEQ ID NO:77, SEQ ID NO:79, SEQ ID NO:81, SEQ ID NO:83, SEQ ID NO:85, SEQ ID NO:87, SEQ ID NO:89, SEQ ID NO:91, SEQ ID NO:93, SEQ ID NO:95, SEQ ID NO:97, SEQ ID NO:99, SEQ ID NO:101, SEQ ID NO:103, SEQ ID NO:105, SEQ ID NO:107, SEQ ID NO:109, SEQ ID NO:111, SEQ ID NO:113, SEQ ID NO:115, SEQ ID NO:117, SEQ ID NO:119, SEQ ID NO:121, SEQ ID NO:123, SEQ ID NO:125, SEQ ID NO:127, SEQ ID NO:129, SEQ ID NO:131, SEQ ID NO:133, SEQ ID NO:135, SEQ ID NO:137, SEQ ID NO:139, SEQ ID NO:141, SEQ ID NO:143, SEQ ID NO:145, SEQ ID NO:147, SEQ ID NO:149, SEQ ID NO:151, SEQ ID NO:153, SEQ ID NO:155, SEQ ID NO:157, SEQ ID NO:159, SEQ ID NO:161, SEQ ID NO:163, SEQ ID NO:165, SEQ ID NO:167, SEQ ID NO:169, SEQ ID NO:171, SEQ ID NO:173, SEQ ID NO:175, SEQ ID NO:177, SEQ ID NO:179, SEQ ID NO:181, SEQ ID NO:183, SEQ ID NO:185, SEQ ID NO:187, SEQ ID NO:189, SEQ ID NO:191, SEQ ID NO:193, SEQ ID NO:195, SEQ ID NO:197, SEQ ID NO:199, SEQ ID NO:201, SEQ ID NO:203, SEQ ID NO:205, SEQ ID NO:207, SEQ ID NO:209, SEQ ID NO:211, SEQ ID NO:213, SEQ ID NO:215, SEQ ID NO:217, SEQ ID NO:219, SEQ ID NO:221, SEQ ID NO:223, SEQ ID NO:225, SEQ ID NO:227, SEQ ID NO:229, SEQ ID NO:231, or SEQ ID NO:233, or a codon degenerate nucleotide sequence of any of the foregoing. In some embodiments, the nucleotide sequence is codon-optimized. 
     In some embodiments, a modified host cell of the disclosure comprises one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the cannabidiolic acid synthase (CBDAS) polypeptide disclosed herein, wherein the nucleotide sequence is that set forth in SEQ ID NO:49, SEQ ID NO:51, SEQ ID NO:53, SEQ ID NO:55, SEQ ID NO:57, SEQ ID NO:59, SEQ ID NO:61, SEQ ID NO:63, SEQ ID NO:65, SEQ ID NO:67, SEQ ID NO:69, SEQ ID NO:71, SEQ ID NO:73, SEQ ID NO:75, SEQ ID NO:77, SEQ ID NO:79, SEQ ID NO:81, SEQ ID NO:83, SEQ ID NO:85, SEQ ID NO:87, SEQ ID NO:89, SEQ ID NO:91, SEQ ID NO:93, SEQ ID NO:95, SEQ ID NO:97, SEQ ID NO:99, SEQ ID NO:101, SEQ ID NO:103, SEQ ID NO:105, SEQ ID NO:107, SEQ ID NO:109, SEQ ID NO:111, SEQ ID NO:113, SEQ ID NO:115, SEQ ID NO:117, SEQ ID NO:119, SEQ ID NO:121, SEQ ID NO:123, SEQ ID NO:125, SEQ ID NO:127, SEQ ID NO:129, SEQ ID NO:131, SEQ ID NO:133, SEQ ID NO:135, SEQ ID NO:137, SEQ ID NO:139, SEQ ID NO:141, SEQ ID NO:143, SEQ ID NO:145, SEQ ID NO:147, SEQ ID NO:149, SEQ ID NO:151, SEQ ID NO:153, SEQ ID NO:155, SEQ ID NO:157, SEQ ID NO:159, SEQ ID NO:161, SEQ ID NO:163, SEQ ID NO:165, SEQ ID NO:167, SEQ ID NO:169, SEQ ID NO:171, SEQ ID NO:173, SEQ ID NO:175, SEQ ID NO:177, SEQ ID NO:179, SEQ ID NO:181, SEQ ID NO:183, SEQ ID NO:185, SEQ ID NO:187, SEQ ID NO:189, SEQ ID NO:191, SEQ ID NO:193, SEQ ID NO:195, SEQ ID NO:197, SEQ ID NO:199, SEQ ID NO:201, SEQ ID NO:203, SEQ ID NO:205, SEQ ID NO:207, SEQ ID NO:209, SEQ ID NO:211, SEQ ID NO:213, SEQ ID NO:215, SEQ ID NO:217, SEQ ID NO:219, SEQ ID NO:221, SEQ ID NO:223, SEQ ID NO:225, SEQ ID NO:227, SEQ ID NO:229, SEQ ID NO:231, SEQ ID NO:233, SEQ ID NO:299, SEQ ID NO:301, or SEQ ID NO:303. In some embodiments, the nucleotide sequence is codon-optimized. 
     In some embodiments, a modified host cell of the disclosure comprises one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the cannabidiolic acid synthase (CBDAS) polypeptide disclosed herein, wherein the nucleotide sequence is that set forth in SEQ ID NO:49, SEQ ID NO:51, SEQ ID NO:53, SEQ ID NO:55, SEQ ID NO:57, SEQ ID NO:59, SEQ ID NO:61, SEQ ID NO:63, SEQ ID NO:65, SEQ ID NO:67, SEQ ID NO:69, SEQ ID NO:71, SEQ ID NO:73, SEQ ID NO:75, SEQ ID NO:77, SEQ ID NO:79, SEQ ID NO:81, SEQ ID NO:83, SEQ ID NO:85, SEQ ID NO:87, SEQ ID NO:89, SEQ ID NO:91, SEQ ID NO:93, SEQ ID NO:95, SEQ ID NO:97, SEQ ID NO:99, SEQ ID NO:101, SEQ ID NO:103, SEQ ID NO:105, SEQ ID NO:107, SEQ ID NO:109, SEQ ID NO:111, SEQ ID NO:113, SEQ ID NO:115, SEQ ID NO:117, SEQ ID NO:119, SEQ ID NO:121, SEQ ID NO:123, SEQ ID NO:125, SEQ ID NO:127, SEQ ID NO:129, SEQ ID NO:131, SEQ ID NO:133, SEQ ID NO:135, SEQ ID NO:137, SEQ ID NO:139, SEQ ID NO:141, SEQ ID NO:143, SEQ ID NO:145, SEQ ID NO:147, SEQ ID NO:149, SEQ ID NO:151, SEQ ID NO:153, SEQ ID NO:155, SEQ ID NO:157, SEQ ID NO:159, SEQ ID NO:161, SEQ ID NO:163, SEQ ID NO:165, SEQ ID NO:167, SEQ ID NO:169, SEQ ID NO:171, SEQ ID NO:173, SEQ ID NO:175, SEQ ID NO:177, SEQ ID NO:179, SEQ ID NO:181, SEQ ID NO:183, SEQ ID NO:185, SEQ ID NO:187, SEQ ID NO:189, SEQ ID NO:191, SEQ ID NO:193, SEQ ID NO:195, SEQ ID NO:197, SEQ ID NO:199, SEQ ID NO:201, SEQ ID NO:203, SEQ ID NO:205, SEQ ID NO:207, SEQ ID NO:209, SEQ ID NO:211, SEQ ID NO:213, SEQ ID NO:215, SEQ ID NO:217, SEQ ID NO:219, SEQ ID NO:221, SEQ ID NO:223, SEQ ID NO:225, SEQ ID NO:227, SEQ ID NO:229, SEQ ID NO:231, SEQ ID NO:233, SEQ ID NO:299, SEQ ID NO:301, or SEQ ID NO:303, or a codon degenerate nucleotide sequence of any of the foregoing. In some embodiments, the nucleotide sequence is codon-optimized. 
     In some embodiments, a modified host cell of the disclosure comprises one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the cannabidiolic acid synthase (CBDAS) polypeptide disclosed herein, wherein the nucleotide sequence is that set forth in SEQ ID NO:59, SEQ ID NO:63, SEQ ID NO:65, SEQ ID NO:67, SEQ ID NO:69, SEQ ID NO:71, SEQ ID NO:73, SEQ ID NO:75, SEQ ID NO:77, SEQ ID NO:79, SEQ ID NO:81, SEQ ID NO:87, SEQ ID NO:89, SEQ ID NO:91, SEQ ID NO:95, SEQ ID NO:101, SEQ ID NO:105, SEQ ID NO:111, SEQ ID NO:115, SEQ ID NO:117, SEQ ID NO:119, SEQ ID NO:121, SEQ ID NO:123, SEQ ID NO:125, SEQ ID NO:127, SEQ ID NO:129, SEQ ID NO:131, SEQ ID NO:133, SEQ ID NO:135, SEQ ID NO:137, SEQ ID NO:139, SEQ ID NO:141, SEQ ID NO:143, SEQ ID NO:145, SEQ ID NO:147, SEQ ID NO:149, SEQ ID NO:151, SEQ ID NO:153, SEQ ID NO:155, SEQ ID NO:157, SEQ ID NO:159, SEQ ID NO:161, SEQ ID NO:163, SEQ ID NO:165, SEQ ID NO:167, SEQ ID NO:169, SEQ ID NO:171, SEQ ID NO:173, SEQ ID NO:175, SEQ ID NO:177, SEQ ID NO:179, SEQ ID NO:181, SEQ ID NO:183, SEQ ID NO:185, SEQ ID NO:187, SEQ ID NO:189, SEQ ID NO:191, SEQ ID NO:193, SEQ ID NO:195, SEQ ID NO:197, SEQ ID NO:199, SEQ ID NO:201, SEQ ID NO:205, SEQ ID NO:207, SEQ ID NO:209, SEQ ID NO:211, SEQ ID NO:213, SEQ ID NO:215, SEQ ID NO:217, SEQ ID NO:219, SEQ ID NO:221, SEQ ID NO:223, SEQ ID NO:225, SEQ ID NO:227, SEQ ID NO:229, SEQ ID NO:231, or SEQ ID NO:233. In some embodiments, the nucleotide sequence is codon-optimized. 
     In some embodiments, a modified host cell of the disclosure comprises one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the cannabidiolic acid synthase (CBDAS) polypeptide disclosed herein, wherein the nucleotide sequence is that set forth in SEQ ID NO:59, SEQ ID NO:63, SEQ ID NO:65, SEQ ID NO:67, SEQ ID NO:69, SEQ ID NO:71, SEQ ID NO:73, SEQ ID NO:75, SEQ ID NO:77, SEQ ID NO:79, SEQ ID NO:81, SEQ ID NO:87, SEQ ID NO:89, SEQ ID NO:91, SEQ ID NO:95, SEQ ID NO:101, SEQ ID NO:105, SEQ ID NO:111, SEQ ID NO:115, SEQ ID NO:117, SEQ ID NO:119, SEQ ID NO:121, SEQ ID NO:123, SEQ ID NO:125, SEQ ID NO:127, SEQ ID NO:129, SEQ ID NO:131, SEQ ID NO:133, SEQ ID NO:135, SEQ ID NO:137, SEQ ID NO:139, SEQ ID NO:141, SEQ ID NO:143, SEQ ID NO:145, SEQ ID NO:147, SEQ ID NO:149, SEQ ID NO:151, SEQ ID NO:153, SEQ ID NO:155, SEQ ID NO:157, SEQ ID NO:159, SEQ ID NO:161, SEQ ID NO:163, SEQ ID NO:165, SEQ ID NO:167, SEQ ID NO:169, SEQ ID NO:171, SEQ ID NO:173, SEQ ID NO:175, SEQ ID NO:177, SEQ ID NO:179, SEQ ID NO:181, SEQ ID NO:183, SEQ ID NO:185, SEQ ID NO:187, SEQ ID NO:189, SEQ ID NO:191, SEQ ID NO:193, SEQ ID NO:195, SEQ ID NO:197, SEQ ID NO:199, SEQ ID NO:201, SEQ ID NO:205, SEQ ID NO:207, SEQ ID NO:209, SEQ ID NO:211, SEQ ID NO:213, SEQ ID NO:215, SEQ ID NO:217, SEQ ID NO:219, SEQ ID NO:221, SEQ ID NO:223, SEQ ID NO:225, SEQ ID NO:227, SEQ ID NO:229, SEQ ID NO:231, or SEQ ID NO:233, or a codon degenerate sequence of any of the foregoing. In some embodiments, the nucleotide sequence is codon-optimized. 
     In some embodiments, a modified host cell of the disclosure comprises one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the cannabidiolic acid synthase (CBDAS) polypeptide disclosed herein, wherein the nucleotide sequence is that set forth in SEQ ID NO:65, SEQ ID NO:69, SEQ ID NO:71, SEQ ID NO:79, SEQ ID NO: 81, SEQ ID NO:129, SEQ ID NO:135, SEQ ID NO:141, SEQ ID NO:145, SEQ ID NO:149, SEQ ID NO:155, SEQ ID NO:157, SEQ ID NO:159, SEQ ID NO:167, SEQ ID NO:169, SEQ ID NO:171, SEQ ID NO:175, SEQ ID NO:181, SEQ ID NO:183, SEQ ID NO:185, SEQ ID NO:189, SEQ ID NO:191, SEQ ID NO:193, SEQ ID NO:195, SEQ ID NO:197, SEQ ID NO:205, SEQ ID NO:213, SEQ ID NO:215, SEQ ID NO:217, SEQ ID NO:229, or SEQ ID NO:231. In some embodiments, the nucleotide sequence is codon-optimized. 
     In some embodiments, a modified host cell of the disclosure comprises one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the cannabidiolic acid synthase (CBDAS) polypeptide disclosed herein, wherein the nucleotide sequence is that set forth in SEQ ID NO:65, SEQ ID NO:69, SEQ ID NO:71, SEQ ID NO:79, SEQ ID NO: 81, SEQ ID NO:129, SEQ ID NO:135, SEQ ID NO:141, SEQ ID NO:145, SEQ ID NO:149, SEQ ID NO:155, SEQ ID NO:157, SEQ ID NO:159, SEQ ID NO:167, SEQ ID NO:169, SEQ ID NO:171, SEQ ID NO:175, SEQ ID NO:181, SEQ ID NO:183, SEQ ID NO:185, SEQ ID NO:189, SEQ ID NO:191, SEQ ID NO:193, SEQ ID NO:195, SEQ ID NO:197, SEQ ID NO:205, SEQ ID NO:213, SEQ ID NO:215, SEQ ID NO:217, SEQ ID NO:229, or SEQ ID NO:231, or a codon degenerate sequence of any of the foregoing. In some embodiments, the nucleotide sequence is codon-optimized. 
     In some embodiments, a modified host cell of the disclosure comprises one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the cannabidiolic acid synthase (CBDAS) polypeptide disclosed herein, wherein the nucleotide sequence is that set forth in SEQ ID NO:221, SEQ ID NO:223, SEQ ID NO:225, SEQ ID NO:227, SEQ ID NO:229, SEQ ID NO:231, or SEQ ID NO:233. In some embodiments, the nucleotide sequence is codon-optimized. 
     In some embodiments, a modified host cell of the disclosure comprises one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the cannabidiolic acid synthase (CBDAS) polypeptide disclosed herein, wherein the nucleotide sequence is that set forth in SEQ ID NO:221, SEQ ID NO:223, SEQ ID NO:225, SEQ ID NO:227, SEQ ID NO:229, SEQ ID NO:231, or SEQ ID NO:233, or a codon degenerate nucleotide sequence of any of the foregoing. In some embodiments, the nucleotide sequence is codon-optimized. 
     In some embodiments, a modified host cell of the disclosure comprises one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the cannabidiolic acid synthase (CBDAS) polypeptide disclosed herein, wherein the nucleotide sequence is that set forth in SEQ ID NO:59, SEQ ID NO:63, SEQ ID NO:65, SEQ ID NO:67, SEQ ID NO:69, SEQ ID NO:71, SEQ ID NO:79, SEQ ID NO:81, SEQ ID NO:101, SEQ ID NO:103, SEQ ID NO:105, SEQ ID NO:115, SEQ ID NO:117, SEQ ID NO:119, SEQ ID NO:121, SEQ ID NO:123, SEQ ID NO:129, SEQ ID NO:131, SEQ ID NO:133, SEQ ID NO:135, SEQ ID NO:137, SEQ ID NO:139, SEQ ID NO:143, SEQ ID NO:145, SEQ ID NO:147, SEQ ID NO:149, SEQ ID NO:151, SEQ ID NO:153, SEQ ID NO:155, SEQ ID NO:157, SEQ ID NO:159, SEQ ID NO:161, SEQ ID NO:163, SEQ ID NO:165, SEQ ID NO:167, SEQ ID NO:169, SEQ ID NO:171, SEQ ID NO:173, SEQ ID NO:175, SEQ ID NO:177, SEQ ID NO:179, SEQ ID NO:181, SEQ ID NO:183, SEQ ID NO:185, SEQ ID NO:187, SEQ ID NO:189, SEQ ID NO:191, SEQ ID NO:193, SEQ ID NO:195, SEQ ID NO:197, SEQ ID NO:199, SEQ ID NO:201, SEQ ID NO:203, SEQ ID NO:205, SEQ ID NO:207, SEQ ID NO:209, SEQ ID NO:211, SEQ ID NO:213, SEQ ID NO:215, SEQ ID NO:217, SEQ ID NO:223, SEQ ID NO:225, SEQ ID NO:227, SEQ ID NO:229, SEQ ID NO:231, or SEQ ID NO:233. In some embodiments, the nucleotide sequence is codon-optimized. 
     In some embodiments, a modified host cell of the disclosure comprises one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the cannabidiolic acid synthase (CBDAS) polypeptide disclosed herein, wherein the nucleotide sequence is that set forth in SEQ ID NO:59, SEQ ID NO:63, SEQ ID NO:65, SEQ ID NO:67, SEQ ID NO:69, SEQ ID NO:71, SEQ ID NO:79, SEQ ID NO:81, SEQ ID NO:101, SEQ ID NO:103, SEQ ID NO:105, SEQ ID NO:115, SEQ ID NO:117, SEQ ID NO:119, SEQ ID NO:121, SEQ ID NO:123, SEQ ID NO:129, SEQ ID NO:131, SEQ ID NO:133, SEQ ID NO:135, SEQ ID NO:137, SEQ ID NO:139, SEQ ID NO:143, SEQ ID NO:145, SEQ ID NO:147, SEQ ID NO:149, SEQ ID NO:151, SEQ ID NO:153, SEQ ID NO:155, SEQ ID NO:157, SEQ ID NO:159, SEQ ID NO:161, SEQ ID NO:163, SEQ ID NO:165, SEQ ID NO:167, SEQ ID NO:169, SEQ ID NO:171, SEQ ID NO:173, SEQ ID NO:175, SEQ ID NO:177, SEQ ID NO:179, SEQ ID NO:181, SEQ ID NO:183, SEQ ID NO:185, SEQ ID NO:187, SEQ ID NO:189, SEQ ID NO:191, SEQ ID NO:193, SEQ ID NO:195, SEQ ID NO:197, SEQ ID NO:199, SEQ ID NO:201, SEQ ID NO:203, SEQ ID NO:205, SEQ ID NO:207, SEQ ID NO:209, SEQ ID NO:211, SEQ ID NO:213, SEQ ID NO:215, SEQ ID NO:217, SEQ ID NO:223, SEQ ID NO:225, SEQ ID NO:227, SEQ ID NO:229, SEQ ID NO:231, or SEQ ID NO:233, or a codon degenerate sequence of any of the foregoing. In some embodiments, the nucleotide sequence is codon-optimized. 
     In some embodiments, a modified host cell of the disclosure comprises one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the cannabidiolic acid synthase (CBDAS) polypeptide disclosed herein, wherein the nucleotide sequence is that set forth in SEQ ID NO:59, SEQ ID NO:81, SEQ ID NO:91, SEQ ID NO:103, SEQ ID NO:155, SEQ ID NO:159, SEQ ID NO:161, SEQ ID NO:171, SEQ ID NO:173, SEQ ID NO:175, SEQ ID NO:183, SEQ ID NO:197, SEQ ID NO:201, or SEQ ID NO:229. In some embodiments, the nucleotide sequence is codon-optimized. 
     In some embodiments, a modified host cell of the disclosure comprises one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the cannabidiolic acid synthase (CBDAS) polypeptide disclosed herein, wherein the nucleotide sequence is that set forth in SEQ ID NO:59, SEQ ID NO:81, SEQ ID NO:91, SEQ ID NO:103, SEQ ID NO:155, SEQ ID NO:159, SEQ ID NO:161, SEQ ID NO:171, SEQ ID NO:173, SEQ ID NO:175, SEQ ID NO:183, SEQ ID NO:197, SEQ ID NO:201, or SEQ ID NO:229, or a codon degenerate sequence of any of the foregoing. In some embodiments, the nucleotide sequence is codon-optimized. 
     In some embodiments, a modified host cell of the disclosure comprises one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the cannabidiolic acid synthase (CBDAS) polypeptide disclosed herein, wherein the nucleotide sequence is that set forth in SEQ ID NO:81, SEQ ID NO:155, SEQ ID NO:159, SEQ ID NO:171, SEQ ID NO:175, SEQ ID NO:183, or SEQ ID NO:197. In some embodiments, the nucleotide sequence is codon-optimized. 
     In some embodiments, a modified host cell of the disclosure comprises one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the cannabidiolic acid synthase (CBDAS) polypeptide disclosed herein, wherein the nucleotide sequence is that set forth in SEQ ID NO:81, SEQ ID NO:155, SEQ ID NO:159, SEQ ID NO:171, SEQ ID NO:175, SEQ ID NO:183, or SEQ ID NO:197, or a codon degenerate sequence of any of the foregoing. In some embodiments, the nucleotide sequence is codon-optimized. 
     In some embodiments, a modified host cell of the disclosure comprises one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the cannabidiolic acid synthase (CBDAS) polypeptide disclosed herein, wherein the nucleotide sequence is that set forth in SEQ ID NO:299, SEQ ID NO:301, or SEQ ID NO:303. In some embodiments, the nucleotide sequence is codon-optimized. 
     In some embodiments, a modified host cell of the disclosure comprises one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the cannabidiolic acid synthase (CBDAS) polypeptide disclosed herein, wherein the nucleotide sequence is that set forth in SEQ ID NO:299, SEQ ID NO:301, or SEQ ID NO:303, or a codon degenerate nucleotide sequence of any of the foregoing. In some embodiments, the nucleotide sequence is codon-optimized. 
     In some embodiments, a modified host cell of the disclosure comprises one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the cannabidiolic acid synthase (CBDAS) polypeptide disclosed herein, wherein the nucleotide sequence is that set forth in SEQ ID NO:299. In some embodiments, the nucleotide sequence is codon-optimized. 
     In some embodiments, a modified host cell of the disclosure comprises one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the cannabidiolic acid synthase (CBDAS) polypeptide disclosed herein, wherein the nucleotide sequence is that set forth in SEQ ID NO:299, or a codon degenerate nucleotide sequence of any of the foregoing. In some embodiments, the nucleotide sequence is codon-optimized. 
     In some embodiments, a modified host cell of the disclosure comprises one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the cannabidiolic acid synthase (CBDAS) polypeptide disclosed herein, wherein the nucleotide sequence is that set forth in SEQ ID NO:313, SEQ ID NO:315, SEQ ID NO:317, or SEQ ID NO:319. In some embodiments, the nucleotide sequence is codon-optimized. 
     In some embodiments, a modified host cell of the disclosure comprises one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the cannabidiolic acid synthase (CBDAS) polypeptide disclosed herein, wherein the nucleotide sequence is that set forth in SEQ ID NO:313, SEQ ID NO:315, SEQ ID NO:317, or SEQ ID NO:319, or a codon degenerate nucleotide sequence of any of the foregoing. In some embodiments, the nucleotide sequence is codon-optimized. 
     In some embodiments, a modified host cell of the disclosure comprises one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the cannabidiolic acid synthase (CBDAS) polypeptide disclosed herein, wherein the nucleotide sequence is that set forth in SEQ ID NO:313. In some embodiments, the nucleotide sequence is codon-optimized. 
     In some embodiments, a modified host cell of the disclosure comprises one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the cannabidiolic acid synthase (CBDAS) polypeptide disclosed herein, wherein the nucleotide sequence is that set forth in SEQ ID NO:313, or a codon degenerate nucleotide sequence of any of the foregoing. In some embodiments, the nucleotide sequence is codon-optimized. 
     In some embodiments, a modified host cell of the disclosure comprises one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the cannabidiolic acid synthase (CBDAS) polypeptide disclosed herein, wherein the nucleotide sequence is that set forth in SEQ ID NO:315. In some embodiments, the nucleotide sequence is codon-optimized. 
     In some embodiments, a modified host cell of the disclosure comprises one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the cannabidiolic acid synthase (CBDAS) polypeptide disclosed herein, wherein the nucleotide sequence is that set forth in SEQ ID NO:315, or a codon degenerate nucleotide sequence of any of the foregoing. In some embodiments, the nucleotide sequence is codon-optimized. 
     In some embodiments, a modified host cell of the disclosure comprises one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the cannabidiolic acid synthase (CBDAS) polypeptide disclosed herein, wherein the nucleotide sequence is that set forth in SEQ ID NO:317. In some embodiments, the nucleotide sequence is codon-optimized. 
     In some embodiments, a modified host cell of the disclosure comprises one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the cannabidiolic acid synthase (CBDAS) polypeptide disclosed herein, wherein the nucleotide sequence is that set forth in SEQ ID NO:317, or a codon degenerate nucleotide sequence of any of the foregoing. In some embodiments, the nucleotide sequence is codon-optimized. 
     In some embodiments, a modified host cell of the disclosure comprises one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the cannabidiolic acid synthase (CBDAS) polypeptide disclosed herein, wherein the nucleotide sequence is that set forth in SEQ ID NO:319. In some embodiments, the nucleotide sequence is codon-optimized. 
     In some embodiments, a modified host cell of the disclosure comprises one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the cannabidiolic acid synthase (CBDAS) polypeptide disclosed herein, wherein the nucleotide sequence is that set forth in SEQ ID NO:319, or a codon degenerate nucleotide sequence of any of the foregoing. In some embodiments, the nucleotide sequence is codon-optimized. 
     In some embodiments, at least one of the one or more nucleic acids comprising a nucleotide sequence encoding the engineered variant of the disclosure is operably linked to an inducible promoter. In some embodiments, at least one of the one or more nucleic acids comprising a nucleotide sequence encoding the engineered variant of the disclosure is operably linked to a constitutive promoter. 
     Geranyl Pyrophosphate: Olivetolic Acid Geranyltransferase (GOT) Polypeptides 
     A modified host cell of the present disclosure may comprise one or more heterologous nucleic acids comprising a nucleotide sequence encoding a geranyl pyrophosphate:olivetolic acid geranyltransferase (GOT) polypeptide. 
     Exemplary GOT polypeptides disclosed herein may include a full-length GOT polypeptide, a fragment of a GOT polypeptide, a variant of a GOT polypeptide, a truncated GOT polypeptide, or a fusion polypeptide that has at least one activity of a GOT polypeptide. In some embodiments, the GOT polypeptide has aromatic prenyltransferase (PT) activity. In some embodiments, the GOT polypeptide modifies a cannabinoid precursor or a cannabinoid precursor derivative. In certain such embodiments, the GOT polypeptide modifies olivetolic acid or an olivetolic acid derivative. 
     In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a GOT polypeptide, wherein the GOT polypeptide comprises the amino acid sequence set forth in SEQ ID NO:17. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a GOT polypeptide, wherein the GOT polypeptide comprises the amino acid sequence set forth in SEQ ID NO:17, or a conservatively substituted amino acid sequence thereof. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a GOT polypeptide, wherein the GOT polypeptide comprises an amino acid sequence having at least 65%, at least 70%, at least 75%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, at least 99.6%, at least 99.7%, at least 99.8%, at least 99.9%, or 100% amino acid sequence identity to SEQ ID NO:17. 
     In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a GOT polypeptide, wherein the GOT polypeptide comprises an amino acid sequence having at least 65%, at least 70%, or at least 75% amino acid sequence identity to SEQ ID NO:17. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a GOT polypeptide, wherein the GOT polypeptide comprises an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, or at least 84% amino acid sequence identity to SEQ ID NO:17. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a GOT polypeptide, wherein the GOT polypeptide comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, at least 99.6%, at least 99.7%, at least 99.8%, at least 99.9%, or 100% amino acid sequence identity to SEQ ID NO:17. 
     Exemplary heterologous nucleic acids disclosed herein may include nucleic acids comprising a nucleotide sequence that encodes a GOT polypeptide, such as, a full-length GOT polypeptide, a fragment of a GOT polypeptide, a variant of a GOT polypeptide, a truncated GOT polypeptide, or a fusion polypeptide that has at least one activity of a GOT polypeptide. In some embodiments, the nucleotide sequence is codon-optimized. 
     In some embodiments, the GOT polypeptide is overexpressed in the modified host cell. Overexpression may be achieved by increasing the copy number of the one or more heterologous nucleic acids comprising a nucleotide sequence encoding the GOT polypeptide, e.g., through use of a high copy number expression vector (e.g., a plasmid that exists at 10-40 copies or about 100 copies per cell) and/or by operably linking the nucleotide sequence encoding the GOT polypeptide to a strong promoter. In some embodiments, the modified host cell has one copy of a heterologous nucleic acid comprising a nucleotide sequence encoding the GOT polypeptide. In some embodiments, the modified host cell has two copies of a heterologous nucleic acid comprising a nucleotide sequence encoding the GOT polypeptide. In some embodiments, the modified host cell has three copies of a heterologous nucleic acid comprising a nucleotide sequence encoding the GOT polypeptide. In some embodiments, the modified host cell has four copies of a heterologous nucleic acid comprising a nucleotide sequence encoding the GOT polypeptide. In some embodiments, the modified host cell has five copies of a heterologous nucleic acid comprising a nucleotide sequence encoding the GOT polypeptide. In some embodiments, the modified host cell has six copies of a heterologous nucleic acid comprising a nucleotide sequence encoding the GOT polypeptide. In some embodiments, the modified host cell has seven copies of a heterologous nucleic acid comprising a nucleotide sequence encoding the GOT polypeptide. In some embodiments, the modified host cell has eight copies of a heterologous nucleic acid comprising a nucleotide sequence encoding the GOT polypeptide. In some embodiments, the modified host cell has eight or more copies of a heterologous nucleic acid comprising a nucleotide sequence encoding the GOT polypeptide. Increased copy number of the heterologous nucleic acid and/or codon optimization of the nucleotide sequence may result in an increase in the desired enzyme catalytic activity in the modified host cell. 
     In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a GOT polypeptide, wherein the nucleotide sequence is that set forth in SEQ ID NO:16. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a GOT polypeptide, wherein the nucleotide sequence is that set forth in SEQ ID NO:16, or a codon degenerate nucleotide sequence thereof. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a GOT polypeptide, wherein the nucleotide sequence has at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, at least 99.6%, at least 99.7%, at least 99.8%, at least 99.9%, or 100% sequence identity to SEQ ID NO:16. 
     In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a GOT polypeptide, wherein the nucleotide sequence has at least 80%, at least 81%, at least 82%, at least 83%, or at least 84% sequence identity to SEQ ID NO:16. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a GOT polypeptide, wherein the nucleotide sequence has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, at least 99.6%, at least 99.7%, at least 99.8%, at least 99.9%, or 100% sequence identity to SEQ ID NO:16. 
     In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a GOT polypeptide, wherein the nucleotide sequence has at least 80% sequence identity to SEQ ID NO:16. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a GOT polypeptide, wherein the nucleotide sequence has at least 85% sequence identity to SEQ ID NO:16. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a GOT polypeptide, wherein the nucleotide sequence has at least 90% sequence identity to SEQ ID NO:16. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a GOT polypeptide, wherein the nucleotide sequence has at least 95% sequence identity to SEQ ID NO:16. 
     NphB Polypeptides 
     In some embodiments, a NphB polypeptide is used instead of a GOT polypeptide to generate cannabigerolic acid from GPP and olivetolic acid. A modified host cell of the present disclosure may comprise one or more heterologous nucleic acids comprising a nucleotide sequence encoding a NphB polypeptide. 
     Exemplary NphB polypeptides disclosed herein may include a full-length NphB polypeptide, a fragment of a NphB polypeptide, a variant of a NphB polypeptide, a truncated NphB polypeptide, or a fusion polypeptide that has at least one activity of a NphB polypeptide. In some embodiments, the NphB polypeptide has aromatic prenyltransferase (PT) activity. In some embodiments, the NphB polypeptide modifies a cannabinoid precursor or a cannabinoid precursor derivative. In certain such embodiments, the NphB polypeptide modifies olivetolic acid or an olivetolic acid derivative. 
     In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a NphB polypeptide, wherein the NphB polypeptide comprises the amino acid sequence set forth in SEQ ID NO:294. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a NphB polypeptide, wherein the NphB polypeptide comprises the amino acid sequence set forth in SEQ ID NO:294, or a conservatively substituted amino acid sequence thereof. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a NphB polypeptide, wherein the NphB polypeptide comprises an amino acid sequence having at least 65%, at least 70%, or at least 75% amino acid sequence identity to SEQ ID NO:294. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a NphB polypeptide, wherein the NphB polypeptide comprises an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, or at least 84% amino acid sequence identity to SEQ ID NO:294. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a NphB polypeptide, wherein the NphB polypeptide comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, at least 99.6%, at least 99.7%, at least 99.8%, at least 99.9%, or 100% amino acid sequence identity to SEQ ID NO:294. 
     Exemplary heterologous nucleic acids disclosed herein may include nucleic acids comprising a nucleotide sequence that encodes a NphB polypeptide, such as, a full-length NphB polypeptide, a fragment of a NphB polypeptide, a variant of a NphB polypeptide, a truncated NphB polypeptide, or a fusion polypeptide that has at least one activity of a NphB polypeptide. In some embodiments, the nucleotide sequence is codon-optimized. 
     In some embodiments, the NphB polypeptide is overexpressed in the modified host cell. Overexpression may be achieved by increasing the copy number of the one or more heterologous nucleic acids comprising a nucleotide sequence encoding the NphB polypeptide, e.g., through use of a high copy number expression vector (e.g., a plasmid that exists at 10-40 copies or about 100 copies per cell) and/or by operably linking the nucleotide sequence encoding the NphB polypeptide to a strong promoter. In some embodiments, the modified host cell has one copy of a heterologous nucleic acid comprising a nucleotide sequence encoding the NphB polypeptide. In some embodiments, the modified host cell has two copies of a heterologous nucleic acid comprising a nucleotide sequence encoding the NphB polypeptide. In some embodiments, the modified host cell has three copies of a heterologous nucleic acid comprising a nucleotide sequence encoding the NphB polypeptide. In some embodiments, the modified host cell has four copies of a heterologous nucleic acid comprising a nucleotide sequence encoding the NphB polypeptide. In some embodiments, the modified host cell has five copies of a heterologous nucleic acid comprising a nucleotide sequence encoding the NphB polypeptide. In some embodiments, the modified host cell has six copies of a heterologous nucleic acid comprising a nucleotide sequence encoding the NphB polypeptide. In some embodiments, the modified host cell has seven copies of a heterologous nucleic acid comprising a nucleotide sequence encoding the NphB polypeptide. In some embodiments, the modified host cell has eight copies of a heterologous nucleic acid comprising a nucleotide sequence encoding the NphB polypeptide. In some embodiments, the modified host cell has eight or more copies of a heterologous nucleic acid comprising a nucleotide sequence encoding the NphB polypeptide. Increased copy number of the heterologous nucleic acid and/or codon optimization of the nucleotide sequence may result in an increase in the desired enzyme catalytic activity in the modified host cell. 
     In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a NphB polypeptide, wherein the nucleotide sequence is that set forth in SEQ ID NO:293. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a NphB polypeptide, wherein the nucleotide sequence is that set forth in SEQ ID NO:293, or a codon degenerate nucleotide sequence thereof. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a NphB polypeptide, wherein the nucleotide sequence has at least 80%, at least 81%, at least 82%, at least 83%, or at least 84% sequence identity to SEQ ID NO:293. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a NphB polypeptide, wherein the nucleotide sequence has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, at least 99.6%, at least 99.7%, at least 99.8%, at least 99.9%, or 100% sequence identity to SEQ ID NO:293. 
     In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a NphB polypeptide, wherein the nucleotide sequence has at least 80% sequence identity to SEQ ID NO:293. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a NphB polypeptide, wherein the nucleotide sequence has at least 85% sequence identity to SEQ ID NO:293. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a NphB polypeptide, wherein the nucleotide sequence has at least 90% sequence identity to SEQ ID NO:293. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a NphB polypeptide, wherein the nucleotide sequence has at least 95% sequence identity to SEQ ID NO:293. 
     Polypeptides that Generate Acyl-CoA Compounds or Acyl-CoA Compound Derivatives 
     A modified host cell of the present disclosure may comprise one or more heterologous nucleic acids comprising a nucleotide sequence encoding a polypeptide that generates acyl-CoA compounds or acyl-CoA compound derivatives. Such polypeptides may include, but are not limited to, acyl-activating enzyme (AAE) polypeptides, fatty acyl-CoA synthetases (FAA) polypeptides, or fatty acyl-CoA ligase polypeptides. In some embodiments, a modified host cell of the present disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding an AAE polypeptide. 
     AAE polypeptides, FAA polypeptides, and fatty acyl-CoA ligase polypeptides can convert carboxylic acids to their CoA forms and generate acyl-CoA compounds or acyl-CoA compound derivatives. Promiscuous acyl-activating enzyme polypeptides, such as CsAAE1 and CsAAE3 polypeptides, FAA polypeptides, or fatty acyl-CoA ligase polypeptides, may permit generation of cannabinoid derivatives (e.g., cannabigerolic acid derivatives), as well as cannabinoids (e.g., cannabigerolic acid). In some embodiments, unsubstituted or substituted hexanoic acid or carboxylic acids other than unsubstituted or substituted hexanoic acid are fed to modified host cells expressing an AAE polypeptide, FAA polypeptide, or fatty acyl-CoA ligase polypeptide (e.g., are present in the culture medium in which the cells are grown) to generate hexanoyl-CoA, acyl-CoA compounds, derivatives of hexanoyl-CoA, or derivatives of acyl-CoA compounds. The hexanoyl-CoA, acyl-CoA compounds, derivatives of hexanoyl-CoA, or derivatives of acyl-CoA compounds can then be further utilized by a modified host cell to generate cannabinoids or cannabinoid derivatives. In certain such embodiments, the cell culture medium comprising the modified host cells comprises unsubstituted or substituted hexanoic acid. In some embodiments, the cell culture medium comprising the modified host cells comprises a carboxylic acid other than unsubstituted or substituted hexanoic acid. 
     Exemplary AAE, FAA, or fatty acyl-CoA ligase polypeptides disclosed herein may include a full-length AAE, FAA, or fatty acyl-CoA ligase polypeptide; a fragment of an AAE, FAA, or fatty acyl-CoA ligase polypeptide; a variant of an AAE, FAA, or fatty acyl-CoA ligase polypeptide; a truncated AAE, FAA, or fatty acyl-CoA ligase polypeptide; or a fusion polypeptide that has at least one activity of an AAE, FAA, or fatty acyl-CoA ligase polypeptide. 
     In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding an AAE polypeptide, wherein the AAE polypeptide comprises the amino acid sequence set forth in SEQ ID NO:23. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding an AAE polypeptide, wherein the AAE polypeptide comprises the amino acid sequence set forth in SEQ ID NO:23, or a conservatively substituted amino acid sequence thereof. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding an AAE polypeptide, wherein the AAE polypeptide comprises an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, or at least 75% amino acid sequence identity to SEQ ID NO:23. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding an AAE polypeptide, wherein the AAE polypeptide comprises an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, or at least 84% amino acid sequence identity to SEQ ID NO:23. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding an AAE polypeptide, wherein the AAE polypeptide comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, at least 99.6%, at least 99.7%, at least 99.8%, at least 99.9%, or 100% amino acid sequence identity to SEQ ID NO:23. 
     Exemplary heterologous nucleic acids disclosed herein may include nucleic acids comprising a nucleotide sequence that encodes an AAE, FAA, or fatty acyl-CoA ligase polypeptide, such as, a full-length AAE, FAA, or fatty acyl-CoA ligase polypeptide; a fragment of an AAE, FAA, or fatty acyl-CoA ligase polypeptide; a variant of an AAE, FAA, or fatty acyl-CoA ligase polypeptide; a truncated AAE, FAA, or fatty acyl-CoA ligase polypeptide; or a fusion polypeptide that has at least one activity of an AAE, FAA, or fatty acyl-CoA ligase polypeptide. In some embodiments, the nucleotide sequence is codon-optimized. 
     In some embodiments, one or more AAE, FAA, or fatty acyl-CoA ligase polypeptide are overexpressed in the modified host cell. Overexpression may be achieved by increasing the copy number of the one or more heterologous nucleic acids comprising a nucleotide sequence encoding the AAE, FAA, or fatty acyl-CoA ligase polypeptide, e.g., through use of a high copy number expression vector (e.g., a plasmid that exists at 10-40 copies or about 100 copies per cell) and/or by operably linking a nucleotide sequence encoding the AAE, FAA, or fatty acyl-CoA ligase polypeptide to a strong promoter. In some embodiments, the modified host cell has one copy of a heterologous nucleic acid comprising a nucleotide sequence encoding an AAE, FAA, or fatty acyl-CoA ligase polypeptide. In some embodiments, the modified host cell has two copies of a heterologous nucleic acid comprising a nucleotide sequence encoding an AAE, FAA, or fatty acyl-CoA ligase polypeptide. In some embodiments, the modified host cell has three copies of a heterologous nucleic acid comprising a nucleotide sequence encoding an AAE, FAA, or fatty acyl-CoA ligase polypeptide. In some embodiments, the modified host cell has four copies of a heterologous nucleic acid comprising a nucleotide sequence encoding an AAE, FAA, or fatty acyl-CoA ligase polypeptide. In some embodiments, the modified host cell has five copies of a heterologous nucleic acid comprising a nucleotide sequence encoding an AAE, FAA, or fatty acyl-CoA ligase polypeptide. In some embodiments, the modified host cell has six copies of a heterologous nucleic acid comprising a nucleotide sequence encoding an AAE, FAA, or fatty acyl-CoA ligase polypeptide. In some embodiments, the modified host cell has seven copies of a heterologous nucleic acid comprising a nucleotide sequence encoding an AAE, FAA, or fatty acyl-CoA ligase polypeptide. In some embodiments, the modified host cell has eight copies of a heterologous nucleic acid comprising a nucleotide sequence encoding an AAE, FAA, or fatty acyl-CoA ligase polypeptide. In some embodiments, the modified host cell has eight or more copies of a heterologous nucleic acid comprising a nucleotide sequence encoding an AAE, FAA, or fatty acyl-CoA ligase polypeptide. Increased copy number of the heterologous nucleic acid and/or codon optimization of the nucleotide sequence may result in an increase in the desired enzyme catalytic activity in the modified host cell. 
     In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding an AAE polypeptide, wherein the nucleotide sequence is that set forth in SEQ ID NO:22. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding an AAE polypeptide, wherein the nucleotide sequence is that set forth in SEQ ID NO:22, or a codon degenerate nucleotide sequence thereof. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding an AAE polypeptide, wherein the nucleotide sequence has at least 80%, at least 81%, at least 82%, at least 83%, or at least 84% sequence identity to SEQ ID NO:22. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding an AAE polypeptide, wherein the nucleotide sequence has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, at least 99.6%, at least 99.7%, at least 99.8%, at least 99.9%, or 100% sequence identity to SEQ ID NO:22. 
     Polypeptides that Condense an Acyl-CoA Compound or an Acyl-CoA Compound Derivative with Malonyl-CoA to Generate Olivetolic Acid or Derivatives of Olivetolic Acid 
     A modified host cell of the present disclosure may comprise one or more heterologous nucleic acids comprising a nucleotide sequence encoding one or more polypeptides that condense an acyl-CoA compound, such as hexanoyl-CoA, or an acyl-CoA compound derivative, such as a hexanoyl-CoA derivative, with malonyl-CoA to generate olivetolic acid, or a derivative of olivetolic acid. Polypeptides that react an acyl-CoA compound or an acyl-CoA compound derivative with malonyl-CoA to generate olivetolic acid, or a derivative of olivetolic acid, may include TKS and OAC polypeptides. TKS and OAC polypeptides have been found to have broad substrate specificity, enabling production of cannabinoid derivatives or cannabinoids. In some embodiments, a modified host cell of the present disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a TKS polypeptide. In some embodiments, a modified host cell of the present disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding an OAC polypeptide. 
     Exemplary TKS or OAC polypeptides disclosed herein may include a full-length TKS or OAC polypeptide, a fragment of a TKS or OAC polypeptide, a variant of a TKS or OAC polypeptide, a truncated TKS or OAC polypeptide, or a fusion polypeptide that has at least one activity of a TKS or OAC polypeptide. 
     In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a TKS polypeptide, wherein the TKS polypeptide comprises the amino acid sequence set forth in SEQ ID NO:19. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a TKS polypeptide, wherein the TKS polypeptide comprises the amino acid sequence set forth in SEQ ID NO:19, or a conservatively substituted amino acid sequence thereof. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a TKS polypeptide, wherein the TKS polypeptide comprises an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, or at least 75% amino acid sequence identity to SEQ ID NO:19. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a TKS polypeptide, wherein the TKS polypeptide comprises an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, or at least 84% amino acid sequence identity to SEQ ID NO:19. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a TKS polypeptide, wherein the TKS polypeptide comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, at least 99.6%, at least 99.7%, at least 99.8%, at least 99.9%, or 100% amino acid sequence identity to SEQ ID NO:19. 
     In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding an OAC polypeptide, wherein the OAC polypeptide comprises the amino acid sequence set forth in SEQ ID NO:21 or SEQ ID NO:48. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding an OAC polypeptide, wherein the OAC polypeptide comprises the amino acid sequence set forth in SEQ ID NO:21 or SEQ ID NO:48, or a conservatively substituted amino acid sequence thereof. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding an OAC polypeptide, wherein the OAC polypeptide comprises an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, or at least 75% amino acid sequence identity to SEQ ID NO:21 or SEQ ID NO:48. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding an OAC polypeptide, wherein the OAC polypeptide comprises an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, or at least 84% amino acid sequence identity to SEQ ID NO:21 or SEQ ID NO:48. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding an OAC polypeptide, wherein the OAC polypeptide comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, at least 99.6%, at least 99.7%, at least 99.8%, at least 99.9%, or 100% amino acid sequence identity to SEQ ID NO:21 or SEQ ID NO:48. 
     In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding an OAC polypeptide, wherein the OAC polypeptide comprises the amino acid sequence set forth in SEQ ID NO:21. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding an OAC polypeptide, wherein the OAC polypeptide comprises the amino acid sequence set forth in SEQ ID NO:21, or a conservatively substituted amino acid sequence thereof. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding an OAC polypeptide, wherein the OAC polypeptide comprises an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, or at least 75% amino acid sequence identity to SEQ ID NO:21. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding an OAC polypeptide, wherein the OAC polypeptide comprises an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, or at least 84% amino acid sequence identity to SEQ ID NO:21. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding an OAC polypeptide, wherein the OAC polypeptide comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, at least 99.6%, at least 99.7%, at least 99.8%, at least 99.9%, or 100% amino acid sequence identity to SEQ ID NO:21. 
     In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding an OAC polypeptide, wherein the OAC polypeptide is a variant OAC (Y27F variant) polypeptide comprising the amino acid sequence set forth in SEQ ID NO:48. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding an OAC polypeptide, wherein the OAC polypeptide is a variant OAC (Y27F variant) polypeptide comprising the amino acid sequence set forth in SEQ ID NO:48, or a conservatively substituted amino acid sequence thereof. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding an OAC polypeptide, wherein the OAC polypeptide is a variant OAC (Y27F variant) polypeptide comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, or at least 75% amino acid sequence identity to SEQ ID NO:48. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding an OAC polypeptide, wherein the OAC polypeptide is a variant OAC (Y27F variant) polypeptide comprising an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, or at least 84% amino acid sequence identity to SEQ ID NO:48. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding an OAC polypeptide, wherein the OAC polypeptide is a variant OAC (Y27F variant) polypeptide comprising an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, at least 99.6%, at least 99.7%, at least 99.8%, at least 99.9%, or 100% amino acid sequence identity to SEQ ID NO:48. 
     Exemplary heterologous nucleic acids disclosed herein may include nucleic acids comprising a nucleotide sequence that encodes a TKS or OAC polypeptide, such as, a full-length TKS or OAC polypeptide, a fragment of a TKS or OAC polypeptide, a variant of a TKS or OAC polypeptide, a truncated TKS or OAC polypeptide, or a fusion polypeptide that has at least one activity of a TKS or OAC polypeptide. In some embodiments, the nucleotide sequence is codon-optimized. 
     In some embodiments, the TKS polypeptide is overexpressed in the modified host cell. Overexpression may be achieved by increasing the copy number of the one or more heterologous nucleic acids comprising a nucleotide sequence encoding the TKS polypeptide, e.g., through use of a high copy number expression vector (e.g., a plasmid that exists at 10-40 copies or about 100 copies per cell) and/or by operably linking the nucleotide sequence encoding the TKS polypeptide to a strong promoter. In some embodiments, the modified host cell has one copy of a heterologous nucleic acid comprising a nucleotide sequence encoding the TKS polypeptide. In some embodiments, the modified host cell has two copies of a heterologous nucleic acid comprising a nucleotide sequence encoding the TKS polypeptide. In some embodiments, the modified host cell has three copies of a heterologous nucleic acid comprising a nucleotide sequence encoding the TKS polypeptide. In some embodiments, the modified host cell has four copies of a heterologous nucleic acid comprising a nucleotide sequence encoding the TKS polypeptide. In some embodiments, the modified host cell has five copies of a heterologous nucleic acid comprising a nucleotide sequence encoding the TKS polypeptide. In some embodiments, the modified host cell has six copies of a heterologous nucleic acid comprising a nucleotide sequence encoding the TKS polypeptide. In some embodiments, the modified host cell has seven copies of a heterologous nucleic acid comprising a nucleotide sequence encoding the TKS polypeptide. In some embodiments, the modified host cell has eight copies of a heterologous nucleic acid comprising a nucleotide sequence encoding the TKS polypeptide. In some embodiments, the modified host cell has nine copies of a heterologous nucleic acid comprising a nucleotide sequence encoding the TKS polypeptide. In some embodiments, the modified host cell has ten copies of a heterologous nucleic acid comprising a nucleotide sequence encoding the TKS polypeptide. In some embodiments, the modified host cell has eleven copies of a heterologous nucleic acid comprising a nucleotide sequence encoding the TKS polypeptide. In some embodiments, the modified host cell has twelve copies of a heterologous nucleic acid comprising a nucleotide sequence encoding the TKS polypeptide. In some embodiments, the modified host cell has twelve or more copies of a heterologous nucleic acid comprising a nucleotide sequence encoding the TKS polypeptide. Increased copy number of the heterologous nucleic acid and/or codon optimization of the nucleotide sequence may result in an increase in the desired enzyme catalytic activity in the modified host cell. 
     In some embodiments, the OAC polypeptide is overexpressed in the modified host cell. Overexpression may be achieved by increasing the copy number of the one or more heterologous nucleic acids comprising a nucleotide sequence encoding the OAC polypeptide, e.g., through use of a high copy number expression vector (e.g., a plasmid that exists at 10-40 copies or about 100 copies per cell) and/or by operably linking the nucleotide sequence encoding the OAC polypeptide to a strong promoter. In some embodiments, the modified host cell has one copy of a heterologous nucleic acid comprising a nucleotide sequence encoding the OAC polypeptide. In some embodiments, the modified host cell has two copies of a heterologous nucleic acid comprising a nucleotide sequence encoding the OAC polypeptide. In some embodiments, the modified host cell has three copies of a heterologous nucleic acid comprising a nucleotide sequence encoding the OAC polypeptide. In some embodiments, the modified host cell has four copies of a heterologous nucleic acid comprising a nucleotide sequence encoding the OAC polypeptide. In some embodiments, the modified host cell has five copies of a heterologous nucleic acid comprising a nucleotide sequence encoding the OAC polypeptide. In some embodiments, the modified host cell has six copies of a heterologous nucleic acid comprising a nucleotide sequence encoding the OAC polypeptide. In some embodiments, the modified host cell has seven copies of a heterologous nucleic acid comprising a nucleotide sequence encoding the OAC polypeptide. In some embodiments, the modified host cell has eight copies of a heterologous nucleic acid comprising a nucleotide sequence encoding the OAC polypeptide. In some embodiments, the modified host cell has nine copies of a heterologous nucleic acid comprising a nucleotide sequence encoding the OAC polypeptide. In some embodiments, the modified host cell has ten copies of a heterologous nucleic acid comprising a nucleotide sequence encoding the OAC polypeptide. In some embodiments, the modified host cell has eleven copies of a heterologous nucleic acid comprising a nucleotide sequence encoding the OAC polypeptide. In some embodiments, the modified host cell has twelve copies of a heterologous nucleic acid comprising a nucleotide sequence encoding the OAC polypeptide. In some embodiments, the modified host cell has twelve or more copies of a heterologous nucleic acid comprising a nucleotide sequence encoding the OAC polypeptide. Increased copy number of the heterologous nucleic acid and/or codon optimization of the nucleotide sequence may result in an increase in the desired enzyme catalytic activity in the modified host cell. 
     In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a TKS polypeptide, wherein the nucleotide sequence is that set forth in SEQ ID NO:18. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a TKS polypeptide, wherein the nucleotide sequence is that set forth in SEQ ID NO:18, or a codon degenerate nucleotide sequence thereof. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a TKS polypeptide, wherein the nucleotide sequence has at least 80%, at least 81%, at least 82%, at least 83%, or at least 84% sequence identity to SEQ ID NO:18. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a TKS polypeptide, wherein the nucleotide sequence has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, at least 99.6%, at least 99.7%, at least 99.8%, at least 99.9%, or 100% sequence identity to SEQ ID NO:18. 
     In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding an OAC polypeptide, wherein the nucleotide sequence is that set forth in SEQ ID NO:20 or SEQ ID NO:47. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding an OAC polypeptide, wherein the nucleotide sequence is that set forth in SEQ ID NO:20 or SEQ ID NO:47, or a codon degenerate nucleotide sequence of any of the foregoing. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding an OAC polypeptide, wherein the nucleotide sequence has at least 80%, at least 81%, at least 82%, at least 83%, or at least 84% sequence identity to SEQ ID NO:20 or SEQ ID NO:47. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding an OAC polypeptide, wherein the nucleotide sequence has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, at least 99.6%, at least 99.7%, at least 99.8%, at least 99.9%, or 100% sequence identity to SEQ ID NO:20 or SEQ ID NO:47. 
     In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding an OAC polypeptide, wherein the nucleotide sequence is that set forth in SEQ ID NO:20. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding an OAC polypeptide, wherein the nucleotide sequence is that set forth in SEQ ID NO:20, or a codon degenerate nucleotide sequence thereof. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding an OAC polypeptide, wherein the nucleotide sequence has at least 80%, at least 81%, at least 82%, at least 83%, or at least 84% sequence identity to SEQ ID NO:20. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding an OAC polypeptide, wherein the nucleotide sequence has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, at least 99.6%, at least 99.7%, at least 99.8%, at least 99.9%, or 100% sequence identity to SEQ ID NO:20. 
     In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding an OAC polypeptide, wherein the OAC polypeptide is a variant OAC (Y27F variant) polypeptide, wherein the nucleotide sequence is that set forth in SEQ ID NO:47. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding an OAC polypeptide, wherein the OAC polypeptide is a variant OAC (Y27F variant) polypeptide, wherein the nucleotide sequence is that set forth in SEQ ID NO:47, or a codon degenerate nucleotide sequence thereof. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding an OAC polypeptide, wherein the OAC polypeptide is a variant OAC (Y27F variant) polypeptide, wherein the nucleotide sequence has at least 80%, at least 81%, at least 82%, at least 83%, or at least 84% sequence identity to SEQ ID NO:47. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding an OAC polypeptide, wherein the OAC polypeptide is a variant OAC (Y27F variant) polypeptide, wherein the nucleotide sequence has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, at least 99.6%, at least 99.7%, at least 99.8%, at least 99.9%, or 100% sequence identity to SEQ ID NO:47. 
     Polypeptides that Generate Geranyl Pyrophosphate 
     A modified host cell of the present disclosure may comprise one or more heterologous nucleic acids comprising a nucleotide sequence encoding a polypeptide that generates GPP. In some embodiments, the polypeptide that generates GPP is a geranyl pyrophosphate synthetase (GPPS) polypeptide. In some embodiments, the GPPS polypeptide also has farnesyl diphosphate synthase (FPPS) polypeptide activity. In some embodiments, the GPPS polypeptide is modified such that it has reduced FPPS polypeptide activity (e.g., at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or more than at least 90%, less FPPS polypeptide activity) than the corresponding wild-type or parental GPPS polypeptide from which the modified GPPS polypeptide is derived. In some embodiments, the GPPS polypeptide is modified such that it has substantially no FPPS polypeptide activity. In some embodiments, a modified host cell of the present disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a GPPS polypeptide. 
     Exemplary GPPS polypeptides disclosed herein may include a full-length GPPS polypeptide, a fragment of a GPPS polypeptide, a variant of a GPPS polypeptide, a truncated GPPS polypeptide, or a fusion polypeptide that has at least one activity of a GPPS polypeptide. 
     In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a GPPS polypeptide, wherein the GPPS polypeptide is a variant GPPS (ERG20mut, F96W, N127W) polypeptide comprising the amino acid sequence set forth in SEQ ID NO:41. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a GPPS polypeptide, wherein the GPPS polypeptide is a variant GPPS (ERG20mut, F96W, N127W) polypeptide comprising the amino acid sequence set forth in SEQ ID NO:41, or a conservatively substituted amino acid sequence thereof. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a GPPS polypeptide, wherein the GPPS polypeptide is a variant GPPS (ERG20mut, F96W, N127W) polypeptide comprising an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, or at least 75% amino acid sequence identity to SEQ ID NO:41. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a GPPS polypeptide, wherein the GPPS polypeptide is a variant GPPS (ERG20mut, F96W, N127W) polypeptide comprising an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, or at least 84% amino acid sequence identity to SEQ ID NO:41. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a GPPS polypeptide, wherein the GPPS polypeptide is a variant GPPS (ERG20mut, F96W, N127W) polypeptide comprising an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, at least 99.6%, at least 99.7%, at least 99.8%, at least 99.9%, or 100% amino acid sequence identity to SEQ ID NO:41. The mutation in this amino acid sequence shifts the ratio of GPP to farnesyl diphosphate (FPP), increasing the production of the GPP required to produce CBDA. 
     Exemplary heterologous nucleic acids disclosed herein may include nucleic acids comprising a nucleotide sequence that encodes a GPPS polypeptide, such as, a full-length GPPS polypeptide, a fragment of a GPPS polypeptide, a variant of a GPPS polypeptide, a truncated GPPS polypeptide, or a fusion polypeptide that has at least one activity of a GPPS polypeptide. In some embodiments, the nucleotide sequence is codon-optimized. 
     In some embodiments, the GPPS polypeptide is overexpressed in the modified host cell. Overexpression may be achieved by increasing the copy number of the one or more heterologous nucleic acids comprising a nucleotide sequence encoding the GPPS polypeptide, e.g., through use of a high copy number expression vector (e.g., a plasmid that exists at 10-40 copies or about 100 copies per cell) and/or by operably linking the nucleotide sequence encoding the GPPS polypeptide to a strong promoter. In some embodiments, the modified host cell has one copy of a heterologous nucleic acid comprising a nucleotide sequence encoding the GPPS polypeptide. In some embodiments, the modified host cell has two copies of a heterologous nucleic acid comprising a nucleotide sequence encoding the GPPS polypeptide. In some embodiments, the modified host cell has three copies of a heterologous nucleic acid comprising a nucleotide sequence encoding the GPPS polypeptide. In some embodiments, the modified host cell has four copies of a heterologous nucleic acid comprising a nucleotide sequence encoding the GPPS polypeptide. In some embodiments, the modified host cell has five copies of a heterologous nucleic acid comprising a nucleotide sequence encoding the GPPS polypeptide. In some embodiments, the modified host cell has six copies of a heterologous nucleic acid comprising a nucleotide sequence encoding the GPPS polypeptide. In some embodiments, the modified host cell has seven copies of a heterologous nucleic acid comprising a nucleotide sequence encoding the GPPS polypeptide. In some embodiments, the modified host cell has eight copies of a heterologous nucleic acid comprising a nucleotide sequence encoding the GPPS polypeptide. In some embodiments, the modified host cell has eight or more copies of a heterologous nucleic acid comprising a nucleotide sequence encoding the GPPS polypeptide. Increased copy number of the heterologous nucleic acid and/or codon optimization of the nucleotide sequence may result in an increase in the desired enzyme catalytic activity in the modified host cell. 
     In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a GPPS polypeptide, wherein the GPPS polypeptide is a variant GPPS (ERG20mut, F96W, N127W) polypeptide, wherein the nucleotide sequence is that set forth in SEQ ID NO:40. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a GPPS polypeptide, wherein the GPPS polypeptide is a variant GPPS (ERG20mut, F96W, N127W) polypeptide, wherein the nucleotide sequence is that set forth in SEQ ID NO:40, or a codon degenerate nucleotide sequence thereof. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a GPPS polypeptide, wherein the GPPS polypeptide is a variant GPPS (ERG20mut, F96W, N127W) polypeptide, wherein the nucleotide sequence has at least 80%, at least 81%, at least 82%, at least 83%, or at least 84% sequence identity to SEQ ID NO:40. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a GPPS polypeptide, wherein the GPPS polypeptide is a variant GPPS (ERG20mut, F96W, N127W) polypeptide, wherein the nucleotide sequence has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, at least 99.6%, at least 99.7%, at least 99.8%, at least 99.9%, or 100% sequence identity to SEQ ID NO:40. 
     Polypeptides that Generate Acetyl-CoA from Pyruvate 
     A modified host cell of the present disclosure may comprise one or more heterologous nucleic acids comprising a nucleotide sequence encoding a polypeptide that generates acetyl-CoA from pyruvate. Polypeptides that generate acetyl-CoA from pyruvate may include a pyruvate decarboxylase (PDC) polypeptide. In some embodiments, a modified host cell of the present disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a PDC polypeptide. 
     Exemplary PDC polypeptides disclosed herein may include a full-length PDC polypeptide, a fragment of a PDC polypeptide, a variant of a PDC polypeptide, a truncated PDC polypeptide, or a fusion polypeptide that has at least one activity of a PDC polypeptide. 
     In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a PDC polypeptide, wherein the PDC polypeptide comprises the amino acid sequence set forth in SEQ ID NO:35. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a PDC polypeptide, wherein the PDC polypeptide comprises the amino acid sequence set forth in SEQ ID NO:35, or a conservatively substituted amino acid sequence thereof. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a PDC polypeptide, wherein the PDC polypeptide comprises an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, or at least 75% amino acid sequence identity to SEQ ID NO:35. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a PDC polypeptide, wherein the PDC polypeptide comprises an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, or at least 84% amino acid sequence identity to SEQ ID NO:35. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a PDC polypeptide, wherein the PDC polypeptide comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, at least 99.6%, at least 99.7%, at least 99.8%, at least 99.9%, or 100% amino acid sequence identity to SEQ ID NO:35. 
     Exemplary heterologous nucleic acids disclosed herein may include nucleic acids comprising a nucleotide sequence that encodes a PDC polypeptide, such as, a full-length PDC polypeptide, a fragment of a PDC polypeptide, a variant of a PDC polypeptide, a truncated PDC polypeptide, or a fusion polypeptide that has at least one activity of a PDC polypeptide. In some embodiments, the nucleotide sequence is codon-optimized. 
     In some embodiments, the PDC polypeptide is overexpressed in the modified host cell. Overexpression may be achieved by increasing the copy number of the one or more heterologous nucleic acids comprising a nucleotide sequence encoding the PDC polypeptide, e.g., through use of a high copy number expression vector (e.g., a plasmid that exists at 10-40 copies or about 100 copies per cell) and/or by operably linking the nucleotide sequence encoding the PDC polypeptide to a strong promoter. In some embodiments, the modified host cell has one copy of a heterologous nucleic acid comprising a nucleotide sequence encoding the PDC polypeptide. In some embodiments, the modified host cell has two copies of a heterologous nucleic acid comprising a nucleotide sequence encoding the PDC polypeptide. In some embodiments, the modified host cell has three copies of a heterologous nucleic acid comprising a nucleotide sequence encoding the PDC polypeptide. In some embodiments, the modified host cell has four copies of a heterologous nucleic acid comprising a nucleotide sequence encoding the PDC polypeptide. In some embodiments, the modified host cell has five copies of a heterologous nucleic acid comprising a nucleotide sequence encoding the PDC polypeptide. In some embodiments, the modified host cell has five or more copies of a heterologous nucleic acid comprising a nucleotide sequence encoding the PDC polypeptide. Increased copy number of the heterologous nucleic acid and/or codon optimization of the nucleotide sequence may result in an increase in the desired enzyme catalytic activity in the modified host cell. 
     In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a PDC polypeptide, wherein the nucleotide sequence is that set forth in SEQ ID NO:34. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a PDC polypeptide, wherein the nucleotide sequence is that set forth in SEQ ID NO:34, or a codon degenerate nucleotide sequence thereof. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a PDC polypeptide, wherein the nucleotide sequence has at least 80%, at least 81%, at least 82%, at least 83%, or at least 84% sequence identity to SEQ ID NO:34. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a PDC polypeptide, wherein the nucleotide sequence has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, at least 99.6%, at least 99.7%, at least 99.8%, at least 99.9%, or 100% sequence identity to SEQ ID NO:34. 
     Polypeptides that Condense Two Molecules of Acetyl-CoA to Generate Acetoacetyl-CoA 
     A modified host cell of the disclosure may comprise one or more heterologous nucleic acids comprising a nucleotide sequence encoding a polypeptide that condenses two molecules of acetyl-CoA to generate acetoacetyl-CoA. In some embodiments, the polypeptide that condenses two molecules of acetyl-CoA to generate acetoacetyl-CoA is an acetoacetyl-CoA thiolase polypeptide. In some embodiments, a modified host cell of the present disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding an acetoacetyl-CoA thiolase polypeptide. 
     Exemplary acetoacetyl-CoA thiolase polypeptides disclosed herein may include a full-length acetoacetyl-CoA thiolase polypeptide, a fragment of an acetoacetyl-CoA thiolase polypeptide, a variant of an acetoacetyl-CoA thiolase polypeptide, a truncated acetoacetyl-CoA thiolase polypeptide, or a fusion polypeptide that has at least one activity of an acetoacetyl-CoA thiolase polypeptide. 
     In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding an acetoacetyl-CoA thiolase polypeptide, wherein the acetoacetyl-CoA thiolase polypeptide comprises the amino acid sequence set forth in SEQ ID NO:31. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding an acetoacetyl-CoA thiolase polypeptide, wherein the acetoacetyl-CoA thiolase polypeptide comprises the amino acid sequence set forth in SEQ ID NO:31, or a conservatively substituted amino acid sequence thereof. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding an acetoacetyl-CoA thiolase polypeptide, wherein the acetoacetyl-CoA thiolase polypeptide comprises an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, or at least 75% amino acid sequence identity to SEQ ID NO:31. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding an acetoacetyl-CoA thiolase polypeptide, wherein the acetoacetyl-CoA thiolase polypeptide comprises an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, or at least 84% amino acid sequence identity to SEQ ID NO:31. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding an acetoacetyl-CoA thiolase polypeptide, wherein the acetoacetyl-CoA thiolase polypeptide comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, at least 99.6%, at least 99.7%, at least 99.8%, at least 99.9%, or 100% amino acid sequence identity to SEQ ID NO:31. 
     Exemplary heterologous nucleic acids disclosed herein may include nucleic acids comprising a nucleotide sequence that encodes an acetoacetyl-CoA thiolase polypeptide, such as, a full-length acetoacetyl-CoA thiolase polypeptide, a fragment of an acetoacetyl-CoA thiolase polypeptide, a variant of an acetoacetyl-CoA thiolase polypeptide, a truncated acetoacetyl-CoA thiolase polypeptide, or a fusion polypeptide that has at least one activity of an acetoacetyl-CoA thiolase polypeptide. In some embodiments, the nucleotide sequence is codon-optimized. 
     In some embodiments, the acetoacetyl-CoA thiolase polypeptide is overexpressed in the modified host cell. Overexpression may be achieved by increasing the copy number of the one or more heterologous nucleic acids comprising a nucleotide sequence encoding the acetoacetyl-CoA thiolase polypeptide, e.g., through use of a high copy number expression vector (e.g., a plasmid that exists at 10-40 copies or about 100 copies per cell) and/or by operably linking the nucleotide sequence encoding the acetoacetyl-CoA thiolase polypeptide to a strong promoter. In some embodiments, the modified host cell has one copy of a heterologous nucleic acid comprising a nucleotide sequence encoding the acetoacetyl-CoA thiolase polypeptide. In some embodiments, the modified host cell has two copies of a heterologous nucleic acid comprising a nucleotide sequence encoding the acetoacetyl-CoA thiolase polypeptide. In some embodiments, the modified host cell has three copies of a heterologous nucleic acid comprising a nucleotide sequence encoding the acetoacetyl-CoA thiolase polypeptide. In some embodiments, the modified host cell has four copies of a heterologous nucleic acid comprising a nucleotide sequence encoding the acetoacetyl-CoA thiolase polypeptide. In some embodiments, the modified host cell has five copies of a heterologous nucleic acid comprising a nucleotide sequence encoding the acetoacetyl-CoA thiolase polypeptide. In some embodiments, the modified host cell has five or more copies of a heterologous nucleic acid comprising a nucleotide sequence encoding the acetoacetyl-CoA thiolase polypeptide. Increased copy number of the heterologous nucleic acid and/or codon optimization of the nucleotide sequence may result in an increase in the desired enzyme catalytic activity in the modified host cell. 
     In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding an acetoacetyl-CoA thiolase polypeptide, wherein the nucleotide sequence is that set forth in SEQ ID NO:30. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding an acetoacetyl-CoA thiolase polypeptide, wherein the nucleotide sequence is that set forth in SEQ ID NO:30, or a codon degenerate nucleotide sequence thereof. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding an acetoacetyl-CoA thiolase polypeptide, wherein the nucleotide sequence has at least 80%, at least 81%, at least 82%, at least 83%, or at least 84% sequence identity to SEQ ID NO:30. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding an acetoacetyl-CoA thiolase polypeptide, wherein the nucleotide sequence has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, at least 99.6%, at least 99.7%, at least 99.8%, at least 99.9%, or 100% sequence identity to SEQ ID NO:30. 
     Mevalonate Pathway Polypeptides 
     A modified host cell of the present disclosure may comprise one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more polypeptides having at least one activity of a polypeptide present in the mevalonate (MEV) pathway. In certain such embodiments, the one or more polypeptides having at least one activity of a polypeptide present in the mevalonate (MEV) pathway comprise one or more MEV pathway polypeptides. 
     In some embodiments, the one or more polypeptides that are part of a biosynthetic pathway that generates GPP are one or more polypeptides having at least one activity of a polypeptide present in the mevalonate pathway. The mevalonate pathway may comprise polypeptides that catalyze the following steps: (a) condensing two molecules of acetyl-CoA to generate acetoacetyl-CoA (e.g., by action of an acetoacetyl-CoA thiolase polypeptide); (b) condensing acetoacetyl-CoA with acetyl-CoA to form hydroxymethylglutaryl-CoA (HMG-CoA) (e.g., by action of a HMGS polypeptide); (c) converting HMG-CoA to mevalonate (e.g., by action of an HMGR polypeptide); (d) phosphorylating mevalonate to mevalonate 5-phosphate (e.g., by action of a MK polypeptide); (e) converting mevalonate 5-phosphate to mevalonate 5-pyrophosphate (e.g., by action of a PMK polypeptide); (f) converting mevalonate 5-pyrophosphate to isopentenyl pyrophosphate (e.g., by action of a mevalonate pyrophosphate decarboxylase (MPD or MVD1) polypeptide); and (g) converting isopentenyl pyrophosphate to dimethylallyl pyrophosphate (e.g., by action of an isopentenyl pyrophosphate isomerase (IDI1) polypeptide). 
     In some embodiments, a modified host cell of the present disclosure comprises one or more heterologous nucleic acids comprising nucleotide sequences encoding a MEV pathway polypeptide. In some embodiments, a modified host cell of the present disclosure comprises one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more MEV pathway polypeptide. In some embodiments, a modified host cell of the present disclosure comprises one or more heterologous nucleic acids comprising nucleotide sequences encoding two or more MEV pathway polypeptides. In some embodiments, a modified host cell of the present disclosure comprises one or more heterologous nucleic acids comprising nucleotide sequences encoding three or more MEV pathway polypeptides. In some embodiments, a modified host cell of the present disclosure comprises one or more heterologous nucleic acids comprising nucleotide sequences encoding four or more MEV pathway polypeptides. In some embodiments, a modified host cell of the present disclosure comprises one or more heterologous nucleic acids comprising nucleotide sequences encoding five or more MEV pathway polypeptides. In some embodiments, a modified host cell of the present disclosure comprises one or more heterologous nucleic acids comprising nucleotide sequences encoding six or more MEV pathway polypeptides. In some embodiments, a modified host cell of the present disclosure comprises one or more heterologous nucleic acids comprising nucleotide sequences encoding all MEV pathway polypeptides. 
     Exemplary MEV pathway polypeptides disclosed herein may include a full-length MEV pathway polypeptide, a fragment of a MEV pathway polypeptide, a variant of a MEV pathway polypeptide, a truncated MEV pathway polypeptide, or a fusion polypeptide that has at least one activity of a MEV pathway polypeptide. In some embodiments, the one or more MEV pathway polypeptides are selected from the group consisting of an acetoacetyl-CoA thiolase polypeptide, a HMGS polypeptide, a HMGR polypeptide, an MK polypeptide, a PMK polypeptide, an MVD1 polypeptide, and an IDI1 polypeptide. 
     In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a HMGS polypeptide, wherein the HMGS polypeptide comprises the amino acid sequence set forth in SEQ ID NO:29. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a HMGS polypeptide, wherein the HMGS polypeptide comprises the amino acid sequence set forth in SEQ ID NO:29, or a conservatively substituted amino acid sequence thereof. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a HMGS polypeptide, wherein the HMGS polypeptide comprises an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, or at least 75% amino acid sequence identity to SEQ ID NO:29. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a HMGS polypeptide, wherein the HMGS polypeptide comprises an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, or at least 84% amino acid sequence identity to SEQ ID NO:29. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a HMGS polypeptide, wherein the HMGS polypeptide comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, at least 99.6%, at least 99.7%, at least 99.8%, at least 99.9%, or 100% amino acid sequence identity to SEQ ID NO:29. 
     In some embodiments, the HMGR polypeptide is a truncated HMGR (tHMGR) polypeptide. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a tHMGR polypeptide, wherein the tHMGR polypeptide comprises the amino acid sequence set forth in SEQ ID NO:27. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a tHMGR polypeptide, wherein the tHMGR polypeptide comprises the amino acid sequence set forth in SEQ ID NO:27, or a conservatively substituted amino acid sequence thereof. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a tHMGR polypeptide, wherein the tHMGR polypeptide comprises an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, or at least 75% amino acid sequence identity to SEQ ID NO:27. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a tHMGR polypeptide, wherein the tHMGR polypeptide comprises an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, or at least 84% amino acid sequence identity to SEQ ID NO:27. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a tHMGR polypeptide, wherein the tHMGR polypeptide comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, at least 99.6%, at least 99.7%, at least 99.8%, at least 99.9%, or 100% amino acid sequence identity to SEQ ID NO:27. 
     In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a MK polypeptide, wherein the MK polypeptide comprises the amino acid sequence set forth in SEQ ID NO:39. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a MK polypeptide, wherein the MK polypeptide comprises the amino acid sequence set forth in SEQ ID NO:39, or a conservatively substituted amino acid sequence thereof. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a MK polypeptide, wherein the MK polypeptide comprises an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, or at least 75% amino acid sequence identity to SEQ ID NO:39. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a MK polypeptide, wherein the MK polypeptide comprises an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, or at least 84% amino acid sequence identity to SEQ ID NO:39. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a MK polypeptide, wherein the MK polypeptide comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, at least 99.6%, at least 99.7%, at least 99.8%, at least 99.9%, or 100% amino acid sequence identity to SEQ ID NO:39. 
     In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a PMK polypeptide, wherein the PMK polypeptide comprises the amino acid sequence set forth in SEQ ID NO:37. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a PMK polypeptide, wherein the PMK polypeptide comprises the amino acid sequence set forth in SEQ ID NO:37, or a conservatively substituted amino acid sequence thereof. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a PMK polypeptide, wherein the PMK polypeptide comprises an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, or at least 75% amino acid sequence identity to SEQ ID NO:37. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a PMK polypeptide, wherein the PMK polypeptide comprises an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, or at least 84% amino acid sequence identity to SEQ ID NO:37. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a PMK polypeptide, wherein the PMK polypeptide comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, at least 99.6%, at least 99.7%, at least 99.8%, at least 99.9%, or 100% amino acid sequence identity to SEQ ID NO:37. 
     In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a MVD1 polypeptide, wherein the MVD1 polypeptide comprises the amino acid sequence set forth in SEQ ID NO:33. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a MVD1 polypeptide, wherein the MVD1 polypeptide comprises the amino acid sequence set forth in SEQ ID NO:33, or a conservatively substituted amino acid sequence thereof. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a MVD1 polypeptide, wherein the MVD1 polypeptide comprises an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, or at least 75% amino acid sequence identity to SEQ ID NO:33. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a MVD1 polypeptide, wherein the MVD1 polypeptide comprises an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, or at least 84% amino acid sequence identity to SEQ ID NO:33. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a MVD1 polypeptide, wherein the MVD1 polypeptide comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, at least 99.6%, at least 99.7%, at least 99.8%, at least 99.9%, or 100% amino acid sequence identity to SEQ ID NO:33. 
     In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding an IDI1 polypeptide, wherein the IDI1 polypeptide comprises the amino acid sequence set forth in SEQ ID NO:25. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding an IDI1 polypeptide, wherein the IDI1 polypeptide comprises the amino acid sequence set forth in SEQ ID NO:25, or a conservatively substituted amino acid sequence thereof. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding an IDI1 polypeptide, wherein the IDI1 polypeptide comprises an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, or at least 75% amino acid sequence identity to SEQ ID NO:25. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding an IDI1 polypeptide, wherein the IDI1 polypeptide comprises an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, or at least 84% amino acid sequence identity to SEQ ID NO:25. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding an IDI1 polypeptide, wherein the IDI1 polypeptide comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, at least 99.6%, at least 99.7%, at least 99.8%, at least 99.9%, or 100% amino acid sequence identity to SEQ ID NO:25. 
     Exemplary heterologous nucleic acids disclosed herein may include nucleic acids comprising a nucleotide sequence that encodes a MEV pathway polypeptide, such as, a full-length MEV pathway polypeptide, a fragment of a MEV pathway polypeptide, a variant of a MEV pathway polypeptide, a truncated MEV pathway polypeptide, or a fusion polypeptide that has at least one activity of a polypeptide that is part of the MEV pathway. In some embodiments, the nucleotide sequence is codon-optimized. 
     In some embodiments, one or more MEV pathway polypeptides are overexpressed in the modified host cell. Overexpression may be achieved by increasing the copy number of the one or more heterologous nucleic acids comprising nucleotide sequences encoding a MEV pathway polypeptide, e.g., through use of a high copy number expression vector (e.g., a plasmid that exists at 10-40 copies or about 100 copies per cell) and/or by operably linking the nucleotide sequences encoding a MEV pathway polypeptide to a strong promoter. In some embodiments, the modified host cell has one copy of a heterologous nucleic acid comprising a nucleotide sequence encoding a MEV pathway polypeptide. In some embodiments, the modified host cell has two copies of a heterologous nucleic acid comprising a nucleotide sequence encoding a MEV pathway polypeptide. In some embodiments, the modified host cell has three copies of a heterologous nucleic acid comprising a nucleotide sequence encoding a MEV pathway polypeptide. In some embodiments, the modified host cell has four copies of a heterologous nucleic acid comprising a nucleotide sequence encoding a MEV pathway polypeptide. In some embodiments, the modified host cell has five copies of a heterologous nucleic acid comprising a nucleotide sequence encoding a MEV pathway polypeptide. In some embodiments, the modified host cell has five or more copies of a heterologous nucleic acid comprising a nucleotide sequence encoding a MEV pathway polypeptide. Increased copy number of the heterologous nucleic acid and/or codon optimization of the nucleotide sequence may result in an increase in the desired enzyme catalytic activity in the modified host cell. 
     In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a HMGS polypeptide, wherein the nucleotide sequence is that set forth in SEQ ID NO:28. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a HMGS polypeptide, wherein the nucleotide sequence is that set forth in SEQ ID NO:28, or a codon degenerate nucleotide sequence thereof. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a HMGS polypeptide, wherein the nucleotide sequence has at least 80%, at least 81%, at least 82%, at least 83%, or at least 84% sequence identity to SEQ ID NO:28. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a HMGS polypeptide, wherein the nucleotide sequence has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, at least 99.6%, at least 99.7%, at least 99.8%, at least 99.9%, or 100% sequence identity to SEQ ID NO:28. 
     In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a tHMGR polypeptide, wherein the nucleotide sequence is that set forth in SEQ ID NO:26. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a tHMGR polypeptide, wherein the nucleotide sequence is that set forth in SEQ ID NO:26, or a codon degenerate nucleotide sequence thereof. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a tHMGR polypeptide, wherein the nucleotide sequence has at least 80%, at least 81%, at least 82%, at least 83%, or at least 84% sequence identity to SEQ ID NO:26. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a tHMGR polypeptide, wherein the nucleotide sequence has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, at least 99.6%, at least 99.7%, at least 99.8%, at least 99.9%, or 100% sequence identity to SEQ ID NO:26. 
     In some embodiments, a modified host cell of the present disclosure comprises two or more heterologous nucleic acids comprising a nucleotide sequence that encodes a tHMGR polypeptide. In some embodiments, a modified host cell of the present disclosure comprises two heterologous nucleic acids comprising a nucleotide sequence that encodes a tHMGR polypeptide. 
     In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a MK polypeptide, wherein the nucleotide sequence is that set forth in SEQ ID NO:38. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a MK polypeptide, wherein the nucleotide sequence is that set forth in SEQ ID NO:38, or a codon degenerate nucleotide sequence thereof. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a MK polypeptide, wherein the nucleotide sequence has at least 80%, at least 81%, at least 82%, at least 83%, or at least 84% sequence identity to SEQ ID NO:38. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a MK polypeptide, wherein the nucleotide sequence has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, at least 99.6%, at least 99.7%, at least 99.8%, at least 99.9%, or 100% sequence identity to SEQ ID NO:38. 
     In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a PMK polypeptide, wherein the nucleotide sequence is that set forth in SEQ ID NO:36. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a PMK polypeptide, wherein the nucleotide sequence is that set forth in SEQ ID NO:36, or a codon degenerate nucleotide sequence thereof. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a PMK polypeptide, wherein the nucleotide sequence has at least 80%, at least 81%, at least 82%, at least 83%, or at least 84% sequence identity to SEQ ID NO:36. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a PMK polypeptide, wherein the nucleotide sequence has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, at least 99.6%, at least 99.7%, at least 99.8%, at least 99.9%, or 100% sequence identity to SEQ ID NO:36. 
     In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a MVD1 polypeptide, wherein the nucleotide sequence is that set forth in SEQ ID NO:32. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a MVD1 polypeptide, wherein the nucleotide sequence is that set forth in SEQ ID NO:32, or a codon degenerate nucleotide sequence thereof. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a MVD1 polypeptide, wherein the nucleotide sequence has at least 80%, at least 81%, at least 82%, at least 83%, or at least 84% sequence identity to SEQ ID NO:32. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a MVD1 polypeptide, wherein the nucleotide sequence has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, at least 99.6%, at least 99.7%, at least 99.8%, at least 99.9%, or 100% sequence identity to SEQ ID NO:32. 
     In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding an IDI1 polypeptide, wherein the nucleotide sequence is that set forth in SEQ ID NO:24. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding an IDI1 polypeptide, wherein the nucleotide sequence is that set forth in SEQ ID NO:24, or a codon degenerate nucleotide sequence thereof. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding an IDI1 polypeptide, wherein the nucleotide sequence has at least 80%, at least 81%, at least 82%, at least 83%, or at least 84% sequence identity to SEQ ID NO:24. In some embodiments, a modified host cell of the disclosure comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding an IDI1 polypeptide, wherein the nucleotide sequence has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, at least 99.6%, at least 99.7%, at least 99.8%, at least 99.9%, or 100% sequence identity to SEQ ID NO:24. 
     Modified Host Cells to Produce Cannabinoids or Cannabinoid Derivatives and/or Express Engineered Variants of the Disclosure 
     The present disclosure provides modified host cells comprising one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure. The modified host cells of the disclosure comprising one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure may be for producing cannabinoids or cannabinoid derivatives and/or for expressing an engineered variant of the disclosure. In some embodiments, the nucleotide sequence encoding an engineered variant of the disclosure is codon-optimized. In some embodiments, the nucleotide sequences encoding the one or more of a KAR2 polypeptide, a PDI1 polypeptide, an ERO1 polypeptide, a FAD1 polypeptide, or an IRE1 polypeptide, and/or one or more polypeptides involved in cannabinoid or cannabinoid precursor (e.g., geranylpyrophosphate (GPP), prenyl phosphates, olivetolic acid, or hexanoyl-CoA) biosynthesis are codon-optimized. 
     The disclosure provides for modified host cells for producing cannabinoids or cannabinoid derivatives. For producing cannabinoids or cannabinoid derivatives, modified host cells disclosed herein may be modified to express or overexpress one or more nucleic acids disclosed herein comprising nucleotide sequences encoding an engineered variant of the disclosure, one or more of a KAR2 polypeptide, a PDI1 polypeptide, an ERO1 polypeptide, a FAD1 polypeptide, or an IRE1 polypeptide, and/or one or more polypeptides involved in cannabinoid or cannabinoid precursor (e.g., geranylpyrophosphate (GPP), prenyl phosphates, olivetolic acid, or hexanoyl-CoA) biosynthesis. A modified host cell for producing cannabinoids or cannabinoid derivatives may comprise a deletion or downregulation of one or more genes encoding one or more of a ROT2 polypeptide or a PEP4 polypeptide. In certain such embodiments, the modified host cell for producing cannabinoids or cannabinoid derivatives may comprise a deletion of one or more genes encoding one or more of a ROT2 polypeptide or a PEP4 polypeptide. In some embodiments, the modified host cell for producing cannabinoids or cannabinoid derivatives may comprise a downregulation of one or more genes encoding one or more of a ROT2 polypeptide or a PEP4 polypeptide. In some embodiments, the nucleotide sequence encoding an engineered variant of the disclosure is codon-optimized. In some embodiments, the nucleotide sequences encoding the one or more of a KAR2 polypeptide, a PDI1 polypeptide, an ERO1 polypeptide, a FAD1 polypeptide, or an IRE1 polypeptide, and/or one or more polypeptides involved in cannabinoid or cannabinoid precursor (e.g., geranylpyrophosphate (GPP), prenyl phosphates, olivetolic acid, or hexanoyl-CoA) biosynthesis are codon-optimized. 
     The disclosure also provides modified host cells modified to express or overexpress one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure. In some embodiments of the modified host cell for expressing an engineered variant of the disclosure, the modified host cell comprises one or more nucleic acids comprising a nucleotide sequence encoding the engineered variant of the disclosure and one or more heterologous nucleic acids disclosed herein comprising nucleotide sequences encoding one or more of a KAR2 polypeptide, a PDI1 polypeptide, an ERO1 polypeptide, a FAD1 polypeptide, or an IRE1 polypeptide. In some embodiments of the modified host cell for expressing an engineered variant of the disclosure, the modified host cell comprises one or more nucleic acids comprising a nucleotide sequence encoding the engineered variant of the disclosure and a deletion or downregulation of one or more genes encoding one or more of a ROT2 polypeptide or a PEP4 polypeptide. In certain such embodiments, the modified host cell may comprise a deletion of one or more genes encoding one or more of a ROT2 polypeptide or a PEP4 polypeptide. In some embodiments, the modified host cell may comprise a downregulation of one or more genes encoding one or more of a ROT2 polypeptide or a PEP4 polypeptide. In some embodiments of the modified host cell for expressing an engineered variant of the disclosure, the nucleotide sequence encoding the engineered variant of the disclosure is a codon-optimized nucleotide sequence. In some embodiments, the nucleotide sequences encoding the one or more of a KAR2 polypeptide, a PDI1 polypeptide, an ERO1 polypeptide, a FAD1 polypeptide, or an IRE1 polypeptide are codon-optimized. In some embodiments of the modified host cell for expressing an engineered variant of the disclosure, the modified host cell comprises one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more polypeptides involved in cannabinoid or cannabinoid precursor biosynthesis. In some embodiments, the nucleotide sequences encoding the one or more polypeptides involved in cannabinoid or cannabinoid precursor biosynthesis are codon-optimized. 
     To produce cannabinoids or cannabinoid derivatives, expression or overexpression of one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure in a modified host cell may be done in combination with expression or overexpression by the modified host cell of one or more heterologous nucleic acids disclosed herein (e.g., one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more of a KAR2 polypeptide, a PDI1 polypeptide, an ERO1 polypeptide, a FAD1 polypeptide, or an IRE1 polypeptide) and/or with deletion or downregulation of one or more genes encoding one or more of a ROT2 polypeptide or a PEP4 polypeptide. In some embodiments, the nucleotide sequences are codon-optimized nucleotide sequences. 
     To express or overexpress an engineered variant of the disclosure, expression or overexpression of one or more nucleic acids comprising a nucleotide sequence encoding the engineered variant in a modified host cell may be done in combination with expression or overexpression by the modified host cell of one or more heterologous nucleic acids disclosed herein (e.g., one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more of a KAR2 polypeptide, a PDI1 polypeptide, an ERO1 polypeptide, a FAD1 polypeptide, or an IRE1 polypeptide) and/or with deletion or downregulation of one or more genes encoding one or more of a ROT2 polypeptide or a PEP4 polypeptide. In some embodiments, the nucleotide sequences are codon-optimized nucleotide sequences. 
     In some embodiments, a modified host cell of the disclosure for producing cannabinoids or cannabinoid derivatives produces a cannabinoid or a cannabinoid derivative in an amount, as measured in mg/L or mM, greater than an amount of the cannabinoid or the cannabinoid derivative produced by a modified host cell comprising one or more nucleic acids comprising a nucleotide sequence encoding a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3, but lacking a nucleic acid comprising a nucleotide sequence encoding an engineered variant, grown under similar culture conditions for the same length of time. In some embodiments, the modified host cell for producing cannabinoids or cannabinoid derivatives produces a cannabinoid or a cannabinoid derivative in an amount, as measured in mg/L or mM, at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 100%, at least 150% at least 200%, at least 500%, or at least 1000% greater than an amount of the cannabinoid or the cannabinoid derivative produced by a modified host cell comprising one or more nucleic acids comprising a nucleotide sequence encoding a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3, but lacking a nucleic acid comprising a nucleotide sequence encoding an engineered variant, grown under similar culture conditions for the same length of time. 
     In some embodiments, a modified host cell of the disclosure comprising one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure produces a cannabinoid or a cannabinoid derivative in an amount, as measured in mg/L or mM, greater than an amount of the cannabinoid or the cannabinoid derivative produced by a modified host cell comprising one or more nucleic acids comprising a nucleotide sequence encoding a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3, but lacking a nucleic acid comprising a nucleotide sequence encoding an engineered variant, grown under similar culture conditions for the same length of time. In some embodiments, the modified host cell comprising one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure produces a cannabinoid or a cannabinoid derivative in an amount, as measured in mg/L or mM, at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 100%, at least 150% at least 200%, at least 500%, or at least 1000% greater than an amount of the cannabinoid or the cannabinoid derivative produced by a modified host cell comprising one or more nucleic acids comprising a nucleotide sequence encoding a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3, but lacking a nucleic acid comprising a nucleotide sequence encoding an engineered variant, grown under similar culture conditions for the same length of time. In some embodiments of the modified host cell of the disclosure comprising one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure, the modified host cell comprises one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more polypeptides involved in cannabinoid or cannabinoid precursor (e.g., geranylpyrophosphate (GPP), prenyl phosphates, olivetolic acid, or hexanoyl-CoA) biosynthesis. In some embodiments, a modified host cell comprising one or more nucleic acids comprising a nucleotide sequence encoding a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3, but lacking a nucleic acid comprising a nucleotide sequence encoding an engineered variant, comprises one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more polypeptides involved in cannabinoid or cannabinoid precursor (e.g., geranylpyrophosphate (GPP), prenyl phosphates, olivetolic acid, or hexanoyl-CoA) biosynthesis. 
     In some embodiments, a modified host cell of the disclosure comprising one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure and one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more of a KAR2 polypeptide, a PDI1 polypeptide, an ERO1 polypeptide, a FAD1 polypeptide, or an IRE1 polypeptide produces a cannabinoid or a cannabinoid derivative in an amount, as measured in mg/L or mM, greater than an amount of the cannabinoid or the cannabinoid derivative produced by a modified host cell comprising one or more nucleic acids comprising a nucleotide sequence encoding a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3 and one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more of a KAR2 polypeptide, a PDI1 polypeptide, an ERO1 polypeptide, a FAD1 polypeptide, or an IRE1 polypeptide, but lacking a nucleic acid comprising a nucleotide sequence encoding an engineered variant, grown under similar culture conditions for the same length of time. In some embodiments, a modified host cell of the disclosure comprising one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure and one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more of a KAR2 polypeptide, a PDI1 polypeptide, an ERO1 polypeptide, a FAD1 polypeptide, or an IRE1 polypeptide produces a cannabinoid or a cannabinoid derivative in an amount, as measured in mg/L or mM, at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 100%, at least 150% at least 200%, at least 500%, or at least 1000% greater than an amount of the cannabinoid or the cannabinoid derivative produced by a modified host cell comprising one or more nucleic acids comprising a nucleotide sequence encoding a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3 and one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more of a KAR2 polypeptide, a PDI1 polypeptide, an ERO1 polypeptide, a FAD1 polypeptide, or an IRE1 polypeptide, but lacking a nucleic acid comprising a nucleotide sequence encoding an engineered variant, grown under similar culture conditions for the same length of time. In some embodiments of the modified host cell of the disclosure comprising one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure and one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more of a KAR2 polypeptide, a PDI1 polypeptide, an ERO1 polypeptide, a FAD1 polypeptide, or an IRE1 polypeptide, the modified host cell comprises one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more polypeptides involved in cannabinoid or cannabinoid precursor (e.g., geranylpyrophosphate (GPP), prenyl phosphates, olivetolic acid, or hexanoyl-CoA) biosynthesis. In some embodiments, a modified host cell comprising one or more nucleic acids comprising a nucleotide sequence encoding a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3 and one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more of a KAR2 polypeptide, a PDI1 polypeptide, an ERO1 polypeptide, a FAD1 polypeptide, or an IRE1 polypeptide, but lacking a nucleic acid comprising a nucleotide sequence encoding an engineered variant, comprises one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more polypeptides involved in cannabinoid or cannabinoid precursor (e.g., geranylpyrophosphate (GPP), prenyl phosphates, olivetolic acid, or hexanoyl-CoA) biosynthesis. 
     In some embodiments, a modified host cell of the disclosure comprising one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure and a deletion or downregulation of one or more genes encoding one or more of a ROT2 polypeptide or a PEP4 polypeptide produces a cannabinoid or a cannabinoid derivative in an amount, as measured in mg/L or mM, greater than an amount of the cannabinoid or the cannabinoid derivative produced by a modified host cell comprising one or more nucleic acids comprising a nucleotide sequence encoding a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3 and a deletion or downregulation of one or more genes encoding one or more of a ROT2 polypeptide or a PEP4 polypeptide, but lacking a nucleic acid comprising a nucleotide sequence encoding an engineered variant, grown under similar culture conditions for the same length of time. In some embodiments, a modified host cell of the disclosure comprising one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure and a deletion or downregulation of one or more genes encoding one or more of a ROT2 polypeptide or a PEP4 polypeptide produces a cannabinoid or a cannabinoid derivative in an amount, as measured in mg/L or mM, at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 100%, at least 150% at least 200%, at least 500%, or at least 1000% greater than an amount of the cannabinoid or the cannabinoid derivative produced by a modified host cell comprising one or more nucleic acids comprising a nucleotide sequence encoding a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3 and a deletion or downregulation of one or more genes encoding one or more of a ROT2 polypeptide or a PEP4 polypeptide, but lacking a nucleic acid comprising a nucleotide sequence encoding an engineered variant, grown under similar culture conditions for the same length of time. In some embodiments of the modified host cell of the disclosure comprising one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure and a deletion or downregulation of one or more genes encoding one or more of a ROT2 polypeptide or a PEP4 polypeptide, the modified host cell comprises one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more polypeptides involved in cannabinoid or cannabinoid precursor (e.g., geranylpyrophosphate (GPP), prenyl phosphates, olivetolic acid, or hexanoyl-CoA) biosynthesis. In some embodiments, a modified host cell comprising one or more nucleic acids comprising a nucleotide sequence encoding a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3 and a deletion or downregulation of one or more genes encoding one or more of a ROT2 polypeptide or a PEP4 polypeptide, but lacking a nucleic acid comprising a nucleotide sequence encoding an engineered variant, comprises one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more polypeptides involved in cannabinoid or cannabinoid precursor (e.g., geranylpyrophosphate (GPP), prenyl phosphates, olivetolic acid, or hexanoyl-CoA) biosynthesis. 
     In some embodiments, a modified host cell of the disclosure comprising one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure, one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more of a KAR2 polypeptide, a PDI1 polypeptide, an ERO1 polypeptide, or an IRE1 polypeptide, and a deletion or downregulation of one or more genes encoding one or more of a ROT2 polypeptide or a PEP4 polypeptide produces a cannabinoid or a cannabinoid derivative in an amount, as measured in mg/L or mM, greater than an amount of the cannabinoid or the cannabinoid derivative produced by a modified host cell comprising one or more nucleic acids comprising a nucleotide sequence encoding a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3, one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more of a KAR2 polypeptide, a PDI1 polypeptide, an ERO1 polypeptide, or an IRE1 polypeptide, and a deletion or downregulation of one or more genes encoding one or more of a ROT2 polypeptide or a PEP4 polypeptide, but lacking a nucleic acid comprising a nucleotide sequence encoding an engineered variant, grown under similar culture conditions for the same length of time. In some embodiments, a modified host cell of the disclosure comprising one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure, one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more of a KAR2 polypeptide, a PDI1 polypeptide, an ERO1 polypeptide, or an IRE1 polypeptide, and a deletion or downregulation of one or more genes encoding one or more of a ROT2 polypeptide or a PEP4 polypeptide produces a cannabinoid or a cannabinoid derivative in an amount, as measured in mg/L or mM, at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 100%, at least 150% at least 200%, at least 500%, or at least 1000% greater than an amount of the cannabinoid or the cannabinoid derivative produced by a modified host cell comprising one or more nucleic acids comprising a nucleotide sequence encoding a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3, one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more of a KAR2 polypeptide, a PDI1 polypeptide, an ERO1 polypeptide, or an IRE1 polypeptide, and a deletion or downregulation of one or more genes encoding one or more of a ROT2 polypeptide or a PEP4 polypeptide, but lacking a nucleic acid comprising a nucleotide sequence encoding an engineered variant, grown under similar culture conditions for the same length of time. In some embodiments of the modified host cell of the disclosure comprising one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure, one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more of a KAR2 polypeptide, a PDI1 polypeptide, an ERO1 polypeptide, or an IRE1 polypeptide, and a deletion or downregulation of one or more genes encoding one or more of a ROT2 polypeptide or a PEP4 polypeptide, the modified host cell comprises one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more polypeptides involved in cannabinoid or cannabinoid precursor (e.g., geranylpyrophosphate (GPP), prenyl phosphates, olivetolic acid, or hexanoyl-CoA) biosynthesis. In some embodiments, a modified host cell comprising one or more nucleic acids comprising a nucleotide sequence encoding a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3, one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more of a KAR2 polypeptide, a PDI1 polypeptide, an ERO1 polypeptide, or an IRE1 polypeptide, and a deletion or downregulation of one or more genes encoding one or more of a ROT2 polypeptide or a PEP4 polypeptide, but lacking a nucleic acid comprising a nucleotide sequence encoding an engineered variant, comprises one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more polypeptides involved in cannabinoid or cannabinoid precursor (e.g., geranylpyrophosphate (GPP), prenyl phosphates, olivetolic acid, or hexanoyl-CoA) biosynthesis. 
     In some embodiments, the modified host cell of the disclosure for producing cannabinoids or cannabinoid derivatives has a growth rate and/or biomass yield similar to, or lower than, a growth rate and/or biomass yield of a modified host cell comprising one or more nucleic acids comprising a nucleotide sequence encoding a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3, but lacking a nucleic acid comprising a nucleotide sequence encoding an engineered variant, grown under similar culture conditions for the same length of time. In some embodiments, the modified host cell of the disclosure for producing cannabinoids or cannabinoid derivatives has a growth rate and/or biomass yield similar to, or lower than, a growth rate and/or biomass yield and an increased titer of CBDA compared to a modified host cell comprising one or more nucleic acids comprising a nucleotide sequence encoding a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3, but lacking a nucleic acid comprising a nucleotide sequence encoding an engineered variant, grown under similar culture conditions for the same length of time. 
     In some embodiments, the modified host cell of the disclosure for producing cannabinoids or cannabinoid derivatives has a faster growth rate and/or higher biomass yield compared to a growth rate and/or higher biomass yield of a modified host cell comprising one or more nucleic acids comprising a nucleotide sequence encoding a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3, but lacking a nucleic acid comprising a nucleotide sequence encoding an engineered variant, grown under similar culture conditions for the same length of time. In some embodiments, the modified host cell of the disclosure for producing cannabinoids or cannabinoid derivatives has a growth rate and/or higher biomass yield at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 100%, at least 150% at least 200%, at least 500%, or at least 1000% faster than a growth rate and/or higher biomass yield of a modified host cell comprising one or more nucleic acids comprising a nucleotide sequence encoding a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3, but lacking a nucleic acid comprising a nucleotide sequence encoding an engineered variant, grown under similar culture conditions for the same length of time. 
     In some embodiments, the modified host cell of the disclosure for expressing an engineered variant of the disclosure has a growth rate and/or biomass yield similar to, or lower than, a growth rate and/or biomass yield of a modified host cell comprising one or more nucleic acids comprising a nucleotide sequence encoding a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3, but lacking a nucleic acid comprising a nucleotide sequence encoding an engineered variant, grown under similar culture conditions for the same length of time. In some embodiments, the modified host cell of the disclosure for expressing an engineered variant of the disclosure has a growth rate and/or biomass yield similar to, or lower than, a growth rate and/or biomass yield and an increased titer of CBDA compared to a modified host cell comprising one or more nucleic acids comprising a nucleotide sequence encoding a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3, but lacking a nucleic acid comprising a nucleotide sequence encoding an engineered variant, grown under similar culture conditions for the same length of time. 
     In some embodiments, the modified host cell of the disclosure for expressing an engineered variant of the disclosure has a faster growth rate and/or higher biomass yield compared to a growth rate and/or higher biomass yield of a modified host cell comprising one or more nucleic acids comprising a nucleotide sequence encoding a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3, but lacking a nucleic acid comprising a nucleotide sequence encoding an engineered variant, grown under similar culture conditions for the same length of time. In some embodiments, the modified host cell of the disclosure for expressing an engineered variant of the disclosure has a growth rate and/or higher biomass yield at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 100%, at least 150% at least 200%, at least 500%, or at least 1000% faster than a growth rate and/or higher biomass yield of a modified host cell comprising one or more nucleic acids comprising a nucleotide sequence encoding a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3, but lacking a nucleic acid comprising a nucleotide sequence encoding an engineered variant, grown under similar culture conditions for the same length of time. 
     In some embodiments, the modified host cell of the disclosure comprising one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure has a growth rate and/or biomass yield similar to, or lower than, a growth rate and/or biomass yield of a modified host cell comprising one or more nucleic acids comprising a nucleotide sequence encoding a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3, but lacking a nucleic acid comprising a nucleotide sequence encoding an engineered variant, grown under similar culture conditions for the same length of time. In some embodiments, the modified host cell of the disclosure comprising one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure has a growth rate and/or biomass yield similar to, or lower than, a growth rate and/or biomass yield and an increased titer of CBDA compared to a modified host cell comprising one or more nucleic acids comprising a nucleotide sequence encoding a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3, but lacking a nucleic acid comprising a nucleotide sequence encoding an engineered variant, grown under similar culture conditions for the same length of time. 
     In some embodiments, a modified host cell of the disclosure comprising one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure has a faster growth rate and/or higher biomass yield compared to a growth rate and/or higher biomass yield of a modified host cell comprising one or more nucleic acids comprising a nucleotide sequence encoding a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3, but lacking a nucleic acid comprising a nucleotide sequence encoding an engineered variant, grown under similar culture conditions for the same length of time. In some embodiments, the modified host cell of the disclosure comprising one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure has a growth rate and/or higher biomass yield at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 100%, at least 150% at least 200%, at least 500%, or at least 1000% faster than a growth rate and/or higher biomass yield of a modified host cell comprising one or more nucleic acids comprising a nucleotide sequence encoding a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3, but lacking a nucleic acid comprising a nucleotide sequence encoding an engineered variant, grown under similar culture conditions for the same length of time. In some embodiments of the modified host cell of the disclosure comprising one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure, the modified host cell comprises one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more polypeptides involved in cannabinoid or cannabinoid precursor (e.g., geranylpyrophosphate (GPP), prenyl phosphates, olivetolic acid, or hexanoyl-CoA) biosynthesis. In some embodiments, a modified host cell comprising one or more nucleic acids comprising a nucleotide sequence encoding a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3, but lacking a nucleic acid comprising a nucleotide sequence encoding an engineered variant, comprises one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more polypeptides involved in cannabinoid or cannabinoid precursor (e.g., geranylpyrophosphate (GPP), prenyl phosphates, olivetolic acid, or hexanoyl-CoA) biosynthesis. 
     In some embodiments, a modified host cell of the disclosure comprising one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure and one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more of a KAR2 polypeptide, a PDI1 polypeptide, an ERO1 polypeptide, a FAD1 polypeptide, or an IRE1 polypeptide has a faster growth rate and/or higher biomass yield compared to a growth rate and/or higher biomass yield of a modified host cell comprising one or more nucleic acids comprising a nucleotide sequence encoding a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3 and one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more of a KAR2 polypeptide, a PDI1 polypeptide, an ERO1 polypeptide, a FAD1 polypeptide, or an IRE1 polypeptide, but lacking a nucleic acid comprising a nucleotide sequence encoding an engineered variant, grown under similar culture conditions for the same length of time. In some embodiments, a modified host cell of the disclosure comprising one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure and one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more of a KAR2 polypeptide, a PDI1 polypeptide, an ERO1 polypeptide, a FAD1 polypeptide, or an IRE1 polypeptide has a growth rate and/or higher biomass yield at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 100%, at least 150% at least 200%, at least 500%, or at least 1000% faster than a growth rate and/or higher biomass yield of a modified host cell comprising one or more nucleic acids comprising a nucleotide sequence encoding a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3 and one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more of a KAR2 polypeptide, a PDI1 polypeptide, an ERO1 polypeptide, a FAD1 polypeptide, or an IRE1 polypeptide, but lacking a nucleic acid comprising a nucleotide sequence encoding an engineered variant, grown under similar culture conditions for the same length of time. In some embodiments of the modified host cell of the disclosure comprising one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure and one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more of a KAR2 polypeptide, a PDI1 polypeptide, an ERO1 polypeptide, a FAD1 polypeptide, or an IRE1 polypeptide, the modified host cells comprises one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more polypeptides involved in cannabinoid or cannabinoid precursor (e.g., geranylpyrophosphate (GPP), prenyl phosphates, olivetolic acid, or hexanoyl-CoA) biosynthesis. In some embodiments, a modified host cell comprising one or more nucleic acids comprising a nucleotide sequence encoding a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3 and one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more of a KAR2 polypeptide, a PDI1 polypeptide, an ERO1 polypeptide, a FAD1 polypeptide, or an IRE1 polypeptide, but lacking a nucleic acid comprising a nucleotide sequence encoding an engineered variant, comprises one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more polypeptides involved in cannabinoid or cannabinoid precursor (e.g., geranylpyrophosphate (GPP), prenyl phosphates, olivetolic acid, or hexanoyl-CoA) biosynthesis. 
     In some embodiments, a modified host cell of the disclosure comprising one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure and a deletion or downregulation of one or more genes encoding one or more of a ROT2 polypeptide or a PEP4 polypeptide has a faster growth rate and/or higher biomass yield compared to a growth rate and/or higher biomass yield of a modified host cell comprising one or more nucleic acids comprising a nucleotide sequence encoding a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3 and a deletion or downregulation of one or more genes encoding one or more of a ROT2 polypeptide or a PEP4 polypeptide, but lacking a nucleic acid comprising a nucleotide sequence encoding an engineered variant, grown under similar culture conditions for the same length of time. In some embodiments, a modified host cell of the disclosure comprising one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure and a deletion or downregulation of one or more genes encoding one or more of a ROT2 polypeptide or a PEP4 polypeptide has a growth rate and/or higher biomass yield at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 100%, at least 150% at least 200%, at least 500%, or at least 1000% faster than a growth rate and/or higher biomass yield of a modified host cell comprising one or more nucleic acids comprising a nucleotide sequence encoding a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3 and a deletion or downregulation of one or more genes encoding one or more of a ROT2 polypeptide or a PEP4 polypeptide, but lacking a nucleic acid comprising a nucleotide sequence encoding an engineered variant, grown under similar culture conditions for the same length of time. In some embodiments of the modified host cell of the disclosure comprising one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure and a deletion or downregulation of one or more genes encoding one or more of a ROT2 polypeptide or a PEP4 polypeptide, the modified host cell comprises one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more polypeptides involved in cannabinoid or cannabinoid precursor (e.g., geranylpyrophosphate (GPP), prenyl phosphates, olivetolic acid, or hexanoyl-CoA) biosynthesis. In some embodiments, a modified host cell comprising one or more nucleic acids comprising a nucleotide sequence encoding a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3 and a deletion or downregulation of one or more genes encoding one or more of a ROT2 polypeptide or a PEP4 polypeptide, but lacking a nucleic acid comprising a nucleotide sequence encoding an engineered variant, comprises one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more polypeptides involved in cannabinoid or cannabinoid precursor (e.g., geranylpyrophosphate (GPP), prenyl phosphates, olivetolic acid, or hexanoyl-CoA) biosynthesis. 
     In some embodiments, a modified host cell of the disclosure comprising one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure, one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more of a KAR2 polypeptide, a PDI1 polypeptide, an ERO1 polypeptide, or an IRE1 polypeptide, and a deletion or downregulation of one or more genes encoding one or more of a ROT2 polypeptide or a PEP4 polypeptide has a faster growth rate and/or higher biomass yield compared to a growth rate and/or higher biomass yield of a modified host cell comprising one or more nucleic acids comprising a nucleotide sequence encoding a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3, one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more of a KAR2 polypeptide, a PDI1 polypeptide, an ERO1 polypeptide, or an IRE1 polypeptide, and a deletion or downregulation of one or more genes encoding one or more of a ROT2 polypeptide or a PEP4 polypeptide, but lacking a nucleic acid comprising a nucleotide sequence encoding an engineered variant, grown under similar culture conditions for the same length of time. In some embodiments, a modified host cell of the disclosure comprising one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure, one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more of a KAR2 polypeptide, a PDI1 polypeptide, an ERO1 polypeptide, or an IRE1 polypeptide, and a deletion or downregulation of one or more genes encoding one or more of a ROT2 polypeptide or a PEP4 polypeptide has a growth rate and/or higher biomass yield at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 100%, at least 150% at least 200%, at least 500%, or at least 1000% faster than a growth rate and/or higher biomass yield of a modified host cell comprising one or more nucleic acids comprising a nucleotide sequence encoding a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3, one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more of a KAR2 polypeptide, a PDI1 polypeptide, an ERO1 polypeptide, or an IRE1 polypeptide, and a deletion or downregulation of one or more genes encoding one or more of a ROT2 polypeptide or a PEP4 polypeptide, but lacking a nucleic acid comprising a nucleotide sequence encoding an engineered variant, grown under similar culture conditions for the same length of time. In some embodiments of the modified host cell of the disclosure comprising one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure, one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more of a KAR2 polypeptide, a PDI1 polypeptide, an ERO1 polypeptide, or an IRE1 polypeptide, and a deletion or downregulation of one or more genes encoding one or more of a ROT2 polypeptide or a PEP4 polypeptide, the modified host cell comprises one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more polypeptides involved in cannabinoid or cannabinoid precursor (e.g., geranylpyrophosphate (GPP), prenyl phosphates, olivetolic acid, or hexanoyl-CoA) biosynthesis. In some embodiments, a modified host cell comprising one or more nucleic acids comprising a nucleotide sequence encoding a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3, one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more of a KAR2 polypeptide, a PDI1 polypeptide, an ERO1 polypeptide, or an IRE1 polypeptide, and a deletion or downregulation of one or more genes encoding one or more of a ROT2 polypeptide or a PEP4 polypeptide, but lacking a nucleic acid comprising a nucleotide sequence encoding an engineered variant, comprises one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more polypeptides involved in cannabinoid or cannabinoid precursor (e.g., geranylpyrophosphate (GPP), prenyl phosphates, olivetolic acid, or hexanoyl-CoA) biosynthesis. 
     In some embodiments, a modified host cell of the disclosure for producing cannabinoids or cannabinoid derivatives produces CBDA from CBGA in an increased ratio of CBDA over THCA compared to that produced by a modified host cell comprising one or more nucleic acids comprising a nucleotide sequence encoding a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3, but lacking a nucleic acid comprising a nucleotide sequence encoding an engineered variant, grown under similar culture conditions for the same length of time. In some embodiments, the modified host cell for producing cannabinoids or cannabinoid derivatives produces CBDA from CBGA in a ratio of CBDA over THCA of about 11:1, about 11.5:1, about 12:1, about 12.5:1, about 13:1, about 13.5:1, about 14:1, about 14.5:1, about 15:1, about 15.5:1, about 16:1, about 16.5:1, about 17:1, about 17.5:1, about 18:1, about 18.5:1, about 19:1, about 19.5:1, about 20:1, about 25:1, about 30:1, about 35:1, about 40:1, about 45:1, about 50:1, about 60:1, about 70:1, about 80:1, about 90:1, about 100:1, about 150:1, about 200:1, about 500:1, or greater than about 500:1. 
     In some embodiments, a modified host cell of the disclosure for expressing an engineered variant of the disclosure produces CBDA from CBGA in an increased ratio of CBDA over THCA compared to that produced by a modified host cell comprising one or more nucleic acids comprising a nucleotide sequence encoding a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3, but lacking a nucleic acid comprising a nucleotide sequence encoding an engineered variant, grown under similar culture conditions for the same length of time. In some embodiments, the modified host cell for expressing an engineered variant of the disclosure produces CBDA from CBGA in a ratio of CBDA over THCA of about 11:1, about 11.5:1, about 12:1, about 12.5:1, about 13:1, about 13.5:1, about 14:1, about 14.5:1, about 15:1, about 15.5:1, about 16:1, about 16.5:1, about 17:1, about 17.5:1, about 18:1, about 18.5:1, about 19:1, about 19.5:1, about 20:1, about 25:1, about 30:1, about 35:1, about 40:1, about 45:1, about 50:1, about 60:1, about 70:1, about 80:1, about 90:1, about 100:1, about 150:1, about 200:1, about 500:1, or greater than about 500:1. 
     In some embodiments, a modified host cell of the disclosure comprising one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure produces CBDA from CBGA in an increased ratio of CBDA over THCA compared to that produced by a modified host cell comprising one or more nucleic acids comprising a nucleotide sequence encoding a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3, but lacking a nucleic acid comprising a nucleotide sequence encoding an engineered variant, grown under similar culture conditions for the same length of time. In some embodiments, a modified host cell of the disclosure comprising one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure produces CBDA from CBGA in a ratio of CBDA over THCA of about 11:1, about 11.5:1, about 12:1, about 12.5:1, about 13:1, about 13.5:1, about 14:1, about 14.5:1, about 15:1, about 15.5:1, about 16:1, about 16.5:1, about 17:1, about 17.5:1, about 18:1, about 18.5:1, about 19:1, about 19.5:1, about 20:1, about 25:1, about 30:1, about 35:1, about 40:1, about 45:1, about 50:1, about 60:1, about 70:1, about 80:1, about 90:1, about 100:1, about 150:1, about 200:1, about 500:1, or greater than about 500:1. In some embodiments of the modified host cell of the disclosure comprising one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure, the modified host cell comprises one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more polypeptides involved in cannabinoid or cannabinoid precursor (e.g., geranylpyrophosphate (GPP), prenyl phosphates, olivetolic acid, or hexanoyl-CoA) biosynthesis. In some embodiments, a modified host cell comprising one or more nucleic acids comprising a nucleotide sequence encoding a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3, but lacking a nucleic acid comprising a nucleotide sequence encoding an engineered variant, comprises one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more polypeptides involved in cannabinoid or cannabinoid precursor (e.g., geranylpyrophosphate (GPP), prenyl phosphates, olivetolic acid, or hexanoyl-CoA) biosynthesis. 
     In some embodiments, a modified host cell of the disclosure comprising one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure and one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more of a KAR2 polypeptide, a PDI1 polypeptide, an ERO1 polypeptide, a FAD1 polypeptide, or an IRE1 polypeptide produces CBDA from CBGA in an increased ratio of CBDA over THCA compared to that produced by a modified host cell comprising one or more nucleic acids comprising a nucleotide sequence encoding a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3 and one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more of a KAR2 polypeptide, a PDI1 polypeptide, an ERO1 polypeptide, a FAD1 polypeptide, or an IRE1 polypeptide, but lacking a nucleic acid comprising a nucleotide sequence encoding an engineered variant, grown under similar culture conditions for the same length of time. In some embodiments, a modified host cell of the disclosure comprising one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure and one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more of a KAR2 polypeptide, a PDI1 polypeptide, an ERO1 polypeptide, a FAD1 polypeptide, or an IRE1 polypeptide produces CBDA from CBGA in a ratio of CBDA over THCA of about 11:1, about 11.5:1, about 12:1, about 12.5:1, about 13:1, about 13.5:1, about 14:1, about 14.5:1, about 15:1, about 15.5:1, about 16:1, about 16.5:1, about 17:1, about 17.5:1, about 18:1, about 18.5:1, about 19:1, about 19.5:1, about 20:1, about 25:1, about 30:1, about 35:1, about 40:1, about 45:1, about 50:1, about 60:1, about 70:1, about 80:1, about 90:1, about 100:1, about 150:1, about 200:1, about 500:1, or greater than about 500:1. In some embodiments of the modified host cell of the disclosure comprising one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure and one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more of a KAR2 polypeptide, a PDI1 polypeptide, an ERO1 polypeptide, a FAD1 polypeptide, or an IRE1 polypeptide, the modified host cell comprises one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more polypeptides involved in cannabinoid or cannabinoid precursor (e.g., geranylpyrophosphate (GPP), prenyl phosphates, olivetolic acid, or hexanoyl-CoA) biosynthesis. In some embodiments, a modified host cell comprising one or more nucleic acids comprising a nucleotide sequence encoding a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3 and one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more of a KAR2 polypeptide, a PDI1 polypeptide, an ERO1 polypeptide, a FAD1 polypeptide, or an IRE1 polypeptide, but lacking a nucleic acid comprising a nucleotide sequence encoding an engineered variant, comprises one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more polypeptides involved in cannabinoid or cannabinoid precursor (e.g., geranylpyrophosphate (GPP), prenyl phosphates, olivetolic acid, or hexanoyl-CoA) biosynthesis. 
     In some embodiments, a modified host cell of the disclosure comprising one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure and a deletion or downregulation of one or more genes encoding one or more of a ROT2 polypeptide or a PEP4 polypeptide produces CBDA from CBGA in an increased ratio of CBDA over THCA compared to that produced by a modified host cell comprising one or more nucleic acids comprising a nucleotide sequence encoding a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3 and a deletion or downregulation of one or more genes encoding one or more of a ROT2 polypeptide or a PEP4 polypeptide, but lacking a nucleic acid comprising a nucleotide sequence encoding an engineered variant, grown under similar culture conditions for the same length of time. In some embodiments, a modified host cell of the disclosure comprising one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure and a deletion or downregulation of one or more genes encoding one or more of a ROT2 polypeptide or a PEP4 polypeptide produces CBDA from CBGA in a ratio of CBDA over THCA of about 11:1, about 11.5:1, about 12:1, about 12.5:1, about 13:1, about 13.5:1, about 14:1, about 14.5:1, about 15:1, about 15.5:1, about 16:1, about 16.5:1, about 17:1, about 17.5:1, about 18:1, about 18.5:1, about 19:1, about 19.5:1, about 20:1, about 25:1, about 30:1, about 35:1, about 40:1, about 45:1, about 50:1, about 60:1, about 70:1, about 80:1, about 90:1, about 100:1, about 150:1, about 200:1, about 500:1, or greater than about 500:1. In some embodiments of the modified host cell of the disclosure comprising one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure and a deletion or downregulation of one or more genes encoding one or more of a ROT2 polypeptide or a PEP4 polypeptide, the modified host cell comprises one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more polypeptides involved in cannabinoid or cannabinoid precursor (e.g., geranylpyrophosphate (GPP), prenyl phosphates, olivetolic acid, or hexanoyl-CoA) biosynthesis. In some embodiments, a modified host cell comprising one or more nucleic acids comprising a nucleotide sequence encoding a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3 and a deletion or downregulation of one or more genes encoding one or more of a ROT2 polypeptide or a PEP4 polypeptide, but lacking a nucleic acid comprising a nucleotide sequence encoding an engineered variant, comprises one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more polypeptides involved in cannabinoid or cannabinoid precursor (e.g., geranylpyrophosphate (GPP), prenyl phosphates, olivetolic acid, or hexanoyl-CoA) biosynthesis. 
     In some embodiments, a modified host cell of the disclosure comprising one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure, one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more of a KAR2 polypeptide, a PDI1 polypeptide, an ERO1 polypeptide, or an IRE1 polypeptide, and a deletion or downregulation of one or more genes encoding one or more of a ROT2 polypeptide or a PEP4 polypeptide produces CBDA from CBGA in an increased ratio of CBDA over THCA compared to that produced by a modified host cell comprising one or more nucleic acids comprising a nucleotide sequence encoding a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3, one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more of a KAR2 polypeptide, a PDI1 polypeptide, an ERO1 polypeptide, or an IRE1 polypeptide, and a deletion or downregulation of one or more genes encoding one or more of a ROT2 polypeptide or a PEP4 polypeptide, but lacking a nucleic acid comprising a nucleotide sequence encoding an engineered variant, grown under similar culture conditions for the same length of time. In some embodiments, a modified host cell of the disclosure comprising one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure, one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more of a KAR2 polypeptide, a PDI1 polypeptide, an ERO1 polypeptide, or an IRE1 polypeptide, and a deletion or downregulation of one or more genes encoding one or more of a ROT2 polypeptide or a PEP4 polypeptide produces CBDA from CBGA in a ratio of CBDA over THCA of about 11:1, about 11.5:1, about 12:1, about 12.5:1, about 13:1, about 13.5:1, about 14:1, about 14.5:1, about 15:1, about 15.5:1, about 16:1, about 16.5:1, about 17:1, about 17.5:1, about 18:1, about 18.5:1, about 19:1, about 19.5:1, about 20:1, about 25:1, about 30:1, about 35:1, about 40:1, about 45:1, about 50:1, about 60:1, about 70:1, about 80:1, about 90:1, about 100:1, about 150:1, about 200:1, about 500:1, or greater than about 500:1. In some embodiments of the modified host cell of the disclosure comprising one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure, one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more of a KAR2 polypeptide, a PDI1 polypeptide, an ERO1 polypeptide, or an IRE1 polypeptide, and a deletion or downregulation of one or more genes encoding one or more of a ROT2 polypeptide or a PEP4 polypeptide, the modified host cell comprises one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more polypeptides involved in cannabinoid or cannabinoid precursor (e.g., geranylpyrophosphate (GPP), prenyl phosphates, olivetolic acid, or hexanoyl-CoA) biosynthesis. In some embodiments, a modified host cell comprising one or more nucleic acids comprising a nucleotide sequence encoding a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3, one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more of a KAR2 polypeptide, a PDI1 polypeptide, an ERO1 polypeptide, or an IRE1 polypeptide, and a deletion or downregulation of one or more genes encoding one or more of a ROT2 polypeptide or a PEP4 polypeptide, but lacking a nucleic acid comprising a nucleotide sequence encoding an engineered variant, comprises one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more polypeptides involved in cannabinoid or cannabinoid precursor (e.g., geranylpyrophosphate (GPP), prenyl phosphates, olivetolic acid, or hexanoyl-CoA) biosynthesis. 
     In some embodiments, a modified host cell of the disclosure for producing cannabinoids or cannabinoid derivatives produces CBDA from CBGA in an increased ratio of CBDA over CBCA compared to that produced by a modified host cell comprising one or more nucleic acids comprising a nucleotide sequence encoding a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3, but lacking a nucleic acid comprising a nucleotide sequence encoding an engineered variant, grown under similar culture conditions for the same length of time. In some embodiments, the modified host cell for producing cannabinoids or cannabinoid derivatives produces CBDA from CBGA in a ratio of CBDA over CBCA of about 11:1, about 11.5:1, about 12:1, about 12.5:1, about 13:1, about 13.5:1, about 14:1, about 14.5:1, about 15:1, about 15.5:1, about 16:1, about 16.5:1, about 17:1, about 17.5:1, about 18:1, about 18.5:1, about 19:1, about 19.5:1, about 20:1, about 25:1, about 30:1, about 35:1, about 40:1, about 45:1, about 50:1, about 60:1, about 70:1, about 80:1, about 90:1, about 100:1, about 150:1, about 200:1, about 500:1, or greater than about 500:1. 
     In some embodiments, a modified host cell of the disclosure for expressing an engineered variant of the disclosure produces CBDA from CBGA in an increased ratio of CBDA over CBCA compared to that produced by a modified host cell comprising one or more nucleic acids comprising a nucleotide sequence encoding a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3, but lacking a nucleic acid comprising a nucleotide sequence encoding an engineered variant, grown under similar culture conditions for the same length of time. In some embodiments, the modified host cell for expressing an engineered variant of the disclosure produces CBDA from CBGA in a ratio of CBDA over CBCA of about 11:1, about 11.5:1, about 12:1, about 12.5:1, about 13:1, about 13.5:1, about 14:1, about 14.5:1, about 15:1, about 15.5:1, about 16:1, about 16.5:1, about 17:1, about 17.5:1, about 18:1, about 18.5:1, about 19:1, about 19.5:1, about 20:1, about 25:1, about 30:1, about 35:1, about 40:1, about 45:1, about 50:1, about 60:1, about 70:1, about 80:1, about 90:1, about 100:1, about 150:1, about 200:1, about 500:1, or greater than about 500:1. 
     In some embodiments, a modified host cell of the disclosure comprising one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure produces CBDA from CBGA in an increased ratio of CBDA over CBCA compared to that produced by a modified host cell comprising one or more nucleic acids comprising a nucleotide sequence encoding a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3, but lacking a nucleic acid comprising a nucleotide sequence encoding an engineered variant, grown under similar culture conditions for the same length of time. In some embodiments, a modified host cell of the disclosure comprising one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure produces CBDA from CBGA in a ratio of CBDA over CBCA of about 11:1, about 11.5:1, about 12:1, about 12.5:1, about 13:1, about 13.5:1, about 14:1, about 14.5:1, about 15:1, about 15.5:1, about 16:1, about 16.5:1, about 17:1, about 17.5:1, about 18:1, about 18.5:1, about 19:1, about 19.5:1, about 20:1, about 25:1, about 30:1, about 35:1, about 40:1, about 45:1, about 50:1, about 60:1, about 70:1, about 80:1, about 90:1, about 100:1, about 150:1, about 200:1, about 500:1, or greater than about 500:1. In some embodiments of the modified host cell of the disclosure comprising one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure, the modified host cell comprises one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more polypeptides involved in cannabinoid or cannabinoid precursor (e.g., geranylpyrophosphate (GPP), prenyl phosphates, olivetolic acid, or hexanoyl-CoA) biosynthesis. In some embodiments, a modified host cell comprising one or more nucleic acids comprising a nucleotide sequence encoding a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3, but lacking a nucleic acid comprising a nucleotide sequence encoding an engineered variant, comprises one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more polypeptides involved in cannabinoid or cannabinoid precursor (e.g., geranylpyrophosphate (GPP), prenyl phosphates, olivetolic acid, or hexanoyl-CoA) biosynthesis. 
     In some embodiments, a modified host cell of the disclosure comprising one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure and one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more of a KAR2 polypeptide, a PDI1 polypeptide, an ERO1 polypeptide, a FAD1 polypeptide, or an IRE1 polypeptide produces CBDA from CBGA in an increased ratio of CBDA over CBCA compared to that produced by a modified host cell comprising one or more nucleic acids comprising a nucleotide sequence encoding a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3 and one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more of a KAR2 polypeptide, a PDI1 polypeptide, an ERO1 polypeptide, a FAD1 polypeptide, or an IRE1 polypeptide, but lacking a nucleic acid comprising a nucleotide sequence encoding an engineered variant, grown under similar culture conditions for the same length of time. In some embodiments, a modified host cell of the disclosure comprising one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure and one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more of a KAR2 polypeptide, a PDI1 polypeptide, an ERO1 polypeptide, a FAD1 polypeptide, or an IRE1 polypeptide produces CBDA from CBGA in a ratio of CBDA over CBCA of about 11:1, about 11.5:1, about 12:1, about 12.5:1, about 13:1, about 13.5:1, about 14:1, about 14.5:1, about 15:1, about 15.5:1, about 16:1, about 16.5:1, about 17:1, about 17.5:1, about 18:1, about 18.5:1, about 19:1, about 19.5:1, about 20:1, about 25:1, about 30:1, about 35:1, about 40:1, about 45:1, about 50:1, about 60:1, about 70:1, about 80:1, about 90:1, about 100:1, about 150:1, about 200:1, about 500:1, or greater than about 500:1. In some embodiments of the modified host cell of the disclosure comprising one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure and one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more of a KAR2 polypeptide, a PDI1 polypeptide, an ERO1 polypeptide, a FAD1 polypeptide, or an IRE1 polypeptide, the modified host cell comprises one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more polypeptides involved in cannabinoid or cannabinoid precursor (e.g., geranylpyrophosphate (GPP), prenyl phosphates, olivetolic acid, or hexanoyl-CoA) biosynthesis. In some embodiments, a modified host cell comprising one or more nucleic acids comprising a nucleotide sequence encoding a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3 and one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more of a KAR2 polypeptide, a PDI1 polypeptide, an ERO1 polypeptide, a FAD1 polypeptide, or an IRE1 polypeptide, but lacking a nucleic acid comprising a nucleotide sequence encoding an engineered variant, comprises one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more polypeptides involved in cannabinoid or cannabinoid precursor (e.g., geranylpyrophosphate (GPP), prenyl phosphates, olivetolic acid, or hexanoyl-CoA) biosynthesis. 
     In some embodiments, a modified host cell of the disclosure comprising one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure and a deletion or downregulation of one or more genes encoding one or more of a ROT2 polypeptide or a PEP4 polypeptide produces CBDA from CBGA in an increased ratio of CBDA over CBCA compared to that produced by a modified host cell comprising one or more nucleic acids comprising a nucleotide sequence encoding a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3 and a deletion or downregulation of one or more genes encoding one or more of a ROT2 polypeptide or a PEP4 polypeptide, but lacking a nucleic acid comprising a nucleotide sequence encoding an engineered variant, grown under similar culture conditions for the same length of time. In some embodiments, a modified host cell of the disclosure comprising one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure and a deletion or downregulation of one or more genes encoding one or more of a ROT2 polypeptide or a PEP4 polypeptide produces CBDA from CBGA in a ratio of CBDA over CBCA of about 11:1, about 11.5:1, about 12:1, about 12.5:1, about 13:1, about 13.5:1, about 14:1, about 14.5:1, about 15:1, about 15.5:1, about 16:1, about 16.5:1, about 17:1, about 17.5:1, about 18:1, about 18.5:1, about 19:1, about 19.5:1, about 20:1, about 25:1, about 30:1, about 35:1, about 40:1, about 45:1, about 50:1, about 60:1, about 70:1, about 80:1, about 90:1, about 100:1, about 150:1, about 200:1, about 500:1, or greater than about 500:1. In some embodiments of the modified host cell of the disclosure comprising one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure and a deletion or downregulation of one or more genes encoding one or more of a ROT2 polypeptide or a PEP4 polypeptide, the modified host cell comprises one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more polypeptides involved in cannabinoid or cannabinoid precursor (e.g., geranylpyrophosphate (GPP), prenyl phosphates, olivetolic acid, or hexanoyl-CoA) biosynthesis. In some embodiments, a modified host cell comprising one or more nucleic acids comprising a nucleotide sequence encoding a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3 and a deletion or downregulation of one or more genes encoding one or more of a ROT2 polypeptide or a PEP4 polypeptide, but lacking a nucleic acid comprising a nucleotide sequence encoding an engineered variant, comprises one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more polypeptides involved in cannabinoid or cannabinoid precursor (e.g., geranylpyrophosphate (GPP), prenyl phosphates, olivetolic acid, or hexanoyl-CoA) biosynthesis. 
     In some embodiments, a modified host cell of the disclosure comprising one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure, one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more of a KAR2 polypeptide, a PDI1 polypeptide, an ERO1 polypeptide, or an IRE1 polypeptide, and a deletion or downregulation of one or more genes encoding one or more of a ROT2 polypeptide or a PEP4 polypeptide produces CBDA from CBGA in an increased ratio of CBDA over CBCA compared to that produced by a modified host cell comprising one or more nucleic acids comprising a nucleotide sequence encoding a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3, one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more of a KAR2 polypeptide, a PDI1 polypeptide, an ERO1 polypeptide, or an IRE1 polypeptide, and a deletion or downregulation of one or more genes encoding one or more of a ROT2 polypeptide or a PEP4 polypeptide, but lacking a nucleic acid comprising a nucleotide sequence encoding an engineered variant, grown under similar culture conditions for the same length of time. In some embodiments, a modified host cell of the disclosure comprising one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure, one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more of a KAR2 polypeptide, a PDI1 polypeptide, an ERO1 polypeptide, or an IRE1 polypeptide, and a deletion or downregulation of one or more genes encoding one or more of a ROT2 polypeptide or a PEP4 polypeptide produces CBDA from CBGA in a ratio of CBDA over CBCA of about 11:1, about 11.5:1, about 12:1, about 12.5:1, about 13:1, about 13.5:1, about 14:1, about 14.5:1, about 15:1, about 15.5:1, about 16:1, about 16.5:1, about 17:1, about 17.5:1, about 18:1, about 18.5:1, about 19:1, about 19.5:1, about 20:1, about 25:1, about 30:1, about 35:1, about 40:1, about 45:1, about 50:1, about 60:1, about 70:1, about 80:1, about 90:1, about 100:1, about 150:1, about 200:1, about 500:1, or greater than about 500:1. In some embodiments of the modified host cell of the disclosure comprising one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure, one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more of a KAR2 polypeptide, a PDI1 polypeptide, an ERO1 polypeptide, or an IRE1 polypeptide, and a deletion or downregulation of one or more genes encoding one or more of a ROT2 polypeptide or a PEP4 polypeptide, the modified host cell comprises one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more polypeptides involved in cannabinoid or cannabinoid precursor (e.g., geranylpyrophosphate (GPP), prenyl phosphates, olivetolic acid, or hexanoyl-CoA) biosynthesis. In some embodiments, a modified host cell comprising one or more nucleic acids comprising a nucleotide sequence encoding a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3, one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more of a KAR2 polypeptide, a PDI1 polypeptide, an ERO1 polypeptide, or an IRE1 polypeptide, and a deletion or downregulation of one or more genes encoding one or more of a ROT2 polypeptide or a PEP4 polypeptide, but lacking a nucleic acid comprising a nucleotide sequence encoding an engineered variant, comprises one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more polypeptides involved in cannabinoid or cannabinoid precursor (e.g., geranylpyrophosphate (GPP), prenyl phosphates, olivetolic acid, or hexanoyl-CoA) biosynthesis. 
     In some embodiments, the growth and/or viability of modified host cells of the disclosure for producing cannabinoids or cannabinoid derivatives is not significantly decreased compared to the growth and/or viability of an unmodified host cell. In some embodiments, a culture of modified host cells of the disclosure for producing cannabinoids or cannabinoid derivatives has a cell density that is at least 25% or greater, at least 30% or greater, at least 35% or greater, at least 40% or greater, at least 45% or greater, at least 50% or greater, at least 55% or greater, at least 60% or greater, at least 65% or greater, at least 70% or greater, at least 75% or greater, at least 80% or greater, at least 85% or greater at least 90% or greater, at least 95% or greater, at least 100% or greater, at least 110% or greater, at least 120% or greater, at least 130% or greater, at least 140% or greater, or at least 150% or greater than the cell density of a culture of unmodified control host cells grown for the same period, in the same culture medium, and under the same culture conditions. 
     In some embodiments, the growth and/or viability of modified host cells of the disclosure for expressing an engineered variant of the disclosure is not significantly decreased compared to the growth and/or viability of an unmodified host cell. In some embodiments, a culture of modified host cells of the disclosure for expressing an engineered variant of the disclosure has a cell density that is at least 25% or greater, at least 30% or greater, at least 35% or greater, at least 40% or greater, at least 45% or greater, at least 50% or greater, at least 55% or greater, at least 60% or greater, at least 65% or greater, at least 70% or greater, at least 75% or greater, at least 80% or greater, at least 85% or greater at least 90% or greater, at least 95% or greater, at least 100% or greater, at least 110% or greater, at least 120% or greater, at least 130% or greater, at least 140% or greater, or at least 150% or greater than the cell density of a culture of unmodified control host cells grown for the same period, in the same culture medium, and under the same culture conditions. 
     In some embodiments, the growth and/or viability of modified host cells of the disclosure comprising one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure is not significantly decreased compared to the growth and/or viability of an unmodified host cell. In some embodiments, a culture of modified host cells of the disclosure comprising one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure has a cell density that is at least 25% or greater, at least 30% or greater, at least 35% or greater, at least 40% or greater, at least 45% or greater, at least 50% or greater, at least 55% or greater, at least 60% or greater, at least 65% or greater, at least 70% or greater, at least 75% or greater, at least 80% or greater, at least 85% or greater at least 90% or greater, at least 95% or greater, at least 100% or greater, at least 110% or greater, at least 120% or greater, at least 130% or greater, at least 140% or greater, or at least 150% or greater than the cell density of a culture of unmodified control host cells grown for the same period, in the same culture medium, and under the same culture conditions. In some embodiments of the modified host cell of the disclosure comprising one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure, the modified host cell comprises one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more polypeptides involved in cannabinoid or cannabinoid precursor (e.g., geranylpyrophosphate (GPP), prenyl phosphates, olivetolic acid, or hexanoyl-CoA) biosynthesis. 
     In some embodiments, the growth and/or viability of modified host cells of the disclosure comprising one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure and one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more of a KAR2 polypeptide, a PDI1 polypeptide, an ERO1 polypeptide, a FAD1 polypeptide, or an IRE1 polypeptide is not significantly decreased compared to the growth and/or viability of an unmodified host cell. In some embodiments, a culture of modified host cells of the disclosure comprising one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure and one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more of a KAR2 polypeptide, a PDI1 polypeptide, an ERO1 polypeptide, a FAD1 polypeptide, or an IRE1 polypeptide has a cell density that is at least 25% or greater, at least 30% or greater, at least 35% or greater, at least 40% or greater, at least 45% or greater, at least 50% or greater, at least 55% or greater, at least 60% or greater, at least 65% or greater, at least 70% or greater, at least 75% or greater, at least 80% or greater, at least 85% or greater at least 90% or greater, at least 95% or greater, at least 100% or greater, at least 110% or greater, at least 120% or greater, at least 130% or greater, at least 140% or greater, or at least 150% or greater than the cell density of a culture of unmodified control host cells grown for the same period, in the same culture medium, and under the same culture conditions. In some embodiments of the modified host cell of the disclosure comprising one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure and one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more of a KAR2 polypeptide, a PDI1 polypeptide, an ERO1 polypeptide, a FAD1 polypeptide, or an IRE1 polypeptide, the modified host cell comprises one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more polypeptides involved in cannabinoid or cannabinoid precursor (e.g., geranylpyrophosphate (GPP), prenyl phosphates, olivetolic acid, or hexanoyl-CoA) biosynthesis. 
     In some embodiments, the growth and/or viability of modified host cells of the disclosure comprising one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure and a deletion or downregulation of one or more genes encoding one or more of a ROT2 polypeptide or a PEP4 polypeptide is not significantly decreased compared to the growth and/or viability of an unmodified host cell. In some embodiments, a culture of modified host cells of the disclosure comprising one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure and a deletion or downregulation of one or more genes encoding one or more of a ROT2 polypeptide or a PEP4 polypeptide has a cell density that is at least 25% or greater, at least 30% or greater, at least 35% or greater, at least 40% or greater, at least 45% or greater, at least 50% or greater, at least 55% or greater, at least 60% or greater, at least 65% or greater, at least 70% or greater, at least 75% or greater, at least 80% or greater, at least 85% or greater at least 90% or greater, at least 95% or greater, at least 100% or greater, at least 110% or greater, at least 120% or greater, at least 130% or greater, at least 140% or greater, or at least 150% or greater than the cell density of a culture of unmodified control host cells grown for the same period, in the same culture medium, and under the same culture conditions. In some embodiments of the modified host cell of the disclosure comprising one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure and a deletion or downregulation of one or more genes encoding one or more of a ROT2 polypeptide or a PEP4 polypeptide, the modified host cell comprises one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more polypeptides involved in cannabinoid or cannabinoid precursor (e.g., geranylpyrophosphate (GPP), prenyl phosphates, olivetolic acid, or hexanoyl-CoA) biosynthesis. 
     In some embodiments, the growth and/or viability of modified host cells of the disclosure comprising one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure, one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more of a KAR2 polypeptide, a PDI1 polypeptide, an ERO1 polypeptide, or an IRE1 polypeptide, and a deletion or downregulation of one or more genes encoding one or more of a ROT2 polypeptide or a PEP4 polypeptide is not significantly decreased compared to the growth and/or viability of an unmodified host cell. In some embodiments, a culture of modified host cells of the disclosure comprising one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure, one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more of a KAR2 polypeptide, a PDI1 polypeptide, an ERO1 polypeptide, or an IRE1 polypeptide, and a deletion or downregulation of one or more genes encoding one or more of a ROT2 polypeptide or a PEP4 polypeptide has a cell density that is at least 25% or greater, at least 30% or greater, at least 35% or greater, at least 40% or greater, at least 45% or greater, at least 50% or greater, at least 55% or greater, at least 60% or greater, at least 65% or greater, at least 70% or greater, at least 75% or greater, at least 80% or greater, at least 85% or greater at least 90% or greater, at least 95% or greater, at least 100% or greater, at least 110% or greater, at least 120% or greater, at least 130% or greater, at least 140% or greater, or at least 150% or greater than the cell density of a culture of unmodified control host cells grown for the same period, in the same culture medium, and under the same culture conditions. In some embodiments of the modified host cell of the disclosure comprising one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure, one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more of a KAR2 polypeptide, a PDI1 polypeptide, an ERO1 polypeptide, or an IRE1 polypeptide, and a deletion or downregulation of one or more genes encoding one or more of a ROT2 polypeptide or a PEP4 polypeptide, the modified host cell comprises one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more polypeptides involved in cannabinoid or cannabinoid precursor (e.g., geranylpyrophosphate (GPP), prenyl phosphates, olivetolic acid, or hexanoyl-CoA) biosynthesis. 
     Suitable Host Cells 
     Parent host cells that are suitable for use in generating a modified host cell of the present disclosure may include eukaryotic cells. In some embodiments, the eukaryotic cells are yeast cells. 
     Host cells (including parent host cells and modified host cells) are in some embodiments unicellular organisms, or are grown in culture as single cells. In some embodiments, the host cell is a eukaryotic cell. Suitable eukaryotic host cells may include, but are not limited to, yeast cells and fungal cells. Suitable eukaryotic host cells may include, but are not limited to,  Pichia pastoris  (now known as  Komagataella phaffii ),  Pichia finlandica, Pichia trehalophila, Pichia koclamae, Pichia membranaefaciens, Pichia opuntiae, Pichia thermotolerans, Pichia salictaria, Pichia guercuum, Pichia pijperi, Pichia stiptis, Pichia methanolica, Pichia  sp.,  Saccharomyces cerevisiae, Saccharomyces  sp.,  Hansenula polymorpha  (now known as  Pichia angusta ),  Yarrowia lipolytica, Kluyveromyces  sp.,  Kluyveromyces lactis, Kluyveromyces marxianus, Schizosaccharomyces pombe, Scheffersomyces stipites, Dekkera bruxellensis, Blastobotrys adeninivorans  (formerly  Arxula adeninivorans ),  Candida albicans, Aspergillus nidulans, Aspergillus niger, Aspergillus oryzae, Trichoderma reesei, Chrysosporium lucknowense, Fusarium  sp.,  Fusarium gramineum, Fusarium venenatum, Neurospora crassa , and the like. In some embodiments, the modified host cell disclosed herein is cultured in vitro. 
     In some embodiments, the host cell of the disclosure is a yeast cell. In some embodiments, the host cell is a protease-deficient strain of  Saccharomyces cerevisiae . Protease-deficient yeast strains may be effective in reducing the degradation of expressed heterologous proteins. Examples of proteases deleted in such strains may include one or more of the following: PEP4, PRB1, and KEX1. 
     In some embodiments, the host cell is  Saccharomyces cerevisiae . In some embodiments, the host cell for use in generating a modified host cell of the present disclosure may be selected because of ease of culture; rapid growth; availability of tools for modification, such as promoters and vectors; and the host cell&#39;s safety profile. In some embodiments, the host cell for use in generating a modified host cell of the present disclosure may be selected because of its ability or inability to introduce certain posttranslational modifications onto expressed polypeptides, such as engineered variants of the disclosure. For instance, modified  Komagataella phaffii  host cells may hyperglycosylate engineered variants of the disclosure and hyperglycosylation may alter the activity of the resultant expressed polypeptide. 
     Genetic Modification of Host Cells and Exemplary Modified Host Cells of the Disclosure 
     The present disclosure provides for modified host cells and methods of making modified host cells comprising one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure. In some embodiments, the method of making a modified host cell of the disclosure comprises introducing into a host cell one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure. In some embodiments, the modified host cell of the disclosure comprises one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure. In some embodiments, the nucleic acids comprise codon-optimized nucleotide sequences. In some embodiments, the nucleotide sequence encoding an engineered variant of the disclosure is codon-optimized. In some embodiments, the nucleotide sequences encoding the one or more of a KAR2 polypeptide, a PDI1 polypeptide, an ERO1 polypeptide, a FAD1 polypeptide, or an IRE1 polypeptide, and/or one or more polypeptides involved in cannabinoid or cannabinoid precursor (e.g., geranylpyrophosphate (GPP), prenyl phosphates, olivetolic acid, or hexanoyl-CoA) biosynthesis are codon-optimized. 
     The present disclosure provides for modified host cells and methods of making modified host cells for producing a cannabinoid or a cannabinoid derivative, the method comprising introducing into a host cell one or more nucleic acids (e.g., heterologous) disclosed herein. In some embodiments, the nucleic acids comprise codon-optimized nucleotide sequences. 
     The disclosure provides a method of making a modified host cell for producing a cannabinoid or a cannabinoid derivative, the method comprising a) introducing into a host cell one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure. In certain such embodiments, the method comprises b) introducing into the host cell one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more of a KAR2 polypeptide, a PDI1 polypeptide, an ERO1 polypeptide, or an IRE1 polypeptide. In some embodiments, the method comprises b) introducing into the host cell one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more of a KAR2 polypeptide, a PDI1 polypeptide, an ERO1 polypeptide, or a FAD1 polypeptide. In some embodiments, the nucleotide sequences are codon-optimized. 
     In some embodiments, the modified host cell for producing a cannabinoid or a cannabinoid derivative comprises one or more heterologous nucleic acids comprising nucleotide sequences encoding an engineered variant of the disclosure and one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more of a KAR2 polypeptide, a PDI1 polypeptide, an ERO1 polypeptide, or an IRE1 polypeptide. In certain such embodiments, the modified host cell comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding the KAR2 polypeptide, one or more heterologous nucleic acids comprising a nucleotide sequence encoding the PDI1 polypeptide, one or more heterologous nucleic acids comprising a nucleotide sequence encoding the ERO1 polypeptide, and one or more heterologous nucleic acids comprising a nucleotide sequence encoding the IRE1 polypeptide. In some embodiments, the modified host cell for producing a cannabinoid or a cannabinoid derivative comprises two or more heterologous nucleic acids comprising a nucleotide sequence encoding a KAR2 polypeptide. 
     In some embodiments, the modified host cell for producing a cannabinoid or a cannabinoid derivative comprises one or more heterologous nucleic acids comprising nucleotide sequences encoding an engineered variant of the disclosure and one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more of a KAR2 polypeptide, a PDI1 polypeptide, an ERO1 polypeptide, or a FAD1 polypeptide. In certain such embodiments, the modified host cell comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding the KAR2 polypeptide, one or more heterologous nucleic acids comprising a nucleotide sequence encoding the PDI1 polypeptide, one or more heterologous nucleic acids comprising a nucleotide sequence encoding the ERO1 polypeptide, and one or more heterologous nucleic acids comprising a nucleotide sequence encoding the FAD1 polypeptide. In some embodiments, the modified host cell for producing a cannabinoid or a cannabinoid derivative comprises two or more heterologous nucleic acids comprising a nucleotide sequence encoding a KAR2 polypeptide. 
     In some embodiments, the modified host cell for producing a cannabinoid or a cannabinoid derivative comprises one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure and a deletion or downregulation of one or more genes encoding one or more of a ROT2 polypeptide or a PEP4 polypeptide. In certain such embodiments, the modified host cell comprises a deletion or downregulation of one or more genes encoding the ROT2 polypeptide and the PEP4 polypeptide. The disclosure provides a method of making a modified host cell for producing a cannabinoid or a cannabinoid derivative, the method comprising introducing into a host cell one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure and a deletion or downregulation of one or more genes encoding one or more of a ROT2 polypeptide or a PEP4 polypeptide. 
     In some embodiments, the modified host cell for producing a cannabinoid or a cannabinoid derivative comprises one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure, one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more of a KAR2 polypeptide, a PDI1 polypeptide, an ERO1 polypeptide, or an IRE1 polypeptide, and a deletion or downregulation of one or more genes encoding one or more of a ROT2 polypeptide or a PEP4 polypeptide. In certain such embodiments, the modified host cell comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding the KAR2 polypeptide, one or more heterologous nucleic acids comprising a nucleotide sequence encoding the PDI1 polypeptide, one or more heterologous nucleic acids comprising a nucleotide sequence encoding the ERO1 polypeptide, and one or more heterologous nucleic acids comprising a nucleotide sequence encoding the IRE1 polypeptide and a deletion or downregulation of one or more genes encoding the ROT2 polypeptide and the PEP4 polypeptide. In some embodiments, the modified host cell for producing a cannabinoid or a cannabinoid derivative comprises two or more heterologous nucleic acids comprising a nucleotide sequence encoding a KAR2 polypeptide. 
     The disclosure provides a method of making a modified host cell for producing a cannabinoid or a cannabinoid derivative, the method comprising introducing into a host cell: a) one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure, b) one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more of a KAR2 polypeptide, a PDI1 polypeptide, an ERO1 polypeptide, or an IRE1 polypeptide, and c) a deletion or downregulation of one or more genes encoding one or more of a ROT2 polypeptide or a PEP4 polypeptide. 
     The disclosure provides a method of making a modified host cell for producing a cannabinoid or a cannabinoid derivative, the method comprising introducing into a host cell: a) one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure and b) one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more of a KAR2 polypeptide, a PDI1 polypeptide, an ERO1 polypeptide, or a FAD1 polypeptide. 
     In some embodiments, the modified host cell for producing a cannabinoid or a cannabinoid derivative may comprise one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure and express or overexpress combinations of heterologous nucleic acids comprising nucleotide sequences encoding one or more polypeptides involved in cannabinoid or cannabinoid precursor (e.g., geranylpyrophosphate (GPP), prenyl phosphates, olivetolic acid, or hexanoyl-CoA) biosynthesis. In some embodiments, the methods of making a modified host cell for producing a cannabinoid or a cannabinoid derivative comprise introducing into a host cell one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more polypeptides involved in cannabinoid or cannabinoid precursor biosynthesis. In some embodiments disclosed herein, the nucleotide sequences encoding the one or more polypeptides involved in cannabinoid or cannabinoid precursor biosynthesis are codon-optimized. 
     In some embodiments, the modified host cell for producing a cannabinoid or a cannabinoid derivative comprises one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure, one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more of a KAR2 polypeptide, a PDI1 polypeptide, an ERO1 polypeptide, or an IRE1 polypeptide, a deletion or downregulation of one or more genes encoding one or more of a ROT2 polypeptide or a PEP4 polypeptide, and one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more polypeptides involved in cannabinoid or cannabinoid precursor (e.g., geranylpyrophosphate (GPP), prenyl phosphates, olivetolic acid, or hexanoyl-CoA) biosynthesis. In certain such embodiments, the modified host cell comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding the KAR2 polypeptide, one or more heterologous nucleic acids comprising a nucleotide sequence encoding the PDI1 polypeptide, one or more heterologous nucleic acids comprising a nucleotide sequence encoding the ERO1 polypeptide, one or more heterologous nucleic acids comprising a nucleotide sequence encoding the IRE1 polypeptide and a deletion or downregulation of the genes encoding the ROT2 polypeptide and the PEP4 polypeptide. In some embodiments, the modified host cell for producing a cannabinoid or a cannabinoid derivative comprises two or more heterologous nucleic acids comprising a nucleotide sequence encoding a KAR2 polypeptide. 
     In some embodiments, the modified host cell for producing a cannabinoid or a cannabinoid derivative comprises one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure, one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more of a KAR2 polypeptide, a PDI1 polypeptide, an ERO1 polypeptide, or a FAD1 polypeptide, and one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more polypeptides involved in cannabinoid or cannabinoid precursor (e.g., geranylpyrophosphate (GPP), prenyl phosphates, olivetolic acid, or hexanoyl-CoA) biosynthesis. In certain such embodiments, the modified host cell comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding the KAR2 polypeptide, one or more heterologous nucleic acids comprising a nucleotide sequence encoding the PDI1 polypeptide, one or more heterologous nucleic acids comprising a nucleotide sequence encoding the ERO1 polypeptide, and one or more heterologous nucleic acids comprising a nucleotide sequence encoding the FAD1 polypeptide. In some embodiments, the modified host cell for producing a cannabinoid or a cannabinoid derivative comprises two or more heterologous nucleic acids comprising a nucleotide sequence encoding a KAR2 polypeptide. 
     The present disclosure provides for a method of making a modified host cell for expressing an engineered variant of the disclosure, the method comprising introducing into a host cell one or more nucleic acids disclosed herein. The disclosure provides a method of making a modified host cell for expressing an engineered variant of the disclosure, the method comprising introducing into a host cell: a) one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure and b) one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more of a KAR2 polypeptide, a PDI1 polypeptide, an ERO1 polypeptide, or an IRE1 polypeptide. The disclosure provides a method of making a modified host cell for expressing an engineered variant of the disclosure, the method comprising introducing into a host cell: a) one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure and b) one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more of a KAR2 polypeptide, a PDI1 polypeptide, an ERO1 polypeptide, or a FAD1 polypeptide. In some embodiments, the nucleotide sequences are codon-optimized. 
     In some embodiments, the modified host cell for expressing an engineered variant of the disclosure comprises one or more nucleic acids comprising a nucleotide sequence encoding the engineered variant of the disclosure and comprises one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more of a KAR2 polypeptide, a PDI1 polypeptide, an ERO1 polypeptide, or an IRE1 polypeptide. In certain such embodiments, the modified host cell comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding the KAR2 polypeptide, one or more heterologous nucleic acids comprising a nucleotide sequence encoding the PDI1 polypeptide, one or more heterologous nucleic acids comprising a nucleotide sequence encoding the ERO1 polypeptide, and one or more heterologous nucleic acids comprising a nucleotide sequence encoding the IRE1 polypeptide. In some embodiments, the modified host cell for expressing an engineered variant of the disclosure comprises two or more heterologous nucleic acids comprising a nucleotide sequence encoding a KAR2 polypeptide. 
     In some embodiments, the modified host cell for expressing an engineered variant of the disclosure comprises one or more nucleic acids comprising a nucleotide sequence encoding the engineered variant of the disclosure and comprises one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more of a KAR2 polypeptide, a PDI1 polypeptide, an ERO1 polypeptide, or a FAD1 polypeptide. In certain such embodiments, the modified host cell comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding the KAR2 polypeptide, one or more heterologous nucleic acids comprising a nucleotide sequence encoding the PDI1 polypeptide, one or more heterologous nucleic acids comprising a nucleotide sequence encoding the ERO1 polypeptide, and one or more heterologous nucleic acids comprising a nucleotide sequence encoding the FAD1 polypeptide. In some embodiments, the modified host cell for expressing an engineered variant of the disclosure comprises two or more heterologous nucleic acids comprising a nucleotide sequence encoding a KAR2 polypeptide. 
     In some embodiments, the modified host cell for expressing an engineered variant of the disclosure comprising one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure comprises a deletion or downregulation of one or more genes encoding one or more of a ROT2 polypeptide or a PEP4 polypeptide. In certain such embodiments, the modified host cell comprises a deletion or downregulation of one or more genes encoding the ROT2 polypeptide and the PEP4 polypeptide. The disclosure provides a method of making a modified host cell for expressing an engineered variant of the disclosure, the method comprising introducing into a host cell: a) one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure and b) a deletion or downregulation of one or more genes encoding one or more of a ROT2 polypeptide or a PEP4 polypeptide. 
     In some embodiments, the modified host cell for expressing an engineered variant of the disclosure comprises one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure, one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more of a KAR2 polypeptide, a PDI1 polypeptide, an ERO1 polypeptide, or an IRE1 polypeptide, and a deletion or downregulation of one or more genes encoding one or more of a ROT2 polypeptide or a PEP4 polypeptide. In certain such embodiments, the modified host cell comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding the KAR2 polypeptide, one or more heterologous nucleic acids comprising a nucleotide sequence encoding the PDI1 polypeptide, one or more heterologous nucleic acids comprising a nucleotide sequence encoding the ERO1 polypeptide, and one or more heterologous nucleic acids comprising a nucleotide sequence encoding the IRE1 polypeptide and a deletion or downregulation of one or more genes encoding the ROT2 polypeptide and the PEP4 polypeptide. In some embodiments, the modified host cell for expressing an engineered variant of the disclosure comprises two or more heterologous nucleic acids comprising a nucleotide sequence encoding a KAR2 polypeptide. 
     The disclosure provides a method of making a modified host cell for expressing an engineered variant of the disclosure, the method comprising introducing into a host cell: a) one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure, b) one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more of a KAR2 polypeptide, a PDI1 polypeptide, an ERO1 polypeptide, or an IRE1 polypeptide, and c) a deletion or downregulation of one or more genes encoding one or more of a ROT2 polypeptide or a PEP4 polypeptide. 
     The disclosure provides a method of making a modified host cell for expressing an engineered variant of the disclosure, the method comprising introducing into a host cell: a) one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure and b) one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more of a KAR2 polypeptide, a PDI1 polypeptide, an ERO1 polypeptide, or a FAD1 polypeptide. 
     In some embodiments, the modified host cell for expressing an engineered variant of the disclosure may comprise one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure and express or overexpress combinations of heterologous nucleic acids comprising nucleotide sequences encoding one or more polypeptides involved in cannabinoid or cannabinoid precursor (e.g., geranylpyrophosphate (GPP), prenyl phosphates, olivetolic acid, or hexanoyl-CoA) biosynthesis. In some embodiments, the methods of making a modified host cell for expressing an engineered variant of the disclosure comprise introducing into a host cell one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more polypeptides involved in cannabinoid or cannabinoid precursor biosynthesis. In some embodiments disclosed herein, the nucleotide sequences encoding the one or more polypeptides involved in cannabinoid or cannabinoid precursor biosynthesis are codon-optimized. 
     In some embodiments, the modified host cell for expressing an engineered variant of the disclosure comprises one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure, one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more of a KAR2 polypeptide, a PDI1 polypeptide, an ERO1 polypeptide, or an IRE1 polypeptide, a deletion or downregulation of one or more genes encoding one or more of a ROT2 polypeptide or a PEP4 polypeptide, and one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more polypeptides involved in cannabinoid or cannabinoid precursor (e.g., geranylpyrophosphate (GPP), prenyl phosphates, olivetolic acid, or hexanoyl-CoA) biosynthesis. In certain such embodiments, the modified host cell comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding the KAR2 polypeptide, one or more heterologous nucleic acids comprising a nucleotide sequence encoding the PDI1 polypeptide, one or more heterologous nucleic acids comprising a nucleotide sequence encoding the ERO1 polypeptide, one or more heterologous nucleic acids comprising a nucleotide sequence encoding the IRE1 polypeptide and a deletion or downregulation of the genes encoding the ROT2 polypeptide and the PEP4 polypeptide. In some embodiments, the modified host cell for expressing an engineered variant of the disclosure comprises two or more heterologous nucleic acids comprising a nucleotide sequence encoding a KAR2 polypeptide. 
     In some embodiments, the modified host cell for expressing an engineered variant of the disclosure comprises one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure, one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more of a KAR2 polypeptide, a PDI1 polypeptide, an ERO1 polypeptide, or a FAD1 polypeptide and one or more heterologous nucleic acids comprising nucleotide sequences encoding one or more polypeptides involved in cannabinoid or cannabinoid precursor (e.g., geranylpyrophosphate (GPP), prenyl phosphates, olivetolic acid, or hexanoyl-CoA) biosynthesis. In certain such embodiments, the modified host cell comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding the KAR2 polypeptide, one or more heterologous nucleic acids comprising a nucleotide sequence encoding the PDI1 polypeptide, one or more heterologous nucleic acids comprising a nucleotide sequence encoding the ERO1 polypeptide, one or more heterologous nucleic acids comprising a nucleotide sequence encoding the FAD1 polypeptide. In some embodiments, the modified host cell for expressing an engineered variant of the disclosure comprises two or more heterologous nucleic acids comprising a nucleotide sequence encoding a KAR2 polypeptide. 
     To modify a parent host cell to produce a modified host cell of the present disclosure, one or more nucleic acids (e.g., heterologous) disclosed herein may be introduced stably or transiently into a host cell, using established techniques. Such techniques may include, but are not limited to, electroporation, calcium phosphate precipitation, DEAE-dextran mediated transfection, liposome-mediated transfection, the lithium acetate method, and the like. See Gietz, R. D. and R. A. Woods. (2002) TRANSFORMATION OF YEAST BY THE Liac/SS CARRIER DNA/PEG METHOD. For stable transformation, a plasmid, vector, expression construct, etc. comprising one or more nucleic acids (e.g., heterologous) disclosed herein will generally further include a selectable marker, e.g., any of several well-known selectable markers such as neomycin resistance, ampicillin resistance, tetracycline resistance, chloramphenicol resistance, kanamycin resistance, and the like. In some embodiments, the selectable marker gene to provide a phenotypic trait for selection of transformed host cells is dihydrofolate reductase. In some embodiments, a parent host cell is modified to produce a modified host cell of the present disclosure using a CRISPR/Cas9 system to modify a parent host cell with one or more nucleic acids (e.g., heterologous) disclosed herein. 
     In some embodiments, varying polypeptide expression level, such as engineered variant expression level, and/or the production of cannabinoids or cannabinoid derivatives in a modified host cell may be done by changing the gene copy number, promoter strength, and/or promoter regulation and/or by codon-optimization. 
     One or more nucleic acids (e.g., heterologous) disclosed herein, such as one or more nucleic acids comprising a nucleotide sequence encoding an engineered variant of the disclosure, can be present in an expression vector or construct. Suitable expression vectors may include, but are not limited to, plasmids, yeast plasmids, yeast artificial chromosomes, and any other vectors specific for specific hosts of interest (such as yeast). Thus, for example, one or more nucleic acids (e.g., heterologous) comprising nucleotide sequences encoding a mevalonate pathway gene product(s) is included in any one of a variety of expression vectors for expressing the mevalonate pathway gene product(s). Such vectors may include chromosomal, non-chromosomal, and synthetic DNA sequences. 
     The present disclosure provides for a method of making a modified host cell of the disclosure, the method comprising introducing into a host cell one or more vectors disclosed herein. 
     The present disclosure provides for a method of making a modified host cell for producing a cannabinoid or a cannabinoid derivative, the method comprising introducing into a host cell one or more vectors disclosed herein. In certain such embodiments, the one or more vectors comprise one or more vectors comprising one or more nucleic acids (e.g., heterologous) comprising a nucleotide sequence encoding an engineered variant of the disclosure. In certain such embodiments, the one or more vectors comprise one or more vectors comprising one or more nucleic acids (e.g., heterologous) comprising nucleotide sequences encoding one or more secretory pathway polypeptides. In some embodiments, the method comprises introducing into the host cell a deletion or downregulation of one or more genes encoding one or more secretory pathway polypeptides. In some embodiments, the nucleotide sequences encoding the one or more secretory pathway polypeptides are codon-optimized. In some embodiments, the one or more vectors comprise one or more vectors comprising one or more nucleic acids (e.g., heterologous) comprising nucleotide sequences encoding one or more polypeptides involved in cannabinoid or cannabinoid precursor biosynthesis. In some embodiments, the nucleotide sequences encoding the one or more polypeptides involved in cannabinoid or cannabinoid precursor biosynthesis are codon-optimized. 
     The present disclosure provides for a method of making a modified host cell for expressing a cannabinoid synthase polypeptide, the method comprising introducing into a host cell one or more vectors disclosed herein. In certain such embodiments, the one or more vectors comprise one or more vectors comprising one or more nucleic acids (e.g., heterologous) comprising a nucleotide sequence encoding an engineered variant of the disclosure. In certain such embodiments, the one or more vectors comprise one or more vectors comprising one or more nucleic acids (e.g., heterologous) comprising nucleotide sequences encoding one or more secretory pathway polypeptides. In some embodiments, the nucleotide sequences encoding the one or more secretory pathway polypeptides are codon-optimized. In some embodiments, the method comprises introducing into the host cell a deletion or downregulation of one or more genes encoding one or more secretory pathway polypeptides. In some embodiments, the one or more vectors comprise one or more vectors comprising one or more nucleic acids (e.g., heterologous) comprising nucleotide sequences encoding one or more polypeptides involved in cannabinoid or cannabinoid precursor biosynthesis. In some embodiments, the nucleotide sequences encoding the one or more polypeptides involved in cannabinoid or cannabinoid precursor biosynthesis are codon-optimized. 
     Numerous additional suitable expression vectors are known to those of skill in the art, and many are commercially available. The following vectors are provided by way of example; for yeast, the low copy CEN ARS and high copy 2 micron plasmids. However, any other plasmid or other vector may be used so long as it is compatible with the host cell. 
     In some embodiments, one or more of the nucleic acids (e.g., heterologous) disclosed herein are present in a single expression vector. In some embodiments, two or more of the nucleic acids (e.g., heterologous) disclosed herein are present in a single expression vector. In some embodiments, three or more of the nucleic acids (e.g., heterologous) disclosed herein are present in a single expression vector. In some embodiments, four or more of the nucleic acids (e.g., heterologous) disclosed herein are present in a single expression vector. In some embodiments, five or more of the nucleic acids (e.g., heterologous) disclosed herein are present in a single expression vector. In some embodiments, six or more of the nucleic acids (e.g., heterologous) disclosed herein are present in a single expression vector. In some embodiments, seven or more of the nucleic acids (e.g., heterologous) disclosed herein are present in a single expression vector. 
     In some embodiments, two or more nucleic acids (e.g., heterologous) disclosed herein are in separate expression vectors. In some embodiments, three or more nucleic acids (e.g., heterologous) disclosed herein are in separate expression vectors. In some embodiments, four or more nucleic acids (e.g., heterologous) disclosed herein are in separate expression vectors. In some embodiments, five or more nucleic acids (e.g., heterologous) disclosed herein are in separate expression vectors. In some embodiments, six or more nucleic acids (e.g., heterologous) disclosed herein are in separate expression vectors. In some embodiments, seven or more nucleic acids (e.g., heterologous) disclosed herein are in separate expression vectors. In some embodiments, eight or more nucleic acids (e.g., heterologous) disclosed herein are in separate expression vectors. In some embodiments, nine or more nucleic acids (e.g., heterologous) disclosed herein are in separate expression vectors. In some embodiments, ten or more nucleic acids (e.g., heterologous) disclosed herein are in separate expression vectors. 
     In some embodiments, one or more of the nucleic acids (e.g., heterologous) disclosed herein are present in a single expression construct. In some embodiments, two or more of the nucleic acids (e.g., heterologous) disclosed herein are present in a single expression construct. In some embodiments, three or more of the nucleic acids (e.g., heterologous) disclosed herein are present in a single expression construct. In some embodiments, four or more of the nucleic acids (e.g., heterologous) disclosed herein are present in a single expression construct. In some embodiments, five or more of the nucleic acids (e.g., heterologous) disclosed herein are present in a single expression construct. In some embodiments, six or more of the nucleic acids (e.g., heterologous) disclosed herein are present in a single expression construct. In some embodiments, seven or more of the nucleic acids (e.g., heterologous) disclosed herein are present in a single expression construct. 
     In some embodiments, two or more nucleic acids (e.g., heterologous) disclosed herein are in separate expression constructs. In some embodiments, three or more nucleic acids (e.g., heterologous) disclosed herein are in separate expression constructs. In some embodiments, four or more nucleic acids (e.g., heterologous) disclosed herein are in separate expression constructs. In some embodiments, five or more nucleic acids (e.g., heterologous) disclosed herein are in separate expression constructs. In some embodiments, six or more nucleic acids (e.g., heterologous) disclosed herein are in separate expression constructs. In some embodiments, seven or more nucleic acids (e.g., heterologous) disclosed herein are in separate expression constructs. In some embodiments, eight or more nucleic acids (e.g., heterologous) disclosed herein are in separate expression constructs. In some embodiments, nine or more nucleic acids (e.g., heterologous) disclosed herein are in separate expression constructs. In some embodiments, ten or more nucleic acids (e.g., heterologous) disclosed herein are in separate expression constructs. 
     In some embodiments, one or more of the nucleic acids (e.g., heterologous) disclosed herein is present in a high copy number plasmid, e.g., a plasmid that exists in about 10-50 copies per cell, or more than 50 copies per cell. In some embodiments, one or more of the nucleic acids (e.g., heterologous) disclosed herein is present in a low copy number plasmid. In some embodiments, one or more of the nucleic acids (e.g., heterologous) disclosed herein is present in a medium copy number plasmid. The copy number of the plasmid may be selected to reduce expression of one or more polypeptides disclosed herein, such as an engineered variant of the disclosure. Reducing expression by limiting the copy number of the plasmid may prevent saturation of the secretory pathway leading to possible protein degradation and/or modified host cell death or a loss of modified host cell viability. 
     In some embodiments, the modified host cell has one copy of a nucleic acid (e.g., heterologous) comprising a nucleotide sequence encoding a polypeptide disclosed herein. In some embodiments, the modified host cell has two copies of a nucleic acid (e.g., heterologous) comprising a nucleotide sequence encoding a polypeptide disclosed herein. In some embodiments, the modified host cell has three copies of a nucleic acid (e.g., heterologous) comprising a nucleotide sequence encoding a polypeptide disclosed herein. In some embodiments, the modified host cell has four copies of a nucleic acid (e.g., heterologous) comprising a nucleotide sequence encoding a polypeptide disclosed herein. In some embodiments, the modified host cell has five copies of a nucleic acid (e.g., heterologous) comprising a nucleotide sequence encoding a polypeptide disclosed herein. In some embodiments, the modified host cell has six copies of a nucleic acid (e.g., heterologous) comprising a nucleotide sequence encoding a polypeptide disclosed herein. In some embodiments, the modified host cell has seven copies of a nucleic acid (e.g., heterologous) comprising a nucleotide sequence encoding a polypeptide disclosed herein. In some embodiments, the modified host cell has eight copies of a nucleic acid (e.g., heterologous) comprising a nucleotide sequence encoding a polypeptide disclosed herein. In some embodiments, the modified host cell has nine copies of a nucleic acid (e.g., heterologous) comprising a nucleotide sequence encoding a polypeptide disclosed herein. In some embodiments, the modified host cell has ten copies of a nucleic acid (e.g., heterologous) comprising a nucleotide sequence encoding a polypeptide disclosed herein. In some embodiments, the modified host cell has eleven copies of a nucleic acid (e.g., heterologous) comprising a nucleotide sequence encoding a polypeptide disclosed herein. In some embodiments, the modified host cell has twelve copies of a nucleic acid (e.g., heterologous) comprising a nucleotide sequence encoding a polypeptide disclosed herein. In some embodiments, the modified host cell has twelve or more copies of a nucleic acid (e.g., heterologous) comprising a nucleotide sequence encoding a polypeptide disclosed herein. 
     Depending on the host/vector or host/construct system utilized, any of a number of suitable transcription and translation control elements, including constitutive and inducible promoters, transcription enhancer elements, transcription terminators, etc. may be used in the expression vector or construct (see e.g., Bitter et al. (1987) Methods in Enzymology,  153:516-544). 
     In some embodiments, the nucleic acids (e.g., heterologous) disclosed herein are operably linked to a promoter. In some embodiments, the promoter is a constitutive promoter. In some embodiments, the promoter is an inducible promoter. In some embodiments, the promoter is functional in a eukaryotic cell. In some embodiments, the promoter can be a strong driver of expression. In some embodiments, the promoter can be a weak driver of expression. In some embodiments, the promoter can be a medium driver of expression. The promoter may be selected to reduce expression of one or more polypeptides disclosed herein, such as an engineered variant of the disclosure. Reducing expression through promoter selection may prevent saturation of the secretory pathway leading to possible protein degradation and/or modified host cell death or a loss of modified host cell viability. Examples of strong constitutive promoters include, but are not limited to: pTDH3 and pFBA1. Examples of medium constitutive promoters include, but are not limited to: pACT1 and pCYC1. An example of a weak constitutive promoter includes, but is not limited to: pSLN1. Examples of strong inducible promoters include, but are not limited to: pGAL1 and pGAL10. An example of a medium inducible promoter includes, but is not limited to: pGAL7. An example of a weak inducible promoter includes, but is not limited to: pGAL3. 
     Non-limiting examples of suitable eukaryotic promoters may include CMV immediate early, HSV thymidine kinase, early and late SV40, LTRs from retrovirus, and mouse metallothionein-I. Selection of the appropriate vector, construct, and promoter is well within the level of ordinary skill in the art. The expression vector or construct may also contain a ribosome binding site for translation initiation and a transcription terminator. The expression vector or construct may also include appropriate sequences for amplifying expression. 
     Inducible promoters are well known in the art. Suitable inducible promoters may include, but are not limited to, a tetracycline-inducible promoter; an estradiol inducible promoter, a sugar inducible promoter, e.g., pGal1 or pSUC2, an amino acid inducible promoter, e.g., pMet25; a metal inducible promoter, e.g., pCup1, a methanol-inducible promoter, e.g., pAOX1, and the like. 
     In yeast, a number of vectors or constructs containing constitutive or inducible promoters may be used. For a review see, Current Protocols in Molecular Biology, Vol. 2, 1988, Ed. Ausubel, et al., Greene Publish. Assoc. &amp; Wiley Interscience, Ch. 13; Grant, et al., 1987, Expression and Secretion Vectors for Yeast, in Methods in Enzymology, Eds. Wu &amp; Grossman, 31987, Acad. Press, N.Y., Vol. 153, pp. 516-544; Glover, 1986, DNA Cloning, Vol. II, IRL Press, Wash., D.C., Ch. 3; and Bitter, 1987, Heterologous Gene Expression in Yeast, Methods in Enzymology, Eds. Berger &amp; Kimmel, Acad. Press, N.Y., Vol. 152, pp. 673-684; and The Molecular Biology of the Yeast  Saccharomyces,  1982, Eds. Strathern et al., Cold Spring Harbor Press, Vols. I and II. A constitutive yeast promoter such as pADH, pTDH3, pFBA1, pACT1, pCYC1, and pSLN1 or an inducible promoter such as pGAL1, pGAL10, pGAL7, and pGAL3 may be used (Cloning in Yeast, Ch. 3, R. Rothstein In: DNA Cloning Vol. 11, A Practical Approach, Ed. D M Glover, 1986, IRL Press, Wash., D.C.). Alternatively, vectors may be used which promote integration of foreign DNA sequences into the yeast chromosome. Generally, recombinant expression vectors will include origins of replication and selectable markers permitting transformation of the host cell, e.g., the  S. cerevisiae  TRP1 gene or a gene cassette encoding resistance to an antibiotic, etc.; and a promoter derived from a highly-expressed gene to direct transcription of the coding sequence. Such promoters can be derived from genetic sequences encoding glycolytic enzymes such as 3-phosphoglycerate kinase (PGK), α-factor, acid phosphatase, or heat shock proteins, among others. 
     In some embodiments, one or more nucleic acids (e.g., heterologous) disclosed herein is integrated into the genome of the modified host cell disclosed herein. In some embodiments, one or more nucleic acids (e.g., heterologous) disclosed herein is integrated into a chromosome of the modified host cell disclosed herein. In some embodiments, one or more nucleic acids (e.g., heterologous) disclosed herein remains episomal (i.e., is not integrated into the genome or a chromosome of the modified host cell). In some embodiments, at least one of the one or more nucleic acids (e.g., heterologous) disclosed herein is maintained extrachromosomally (e.g., on a plasmid or artificial chromosome). The gene copy number of one or more genes encoding one or more polypeptides disclosed herein, such as an engineered variant of the disclosure, may be selected to reduce expression of the one or more polypeptides disclosed herein, such as an engineered variant of the disclosure. Reducing expression by limiting the gene copy number may prevent saturation of the secretory pathway leading to possible protein degradation and/or modified host cell death or a loss of modified host cell viability. 
     As will be appreciated by the skilled artisan, slight changes in nucleotide sequence do not necessarily alter the amino acid sequence of the encoded polypeptide. It will be appreciated by persons skilled in the art that changes in the identities of nucleotides in a specific gene sequence that change the amino acid sequence of the encoded polypeptide may result in reduced or enhanced effectiveness of the genes and that, in some applications (e.g., anti-sense, co-suppression, or RNAi), partial sequences often work as effectively as full length versions. The ways in which the nucleotide sequence can be varied or shortened are well known to persons skilled in the art, as are ways of testing the effectiveness of the altered genes. In certain embodiments, effectiveness may easily be tested by, for example, conventional gas chromatography. All such variations of the genes are therefore included as part of the present disclosure. 
     Genomic deletion of the open reading frame encoding the protein may abolish all expression of a gene. Downregulation of a gene can be accomplished in several ways at the DNA, RNA, or protein level, with the result being a reduction in the amount of active protein in the cell. Truncations of the open reading frame or the introduction of mutations that destabilize the protein or reduce catalytic activity achieve a similar goal, as does fusing a “degron” polypeptide that destabilizes the protein. Engineering of the regulatory regions of the gene can also be used to change gene expression. Alteration of the promoter sequence or replacement with a different promoter is one method. Truncation of the terminator, known as decreased abundance of mRNA perturbation (DAmP), is also known to reduce gene expression. Other methods that reduce the stability of the mRNA include the use of cis- or trans-acting ribozymes, e.g., self-cleaving ribozymes, or RNA elements that recruit an exonuclease, or antisense DNA. RNAi may be used to silence genes in budding yeast strains via import of the required protein factors from other species, e.g., Drosha or Dice (Drinnenberg et al 2009). Gene expression may also be silenced in  S. cerevisiae  via recruitment of native or heterologous silencing factors or repressors, which may be accomplished at arbitrary loci using the D-Cas9 CRISPR system (Qi et al 2013). Protein level can also be reduced by engineering the amino acid sequence of the target protein. A variety of degron sequences may be used to target the protein for rapid degradation, including, but not limited to, ubiquitin fusions and N-end rule residues at the amino terminus. These methods may be implemented in a constitutive or conditional fashion. 
     Induction Systems 
     To adapt to a constantly changing environment, microbes such as yeast have evolved a wide range of natural inducible promoter systems. Any promoter that is regulated by a small molecule or change in environment (temperature, pH, oxygen level, osmolarity, oxidative damage) can in principle be converted into an inducible system for the expression of heterologous genes. The best known system in  S. cerevisiae  is the galactose regulon, which is strongly repressed by glucose and activated by galactose. Heterologous genetic pathways under the control of galactose-inducible promoters are regulated in the same way, and thus an engineered strain can be grown in glucose media to build biomass, and then switched to galactose to induce pathway expression. A range of expression levels can be achieved, from very strong pGAL1 to relatively weak pGAL3. However, galactose may be expensive and a poor carbon source for  S. cerevisiae . Therefore, for industrial applications, it may be advantageous to re-engineer the regulon such that the cells can be induced in a non-galactose media. The galactose regulon can be modified for this purpose in many ways, including:
         Overexpressing the negative regulator of GAL80, GAL3, from an inducible promoter, e.g., pSUC2-GAL3, such that switching from glucose to sucrose relieves GAL80 expression and activates the pathway.   Deleting the repressor GAL80 and replacing the native GAL4 cassette with a version under the control of a sucrose inducible promoter, e.g., pSUC2-GAL4, such that expression is induced by a switch from glucose to sucrose.   Replacing the native GAL80 gene with an inducible version, e.g., pSUC2-GAL80, such that expression is induced by a switch from sucrose to glucose.       

     These strategies often require fine-tuning of the activator and repressor levels to achieve the proper dynamics (very low or no expression in the off state, and desired expression level in the on state). There are a variety of ways to fine tune protein expression, including use of protein stabilization or degradation tags (e.g., degrons) or use of temperature sensitive mutants of the activators or regulators. In the examples above, the pSUC2 promoter is used to induce the galactose regulon in sucrose media. However, any inducible promoter can be used for this purpose, or for control of individual genes outside of the context of the galactose regulon. The list below provides some examples:
         Phosphate regulated promoters, e.g., pPHO5   Carbon source regulated promoters, e.g., pADH2   Amino acid regulated promoters, e.g., pMET25   Metal ion induced promoters, e.g., pCUP1   Temperature regulated promoters, e.g., pHSP12, pHSP26   pH regulated promoters, e.g., pHSP12, pHSP26   Oxygen level regulated promoters, e.g., pDAN1   Oxidative stress regulated promoters, e.g., AHP1, TRR1, TRX2, TSA1, GPX2, GSH1, GSH2, GLR1, SOD1, or SOD2 genes.   ER stress regulated promoters, e.g., unfolded protein response element promoters.       

     In addition to these natural examples, there are a variety of synthetic inducible promoter systems. These are generally based on re-arrangement of native or foreign transcriptional elements into a basal promoter scaffold and/or fusions of activator domains and DNA binding domains to create novel transcription factors. Two examples are provided below:
         Estradiol-inducible systems involving fusion of the estradiol receptor to DNA-binding and transcriptional activation domain, paired with synthetic or native promoters with binding sites.   tet Trans Activator (tTA) or reverse tet Trans Activator (rtTA) systems paired with tetO-containing promoters.       

     In some embodiments, one of the above inducible promoter systems is used in a modified host cell of the disclosure. In some embodiments, the inducible promoter system is a natural inducible promoter system. In some embodiments, the inducible promoter system is a synthetic inducible promoter system. In some embodiments, a suitable media for culturing modified host cells of the disclosure comprises one or more of the inducers disclosed herein. Possible inducers include:
         Phosphate regulated promoters, e.g., pPHO5
           KH 2 PO 4      
           Carbon source regulated promoters, e.g., pADH2
           Galactose (e.g., pGAL1)   Glucose (e.g., pADH2)   Sucrose (e.g., pSUC2, pGPH1, pMAL12)   Maltose (e.g., pMAL12, pMAL32)   
           Amino acid regulated promoters, e.g., pMET25
           Methionine (e.g., pMET25)   Lysine (e.g., pLYS9)   Other amino acids   
           Metal ion induced promoters, e.g., pCUP1
           CuSO 4      
           Temperature regulated promoters, e.g., pHSP12, pHSP26
           Change in temperature, e.g., 30° C. to 37° C.   
           pH regulated promoters, e.g., pHSP12, pHSP26
           Change in pH, e.g., pH 6 to pH 4   
           Oxygen level regulated promoters, e.g., pDAN1
           Change in oxygen level, e.g., 20% to 1% dissolved oxygen levels   
           Oxidative stress regulated promoters, e.g., pSOD1
           Addition of hydrogen peroxide or superoxide-generating drug menadione   
           ER stress regulated promoters, e.g., unfolded protein response element promoters.
           Tunicamycin, or expression of proteins prone to misfolding (e.g., cannabinoid synthases)   
           Estradiol-inducible systems involving fusion of the estradiol receptor to DNA-binding and transcriptional activation domain, paired with synthetic or native promoters with binding sites.
           Estradiol   
           tet Trans Activator (tTA) or reverse tet Trans Activator (rtTA) systems paired with tetO-containing promoters.
           Doxycyclin   
               

     Codon Usage 
     As is well known to those of skill in the art, it is possible to improve the expression of a heterologous nucleic acid in a host organism by replacing the nucleotide sequences coding for a particular amino acid (i.e., a codon) with another codon which is better expressed in the host organism (i.e., codon-optimization). One reason that this effect arises is due to the fact that different organisms show preferences for different codons. In some embodiments, a nucleic acid disclosed herein is modified or optimized such that the nucleotide sequence reflects the codon preference for the particular host cell. For example, the nucleotide sequence will in some embodiments be modified or optimized for yeast codon preference. In some embodiments, a nucleotide sequence disclosed herein is codon-optimized. See, e.g., Bennetzen and Hall (1982)  J. Biol. Chem.  257(6): 3026-3031. 
     Statistical methods have been generated to analyze codon usage bias in various organisms and many computer algorithms have been developed to implement these statistical analyses in the design of codon optimized gene sequences (Lithwick G, Margalit H (2003) Hierarchy of sequence-dependent features associated with prokaryotic translation. Genome Research 13: 2665-73). Other modifications in codon usage to increase protein expression that are not dependent on codon bias have also been described (Welch et al. (2009). In some embodiments, codon optimization of the nucleotide sequence may result in an increase in the desired polypeptide or enzyme catalytic activity in the modified host cell. 
     In some embodiments, the codon usage of a nucleotide sequence is modified or optimized such that the level of translation of the encoded mRNA is decreased. In some embodiments, a codon-optimized nucleotide sequence may be optimized such that the level of translation of the encoded mRNA is decreased. Reducing the level of translation of an mRNA by modifying codon usage may be achieved by modifying the nucleotide sequence to include codons that are rare or not commonly used by the host cell. Codon usage tables for many organisms are available that summarize the percentage of time a specific organism uses a specific codon to encode for an amino acid. Certain codons are used more often than other, “rare” codons. The use of “rare” codons in a nucleotide sequence generally decreases its rate of translation. Thus, e.g., the nucleotide sequence is modified by introducing one or more rare codons, which affect the rate of translation, but not the amino acid sequence of the polypeptide translated. For example, there are six codons that encode for arginine: CGT, CGC, CGA, CGG, AGA, and AGG. In  E. coli  the codons CGT and CGC are used far more often (encoding approximately 40% of the arginines in  E. coli  each) than the codon AGG (encoding approximately 2% of the arginines in  E. coli ). Modifying a CGT codon within the sequence of a gene to an AGG codon would not change the sequence of the polypeptide, but would likely decrease the gene&#39;s rate of translation. 
     In some embodiments, a codon-optimized nucleotide sequence may be optimized for expression in a yeast cell. In certain such embodiments, the yeast cell is  Saccharomyces cerevisiae.    
     Further, it will be appreciated that this disclosure embraces the degeneracy of codon usage as would be understood by one of ordinary skill in the art and illustrated in the following table. 
     Codon Degeneracies 
       
                                             Amino Acid   Codons                          Ala/A   GCT, GCC, GCA, GCG-           Arg/R   CGT, CGC, CGA, CGG, AGA, AGG           Asn/N   AAT, AAC           Asp/D   GAT, GAC           Cys/C   TGT, TGC           Gln/Q   CAA, CAG           Glu/E   GAA, GAG           Gly/G   GGT, GGC, GGA, GGG           His/H   CAT, CAC           Ile/I   ATT, ATC, ATA           Leu/L   TTA, TTG, CTT, CTC, CTA, CTG           Lys/K   AAA, AAG           Met/M   ATG           Phe/F   TTT, TTC           Pro/P   CCT, CCC, CCA, CCG           Ser/S   TCT, TCC, TCA, TCG, AGT, AGC           Thr/T   ACT, ACC, ACA, ACG           Trp/W   TGG           Tyr/Y   TAT, TAC           Val/V   GTT, GTC, GTA, GTG           START   ATG           STOP   TAG, TGA, TAA                        
Methods of Producing a Cannabinoid or a Cannabinoid Derivative or of Expressing and/or Preparing Engineered Variants of the Cannabidiolic Acid Synthase (CBDAS) Polypeptide
 
     The disclosure provides methods for expressing an engineered variant of the cannabidiolic acid synthase (CBDAS) polypeptide of the disclosure. In certain such embodiments, the methods comprise culturing a modified host cell of the disclosure in a culture medium. The disclosure also provides methods for preparing an engineered variant of the cannabidiolic acid synthase (CBDAS) polypeptide of the disclosure. The disclosure also provides methods of producing a cannabinoid or a cannabinoid derivative, the method comprising use of an engineered variant of the disclosure. 
     The present disclosure also provides methods of producing a cannabinoid or a cannabinoid derivative. The methods of the present disclosure may involve production of cannabinoids or cannabinoid derivatives using an engineered variant disclosed herein. The methods may involve culturing a modified host cell of the present disclosure in a culture medium and recovering the produced cannabinoid or cannabinoid derivative. The methods may also involve cell-free production of cannabinoids or cannabinoid derivatives using one or more polypeptides disclosed herein, such as an engineered variant of the disclosure, expressed or overexpressed by a modified host cell of the disclosure. The methods may also involve cell-free production of cannabinoids or cannabinoid derivatives using an engineered variant disclosed herein. 
     Cannabinoids or cannabinoid derivatives that can be produced with the engineered variants, methods, or modified host cells of the present disclosure may include, but are not limited to, cannabichromene (CBC) type (e.g., cannabichromenic acid), cannabidiol (CBD) type (e.g., cannabidiolic acid), Δ 9 -trans-tetrahydrocannabinol (Δ 9 -THC) type (e.g., Δ 9 -tetrahydrocannabinolic acid), Δ 8 -trans-tetrahydrocannabinol (Δ 8 -THC) type, cannabicyclol (CBL) type, cannabielsoin (CBE) type, cannabinol (CBN) type, cannabinodiol (CBND) type, cannabitriol (CBT) type, derivatives of any of the foregoing, and others as listed in Elsohly M. A. and Slade D., Life Sci. 2005 Dec. 22; 78(5):539-48. Epub 2005 Sep. 30. In some embodiments, the cannabinoid or cannabinoid derivative is produced in an amount of more than 100 mg/L culture medium. In some embodiments, the cannabinoid or cannabinoid derivative is produced in an amount of more than 50 mg/L culture medium. 
     Cannabinoids or cannabinoid derivatives that can be produced with the engineered variants, methods, or modified host cells of the present disclosure may also include, but are not limited to, cannabichromenic acid (CBCA), cannabichromene (CBC), cannabichromevarinic acid (CBCVA), cannabichromevarin (CBCV), CBDA, cannabidiol (CBD), cannabidiol monomethylether (CBDM), cannabidiol-C4 (CBD-C4), cannabidivarinic acid (CBDVA), cannabidivarin (CBDV), cannabidiorcol (CBD-C 1 ), Δ 9 -tetrahydrocannabinolic acid A (THCA-A), Δ 9 -tetrahydrocannabinolic acid B (THCA-B), Δ 9 -tetrahydrocannabinol (THC), Δ 9 -tetrahydrocannabinolic acid-C4 (THCA-C4), Δ 9 -tetrahydrocannabinol-C4 (THC-C4), Δ 9 -tetrahydrocannabivarinic acid (THCVA), Δ 9 -tetrahydrocannabivarin (THCV), Δ 9 -tetrahydrocannabiorcolic acid (THCA-C 1 ), Δ 9 -tetrahydrocannabiorcol (THC-C 1 ), Δ 7 -cis-iso-tetrahydrocannabivarin, Δ 8 -tetrahydrocannabinolic acid (Δ 8 -THCA), Δ 8 -tetrahydrocannabinol (Δ 8 -THC), cannabicyclolic acid (CBLA), cannabicyclol (CBL), cannabicyclovarin (CBLV), cannabielsoic acid A (CBEA-A), cannabielsoic acid B (CBEA-B), cannabielsoin (CBE), cannabielsoinic acid, cannabicitranic acid, cannabinolic acid (CBNA), cannabinol (CBN), cannabinol methylether (CBNM), cannabinol-C4, (CBN-C4), cannabivarin (CBV), cannabinol-C2 (CNB-C2), cannabiorcol (CBN-C 1 ), cannabinodiol (CBND), cannabinodivarin (CBVD), cannabitriol (CBT), 10-ethyoxy-9-hydroxy-delta-6a-tetrahydrocannabinol, 8,9-dihydroxyl-delta-6a-tetrahydrocannabinol, cannabitriolvarin (CBTVE), dehydrocannabifuran (DCBF), cannabifuran (CBF), cannabichromanon (CBCN), cannabicitran (CBT), 10-oxo-delta-6a-tetrahydrocannabinol (OTHC), delta-9-cis-tetrahydrocannabinol (cis-THC), 3,4,5,6-tetrahydro-7-hydroxy-alpha-alpha-2-trimethyl-9-n-propyl-2,6-methano-2H-1-benzoxocin-5-methanol (OH-iso-HHCV), cannabiripsol (CBR), trihydroxy-delta-9-tetrahydrocannabinol (triOH-THC), CBGA-hydrocinnamic acid (3-[(2E)-3,7-dimethylocta-2,6-dien-1-yl]-2,4-dihydroxy-6-(2-phenylethyl)benzoic acid), CBG-hydrocinnamic acid (2-[(2E)-3,7-dimethylocta-2,6-dien-1-yl]-5-(2-phenylethyl)benzene-1,3-diol), CBDA-hydrocinnamic acid (2,4-dihydroxy-3-[3-methyl-6-(prop-1-en-2-yl)cyclohex-2-en-1-yl]-6-(2-phenylethyl)benzoic acid), CBD-hydrocinnamic acid (2-[3-methyl-6-(prop-1-en-2-yl)cyclohex-2-en-1-yl]-5-(2-phenylethyl)benzene-1,3-diol), THCA-hydrocinnamic acid (1-hydroxy-6,6,9-trimethyl-3-(2-phenylethyl)-6H,6aH,7H,8H,10aH-benzo[c]isochromene-2-carboxylic acid), THC-hydrocinnamic acid (6,6,9-trimethyl-3-(2-phenylethyl)-6H,6aH,7H,8H,10aH-benzo[c]isochromen-1-ol, perrottetinene), and derivatives of any of the foregoing. In some embodiments, the cannabinoid or cannabinoid derivative is produced in an amount of more than 100 mg/L culture medium. In some embodiments, the cannabinoid or cannabinoid derivative is produced in an amount of more than 50 mg/L culture medium. 
     In some embodiments, the cannabinoid produced with the engineered variants, methods, or modified host cells of the present disclosure is Δ 9 -tetrahydrocannabinolic acid, Δ 9 -tetrahydrocannabinol, Δ 8 -tetrahydrocannabinolic acid, Δ 8 -tetrahydrocannabinol, cannabidiolic acid, cannabidiol, cannabichromenic acid, cannabichromene, cannabinolic acid, cannabinol, cannabidivarinic acid, cannabidivarin, tetrahydrocannabivarinic acid, tetrahydrocannabivarin, cannabichromevarinic acid, cannabichromevarin, cannabigerovarinic acid, cannabigerovarin, cannabicyclolic acid, cannabicyclol, cannabielsoinic acid, cannabielsoin, cannabicitranic acid, or cannabicitran. In some embodiments, the cannabinoid is produced in an amount of more than 100 mg/L culture medium. In some embodiments, the cannabinoid is produced in an amount of more than 50 mg/L culture medium. 
     In some embodiments, the cannabinoid produced with the engineered variants, methods, or modified host cells of the present disclosure is cannabidiolic acid, cannabidiol, cannabidivarinic acid, or cannabidivarin. In some embodiments, the cannabinoid is produced in an amount of more than 100 mg/L culture medium. In some embodiments, the cannabinoid is produced in an amount of more than 50 mg/L culture medium. 
     Additional cannabinoids and cannabinoid derivatives that can be produced with the engineered variants, methods, or modified host cells of the present disclosure may also include, but are not limited to, CBDA, CBD, CBGA, THC, THCA, THCVA, CBDVA, CBCA, CBC, (6aR,10aR)-1-hydroxy-6,6,9-trimethyl-3-butyl-6a,7,8,10a-tetrahydro-6H-dibenzo[b,d]pyran-2-carboxylic acid, (6aR,10aR)-1-hydroxy-6,6,9-trimethyl-3-(3-methylpentyl)-6a,7,8,10a-tetrahydro-6H-dibenzo[b,d]pyran-2-carboxylic acid, (6aR,10aR)-1-hydroxy-6,6,9-trimethyl-3-(4-pentenyl)-6a,7,8,10a-tetrahydro-6H-dibenzo[b,d]pyran-2-carboxylic acid, (6aR,10aR)-1-hydroxy-6,6,9-trimethyl-3-hexyl-6a,7,8,10a-tetrahydro-6H-dibenzo[b,d]pyran-2-carboxylic acid, (6aR,10aR)-1-hydroxy-6,6,9-trimethyl-3-(5-hexynyl)-6a,7,8,10a-tetrahydro-6H-dibenzo[b,d]pyran-2-carboxylic acid, and others as listed in Bow, E. W. and Rimoldi, J. M., “The Structure—Function Relationships of Classical Cannabinoids: CB1/CB2 Modulation,”  Perspectives in Medicinal Chemistry  2016:8 17-39 doi: 10.4137/PMC.S32171, incorporated by reference herein. In some embodiments, the cannabinoid or cannabinoid derivative is produced in an amount of more than 100 mg/L culture medium. In some embodiments, the cannabinoid or cannabinoid derivative is produced in an amount of more than 50 mg/L culture medium. 
     Additional cannabinoids and cannabinoid derivatives that can be produced with the engineered variants, methods, or modified host cells of the present disclosure may also include, but are not limited to, (1′R,2′R)-4-(hexan-2-yl)-5′-methyl-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-2,6-diol, (1′R,2′R)-4-hexyl-5′-methyl-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-2,6-diol, (1′R,2′R)-5′-methyl-4-(3-methylpentyl)-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-2,6-diol, (1′R,2′R)-4-(4-chlorobutyl)-5′-methyl-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-2,6-diol, (1′R,2′R)-5′-methyl-4-(4-methylpentyl)-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-2,6-diol, (1′R,2′R)-5′-methyl-4-(4-(methylthio)butyl)-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-2,6-diol, (1′R,2′R)-5′-methyl-4-((E)-pent-1-en-1-yl)-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-2,6-diol, (1′R,2′R)-5′-methyl-4-((E)-pent-3-en-1-yl)-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-2,6-diol, (1′R,2′R)-5′-methyl-4-((E)-pent-2-en-1-yl)-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-2,6-diol, (1′R,2′R)-4-(but-3-yn-1-yl)-5′-methyl-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-2,6-diol, (1′R,2′R)-4-((E)-but-1-en-1-yl)-5′-methyl-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-2,6-diol, (1′R,2′R)-5′-methyl-4-(pent-4-yn-1-yl)-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-2,6-diol, (1′R,2′R)-5′-methyl-2′-(prop-1-en-2-yl)-4-undecyl-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-2,6-diol, (1′R,2′R)-4-(hex-5-yn-1-yl)-5′-methyl-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-2,6-diol, (1′R,2′R)-4-((E)-hept-1-en-1-yl)-5′-methyl-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-2,6-diol, (1′R,2′R)-5′-methyl-4-octyl-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-2,6-diol, (1′R,2′R)-5′-methyl-4-((E)-oct-1-en-1-yl)-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-2,6-diol, (1′R,2′R)-5′-methyl-4-nonyl-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-2,6-diol, (1′R,2′R)-5′-methyl-4-(3-phenylpropyl)-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-2,6-diol, (1′R,2′R)-5′-methyl-4-(4-phenylbutyl)-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-2,6-diol, (1′R,2′R)-5′-methyl-4-(5-phenylpentyl)-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-2,6-diol, (1′R,2′R)-5′-methyl-4-(6-phenylhexyl)-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-2,6-diol, (1′R,2′R)-5′-methyl-4-(2-methylpentyl)-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-2,6-diol, (1′R,2′R)-4-isopropyl-5′-methyl-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-2,6-diol, (1′R,2′R)-4-decyl-5′-methyl-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-2,6-diol, (1′R,2′R)-5′-methyl-2′-(prop-1-en-2-yl)-4-tridecyl-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-2,6-diol, (E)-3-((1′R,2′R)-2,6-dihydroxy-5′-methyl-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-4-yl)acrylic acid, (Z)-3-((1′R,2′R)-2,6-dihydroxy-5′-methyl-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-4-yl)acrylic acid, 7-((1′R,2′R)-2,6-dihydroxy-5′-methyl-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-4-yl)heptanoic acid, 8-((1′R,2′R)-2,6-dihydroxy-5′-methyl-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-4-yl)octanoic acid, 9-((1′R,2′R)-2,6-dihydroxy-5′-methyl-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-4-yl)nonanoic acid, 11-((1′R,2′R)-2,6-dihydroxy-5′-methyl-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-4-yl)undecanoic acid, (1″R,2″R)-3′,5′-dihydroxy-5″-methyl-2″-(prop-1-en-2-yl)-1″,2″,3″,4″-tetrahydro-[1,1′:4′,1″-terphenyl]-2-carboxylic acid, (1″R,2″R)-3′,5′-dihydroxy-5″-methyl-2″-(prop-1-en-2-yl)-1″,2″,3″,4″-tetrahydro-[1,1′:4′,1″-terphenyl]-3-carboxylic acid, (1″R,2″R)-3′,5′-dihydroxy-5″-methyl-2″-(prop-1-en-2-yl)-1″,2″,3″,4″-tetrahydro-[1,1′:4′,1″-terphenyl]-4-carboxylic acid, (1″R,2″R)-3′,5′-dihydroxy-5″-methyl-2″-(prop-1-en-2-yl)-1″,2″,3″,4″-tetrahydro-[1,1′:4′,1″-terphenyl]-3,5-dicarboxylic acid, (1′R,2′R)-4-(4-hydroxybutyl)-5′-methyl-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-2,6-diol, (1′R,2′R)-4-(4-aminobutyl)-5′-methyl-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-2,6-diol, 5-((1′R,2′R)-2,6-dihydroxy-5′-methyl-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-4-yl)pentanenitrile, (1′R,2′R)-5′-methyl-4-(3-methylhexan-2-yl)-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-2,6-diol, (1′R,2′R)-5′-methyl-2′-(prop-1-en-2-yl)-4-propyl-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-2,6-diol, (1′R,2′R)-4-butyl-5′-methyl-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-2,6-diol, (1′R,2′R)-5′-methyl-4-pentyl-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-2,6-diol, (1′R,2′R)-4-heptyl-5′-methyl-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-2,6-diol, (1′R,2′R)-5′-methyl-4-(pent-4-en-1-yl)-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-2,6-diol, 3-((1′R,2′R)-2,6-dihydroxy-5′-methyl-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-4-yl)propanoic acid, (1′R,2′R)-4,5′-dimethyl-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-2,6-diol, 2-(( 1 ′R,2′R)-2,6-dihydroxy-5′-methyl-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-4-yl)acetic acid, 4-((1′R,2′R)-2,6-dihydroxy-5′-methyl-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-4-yl)butanoic acid, (1′R,2′R)-2,6-dihydroxy-5′-methyl-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-4-carboxylic acid, 5-(( 1 ′R,2′R)-2,6-dihydroxy-5′-methyl-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-4-yl)pentanoic acid, and 6-((1′R,2′R)-2,6-dihydroxy-5′-methyl-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-4-yl)hexanoic acid. In some embodiments, the cannabinoid or cannabinoid derivative is produced in an amount of more than 100 mg/L culture medium. In some embodiments, the cannabinoid or cannabinoid derivative is produced in an amount of more than 50 mg/L culture medium. 
     A cannabinoid derivative may also refer to a compound lacking one or more chemical moieties found in naturally-occurring cannabinoids, yet retains the core structural features (e.g., cyclic core) of a naturally-occurring cannabinoid. Such chemical moieties may include, but are not limited to, methyl, alkyl, alkenyl, methoxy, alkoxy, acetyl, carboxyl, carbonyl, oxo, ester, hydroxyl, and the like. In some embodiments, a cannabinoid derivative may also comprise one or more of any of the functional and/or reactive groups described herein. Functional and reactive groups may be unsubstituted or substituted with one or more functional or reactive groups. 
     A cannabinoid derivative may be a cannabinoid substituted with or comprising one or more functional and/or reactive groups. Functional groups may include, but are not limited to, azido, halo (e.g., chloride, bromide, iodide, fluorine), methyl, alkyl, alkynyl, alkenyl, methoxy, alkoxy, acetyl, amino, carboxyl, carbonyl, oxo, ester, hydroxyl, thio (e.g., thiol), cyano, aryl, heteroaryl, cycloalkyl, cycloalkenyl, cycloalkylalkenyl, cycloalkylalkynyl, cycloalkenylalkyl, cycloalkenylalkenyl, cycloalkenylalkynyl, heterocyclylalkenyl, heterocyclylalkynyl, heteroarylalkenyl, heteroarylalkynyl, arylalkenyl, arylalkynyl, spirocyclyl, heterospirocyclyl, heterocyclyl, thioalkyl (or alkylthio), arylthio, heteroarylthio, sulfone, sulfonyl, sulfoxide, amido, alkylamino, dialkylamino, arylamino, alkylarylamino, diarylamino, N-oxide, imide, enamine, imine, oxime, hydrazone, nitrile, aralkyl, cycloalkylalkyl, haloalkyl, heterocyclylalkyl, heteroarylalkyl, nitro, thioxo, and the like. Suitable reactive groups may include, but are not necessarily limited to, azide, carboxyl, carbonyl, amine (e.g., alkyl amine (e.g., lower alkyl amine), aryl amine), halide, ester (e.g., alkyl ester (e.g., lower alkyl ester, benzyl ester), aryl ester, substituted aryl ester), cyano, thioester, thioether, sulfonyl halide, alcohol, thiol, succinimidyl ester, isothiocyanate, iodoacetamide, maleimide, hydrazine, alkynyl, alkenyl, acetyl, and the like. In some embodiments, the reactive group is selected from a carboxyl, a carbonyl, an amine, an ester, a thioester, a thioether, a sulfonyl halide, an alcohol, a thiol, an alkyne, alkene, an azide, a succinimidyl ester, an isothiocyanate, an iodoacetamide, a maleimide, and a hydrazine. Functional and reactive groups may be unsubstituted or substituted with one or more functional or reactive groups. 
     “Alkyl” may refer to a straight or branched chain saturated hydrocarbon. For example, C 1 -C 6 alkyl groups contain 1 to 6 carbon atoms. Examples of a C 1 -C 6 alkyl group include, but are not limited to, methyl, ethyl, propyl, butyl, pentyl, isopropyl, isobutyl, sec-butyl and tert-butyl, isopentyl, and neopentyl. 
     “Alkenyl” may include an unbranched (i.e., straight) or branched hydrocarbon chain containing 2-12 carbon atoms. The “alkenyl” group contains at least one double bond. The double bond of an alkenyl group can be unconjugated or conjugated to another unsaturated group. Examples of alkenyl groups may include, but are not limited to, ethylenyl, vinyl, allyl, butenyl, pentenyl, hexenyl, butadienyl, pentadienyl, hexadienyl, 2-ethylhexenyl, 2-propyl-2-butenyl, 4-(2-methyl-3-butene)-pentenyl and the like. 
     Compounds disclosed herein, such as cannabinoids and cannabinoid derivatives, may be substituted with one or more substituents, such as those illustrated generally herein, or as exemplified by particular classes, subclasses, and species of the present disclosure. In general, the term “substituted” refers to the replacement of a hydrogen atom in a given structure with a specified substituent. Combinations of substituents envisioned by the present disclosure are typically those that result in the formation of stable or chemically feasible compounds. 
     As used herein, the term “unsubstituted” may mean that the specified group bears no substituents beyond the moiety recited (e.g., where valency satisfied by hydrogen). 
     A reactive group may facilitate covalent attachment of a molecule of interest. Suitable molecules of interest may include, but are not limited to, a detectable label; imaging agents; a toxin (including cytotoxins); a linker; a peptide; a drug (e.g., small molecule drugs); a member of a specific binding pair; an epitope tag; ligands for binding by a target receptor; tags to aid in purification; molecules that increase solubility; and the like. A linker may be a peptide linker or a non-peptide linker. 
     In some embodiments, a cannabinoid derivative substituted with an azide may be reacted with a compound comprising an alkyne group via “click chemistry” to generate a product comprising a heterocycle, also known as an azide-alkyne cycloaddition. In some embodiments, a cannabinoid derivative substituted with an alkyne may be reacted with a compound comprising an azide group via click chemistry to generate a product comprising a heterocycle. 
     Additional molecules of interest that may be desirable for attachment to a cannabinoid derivative may include, but are not necessarily limited to, detectable labels (e.g., spin labels, fluorescence resonance energy transfer (FRET)-type dyes, e.g., for studying structure of biomolecules in vivo); small molecule drugs; cytotoxic molecules (e.g., drugs); imaging agents; ligands for binding by a target receptor; tags to aid in purification by, for example, affinity chromatography (e.g., attachment of a FLAG epitope); molecules that increase solubility (e.g., poly(ethylene glycol)); molecules that enhance bioavailability; molecules that increase in vivo half-life; molecules that target to a particular cell type (e.g., an antibody specific for an epitope on a target cell); molecules that target to a particular tissue; molecules that provide for crossing the blood-brain barrier; and molecules to facilitate selective attachment to a surface, and the like. 
     In some embodiments, a molecule of interest comprises an imaging agent. Suitable imaging agents may include positive contrast agents and negative contrast agents. Suitable positive contrast agents may include, but are not limited to, gadolinium tetraazacyclododecanetetraacetic acid (Gd-DOTA); gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA); gadolinium-1,4,7-tris(carbonylmethyl)-10-(2′-hydroxypropyl)-1,4,7,10-tetraazacyclododecane (Gd-HP-DO3A); Manganese(II)-dipyridoxal diphosphate (Mn-DPDP); Gd-diethylenetriaminepentaacetate-bis(methylamide) (Gd-DTPA-BMA); and the like. Suitable negative contrast agents may include, but are not limited to, a superparamagnetic iron oxide (SPIO) imaging agent; and a perfluorocarbon, where suitable perfluorocarbons may include, but are not limited to, fluoroheptanes, fluorocycloheptanes, fluoromethylcycloheptanes, fluorohexanes, fluorocyclohexanes, fluoropentanes, fluorocyclopentanes, fluoromethylcyclopentanes, fluorodimethylcyclopentanes, fluoromethylcyclobutanes, fluorodimethylcyclobutanes, fluorotrimethylcyclobutanes, fluorobutanes, fluorocyclobutanse, fluoropropanes, fluoroethers, fluoropolyethers, fluorotriethylamines, perfluorohexanes, perfluoropentanes, perfluorobutanes, perfluoropropanes, sulfur hexafluoride, and the like. 
     Additional cannabinoid derivatives that can be produced with an engineered variant, method, or modified host cell of the present disclosure may include derivatives that have been modified via organic synthesis or an enzymatic route to modify drug metabolism and pharmacokinetics (e.g., solubility, bioavailability, absorption, distribution, plasma half-life and metabolic clearance). Modification examples may include, but are not limited to, halogenation, acetylation, and methylation. 
     The cannabinoids or cannabinoid derivatives described herein further include all pharmaceutically acceptable isotopically labeled cannabinoids or cannabinoid derivatives. An “isotopically-” or “radio-labeled” compound is a compound where one or more atoms are replaced or substituted by an atom having an atomic mass or mass number different from the atomic mass or mass number typically found in nature (i.e., naturally occurring). For example, in some embodiments, in the cannabinoids or cannabinoid derivatives described herein, hydrogen atoms are replaced or substituted by one or more deuterium or tritium. Certain isotopically labeled cannabinoids or cannabinoid derivatives of this disclosure, for example, those incorporating a radioactive isotope, are useful in drug and/or substrate tissue distribution studies. The radioactive isotopes tritium, i.e.,  3 H, and carbon 14, i.e.,  14 C, are particularly useful for this purpose in view of their ease of incorporation and ready means of detection. Substitution with heavier isotopes such as deuterium, i.e.,  2 H, may afford certain therapeutic advantages resulting from greater metabolic stability, for example, increased in vivo half-life or reduced dosage requirements, and hence may be preferred in some circumstances. Suitable isotopes that may be incorporated in cannabinoids or cannabinoid derivatives described herein include but are not limited to  2 H (also written as D for deuterium),  3 H (also written as T for tritium),  11 C,  13 C,  14 C,  13 N,  15 N,  15 O,  17 O,  18 O,  18 F,  35 S,  36 Cl,  82 Br,  75 Br,  76 Br,  77 Br,  123 I,  124 I,  125 I, and  131 I. Substitution with positron emitting isotopes, such as  11 C,  18 F,  15 O, and  13 N, can be useful in Positron Emission Topography (PET) studies. 
     The methods of bioproduction, modified host cells, and engineered variants disclosed herein enable synthesis of cannabinoids or cannabinoid derivatives with defined stereochemistries, which is challenging to do using chemical synthesis. Cannabinoids or cannabinoid derivatives disclosed herein may be enantiomers or disastereomers. The term “enantiomers” may refer to a pair of stereoisomers which are non-superimposable mirror images of one another. In some embodiments the cannabinoids or cannabinoid derivatives may be the (S)-enantiomer. In some embodiments the cannabinoids or cannabinoid derivatives may be the (R)-enantiomer. In some embodiments, the cannabinoids or cannabinoid derivatives may be the (+) or (−) enantiomers. The term “diastereomers” may refer to the set of stereoisomers which cannot be made superimposable by rotation around single bonds. For example, cis- and trans-double bonds, endo- and exo-substitution on bicyclic ring systems, and compounds containing multiple stereogenic centers with different relative configurations may be considered to be diastereomers. The term “diastereomer” may refer to any member of this set of compounds. Cannabinoids or cannabinoid derivatives disclosed herein may include a double bond or a fused ring. In certain such embodiments, the double bond or fused ring may be cis or trans, unless the configuration is specifically defined. If the cannabinoid or cannabinoid derivative contains a double bond, the substituent may be in the E or Z configuration, unless the configuration is specifically defined. 
     In some embodiments when the cannabinoid or cannabinoid derivative is recovered from a cell lysate; from a culture medium; from a modified host cell; from both the cell lysate and the culture medium; from both the modified host cell and the culture medium; from the cell lysate, the modified host cell, and the culture medium; or from a cell-free reaction mixture comprising one or more polypeptides and/or engineered variants disclosed herein, the recovered cannabinoid or cannabinoid derivative is in the form of a salt. In certain such embodiments, the salt is a pharmaceutically acceptable salt. In some embodiments, the salt of the recovered cannabinoid or cannabinoid derivative is then purified as disclosed herein. 
     The disclosure includes pharmaceutically acceptable salts of the cannabinoids or cannabinoid derivatives described herein. “Pharmaceutically acceptable salts” may refer to those salts which retain the biological effectiveness and properties of the free bases, which are not biologically or otherwise undesirable. Representative pharmaceutically acceptable salts include, but are not limited to, e.g., water-soluble and water-insoluble salts, such as the acetate, amsonate (4,4-diaminostilbene-2,2-disulfonate), benzenesulfonate, benzonate, bicarbonate, bisulfate, bitartrate, borate, bromide, butyrate, calcium, calcium edetate, camsylate, carbonate, chloride, citrate, clavulariate, dihydrochloride, edetate, edisylate, estolate, esylate, fiunarate, gluceptate, gluconate, glutamate, glycollylarsanilate, hexafluorophosphate, hexylresorcinate, hydrabamine, hydrobromide, hydrochloride, hydroxynaphthoate, iodide, sethionate, lactate, lactobionate, laurate, magnesium, malate, maleate, mandelate, mesylate, methylbromide, methylnitrate, methylsulfate, mucate, napsylate, nitrate, N-methylglucamine ammonium salt, 3-hydroxy-2-naphthoate, oleate, oxalate, palmitate, pamoate (1,1-methene-bis-2-hydroxy-3-naphthoate, einbonate), pantothenate, phosphate/diphosphate, picrate, polygalacturonate, propionate, p-toluenesulfonate, salicylate, stearate, subacetate, succinate, sulfate, sulfosalicylate, suramate, tannate, tartrate, teoclate, tosylate, triethiodide, and valerate salts. 
     “Pharmaceutically acceptable salt” also includes both acid and base addition salts. “Pharmaceutically acceptable acid addition salt” may refer to those salts which retain the biological effectiveness and properties of the free bases, which are not biologically or otherwise undesirable, and which are formed with inorganic acids such as, but are not limited to, hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid and the like, and organic acids such as, but not limited to, acetic acid, 2,2-dichloroacetic acid, adipic acid, alginic acid, ascorbic acid, aspartic acid, benzenesulfonic acid, benzoic acid, 4-acetamidobenzoic acid, camphoric acid, camphor-10-sulfonic acid, capric acid, caproic acid, caprylic acid, carbonic acid, cinnamic acid, citric acid, cyclamic acid, dodecylsulfuric acid, ethane-1,2-disulfonic acid, ethanesulfonic acid, 2-hydroxyethanesulfonic acid, formic acid, fumaric acid, galactaric acid, gentisic acid, glucoheptonic acid, gluconic acid, glucuronic acid, glutamic acid, glutaric acid, 2-oxo-glutaric acid, glycerophosphoric acid, glycolic acid, hippuric acid, isobutyric acid, lactic acid, lactobionic acid, lauric acid, maleic acid, malic acid, malonic acid, mandelic acid, methanesulfonic acid, mucic acid, naphthalene-1,5-disulfonic acid, naphthalene-2-sulfonic acid, 1-hydroxy-2-naphthoic acid, nicotinic acid, oleic acid, orotic acid, oxalic acid, palmitic acid, pamoic acid, propionic acid, pyroglutamic acid, pyruvic acid, salicylic acid, 4-aminosalicylic acid, sebacic acid, stearic acid, succinic acid, tartaric acid, thiocyanic acid, p-toluenesulfonic acid, trifluoroacetic acid, undecylenic acid, and the like. 
     “Pharmaceutically acceptable base addition salt” may refer to those salts which retain the biological effectiveness and properties of the free acids, which are not biologically or otherwise undesirable. These salts are prepared from addition of an inorganic base or an organic base to the free acid. Salts derived from inorganic bases include, but are not limited to, the sodium, potassium, lithium, ammonium, calcium, magnesium, iron, zinc, copper, manganese, aluminum salts and the like. For example, inorganic salts include, but are not limited to, ammonium, sodium, potassium, calcium, and magnesium salts. Salts derived from organic bases include, but are not limited to, salts of primary, secondary, and tertiary amines, substituted amines including naturally occurring substituted amines, cyclic amines and basic ion exchange resins, such as ammonia, isopropylamine, trimethylamine, diethylamine, triethylamine, tripropylamine, diethanolamine, ethanolamine, deanol, 2-dimethylaminoethanol, 2-diethylaminoethanol, dicyclohexylamine, lysine, arginine, histidine, caffeine, procaine, hydrabamine, choline, betaine, benethamine, benzathine, ethylenediamine, glucosamine, methylglucamine, theobromine, triethanolamine, tromethamine, purines, piperazine, piperidine, N-ethylpiperidine, polyamine resins and the like. 
     The disclosure provides a method of producing a cannabinoid or a cannabinoid derivative, the method comprising use of an engineered variant of the disclosure. In certain such embodiments, the cannabinoid or the cannabinoid derivative is produced in an amount, as measured in mg/L or mM, greater than an amount of the cannabinoid or the cannabinoid derivative produced in a method comprising use of a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3 instead of the engineered variant of the disclosure. In certain such embodiments, the engineered variant of the disclosure and the cannabidiolic acid synthase polypeptide having the amino acid sequence of SEQ ID NO:3 are used under similar conditions for the same length of time. In some embodiments of the methods of producing a cannabinoid or a cannabinoid derivative of the disclosure, the cannabinoid or the cannabinoid derivative is produced in an amount, as measured in mg/L or mM, at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 100%, at least 150% at least 200%, at least 500%, or at least 1000% greater than an amount of the cannabinoid or the cannabinoid derivative produced in a method comprising use of a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3 instead of the engineered variant of the disclosure. In certain such embodiments, the engineered variant of the disclosure and the cannabidiolic acid synthase polypeptide having the amino acid sequence of SEQ ID NO:3 are used under similar conditions for the same length of time. 
     In some embodiments of the methods of producing a cannabinoid or a cannabinoid derivative of the disclosure, the cannabinoid is CBDA and the method produces CBDA in an increased ratio of CBDA over THCA compared to that produced in a method comprising use of a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3 instead of the engineered variant of the disclosure. In certain such embodiments, the engineered variant of the disclosure and the cannabidiolic acid synthase polypeptide having the amino acid sequence of SEQ ID NO:3 are used under similar conditions for the same length of time. In some embodiments of the methods of producing a cannabinoid or a cannabinoid derivative of the disclosure, the cannabinoid is CBDA and the method produces CBDA from CBGA in a ratio of CBDA over THCA of about 11:1, about 11.5:1, about 12:1, about 12.5:1, about 13:1, about 13.5:1, about 14:1, about 14.5:1, about 15:1, about 15.5:1, about 16:1, about 16.5:1, about 17:1, about 17.5:1, about 18:1, about 18.5:1, about 19:1, about 19.5:1, about 20:1, about 25:1, about 30:1, about 35:1, about 40:1, about 45:1, about 50:1, about 60:1, about 70:1, about 80:1, about 90:1, about 100:1, about 150:1, about 200:1, about 500:1, or greater than about 500:1. 
     In some embodiments of the methods of producing a cannabinoid or a cannabinoid derivative of the disclosure, the cannabinoid is CBDA and the method produces CBDA in an increased ratio of CBDA over CBCA compared to that produced in a method comprising use of a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3 instead of the engineered variant of the disclosure. In certain such embodiments, the engineered variant of the disclosure and the cannabidiolic acid synthase polypeptide having the amino acid sequence of SEQ ID NO:3 are used under similar conditions for the same length of time. In some embodiments of the methods of producing a cannabinoid or a cannabinoid derivative of the disclosure, the cannabinoid is CBDA and the method produces CBDA from CBGA in a ratio of CBDA over CBCA of about 11:1, about 11.5:1, about 12:1, about 12.5:1, about 13:1, about 13.5:1, about 14:1, about 14.5:1, about 15:1, about 15.5:1, about 16:1, about 16.5:1, about 17:1, about 17.5:1, about 18:1, about 18.5:1, about 19:1, about 19.5:1, about 20:1, about 25:1, about 30:1, about 35:1, about 40:1, about 45:1, about 50:1, about 60:1, about 70:1, about 80:1, about 90:1, about 100:1, about 150:1, about 200:1, about 500:1, or greater than about 500:1. 
     Methods of Using Host Cells to Generate Cannabinoids or Cannabinoid Derivatives 
     The disclosure provides methods of producing a cannabinoid or a cannabinoid derivative, such as those described herein, the method comprising: culturing a modified host cell of the disclosure in a culture medium. In certain such embodiments, the method comprises recovering the produced cannabinoid or cannabinoid derivative. In certain such embodiments, the produced cannabinoid or cannabinoid derivative is then purified as disclosed herein. 
     In some embodiments, culturing of the modified host cells of the disclosure in a culture medium provides for synthesis of a cannabinoid or a cannabinoid derivative, such as those described herein, in an increased amount compared to an unmodified host cell cultured under similar conditions. 
     The disclosure provides methods of producing a cannabinoid or a cannabinoid derivative, such as those described herein, the method comprising: culturing a modified host cell of the disclosure in a culture medium comprising a carboxylic acid. In certain such embodiments, the method comprises recovering the produced cannabinoid or cannabinoid derivative. In certain such embodiments, the produced cannabinoid or cannabinoid derivative is then purified as disclosed herein. 
     In some embodiments, the cannabinoid or cannabinoid derivative is recovered from a cell lysate; from a culture medium; from a modified host cell; from both the cell lysate and the culture medium; from both the modified host cell and the culture medium; or from the cell lysate, the modified host cell, and the culture medium. In certain such embodiments, the recovered cannabinoid or cannabinoid derivative is then purified as disclosed herein. In some embodiments when the cannabinoid or cannabinoid derivative is recovered from the cell lysate; from the culture medium; from the modified host cell; from both the cell lysate and the culture medium; from both the modified host cell and the culture medium; or from the cell lysate, the modified host cell, and the culture medium, the recovered cannabinoid or cannabinoid derivative is in the form of a salt. In certain such embodiments, the salt is a pharmaceutically acceptable salt. In some embodiments, the salt of the recovered cannabinoid or cannabinoid derivative is then purified as disclosed herein. 
     In some embodiments, the modified host cell of the present disclosure is cultured in a culture medium comprising a carboxylic acid. In some embodiments, the carboxylic acid may be substituted with or comprise one or more functional and/or reactive groups. Functional groups may include, but are not limited to, azido, halo (e.g., chloride, bromide, iodide, fluorine), methyl, alkyl, alkynyl, alkenyl, methoxy, alkoxy, acetyl, amino, carboxyl, carbonyl, oxo, ester, hydroxyl, thio (e.g., thiol), cyano, aryl, heteroaryl, cycloalkyl, cycloalkenyl, cycloalkylalkenyl, cycloalkylalkynyl, cycloalkenylalkyl, cycloalkenylalkenyl, cycloalkenylalkynyl, heterocyclylalkenyl, heterocyclylalkynyl, heteroarylalkenyl, heteroarylalkynyl, arylalkenyl, arylalkynyl, spirocyclyl, heterospirocyclyl, heterocyclyl, thioalkyl (or alkylthio), arylthio, heteroarylthio, sulfone, sulfonyl, sulfoxide, amido, alkylamino, dialkylamino, arylamino, alkylarylamino, diarylamino, N-oxide, imide, enamine, imine, oxime, hydrazone, nitrile, aralkyl, cycloalkylalkyl, haloalkyl, heterocyclylalkyl, heteroarylalkyl, nitro, thioxo, and the like. Reactive groups may include, but are not necessarily limited to, azide, halogen, carboxyl, carbonyl, amine (e.g., alkyl amine (e.g., lower alkyl amine), aryl amine), ester (e.g., alkyl ester (e.g., lower alkyl ester, benzyl ester), aryl ester, substituted aryl ester), cyano, thioester, thioether, sulfonyl halide, alcohol, thiol, succinimidyl ester, isothiocyanate, iodoacetamide, maleimide, hydrazine, alkynyl, alkenyl, and the like. In some embodiments, the reactive group is selected from a carboxyl, a carbonyl, an amine, an ester, thioester, thioether, a sulfonyl halide, an alcohol, a thiol, a succinimidyl ester, an isothiocyanate, an iodoacetamide, a maleimide, an azide, an alkyne, an alkene, and a hydrazine. Functional and reactive groups may be unsubstituted or substituted with one or more functional or reactive groups. 
     In some embodiments, the carboxylic acid is isotopically- or radio-labeled. In some embodiments, the carboxylic acid may be an enantiomer or diastereomer. In some embodiments the carboxylic acid may be the (S)-enantiomer. In some embodiments the carboxylic acid may be the (R)-enantiomer. In some embodiments, the carboxylic acid may be the (+) or (−) enantiomer. In some embodiments, the carboxylic acid may include a double bond or a fused ring. In certain such embodiments, the double bond or fused ring may be cis or trans, unless the configuration is specifically defined. If the carboxylic acid contains a double bond, the substituent may be in the E or Z configuration, unless the configuration is specifically defined. 
     In some embodiments, the carboxylic acid comprises a C═C group. In some embodiments, the carboxylic acid comprises an alkyne group. In some embodiments, the carboxylic acid comprises an N 3  group. In some embodiments, the carboxylic acid comprises a halogen. In some embodiments, the carboxylic acid comprises a CN group. In some embodiments, the carboxylic acid comprises iodo. In some embodiments, the carboxylic acid comprises bromo. In some embodiments, the carboxylic acid comprises chloro. In some embodiments, the carboxylic acid comprises fluoro. In some embodiments, the carboxylic acid comprises a carbonyl. In some embodiments, the carboxylic acid comprises an acetyl. In some embodiments, the carboxylic acid comprises an alkyl group. In some embodiments, the carboxylic acid comprises an aryl group. 
     Carboxylic acids may include, but are not limited to, unsubstituted or substituted C 3 -C 18  fatty acids, C 3 -C 18  carboxylic acids, C 1 -C 18  carboxylic acids, butyric acid, isobutyric acid, valeric acid, hexanoic acid, heptanoic acid, octanoic acid, nonanoic acid, decanoic acid, undecanoic acid, lauric acid, myristic acid, C 15 -C 18  fatty acids, C 15 -C 18  carboxylic acids, fumaric acid, itaconic acid, malic acid, succinic acid, maleic acid, malonic acid, glutaric acid, glucaric acid, oxalic acid, adipic acid, pimelic acid, suberic acid, azelaic acid, sebacic acid, dodecanedioic acid, glutaconic acid, ortho-phthalic acid, isophthalic acid, terephthalic acid, citric acid, isocitric acid, aconitic acid, tricarballylic acid, and trimesic acid. Carboxylic acids may include unsubstituted or substituted C 1 -C 18  carboxylic acids. Carboxylic acids may include unsubstituted or substituted C 3 -C 18  carboxylic acids. Carboxylic acids may include unsubstituted or substituted C 3 -C 12  carboxylic acids. Carboxylic acids may include unsubstituted or substituted C 4 -C 10  carboxylic acids. In some embodiments, the carboxylic acid is an unsubstituted or substituted C 4  carboxylic acid. In some embodiments, the carboxylic acid is an unsubstituted or substituted C 5  carboxylic acid. In some embodiments, the carboxylic acid is an unsubstituted or substituted C 6  carboxylic acid. In some embodiments, the carboxylic acid is an unsubstituted or substituted C 7  carboxylic acid. In some embodiments, the carboxylic acid is an unsubstituted or substituted C 8  carboxylic acid. In some embodiments, the carboxylic acid is an unsubstituted or substituted C 9  carboxylic acid. In some embodiments, the carboxylic acid is an unsubstituted or substituted C 10  carboxylic acid. In some embodiments, the carboxylic acid is unsubstituted or substituted butyric acid. In some embodiments, carboxylic acid is unsubstituted or substituted valeric acid. In some embodiments, the carboxylic acid is unsubstituted or substituted hexanoic acid. In some embodiments, the carboxylic acid is unsubstituted or substituted heptanoic acid. In some embodiments, the carboxylic acid is unsubstituted or substituted octanoic acid. In some embodiments, the carboxylic acid is unsubstituted or substituted nonanoic acid. In some embodiments, the carboxylic acid is unsubstituted or substituted decanoic acid. 
     Carboxylic acids may include, but are not limited to, 2-methylhexanoic acid, 3-methylhexanoic acid, 4-methylhexanoic acid, 5-methylhexanoic acid, 2-hexenoic acid, 3-hexenoic acid, 4-hexenoic acid, 5-hexenoic acid, 5-chlorovaleric acid, 5-aminovaleric acid, 5-cyanovaleric acid, 5-(methylsulfanyl)valeric acid, 5-hydroxyvaleric acid, 5-phenylvaleric acid, 2,3-dimethylhexanoic acid, d3-hexanoic acid, 4-pentynoic acid, trans-2-pentenoic acid, 5-hexynoic acid, trans-2-hexenoic acid, 6-heptynoic acid, trans-2-octenoic acid, trans-2-nonenoic acid, 4-phenylbutyric acid, 6-phenylhexanoic acid, 7-phenylyheptanoic acid, and the like. In some embodiments, the carboxylic acid is 2-methylhexanoic acid. In some embodiments, the carboxylic acid is 3-methylhexanoic acid. In some embodiments, the carboxylic acid is 4-methylhexanoic acid. In some embodiments, the carboxylic acid is 5-methylhexanoic acid. In some embodiments, the carboxylic acid is 2-hexenoic acid. In some embodiments, the carboxylic acid is 3-hexenoic acid. In some embodiments, the carboxylic acid is 4-hexenoic acid. In some embodiments, the carboxylic acid is 5-hexenoic acid. In some embodiments, the carboxylic acid is 5-chlorovaleric acid. In some embodiments, the carboxylic acid is 5-aminovaleric acid. In some embodiments, the carboxylic acid is 5-cyanovaleric acid. In some embodiments, the carboxylic acid is 5-(methylsulfanyl)valeric acid. In some embodiments, the carboxylic acid is 5-hydroxyvaleric acid. In some embodiments, the carboxylic acid is 5-phenylvaleric acid. In some embodiments, the carboxylic acid is 2,3-dimethylhexanoic acid. In some embodiments, the carboxylic acid is d3-hexanoic acid. In some embodiments, the carboxylic acid is 4-pentynoic acid. In some embodiments, the carboxylic acid is trans-2-pentenoic acid. In some embodiments, the carboxylic acid is 5-hexynoic acid. In some embodiments, the carboxylic acid is trans-2-hexenoic acid. In some embodiments, the carboxylic acid is 6-heptynoic acid. In some embodiments, the carboxylic acid is trans-2-octenoic acid. In some embodiments, the carboxylic acid is trans-2-nonenoic acid. In some embodiments, the carboxylic acid is 4-phenylbutyric acid. In some embodiments, the carboxylic acid is 6-phenylhexanoic acid. In some embodiments, the carboxylic acid is 7-phenylheptanoic acid. 
     In some embodiments wherein the modified host cell of the present disclosure is cultured in a culture medium comprising a carboxylic acid, the carboxylic acid is an unsubstituted or substituted C 3 -C 18  carboxylic acid. In certain such embodiments, the unsubstituted or substituted C 3 -C 18  carboxylic acid is an unsubstituted or substituted hexanoic acid. In some embodiments, the cannabinoid or cannabinoid derivative is produced in an amount of more than 100 mg/L culture medium. In some embodiments, the cannabinoid or cannabinoid derivative is produced in an amount of more than 50 mg/L culture medium. 
     In some embodiments wherein the modified host cell of the present disclosure is cultured in a culture medium comprising a carboxylic acid, the carboxylic acid is butyric acid, valeric acid, hexanoic acid, octanoic acid, 2-methylhexanoic acid, 3-methylhexanoic acid, 4-methylhexanoic acid, 5-methylhexanoic acid, 2-hexenoic acid, 3-hexenoic acid, 4-hexenoic acid, 5-hexenoic acid, heptanoic acid, 5-chlorovaleric acid, 5-(methylsulfanyl)valeric acid, 4-pentynoic acid, trans-2-pentenoic acid, 5-hexynoic acid, trans-2-hexenoic acid, 6-heptynoic acid, trans-2-octenoic acid, nonanoic acid, trans-2-nonenoic acid, decanoic acid, undecanoic acid, dodecanoic acid, myristic acid, 4-phenylbutyric acid, 5-phenylvaleric acid, 6-phenylhexanoic acid, 7-phenylheptanoic acid, isobutyric acid, fumaric acid, itaconic acid, malic acid, succinic acid, maleic acid, malonic acid, glutaric acid, glucaric acid, oxalic acid, adipic acid, pimelic acid, suberic acid, azelaic acid, sebacic acid, dodecandioic acid, glutaconic acid, ortho-phthalic acid, isophthalic acid, terephthalic acid, citric acid, isocitric acid, aconitic acid, tricarballylic acid, trimesic acid, 5-aminovaleric acid, 5-cyanovaleric acid, 5-hydroxyvaleric acid, or 2,3-dimethylhexanoic acid. In some embodiments, the cannabinoid or cannabinoid derivative is produced in an amount of more than 100 mg/L culture medium. In some embodiments, the cannabinoid or cannabinoid derivative is produced in an amount of more than 50 mg/L culture medium. 
     In some embodiments wherein the modified host cell of the present disclosure is cultured in a culture medium comprising a carboxylic acid, the carboxylic acid is butyric acid, valeric acid, hexanoic acid, octanoic acid, 2-methylhexanoic acid, 3-methylhexanoic acid, 4-methylhexanoic acid, 5-methylhexanoic acid, 2-hexenoic acid, 3-hexenoic acid, 4-hexenoic acid, 5-hexenoic acid, heptanoic acid, 5-chlorovaleric acid, 5-(methylsulfanyl)valeric acid, 4-pentynoic acid, trans-2-pentenoic acid, 5-hexynoic acid, trans-2-hexenoic acid, 6-heptynoic acid, trans-2-octenoic acid, nonanoic acid, trans-2-nonenoic acid, decanoic acid, undecanoic acid, dodecanoic acid, myristic acid, 4-phenylbutyric acid, 5-phenylvaleric acid, 6-phenylhexanoic acid, 7-phenylheptanoic acid, isobutyric acid, fumaric acid, succinic acid, maleic acid, malonic acid, glutaric acid, oxalic acid, adipic acid, pimelic acid, suberic acid, azelaic acid, sebacic acid, dodecandioic acid, ortho-phthalic acid, isophthalic acid, terephthalic acid, trimesic acid, 5-aminovaleric acid, 5-cyanovaleric acid, 5-hydroxyvaleric acid, or 2,3-dimethylhexanoic acid. In some embodiments, the cannabinoid or cannabinoid derivative is produced in an amount of more than 100 mg/L culture medium. In some embodiments, the cannabinoid or cannabinoid derivative is produced in an amount of more than 50 mg/L culture medium. 
     In some embodiments wherein the modified host cell of the present disclosure is cultured in a culture medium comprising a carboxylic acid, the carboxylic acid is 2-methylhexanoic acid, 3-methylhexanoic acid, 4-methylhexanoic acid, 5-methylhexanoic acid, 2-hexenoic acid, 3-hexenoic acid, 4-hexenoic acid, heptanoic acid, 5-chlorovaleric acid, 5-(methylsulfanyl)valeric acid, 4-pentynoic acid, trans-2-pentenoic acid, 5-hexynoic acid, trans-2-hexenoic acid, 6-heptynoic acid, trans-2-octenoic acid, nonanoic acid, trans-2-nonenoic acid, decanoic acid, undecanoic acid, dodecanoic acid, myristic acid, 4-phenylbutyric acid, 5-phenylvaleric acid, 6-phenylhexanoic acid, 7-phenylheptanoic acid, isobutyric acid, fumaric acid, itaconic acid, malic acid, maleic acid, glucaric acid, suberic acid, azelaic acid, sebacic acid, dodecandioic acid, glutaconic acid, ortho-phthalic acid, isophthalic acid, terephthalic acid, citric acid, isocitric acid, aconitic acid, tricarballylic acid, trimesic acid, 5-aminovaleric acid, 5-cyanovaleric acid, 5-hydroxyvaleric acid, or 2,3-dimethylhexanoic acid. In some embodiments, the cannabinoid or cannabinoid derivative is produced in an amount of more than 100 mg/L culture medium. In some embodiments, the cannabinoid or cannabinoid derivative is produced in an amount of more than 50 mg/L culture medium. 
     In some embodiments wherein the modified host cell of the present disclosure is cultured in a culture medium comprising a carboxylic acid, the carboxylic acid is 2-methylhexanoic acid, 3-methylhexanoic acid, 4-methylhexanoic acid, 5-methylhexanoic acid, 2-hexenoic acid, 3-hexenoic acid, 4-hexenoic acid, heptanoic acid, 5-chlorovaleric acid, 5-(methylsulfanyl)valeric acid, 4-pentynoic acid, trans-2-pentenoic acid, 5-hexynoic acid, trans-2-hexenoic acid, 6-heptynoic acid, trans-2-octenoic acid, nonanoic acid, trans-2-nonenoic acid, decanoic acid, undecanoic acid, dodecanoic acid, myristic acid, 4-phenylbutyric acid, 5-phenylvaleric acid, 6-phenylhexanoic acid, 7-phenylheptanoic acid, isobutyric acid, fumaric acid, maleic acid, suberic acid, azelaic acid, sebacic acid, dodecandioic acid, ortho-phthalic acid, isophthalic acid, terephthalic acid, trimesic acid, 5-aminovaleric acid, 5-cyanovaleric acid, 5-hydroxyvaleric acid, or 2,3-dimethylhexanoic acid. In some embodiments, the cannabinoid or cannabinoid derivative is produced in an amount of more than 100 mg/L culture medium. In some embodiments, the cannabinoid or cannabinoid derivative is produced in an amount of more than 50 mg/L culture medium. 
     In some embodiments wherein the modified host cell of the present disclosure is cultured in a culture medium comprising a carboxylic acid, the carboxylic acid is 4-pentynoic acid, trans-2-pentenoic acid, 5-hexynoic acid, trans-2-hexenoic acid, 6-heptynoic acid, trans-2-octenoic acid, nonanoic acid, trans-2-nonenoic acid, decanoic acid, undecanoic acid, dodecanoic acid, 4-phenylbutyric acid, 5-phenylvaleric acid, 6-phenylhexanoic acid, or 7-phenylheptanoic acid. In some embodiments, the cannabinoid or cannabinoid derivative is produced in an amount of more than 100 mg/L culture medium. In some embodiments, the cannabinoid or cannabinoid derivative is produced in an amount of more than 50 mg/L culture medium. 
     In some embodiments wherein the modified host cell of the present disclosure is cultured in a culture medium comprising a carboxylic acid, the carboxylic acid is 2-methylhexanoic acid, 4-methylhexanoic acid, 5-methylhexanoic acid, 2-hexenoic acid, 3-hexenoic acid, 4-hexenoic acid, heptanoic acid, 5-chlorovaleric acid, or 5-(methylsulfanyl)valeric acid. In some embodiments, the cannabinoid or cannabinoid derivative is produced in an amount of more than 100 mg/L culture medium. In some embodiments, the cannabinoid or cannabinoid derivative is produced in an amount of more than 50 mg/L culture medium. 
     The disclosure also provides methods of producing a cannabinoid or a cannabinoid derivative, such as those described herein, the method comprising: culturing a modified host cell of the disclosure in a culture medium comprising olivetolic acid or an olivetolic acid derivative. In certain such embodiments, the method comprises recovering the produced cannabinoid or cannabinoid derivative. In certain such embodiments, the produced cannabinoid or cannabinoid derivative is then purified as disclosed herein. 
     Olivetolic acid derivatives used herein may be substituted with or comprise one or more reactive and/or functional groups as disclosed herein. In some embodiments, an olivetolic acid derivative may lack one or more chemical moieties found in olivetolic acid. In some embodiments when the culture medium comprises an olivetolic acid derivative, the olivetolic acid derivative is orsellinic acid. In some embodiments when the culture medium comprises an olivetolic acid derivative, the olivetolic acid derivative is divarinic acid. In some embodiments, the cannabinoid or cannabinoid derivative is produced in an amount of more than 100 mg/L culture medium. In some embodiments, the cannabinoid or cannabinoid derivative is produced in an amount of more than 50 mg/L culture medium. 
     The disclosure provides methods of using a modified host cell of the disclosure for producing a cannabinoid or cannabinoid derivative. In some embodiments of the methods of using a modified host cell of the disclosure for producing a cannabinoid or cannabinoid derivative, the cannabinoid or the cannabinoid derivative is produced in an amount, as measured in mg/L or mM, greater than an amount of the cannabinoid or the cannabinoid derivative produced in a method instead comprising culturing a modified host cell comprising one or more nucleic acids comprising a nucleotide sequence encoding a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3, but lacking a nucleic acid comprising a nucleotide sequence encoding an engineered variant. In certain such embodiments, the modified host cell of the disclosure and the modified host cell comprising one or more nucleic acids comprising the nucleotide sequence encoding the cannabidiolic acid synthase polypeptide having the amino acid sequence of SEQ ID NO:3, but lacking a nucleic acid comprising a nucleotide sequence encoding an engineered variant, are cultured under similar culture conditions for the same length of time. 
     In some embodiments of the methods of using a modified host cell of the disclosure for producing a cannabinoid or cannabinoid derivative, the cannabinoid or the cannabinoid derivative is produced in an amount, as measured in mg/L or mM, at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 100%, at least 150% at least 200%, at least 500%, or at least 1000% greater than an amount of the cannabinoid or the cannabinoid derivative produced in a method instead comprising culturing a modified host cell comprising one or more nucleic acids comprising a nucleotide sequence encoding a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3, but lacking a nucleic acid comprising a nucleotide sequence encoding an engineered variant. In certain such embodiments, the modified host cell of the disclosure and the modified host cell comprising one or more nucleic acids comprising the nucleotide sequence encoding the cannabidiolic acid synthase polypeptide having the amino acid sequence of SEQ ID NO:3, but lacking a nucleic acid comprising a nucleotide sequence encoding an engineered variant, are cultured under similar culture conditions for the same length of time. 
     In some embodiments of the methods of using a modified host cell of the disclosure for producing a cannabinoid or cannabinoid derivative, the cannabinoid is CBDA and the method produces CBDA in an increased ratio of CBDA over THCA compared to that produced in a method instead comprising culturing a modified host cell comprising one or more nucleic acids comprising a nucleotide sequence encoding a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3, but lacking a nucleic acid comprising a nucleotide sequence encoding an engineered variant, grown under similar culture conditions for the same length of time. In some embodiments of the methods of using a modified host cell of the disclosure for producing a cannabinoid or cannabinoid derivative, the cannabinoid is CBDA and the method produces CBDA from CBGA in a ratio of CBDA over THCA of about 11:1, about 11.5:1, about 12:1, about 12.5:1, about 13:1, about 13.5:1, about 14:1, about 14.5:1, about 15:1, about 15.5:1, about 16:1, about 16.5:1, about 17:1, about 17.5:1, about 18:1, about 18.5:1, about 19:1, about 19.5:1, about 20:1, about 25:1, about 30:1, about 35:1, about 40:1, about 45:1, about 50:1, about 60:1, about 70:1, about 80:1, about 90:1, about 100:1, about 150:1, about 200:1, about 500:1, or greater than about 500:1. 
     In some embodiments of the methods of using a modified host cell of the disclosure for producing a cannabinoid or cannabinoid derivative, the cannabinoid is CBDA and the method produces CBDA in an increased ratio of CBDA over CBCA compared to that produced in a method instead comprising culturing a modified host cell comprising one or more nucleic acids comprising a nucleotide sequence encoding a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3, but lacking a nucleic acid comprising a nucleotide sequence encoding an engineered variant, grown under similar culture conditions for the same length of time. In some embodiments of the methods of using a modified host cell of the disclosure for producing a cannabinoid or cannabinoid derivative, the cannabinoid is CBDA and the method produces CBDA from CBGA in a ratio of CBDA over CBCA of about 11:1, about 11.5:1, about 12:1, about 12.5:1, about 13:1, about 13.5:1, about 14:1, about 14.5:1, about 15:1, about 15.5:1, about 16:1, about 16.5:1, about 17:1, about 17.5:1, about 18:1, about 18.5:1, about 19:1, about 19.5:1, about 20:1, about 25:1, about 30:1, about 35:1, about 40:1, about 45:1, about 50:1, about 60:1, about 70:1, about 80:1, about 90:1, about 100:1, about 150:1, about 200:1, about 500:1, or greater than about 500:1. 
     Exemplary Cell Culture Conditions 
     Suitable media for culturing modified host cells of the disclosure may include standard culture media (e.g., Luria-Bertani broth, optionally supplemented with one or more additional agents, such as an inducer (e.g., where nucleic acids disclosed herein are under the control of an inducible promoter, etc.); standard yeast culture media; and the like). In some embodiments, the culture medium can be supplemented with a fermentable sugar (e.g., a hexose sugar or a pentose sugar, e.g., glucose, xylose, galactose, and the like). Sugars fermentable by yeast may include, but are not limited to, sucrose, dextrose, glucose, fructose, mannose, galactose, and maltose. 
     In some embodiments, the culture medium can be supplemented with unsubstituted or substituted hexanoic acid, carboxylic acids other than unsubstituted or substituted hexanoic acid, olivetolic acid, or olivetolic acid derivatives. In some embodiments, the culture medium can be supplemented with pretreated cellulosic feedstock (e.g., wheat grass, wheat straw, barley straw, sorghum, rice grass, sugarcane straw, bagasse, switchgrass, corn stover, corn fiber, grains, or any combination thereof). In some embodiments, the culture medium can be supplemented with oleic acid. In some embodiments, the culture medium comprises a non-fermentable carbon source. In certain such embodiments, the non-fermentable carbon source comprises ethanol. In some embodiments, the suitable media comprises an inducer. In certain such embodiments, the inducer comprises galactose. In some embodiments, the inducer comprises KH 2 PO 4 , galactose, glucose, sucrose, maltose, an amino acid (e.g., methionine, lysine), CuSO 4 , a change in temperature (e.g., 30° C. to 37° C.), a change in pH (e.g., pH 6 to pH 4), a change in oxygen level (e.g., 20% to 1% dissolved oxygen levels), addition of hydrogen peroxide or superoxide-generating drug menadione, tunicamycin, expression of proteins prone to misfolding (e.g., cannabinoid synthases), estradiol, or doxycycline. Additional induction systems are detailed herein. 
     The carbon source in the suitable media can vary significantly, from simple sugars like glucose to more complex hydrolysates of other biomass, such as yeast extract. The addition of salts generally provide essential elements such as magnesium, nitrogen, phosphorus, and sulfur to allow the cells to synthesize polypeptides and nucleic acids. The suitable media can also be supplemented with selective agents, such as antibiotics, to select for the maintenance of certain plasmids and the like. For example, if a microorganism is resistant to a certain antibiotic, such as ampicillin or tetracycline, then that antibiotic can be added to the medium in order to prevent cells lacking the resistance from growing. The suitable media can be supplemented with other compounds as necessary to select for desired physiological or biochemical characteristics, such as particular amino acids and the like. 
     In some embodiments, modified host cells disclosed herein are grown in minimal medium or minimal media. As used herein, the terms “minimal medium” or “minimal media” may refer to media comprising a defined composition of nutrients, generally chosen for minimal cost, while still allowing for robust growth and production. As used herein, the terms “minimal medium” or “minimal media” may refer to media containing: (1) one or more carbon sources for cellular (e.g., bacterial or yeast) growth; (2) various salts, which can vary among cellular (e.g., bacterial or yeast) species and growing conditions; (3) vitamins and trace elements; and (4) water. Generally, but not always, minimal media lacks one or more amino acids (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more amino acids). Minimal media may also comprise growth factors, inducers, and repressors. In some embodiments, minimal media or minimal medium affords higher biomass formation in a fermentation tank compared to rich medium or rich media. In some embodiments, the minimal medium or minimal media comprises a carboxylic acid (e.g., 1 mM olivetolic acid, 1 mM olivetolic acid derivative, 2 mM unsubstituted or substituted hexanoic acid, or 2 mM of a carboxylic acid other than unsubstituted or substituted hexanoic acid). 
     In some embodiments, modified host cells disclosed herein are grown in rich medium or rich media. In certain such embodiments, the rich medium or rich media comprises yeast extract peptone dextrose (YPD) media comprising water, yeast extract, Bacto peptone, and dextrose (glucose). In certain such embodiments, the rich medium or rich media comprises yeast extract peptone dextrose (YPD) media comprising water, 10 g/L yeast extract, 20 g/L Bacto peptone, and 20 g/L dextrose (glucose). In some embodiments, the rich medium or rich media comprises YP+galactose and glucose. In some embodiments, the rich medium or rich media comprises YP+20 g/L galactose or YP+40 g/L galactose and 1 g/L glucose. In some embodiments, the rich medium or rich media comprises a carboxylic acid (e.g., 1 mM olivetolic acid, 1 mM olivetolic acid derivative, 2 mM unsubstituted or substituted hexanoic acid, or 2 mM of a carboxylic acid other than unsubstituted or substituted hexanoic acid). In some embodiments, rich medium or rich media affords greater cell density in fermentation compared to minimal media or minimal medium. 
     Materials and methods suitable for the maintenance and growth of the recombinant cells of the disclosure are described herein, e.g., in the Examples section. Other materials and methods suitable for the maintenance and growth of cell (e.g., bacterial or yeast) cultures are well known in the art. Exemplary techniques can be found in International Publication No. WO2009/076676, U.S. patent application Ser. No. 12/335,071 (U.S. Publ. No. 2009/0203102), WO 2010/003007, US Publ. No. 2010/0048964, WO 2009/132220, US Publ. No. 2010/0003716, Manual of Methods for General Bacteriology Gerhardt et al, eds), American Society for Microbiology, Washington, D.C. (1994) or Brock in Biotechnology: A Textbook of Industrial Microbiology, Second Edition (1989) Sinauer Associates, Inc., Sunderland, Mass. 
     Standard cell culture conditions can be used to culture the modified host cells disclosed herein (see, for example, WO 2004/033646 and references cited therein). In some embodiments, cells are grown and maintained at an appropriate temperature, gas mixture, and pH (such as at about 20° C. to about 37° C., at about 0.04% to about 84% CO 2 , at about 0% to about 100% dissolved oxygen, and at a pH between about 2 to about 9). In some embodiments, modified host cells disclosed herein are grown at about 34° C. in a suitable cell culture medium. In some embodiments, modified host cells disclosed herein are grown at about 20° C. to about 37° C. in a suitable cell culture medium. While the growth optimum for  S. cerevisiae  is about 30° C., culturing cells at a higher temperature, e.g., 34° C. may be advantageous by reducing the costs to cool industrial fermentation tanks. In some embodiments, modified host cells disclosed herein are grown at about 20° C., about 21° C., about 22° C., about 23° C., about 24° C., about 25° C., about 26° C., about 27° C., about 28° C., about 29° C., about 30° C., about 31° C., about 32° C., about 33° C., about 34° C., about 35° C., about 36° C., or about 37° C. in a suitable cell culture medium. In some embodiments, the pH ranges for fermentation are between about pH 3.0 to about pH 9.0 (such as about pH 3.0, about pH 3.5, about pH 4.0, about pH 4.5, about pH 5.0, about pH 5.5, about pH 6.0, about pH 6.5, about pH 7.0, about pH 7.5, about pH 8.0, about pH 8.5, about pH 6.0 to about pH 8.0 or about pH 6.5 to about pH 7.0). In some embodiments, the pH ranges for fermentation are between about pH 4.5 to about pH 5.5. In some embodiments, the pH ranges for fermentation are between about pH 4.0 to about pH 6.0. In some embodiments, the pH ranges for fermentation are between about pH 3.0 to about pH 6.0. In some embodiments, the pH ranges for fermentation are between about pH 3.0 to about pH 5.5. In some embodiments, the pH ranges for fermentation are between about pH 3.0 to about pH 5.0. In some embodiments, the dissolved oxygen is between about 0% to about 10%, about 0% to about 20%, about 0% to about 30%, about 0% to about 40%, about 0% to about 50%, about 0% to about 60%, about 0% to about 70%, about 0% to about 80%, about 0% to about 90%, about 5% to about 10%, about 5% to about 20%, about 5% to about 30%, about 5% to about 40%, about 5% to about 50%, about 5% to about 60%, about 5% to about 70%, about 5% to about 80%, about 5% to about 90%, about 10% to about 20%, about 10% to about 30%, about 10% to about 40% or about 10% to about 50%. In some embodiments, the CO 2  level is between about 0.04% to about 0.1% CO 2 , about 0.04% to about 1% CO 2 , about 0.04% to about 5% CO 2 , about 0.04% to about 10% CO 2 , about 0.04% to about 20% CO 2 , about 0.04% to about 30% CO 2 , about 0.04% to about 40% CO 2 , about 0.04% to about 50% CO 2 , about 0.04% to about 60% CO 2 , about 0.04% to about 70% CO 2 , about 0.1% to about 5% CO 2 , about 0.1% to about 10% CO 2 , about 0.1% to about 20% CO 2 , about 0.1% to about 30% CO 2 , about 0.1% to about 40% CO 2 , about 0.1% to about 50% CO 2 , about 1% to about 5% CO 2 , about 1% to about 10% CO 2 , about 1% to about 20% CO 2 , about 1% to about 30% CO 2 , about 1% to about 40% CO 2 , about 1% to about 50% CO 2 , about 5% to about 10% CO 2 , about 10% to about 20% CO 2 , about 10% to about 30% CO 2 , about 10% to about 40% CO 2 , about 10% to about 50% CO 2 , about 10% to about 60% CO 2 , about 10% to about 70% CO 2 , about 10% to about 80% CO 2 , about 50% to about 60% CO 2 , about 50% to about 70% CO 2 , or about 50% to about 80% CO 2 . Modified host cells disclosed herein disclosed herein can be grown under aerobic, anoxic, microaerobic, or anaerobic conditions based on the requirements of the cells. 
     Standard culture conditions and modes of fermentation, such as batch, fed-batch, or continuous fermentation that can be used are described in International Publication No. WO 2009/076676, U.S. patent application Ser. No. 12/335,071 (U.S. Publ. No. 2009/0203102), WO 2010/003007, US Publ. No. 2010/0048964, WO 2009/132220, US Publ. No. 2010/0003716, the contents of each of which are incorporated by reference herein in their entireties. Batch and Fed-Batch fermentations are common and well known in the art and examples can be found in Brock, Biotechnology: A Textbook of Industrial Microbiology, Second Edition (1989) Sinauer Associates, Inc. 
     Production and Recovery of Produced Cannabinoids or Cannabinoid Derivatives 
     The present disclosure provides for production of a cannabinoid or a cannabinoid derivative. In some embodiments, a method of the present disclosure provides for production of a cannabinoid or a cannabinoid derivative, such as those disclosed herein, by modified host cells of the disclosure in an amount of from about 1 mg/L culture medium to about 1 g/L culture medium. In some embodiments, a method of the present disclosure provides for production of a cannabinoid or a cannabinoid derivative in an amount of from about 1 mg/L culture medium to about 500 mg/L culture medium. In some embodiments, a method of the present disclosure provides for production of a cannabinoid or a cannabinoid derivative in an amount of from about 1 mg/L culture medium to about 100 mg/L culture medium. For example, in some embodiments, a method of the present disclosure provides for production of a cannabinoid or a cannabinoid derivative in an amount of from about 1 mg/L culture medium to about 5 mg/L culture medium, from about 5 mg/L culture medium to about 10 mg/L culture medium, from about 10 mg/L culture medium to about 25 mg/L culture medium, from about 25 mg/L culture medium to about 50 mg/L culture medium, from about 50 mg/L culture medium to about 75 mg/L culture medium, or from about 75 mg/L culture medium to about 100 mg/L culture medium. In some embodiments, a method of the present disclosure provides for production of a cannabinoid or a cannabinoid derivative in an amount of from about 100 mg/L culture medium to about 150 mg/L culture medium, from about 150 mg/L culture medium to about 200 mg/L culture medium, from about 200 mg/L culture medium to about 250 mg/L culture medium, from about 250 mg/L culture medium to about 500 mg/L culture medium, from about 500 mg/L culture medium to about 750 mg/L culture medium, or from about 750 mg/L culture medium to about 1 g/L culture medium. In some embodiments, a method of the present disclosure provides for production of a cannabinoid or a cannabinoid derivative in an amount of from about from about 50 mg/L culture medium to about 100 mg/L culture medium, 50 mg/L culture medium to about 150 mg/L culture medium, from about 50 mg/L culture medium to about 200 mg/L culture medium, from about 50 mg/L culture medium to about 250 mg/L culture medium, from about 50 mg/L culture medium to about 500 mg/L culture medium, or from about 50 mg/L culture medium to about 750 mg/L culture medium. 
     In some embodiments, a method of the present disclosure provides for production of a cannabinoid or a cannabinoid derivative, such as those disclosed herein, in an amount of from about 50 mg/L culture medium to about 100 g/L culture medium, or more than 100 g/L culture medium. In some embodiments, a method of the present disclosure provides for production of a cannabinoid or a cannabinoid derivative, such as those disclosed herein, in an amount of from about 50 mg/L culture medium to about 100 mg/L culture medium, or more than 100 mg/L culture medium. In some embodiments, a method of the present disclosure provides for production of a cannabinoid or a cannabinoid derivative, such as those disclosed herein, in an amount of more than 50 mg/L culture medium. In some embodiments, a method of the present disclosure provides for production of a cannabinoid or a cannabinoid derivative, such as those disclosed herein, in an amount of more than 100 mg/L culture medium. In some embodiments, a method of the present disclosure provides for production of a cannabinoid or a cannabinoid derivative in an amount of from about 100 mg/L culture medium to about 500 mg/L culture medium, or more than 500 mg/L culture medium. In some embodiments, a method of the present disclosure provides for production of a cannabinoid or a cannabinoid derivative in an amount of from about 500 mg/L culture medium to about 1 g/L culture medium, or more than 1 g/L culture medium. In some embodiments, a method of the present disclosure provides for production of a cannabinoid or a cannabinoid derivative in an amount of from about 1 g/L culture medium to about 10 g/L culture medium, or more than 10 g/L culture medium. In some embodiments, a method of the present disclosure provides for production of a cannabinoid or a cannabinoid derivative in an amount of from about 10 g/L culture medium to about 100 g/L culture medium, or more than 100 g/L culture medium. In some embodiments, a method of the present disclosure provides for production of a cannabinoid or a cannabinoid derivative in an amount of from about 1 g/L culture medium to about 20 g/L culture medium, or more than 20 g/L culture medium. In some embodiments, a method of the present disclosure provides for production of a cannabinoid or a cannabinoid derivative in an amount of from about 1 g/L culture medium to about 30 g/L culture medium, or more than 30 g/L culture medium. In some embodiments, a method of the present disclosure provides for production of a cannabinoid or a cannabinoid derivative in an amount of from about 1 g/L culture medium to about 40 g/L culture medium, or more than 40 g/L culture medium. In some embodiments, a method of the present disclosure provides for production of a cannabinoid or a cannabinoid derivative in an amount of from about 1 g/L culture medium to about 50 g/L culture medium, or more than 50 g/L culture medium. In some embodiments, a method of the present disclosure provides for production of a cannabinoid or a cannabinoid derivative in an amount of from about 1 g/L culture medium to about 60 g/L culture medium, or more than 60 g/L culture medium. In some embodiments, a method of the present disclosure provides for production of a cannabinoid or a cannabinoid derivative in an amount of from about 1 g/L culture medium to about 70 g/L culture medium, or more than 70 g/L culture medium. In some embodiments, a method of the present disclosure provides for production of a cannabinoid or a cannabinoid derivative in an amount of from about 1 g/L culture medium to about 80 g/L culture medium, or more than 80 g/L culture medium. In some embodiments, a method of the present disclosure provides for production of a cannabinoid or a cannabinoid derivative in an amount of from about 1 g/L culture medium to about 90 g/L culture medium, or more than 90 g/L culture medium. In some embodiments, a method of the present disclosure provides for production of a cannabinoid or a cannabinoid derivative in an amount of from about 10 g/L culture medium to about 20 g/L culture medium, or more than 20 g/L culture medium. In some embodiments, a method of the present disclosure provides for production of a cannabinoid or a cannabinoid derivative in an amount of from about 10 g/L culture medium to about 30 g/L culture medium, or more than 30 g/L culture medium. In some embodiments, a method of the present disclosure provides for production of a cannabinoid or a cannabinoid derivative in an amount of from about 10 g/L culture medium to about 40 g/L culture medium, or more than 40 g/L culture medium. In some embodiments, a method of the present disclosure provides for production of a cannabinoid or a cannabinoid derivative in an amount of from about 10 g/L culture medium to about 50 g/L culture medium, or more than 50 g/L culture medium. In some embodiments, a method of the present disclosure provides for production of a cannabinoid or a cannabinoid derivative in an amount of from about 10 g/L culture medium to about 60 g/L culture medium, or more than 60 g/L culture medium. In some embodiments, a method of the present disclosure provides for production of a cannabinoid or a cannabinoid derivative in an amount of from about 10 g/L culture medium to about 70 g/L culture medium, or more than 70 g/L culture medium. In some embodiments, a method of the present disclosure provides for production of a cannabinoid or a cannabinoid derivative in an amount of from about 10 g/L culture medium to about 80 g/L culture medium, or more than 80 g/L culture medium. In some embodiments, a method of the present disclosure provides for production of a cannabinoid or a cannabinoid derivative in an amount of from about 10 g/L culture medium to about 90 g/L culture medium, or more than 90 g/L culture medium. In some embodiments, a method of the present disclosure provides for production of a cannabinoid or a cannabinoid derivative in an amount of from about 50 g/L culture medium to about 100 g/L culture medium, or more than 100 g/L culture medium. In some embodiments, a method of the present disclosure provides for production of a cannabinoid or a cannabinoid derivative in an amount of from about 50 g/L culture medium to about 60 g/L culture medium, or more than 60 g/L culture medium. In some embodiments, a method of the present disclosure provides for production of a cannabinoid or a cannabinoid derivative in an amount of from about 50 g/L culture medium to about 70 g/L culture medium, or more than 70 g/L culture medium. In some embodiments, a method of the present disclosure provides for production of a cannabinoid or a cannabinoid derivative in an amount of from about 50 g/L culture medium to about 80 g/L culture medium, or more than 80 g/L culture medium. In some embodiments, a method of the present disclosure provides for production of a cannabinoid or a cannabinoid derivative in an amount of from about 50 g/L culture medium to about 90 g/L culture medium, or more than 90 g/L culture medium. In some embodiments, a method of the present disclosure provides for production of a cannabinoid or a cannabinoid derivative in an amount of from about 20 g/L culture medium to about 100 g/L culture medium, or more than 100 g/L culture medium. In some embodiments, a method of the present disclosure provides for production of a cannabinoid or a cannabinoid derivative in an amount of from about 20 g/L culture medium to about 30 g/L culture medium, or more than 30 g/L culture medium. In some embodiments, a method of the present disclosure provides for production of a cannabinoid or a cannabinoid derivative in an amount of from about 20 g/L culture medium to about 40 g/L culture medium, or more than 40 g/L culture medium. In some embodiments, a method of the present disclosure provides for production of a cannabinoid or a cannabinoid derivative in an amount of from about 20 g/L culture medium to about 50 g/L culture medium, or more than 50 g/L culture medium. In some embodiments, a method of the present disclosure provides for production of a cannabinoid or a cannabinoid derivative in an amount of from about 20 g/L culture medium to about 60 g/L culture medium, or more than 60 g/L culture medium. In some embodiments, a method of the present disclosure provides for production of a cannabinoid or a cannabinoid derivative in an amount of from about 20 g/L culture medium to about 70 g/L culture medium, or more than 70 g/L culture medium. In some embodiments, a method of the present disclosure provides for production of a cannabinoid or a cannabinoid derivative in an amount of from about 20 g/L culture medium to about 80 g/L culture medium, or more than 80 g/L culture medium. In some embodiments, a method of the present disclosure provides for production of a cannabinoid or a cannabinoid derivative in an amount of from about 20 g/L culture medium to about 90 g/L culture medium, or more than 90 g/L culture medium. 
     In some embodiments, the modified host cell disclosed herein is cultured in a liquid medium comprising a carboxylic acid, olivetolic acid, or an olivetolic acid derivative. 
     In some embodiments, a method of producing a cannabinoid or a cannabinoid derivative, such as those disclosed herein, may involve culturing a modified yeast cell of the present disclosure under conditions that favor production of a cannabinoid or a cannabinoid derivative; wherein the cannabinoid or the cannabinoid derivative is produced by the modified yeast cell and is present in the culture medium (e.g., a liquid culture medium) in which the modified yeast cell is cultured. In some embodiments, the culture medium in which the modified yeast cell is cultured comprises a cannabinoid or a cannabinoid derivative in an amount of from 1 ng/L to 1 g/L (e.g., from 1 ng/L to 50 ng/L, from 50 ng/L to 100 ng/L, from 100 ng/L to 500 ng/L, from 500 ng/L to 1 μg/L, from 1 μg/L to 50 μg/L, from 50 μg/L to 100 μg/L, from 100 μg/L to 500 μg/L, from 500 μg/L to 1 mg/L, from 1 mg/L to 50 mg/L, from 50 mg/L to 100 mg/L, from 100 mg/L to 500 mg/L, or from 500 mg/L to 1 g/L). In certain such embodiments, the modified yeast cell is a modified  S. cerevisiae . In some embodiments, the culture medium in which the modified yeast cell is cultured comprises a cannabinoid or a cannabinoid derivative in an amount from 50 mg/L to 100 mg/L. In certain such embodiments, the modified yeast cell is a modified  S. cerevisiae . In some embodiments, the culture medium in which the modified yeast cell is cultured comprises a cannabinoid or a cannabinoid derivative in an amount from 100 mg/L to 500 mg/L. In certain such embodiments, the modified yeast cell is a modified  S. cerevisiae . In some embodiments, the culture medium in which the modified yeast cell is cultured comprises a cannabinoid or a cannabinoid derivative in an amount from 500 mg/L to 1 g/L. In certain such embodiments, the modified yeast cell is a modified  S. cerevisiae . In some embodiments, the culture medium in which the modified yeast cell is cultured comprises a cannabinoid or a cannabinoid derivative in an amount more than 1 g/L. In certain such embodiments, the modified yeast cell is a modified  S. cerevisiae.    
     In some embodiments, a method of producing a cannabinoid or a cannabinoid derivative, such as those disclosed herein, may involve culturing a modified yeast cell of the present disclosure under conditions that favor fermentation of a sugar, and under conditions that favor production of a cannabinoid or a cannabinoid derivative; wherein the cannabinoid or the cannabinoid derivative is produced by the modified yeast cell and is present in alcohol produced by the modified yeast cell. The present disclosure provides an alcoholic beverage produced by the modified yeast cell, where the alcoholic beverage comprises the cannabinoid or cannabinoid derivative produced by the modified yeast cell. Alcoholic beverages may include beer, wine, and distilled alcoholic beverages. In some embodiments, an alcoholic beverage of the present disclosure comprises a cannabinoid or a cannabinoid derivative in an amount of from 1 ng/L to 1 g/L (e.g., from 1 ng/L to 50 ng/L, from 50 ng/L to 100 ng/L, from 100 ng/L to 500 ng/L, from 500 ng/L to 1 μg/L, from 1 μg/L to 50 μg/L, from 50 μg/L to 100 μg/L, from 100 μg/L to 500 μg/L, from 500 μg/L to 1 mg/L, from 1 mg/L to 50 mg/L, from 50 mg/L to 100 mg/L, from 100 mg/L to 500 mg/L, or from 500 mg/L to 1 g/L). In some embodiments, an alcoholic beverage of the present disclosure comprises a cannabinoid or a cannabinoid derivative in an amount more than 1 g/L. 
     The present disclosure provides a beverage produced by the modified yeast cell, where the beverage comprises the cannabinoid or cannabinoid derivative, such as those disclosed herein, produced by the modified yeast cell. In some embodiments, a beverage of the present disclosure comprises a cannabinoid or a cannabinoid derivative in an amount of from 1 ng/L to 1 g/L (e.g., from 1 ng/L to 50 ng/L, from 50 ng/L to 100 ng/L, from 100 ng/L to 500 ng/L, from 500 ng/L to 1 μg/L, from 1 μg/L to 50 μg/L, from 50 μg/L to 100 μg/L, from 100 μg/L to 500 μg/L, from 500 μg/L to 1 mg/L, from 1 mg/L to 50 mg/L, from 50 mg/L to 100 mg/L, from 100 mg/L to 500 mg/L, or from 500 mg/L to 1 g/L). In some embodiments, a beverage of the present disclosure comprises a cannabinoid or a cannabinoid derivative in an amount more than 1 g/L. In some embodiments, a beverage of the present disclosure is non-alcoholic. 
     In some embodiments, a method of the present disclosure provides for increased production of a cannabinoid or a cannabinoid derivative, such as those disclosed herein. In certain such embodiments, culturing of the modified host cell disclosed herein in a culture medium provides for synthesis of a cannabinoid or a cannabinoid derivative in an increased amount compared to an unmodified host cell cultured under similar conditions. The production of a cannabinoid or a cannabinoid derivative by the modified host cells disclosed herein may be increased by about 5% to about 1,000,000 folds compared to an unmodified host cell cultured under similar conditions. The production of a cannabinoid or a cannabinoid derivative by the modified host cells disclosed herein may be increased by about 10% to about 1,000,000 folds (e.g., about 50% to about 1,000,000 folds, about 1 to about 500,000 folds, about 1 to about 50,000 folds, about 1 to about 5,000 folds, about 1 to about 1,000 folds, about 1 to about 500 folds, about 1 to about 100 folds, about 1 to about 50 folds, about 5 to about 100,000 folds, about 5 to about 10,000 folds, about 5 to about 1,000 folds, about 5 to about 500 folds, about 5 to about 100 folds, about 10 to about 50,000 folds, about 50 to about 10,000 folds, about 100 to about 5,000 folds, about 200 to about 1,000 folds, about 50 to about 500 folds, or about 50 to about 200 folds) compared to the production of a cannabinoid or a cannabinoid derivative by unmodified host cells cultured under similar conditions. The production of a cannabinoid or a cannabinoid derivative by modified host cells disclosed herein may also be increased by at least about any of 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 1 fold, 2 folds, 5 folds, 10 folds, 20 folds, 50 folds, 100 folds, 200 folds, 500 folds, 1000 folds, 2000 folds, 5000 folds, 10,000 folds, 20,000 folds, 50,000 folds, 100,000 folds, 200,000 folds, 500,000 folds, or 1,000,000 folds or more compared to the production of a cannabinoid or a cannabinoid derivative by unmodified host cells cultured under similar conditions. 
     In some embodiments, the production of a cannabinoid or a cannabinoid derivative, such as those disclosed herein, by modified host cells of the disclosure may also be increased by at least about any of 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% compared to the production of a cannabinoid or a cannabinoid derivative by unmodified host cells cultured under similar conditions. In some embodiments, the production of a cannabinoid or a cannabinoid derivative by modified host cells disclosed herein may also be increased by at least about any of 1-20%, 2-20%, 5-20%, 10-20%, 15-20%, 1-15%, 1-10%, 2-15%, 2-10%, 5-15%, 10-15%, 1-50%, 10-50%, 20-50%, 30-50%, 40-50%, 50-100%, 50-60%, 50-70%, 50-80%, 50-90%, or 50-100% compared to the production of a cannabinoid or a cannabinoid derivative by unmodified host cells cultured under similar conditions. 
     In some embodiments, production of a cannabinoid or a cannabinoid derivative by modified host cells of the disclosure is determined by LC-MS analysis. In certain such embodiments, each cannabinoid or cannabinoid derivative is identified by retention time, determined from an authentic standard, and multiple reaction monitoring (MRM) transition. 
     In some embodiments, the modified host cell of the disclosure is a yeast cell. In certain such embodiments, the modified host cell disclosed herein is cultured in a bioreactor. In some embodiments, the modified host cell is cultured in a culture medium supplemented with unsubstituted or substituted hexanoic acid, a carboxylic acid other than unsubstituted or substituted hexanoic acid, olivetolic acid, or an olivetolic acid derivative. In some embodiments, the modified yeast cell is a modified  S. cerevisiae.    
     In some embodiments, the cannabinoid or cannabinoid derivative, such as those disclosed herein, is recovered from a cell lysate, e.g., by lysing the modified host cell disclosed herein and recovering the cannabinoid or cannabinoid derivative derivative from the lysate. In other cases, the cannabinoid or cannabinoid derivative is recovered from the culture medium in which the modified host cell disclosed herein is cultured. In other cases, the cannabinoid or cannabinoid derivative is recovered from both the cell lysate and the culture medium. In other cases, the cannabinoid or cannabinoid derivative is recovered from a modified host cell. In other cases, the cannabinoid or cannabinoid derivative is recovered from both the modified host cell and the culture medium. In other cases, the cannabinoid or cannabinoid derivative is recovered from the cell lysate, the modified host cell, and the culture medium. In some embodiments when the cannabinoid or cannabinoid derivative is recovered from a cell lysate; from a culture medium; from a modified host cell; from both the cell lysate and the culture medium; from both the modified host cell and the culture medium; or from the cell lysate, the modified host cell, and the culture medium, the recovered cannabinoid or cannabinoid derivative is in the form of a salt. In certain such embodiments, the salt is a pharmaceutically acceptable salt. In some embodiments, the salt of the recovered cannabinoid or cannabinoid derivative is then purified as disclosed herein. 
     In some embodiments, the recovered cannabinoid or cannabinoid derivative, such as those disclosed herein, is then purified. In some embodiments, whole-cell broth from cultures comprising modified host cells of the disclosure may be extracted with a suitable organic solvent to afford cannabinoids or cannabinoid derivatives. Suitable organic solvents include, but are not limited to, hexane, heptane, ethyl acetate, petroleum ether, and di-ethyl ether, chloroform, and ethyl acetate. In some embodiments, the suitable organic solvent comprises hexane. In some embodiments, the suitable organic solvent may be added to the whole-cell broth from fermentations comprising modified host cells of the disclosure at a 10:1 ratio (10 parts whole-cell broth−1 part organic solvent) and stirred for 30 minutes. In certain such embodiments, the organic fraction may be separated and extracted twice with an equal volume of acidic water (pH 2.5). The organic layer may then be separated and dried in a concentrator (rotary evaporator or thin film evaporator under reduced pressure) to obtain crude cannabinoid or cannabinoid derivative crystals. In certain such embodiments, the crude crystals may be heated or exposed to light to decarboxylate the crude cannabinoid or cannabinoid derivative. In certain such embodiments, the crude crystals may be heated to 105° C. for 15 minutes followed by 145° C. for 55 minutes to decarboxylate the crude cannabinoid or cannabinoid derivative. In certain such embodiments, the crude crystalline product may be re-dissolved and recrystallized in a suitable solvent (e.g., n-pentane) and filtered to remove any insoluble material. In certain such embodiments, the solvent may then be removed e.g., by rotary evaporation, to produce pure crystalline product. 
     In some embodiments, the cannabinoid or cannabinoid derivative is pure, e.g., at least about 40% pure, at least about 50% pure, at least about 60% pure, at least about 70% pure, at least about 80% pure, at least about 90% pure, at least about 95% pure, at least about 98%, or more than 98% pure, where “pure” in the context of a cannabinoid or a cannabinoid derivative may refer to a cannabinoid or a cannabinoid derivative that is free from other cannabinoids or cannabinoid derivatives, macromolecules, contaminants, etc. 
     Methods of Preparing Engineered Variants of a Cannabidiolic Acid Synthase (CBDAS) Polypeptide 
     In an aspect, the present disclosure provides methods for preparing engineered variants of a cannabidiolic acid synthase (CBDAS) polypeptide. In certain such embodiments, the methods may comprise culturing a modified host cell of the disclosure in a culture medium. In some embodiments, the modified host cell of the disclosure is a  Pichia  sp. The method can comprise isolating and/or purifying the expressed engineered variants, as described herein. 
     In some embodiments, the method for preparing engineered variants comprises the step of isolating or purifying the engineered variants. The engineered variants of the disclosure can be expressed in modified host cells, as described herein, and isolated from the modified host cells and/or culture medium using any one or more of the well known techniques used for protein purification, including, among others, lysozyme treatment, sonication, filtration, salting-out, ultra-centrifugation, and chromatography. Chromatographic techniques for isolation of the engineered variants of the disclosure may include, among others, reverse phase chromatography high performance liquid chromatography, ion exchange chromatography, gel electrophoresis, and affinity chromatography. In some embodiments, affinity chromatography is used. 
     In some embodiments, the engineered variants of the disclosure expressed in the modified host cells of the disclosure can be prepared and used in various forms including but not limited to crude extracts (e.g., cell-free lysates), powders (e.g., shake-flask powders), lyophilizates, frozen stocks made with glycerol or another cryoprotectant, and substantially pure preparations (e.g., DSP powders). 
     In some embodiments, the engineered variants of the disclosure expressed in the modified host cells of the disclosure can be prepared and used in purified form. Generally, conditions for purifying a particular engineered variant will depend, in part, on factors such as net charge, hydrophobicity, hydrophilicity, molecular weight, molecular shape, etc., and will be apparent to those having skill in the art. 
     Cell-Free Methods of Producing Cannabinoids or Cannabinoid Derivatives 
     The methods of the disclosure may involve cell-free production of cannabinoids or cannabinoid derivatives, such as those disclosed herein, using engineered variants disclosed herein expressed or overexpressed by a modified host cell of the disclosure. In some embodiments, an engineered variant disclosed herein is used in a cell-free system for the production of cannabinoids or cannabinoid derivatives. In certain such embodiments, the engineered variant of the disclosure is isolated and/or purified. In some embodiments, appropriate starting materials for use in producing cannabinoids or cannabinoid derivatives may be mixed together with engineered variants disclosed herein in a suitable reaction vessel to effect the reaction. The engineered variants disclosed herein may be used in combination to effect a complete synthesis of a cannabinoid or cannabinoid derivative from the appropriate starting materials. In some embodiments, the cannabinoid or cannabinoid derivative is recovered from a cell-free reaction mixture comprising engineered disclosed herein. 
     In some embodiments, the recovered cannabinoids or cannabinoid derivatives, such as those disclosed herein, are then purified. In certain such embodiments, a cell-free reaction mixture comprising an engineered variant disclosed herein may be extracted with a suitable organic solvent to afford cannabinoids or cannabinoid derivatives. Suitable organic solvents include, but are not limited to, hexane, heptane, ethyl acetate, petroleum ether, and di-ethyl ether, chloroform, and ethyl acetate. In some embodiments, the suitable organic solvent comprises hexane. In some embodiments, the suitable organic solvent may be added to the cell-free reaction mixture comprising one or more of the polypeptides disclosed herein at a 10:1 ratio (10 parts reaction mixture−1 part organic solvent) and stirred for 30 minutes. In certain such embodiments, the organic fraction may be separated and extracted twice with an equal volume of acidic water (pH 2.5). The organic layer may then be separated and dried in a concentrator (rotary evaporator or thin film evaporator under reduced pressure) to obtain crude cannabinoid or cannabinoid derivative crystals. In certain such embodiments, the crude crystals may be heated or exposed to light to decarboxylate the crude cannabinoid or cannabinoid derivative. In certain such embodiments, the crude crystals may be heated to 105° C. for 15 minutes followed by 145° C. for 55 minutes to decarboxylate the crude cannabinoid or cannabinoid derivative. In certain such embodiments, the crude crystalline product may be re-dissolved and recrystallized in a suitable solvent (e.g., n-pentane) and filtered to remove any insoluble material. In certain such embodiments, the solvent may then be removed e.g., by rotary evaporation, to produce pure crystalline product. 
     In some embodiments when the cannabinoid or cannabinoid derivative is recovered from a cell-free reaction mixture comprising one or more engineered variants disclosed herein, the recovered cannabinoid or cannabinoid derivative is in the form of a salt. In certain such embodiments, the salt is a pharmaceutically acceptable salt. In some embodiments, the salt of the recovered cannabinoid or cannabinoid derivative is then purified as disclosed herein. 
     In some embodiments, cell-free production of a cannabinoid or a cannabinoid derivative by engineered variants disclosed herein is determined by LC-MS analysis. In certain such embodiments, each cannabinoid or cannabinoid derivative is identified by retention time, determined from an authentic standard, and multiple reaction monitoring (MRM) transition. 
     In some embodiments when the cannabinoid or cannabinoid derivative is recovered from a cell-free reaction mixture comprising one or more polypeptides and/or engineered variants disclosed herein, the recovered cannabinoid or cannabinoid derivative is in the form of a salt. In certain such embodiments, the salt is a pharmaceutically acceptable salt. In some embodiments, the salt of the recovered cannabinoid or cannabinoid derivative is then purified as disclosed herein. 
     Examples of Non-Limiting Embodiments of the Disclosure 
     Embodiments of the present subject matter disclosed herein may be beneficial alone or in combination with one or more other embodiments. Without limiting the foregoing description, certain non-limiting embodiments of the disclosure, numbered I-1 to I-132 are provided below. As will be apparent to those of skill in the art upon reading this disclosure, each of the individually numbered embodiments may be used or combined with any of the preceding or following individually numbered embodiments. This is intended to provide support for all such combinations of embodiments and is not limited to combinations of embodiments explicitly provided below. 
     Some embodiments of the disclosure are of Embodiment I: 
     Embodiment I-1. An engineered variant of a cannabidiolic acid synthase (CBDAS) polypeptide comprising an amino acid sequence of SEQ ID NO:3 with one or more amino acid substitutions. 
     Embodiment I-2. The engineered variant of Embodiment I-1, wherein the engineered variant comprises an amino acid sequence with at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO:3. 
     Embodiment I-3. The engineered variant of Embodiment I-1 or I-2, wherein the engineered variant comprises at least one amino acid substitution in a signal polypeptide, a flavin adenine dinucleotide (FAD) binding domain, a berberine bridge enzyme (BBE) domain, or a combination of the foregoing. 
     Embodiment I-4. The engineered variant of Embodiment I-3, wherein the engineered variant comprises at least one amino acid substitution in the signal polypeptide. 
     Embodiment I-5. The engineered variant of Embodiment I-3 or I-4, wherein the engineered variant comprises at least one amino acid substitution in the FAD binding domain. 
     Embodiment I-6. The engineered variant of any one of Embodiments I-3 to I-5, wherein the engineered variant comprises at least one amino acid substitution in the BBE domain. 
     Embodiment I-7. The engineered variant of any one of Embodiments I-3 to I-6, wherein the engineered variant comprises substitution of at least one surface exposed amino acid. 
     Embodiment I-8. The engineered variant of Embodiment I-1 or I-2, wherein the engineered variant comprises at least one amino acid substitution at an amino acid selected from the group consisting of C12, F17, F18, S20, R31, N33, P43, L49, K50, L51, Q55, N56, N57, L59, M61, S62, V63, S66, L71, S75, I97, L98, S100, V103, T109, Q124, V125, I129, L132, S137, H143, V149, W161, K165, E167, N168, S170, L171, A172, Y175, C180, A181, N196, H208, A235, A250, M256, K260, L268, H309, T310, F316, L326, G378, K389, E406, S428, L439, N466, K474, Y499, N527, P538, R541, H542, R543, and H544. 
     Embodiment I-9. The engineered variant of Embodiment I-8, wherein the engineered variant comprises at least one amino acid substitution at an amino acid selected from the group consisting of R31, P43, L49, K50, L51, Q55, N56, N57, M61, S62, L71, I97, S100, V103, T109, Q124, V125, I129, L132, S137, H143, V149, W161, K165, E167, N168, S170, L171, A172, Y175, C180, A181, N196, H208, A235, A250, M256, K260, L268, H309, T310, F316, L326, G378, K389, S428, L439, N466, K474, Y499, N527, P538, R541, H542, R543, and H544. 
     Embodiment I-10. The engineered variant of Embodiment I-8 or I-9, wherein the engineered variant comprises at least one amino acid substitution at an amino acid selected from the group consisting of L49, K50, N56, N57, V125, L132, V149, W161, K165, S170, L171, A172, N196, A235, K260, L268, T310, F316, L326, G378, S428, Y499, N527, H543, and H544. 
     Embodiment I-11. The engineered variant of Embodiment I-8 or I-9, wherein the engineered variant comprises at least one amino acid substitution at an amino acid selected from the group consisting of R541, H542, R543, and H544. 
     Embodiment I-12. The engineered variant of Embodiment I-1 or I-2, wherein the engineered variant comprises at least one amino acid substitution at an amino acid selected from the group consisting of R31, N57, M61, L71, S170, A172, Y175, N196, H208, A235, K260, G378, K389, and R543. 
     Embodiment I-13. The engineered variant of Embodiment I-12, wherein the engineered variant comprises at least one amino acid substitution at an amino acid selected from the group consisting of N57, S170, A172, N196, A235, K260, and G378. 
     Embodiment I-14. The engineered variant of Embodiment I-1 or I-2, wherein the engineered variant comprises at least one amino acid substitution selected from the group consisting of C12F, F17M, F18T, F18W, S20G, R31Q, N33K, P43E, L49E, L49K, L49Q, K50T, L51I, Q55E, Q55P, N56E, N57D, N57E, L59E, M61H, M61S, M61W, S62N, S62Q, V63M, S66D, L71A, L71H, L71Q, S75D, S75E, I97V, L98V, S100A, V103A, V103F, T109V, Q124D, Q124E, Q124N, V125E, V125Q, I129V, L132M, S137G, H143D, V149I, W161K, W161R, W161Y, K165A, E167P, N168S, S170T, L171I, A172V, Y175F, C180A, A181V, N196Q, N196T, N196V, H208T, A235P, A250T, M256V, K260C, K260W, L268I, H309V, T310A, T310C, F316Y, L326I, G378T, G378S, K389E, E406K, S428L, L439M, N466D, K474S, Y499M, Y499V, N527E, P538T, R541E, R541V, H542V, R543A, R543E, H544E, and H544D. 
     Embodiment I-15. The engineered variant of Embodiment I-14, wherein the engineered variant comprises at least one amino acid substitution selected from the group consisting of R31Q, P43E, L49E, L49K, L49Q, K50T, L51I, Q55E, Q55P, N56E, N57D, M61H, M61S, M61W, S62Q, L71A, L71Q, I97V, S100A, V103A, V103F, T109V, Q124D, Q124E, Q124N, V125E, V125Q, I129V, L132M, S137G, H143D, V149I, W161K, W161R, W161Y, K165A, E167P, N168S, S170T, L171I, A172V, Y175F, C180A, A181V, N196Q, N196T, N196V, H208T, A235P, A250T, M256V, K260C, K260W, L268I, H309V, T310A, T310C, F316Y, L326I, G378T, G378S, K389E, S428L, L439M, N466D, K474S, Y499M, Y499V, N527E, P538T, R541E, R541V, H542V, R543A, R543E, H544E, and H544D. 
     Embodiment I-16. The engineered variant of Embodiment I-14 or I-15, wherein the engineered variant comprises at least one amino acid substitution selected from the group consisting of L49E, L49Q, K50T, N56E, N57D, V125E, L132M, V149I, W161R, K165A, S170T, L171I, A172V, N196Q, N196T, N196V, A235P, K260W, K260C, L268I, T310A, T310C, F316Y, L326I, G378T, S428L, Y499M, Y499V, N527E, H543E, and H544E. 
     Embodiment I-17. The engineered variant of Embodiment I-14 or I-15, wherein the engineered variant comprises at least one amino acid substitution selected from the group consisting of R541E, R541V, H542V, R543A, R543E, H544E, and H544D. 
     Embodiment I-18. The engineered variant of Embodiment I-1 or I-2, wherein the engineered variant comprises at least one amino acid substitution selected from the group consisting of R31Q, N57D, M61W, L71H, S170T, A172V, Y175F, N196V, H208T, A235P, K260W, G378T, K389E, and R543E. 
     Embodiment I-19. The engineered variant of Embodiment I-18, wherein the engineered variant comprises at least one amino acid substitution selected from the group consisting of N57D, S170T, A172V, N196V, A235P, K260W, and G378T. 
     Embodiment I-20. The engineered variant of Embodiment I-1 or I-2, wherein the engineered variant comprises an amino acid sequence selected from the group consisting of SEQ ID NO:50, SEQ ID NO:52, SEQ ID NO:54, SEQ ID NO:56, SEQ ID NO:58, SEQ ID NO:60, SEQ ID NO:62, SEQ ID NO:64, SEQ ID NO:66, SEQ ID NO:68, SEQ ID NO:70, SEQ ID NO:72, SEQ ID NO:74, SEQ ID NO:76, SEQ ID NO:78, SEQ ID NO:80, SEQ ID NO:82, SEQ ID NO:84, SEQ ID NO:86, SEQ ID NO:88, SEQ ID NO:90, SEQ ID NO:92, SEQ ID NO:94, SEQ ID NO:96, SEQ ID NO:98, SEQ ID NO:100, SEQ ID NO:102, SEQ ID NO:104, SEQ ID NO:106, SEQ ID NO:108, SEQ ID NO:110, SEQ ID NO:112, SEQ ID NO:114, SEQ ID NO:116, SEQ ID NO:118, SEQ ID NO:120, SEQ ID NO:122, SEQ ID NO:124, SEQ ID NO:126, SEQ ID NO:128, SEQ ID NO:130, SEQ ID NO:132, SEQ ID NO:134, SEQ ID NO:136, SEQ ID NO:138, SEQ ID NO:140, SEQ ID NO:142, SEQ ID NO:144, SEQ ID NO:146, SEQ ID NO:148, SEQ ID NO:150, SEQ ID NO:152, SEQ ID NO:154, SEQ ID NO:156, SEQ ID NO:158, SEQ ID NO:160, SEQ ID NO:162, SEQ ID NO:164, SEQ ID NO:166, SEQ ID NO:168, SEQ ID NO:170, SEQ ID NO:172, SEQ ID NO:174, SEQ ID NO:176, SEQ ID NO:178, SEQ ID NO:180, SEQ ID NO:182, SEQ ID NO:184, SEQ ID NO:186, SEQ ID NO:188, SEQ ID NO:190, SEQ ID NO:192, SEQ ID NO:194, SEQ ID NO:196, SEQ ID NO:198, SEQ ID NO:200, SEQ ID NO:202, SEQ ID NO:204, SEQ ID NO:206, SEQ ID NO:208, SEQ ID NO:210, SEQ ID NO:212, SEQ ID NO:214, SEQ ID NO:216, SEQ ID NO:218, SEQ ID NO:220, SEQ ID NO:222, SEQ ID NO:224, SEQ ID NO:226, SEQ ID NO:228, SEQ ID NO:230, SEQ ID NO:232, and SEQ ID NO:234. 
     Embodiment I-21. The engineered variant of Embodiment I-20, wherein the engineered variant comprises an amino acid sequence selected from the group consisting of SEQ ID NO:60, SEQ ID NO:64, SEQ ID NO:66, SEQ ID NO:68, SEQ ID NO:70, SEQ ID NO:72, SEQ ID NO:74, SEQ ID NO:76, SEQ ID NO:78, SEQ ID NO:80, SEQ ID NO:82, SEQ ID NO:88, SEQ ID NO:90, SEQ ID NO:92, SEQ ID NO:96, SEQ ID NO:102, SEQ ID NO:106, SEQ ID NO:112, SEQ ID NO:116, SEQ ID NO:118, SEQ ID NO:120, SEQ ID NO:122, SEQ ID NO:124, SEQ ID NO:126, SEQ ID NO:128, SEQ ID NO:130, SEQ ID NO:132, SEQ ID NO:134, SEQ ID NO:136, SEQ ID NO:138, SEQ ID NO:140, SEQ ID NO:142, SEQ ID NO:144, SEQ ID NO:146, SEQ ID NO:148, SEQ ID NO:150, SEQ ID NO:152, SEQ ID NO:154, SEQ ID NO:156, SEQ ID NO:158, SEQ ID NO:160, SEQ ID NO:162, SEQ ID NO:164, SEQ ID NO:166, SEQ ID NO:168, SEQ ID NO:170, SEQ ID NO:172, SEQ ID NO:174, SEQ ID NO:176, SEQ ID NO:178, SEQ ID NO:180, SEQ ID NO:182, SEQ ID NO:184, SEQ ID NO:186, SEQ ID NO:188, SEQ ID NO:190, SEQ ID NO:192, SEQ ID NO:194, SEQ ID NO:196, SEQ ID NO:198, SEQ ID NO:200, SEQ ID NO:202, SEQ ID NO:206, SEQ ID NO:208, SEQ ID NO:210, SEQ ID NO:212, SEQ ID NO:214, SEQ ID NO:216, SEQ ID NO:218, SEQ ID NO:220, SEQ ID NO:222, SEQ ID NO:224, SEQ ID NO:226, SEQ ID NO:228, SEQ ID NO:230, SEQ ID NO:232, and SEQ ID NO:234. 
     Embodiment I-22. The engineered variant of Embodiment I-20 or I-21, wherein the engineered variant comprises an amino acid sequence selected from the group consisting of SEQ ID NO:66, SEQ ID NO:70, SEQ ID NO:72, SEQ ID NO:80, SEQ ID NO:82, SEQ ID NO:130, SEQ ID NO:136, SEQ ID NO:142, SEQ ID NO:146, SEQ ID NO:150, SEQ ID NO:156, SEQ ID NO:158, SEQ ID NO:160, SEQ ID NO:168, SEQ ID NO:170, SEQ ID NO:172, SEQ ID NO:176, SEQ ID NO:182, SEQ ID NO:184, SEQ ID NO:186, SEQ ID NO:190, SEQ ID NO:192, SEQ ID NO:194, SEQ ID NO:196, SEQ ID NO:198, SEQ ID NO:206, SEQ ID NO:214, SEQ ID NO:216, SEQ ID NO:218, SEQ ID NO:230, and SEQ ID NO:232. 
     Embodiment I-23. The engineered variant of Embodiment I-20 or I-21, wherein the engineered variant comprises an amino acid sequence selected from the group consisting of SEQ ID NO:222, SEQ ID NO:224, SEQ ID NO:226, SEQ ID NO:228, SEQ ID NO:230, SEQ ID NO:232, and SEQ ID NO:234. 
     Embodiment I-24. The engineered variant of Embodiment I-1 or I-2, wherein the engineered variant comprises an amino acid sequence selected from the group consisting of SEQ ID NO:60, SEQ ID NO:82, SEQ ID NO:92, SEQ ID NO:104, SEQ ID NO:156, SEQ ID NO:160, SEQ ID NO:162, SEQ ID NO:172, SEQ ID NO:174, SEQ ID NO:176, SEQ ID NO:184, SEQ ID NO:198, SEQ ID NO:202, and SEQ ID NO:230. 
     Embodiment I-25. The engineered variant of Embodiment I-24, wherein the engineered variant comprises an amino acid sequence selected from the group consisting of SEQ ID NO:82, SEQ ID NO:156, SEQ ID NO:160, SEQ ID NO:172, SEQ ID NO:176, SEQ ID NO:184, and SEQ ID NO:198. 
     Embodiment I-26. The engineered variant of any one of Embodiments I-1 to I-19, wherein the engineered variant comprises an amino acid sequence of SEQ ID NO:3 with at least 1, at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 21, at least 22, at least 23, at least 24, at least 25, at least 26, at least 27, at least 28, at least 29, or at least 30 amino acid substitutions. 
     Embodiment I-27. The engineered variant of any one of Embodiments I-1 to I-26, wherein the engineered variant comprises at least one immutable amino acid in a flavin adenine dinucleotide (FAD) binding domain, a berberine bridge enzyme (BBE) domain, or a combination of the foregoing. 
     Embodiment I-28. The engineered variant of Embodiment I-27, wherein the engineered variant comprises at least one immutable amino acid in the FAD binding domain. 
     Embodiment I-29. The engineered variant of Embodiment I-28, wherein the engineered variant comprises at least 1, at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, or at least 15 immutable amino acids in the FAD binding domain. 
     Embodiment I-30. The engineered variant of any one of Embodiments I-27 to I-29, wherein the engineered variant comprises at least one immutable amino acid in the BBE domain. 
     Embodiment I-31. The engineered variant of Embodiment I-30, wherein the engineered variant comprises at least 1, at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, or at least 15 immutable amino acids in the BBE domain. 
     Embodiment I-32. The engineered variant of any one of Embodiments I-1 to I-19, wherein the engineered variant comprises at least one immutable amino acid selected from the group consisting of A28, F34, L35, C37, L64, N70, P87, I93, C99, R108, R110, G112, E117, G118, 5120, P126, F127, D131, D141, W148, G152, A153, L155, G156, E157, Y159, Y160, N163, A173, G174, C176, P177, T178, V179, G182, G183, H184, F185, G187, G188, G189, Y190, G191, P192, L193, R195, A201, D202, I205, D206, V210, G214, G223, D225, L226, F227, W228, R231, G234, 5237, F238, G239, K245, I246, L248, V251, V259, Q276, F312, 5313, L323, C341, F352, 5354, F380, K381, I382, K383, D385, Y386, 1391, M412, L415, G419, M422, I425, I430, P431, P433, H434, R435, G437, Y440, W443, Y444, I445, I464, Y465, M468, T469, Y471, V472, P476, R484, N498, A502, N513, F514, K521, N528, F529, E533, Q534, and S535. 
     Embodiment I-33. The engineered variant of Embodiment I-32, wherein the engineered variant comprises at least one immutable amino acid selected from the group consisting of C37, N70, I93, C99, E117, 5120, F127, D131, G156, E157, Y159, G174, C176, G182, G183, F185, G187, G188, G189, Y190, G191, P192, R195, D202, D206, G214, W228, G234, F238, L248, Q276, 5313, L323, 5354, K381, K383, D385, G419, M422, R435, Y440, W443, Y444, Y471, P476, N513, F514, N528, and Q534. 
     Embodiment I-34. The engineered variant of any one of Embodiments I-1 to I-33, wherein the engineered variant comprises at least 1, at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 21, at least 22, at least 23, at least 24, or at least 25 immutable amino acids. 
     Embodiment I-35. The engineered variant of any one of Embodiments I-1 to I-34, wherein the engineered variant produces cannabidiolic acid (CBDA) from cannabigerolic acid (CBGA) in a greater amount, as measured in mg/L or mM, than an amount of CBDA produced from CBGA by a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3 under similar conditions for the same length of time. 
     Embodiment I-36. The engineered variant of any one of Embodiments I-1 to I-35, wherein the engineered variant produces cannabidiolic acid (CBDA) from cannabigerolic acid (CBGA) in an amount, as measured in mg/L or mM, at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 100%, at least 150% at least 200%, at least 500%, or at least 1000% greater than an amount of CBDA produced from CBGA by a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3 under similar conditions for the same length of time. 
     Embodiment I-37. The engineered variant of any one of Embodiments I-1 to I-36, wherein the engineered variant produces cannabidiolic acid (CBDA) from cannabigerolic acid (CBGA) in an increased ratio of CBDA over tetrahydrocannabinolic acid (THCA) compared to that produced by a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3 under similar conditions for the same length of time. 
     Embodiment I-38. The engineered variant of any one of Embodiments I-1 to I-37, wherein the engineered variant produces CBDA from CBGA in a ratio of CBDA over THCA of about 11:1, about 11.5:1, about 12:1, about 12.5:1, about 13:1, about 13.5:1, about 14:1, about 14.5:1, about 15:1, about 15.5:1, about 16:1, about 16.5:1, about 17:1, about 17.5:1, about 18:1, about 18.5:1, about 19:1, about 19.5:1, about 20:1, about 25:1, about 30:1, about 35:1, about 40:1, about 45:1, about 50:1, about 60:1, about 70:1, about 80:1, about 90:1, about 100:1, about 150:1, about 200:1, about 500:1, or greater than about 500:1. 
     Embodiment I-39. The engineered variant of any one of Embodiments I-1 to I-19 or I-26 to I-38, wherein the engineered variant comprises a truncation at an N-terminus, at a C-terminus, or at both the N- and C-termini. 
     Embodiment I-40. The engineered variant of Embodiment I-39, wherein the truncated engineered variant comprises a signal polypeptide or a membrane anchor. 
     Embodiment I-41. The engineered variant of Embodiment I-39 or I-40, wherein the engineered variant lacks a native signal polypeptide. 
     Embodiment I-42. The engineered variant of any one of Embodiments I-39 to I-41, wherein the engineered variant comprises a truncation of at least 1, at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, or at least 10 amino acids at the C-terminus. 
     Embodiment I-43. A nucleic acid comprising a nucleotide sequence encoding an engineered variant of any one of Embodiments I-1 to I-42. 
     Embodiment I-44. A nucleic acid comprising a nucleotide sequence encoding an engineered variant of a cannabidiolic acid synthase (CBDAS) polypeptide comprising an amino acid sequence of SEQ ID NO:3 with one or more amino acid substitutions, wherein the nucleotide sequence is selected from the group consisting of SEQ ID NO:49, SEQ ID NO:51, SEQ ID NO:53, SEQ ID NO:55, SEQ ID NO:57, SEQ ID NO:59, SEQ ID NO:61, SEQ ID NO:63, SEQ ID NO:65, SEQ ID NO:67, SEQ ID NO:69, SEQ ID NO:71, SEQ ID NO:73, SEQ ID NO:75, SEQ ID NO:77, SEQ ID NO:79, SEQ ID NO:81, SEQ ID NO:83, SEQ ID NO:85, SEQ ID NO:87, SEQ ID NO:89, SEQ ID NO:91, SEQ ID NO:93, SEQ ID NO:95, SEQ ID NO:97, SEQ ID NO:99, SEQ ID NO:101, SEQ ID NO:103, SEQ ID NO:105, SEQ ID NO:107, SEQ ID NO:109, SEQ ID NO:111, SEQ ID NO:113, SEQ ID NO:115, SEQ ID NO:117, SEQ ID NO:119, SEQ ID NO:121, SEQ ID NO:123, SEQ ID NO:125, SEQ ID NO:127, SEQ ID NO:129, SEQ ID NO:131, SEQ ID NO:133, SEQ ID NO:135, SEQ ID NO:137, SEQ ID NO:139, SEQ ID NO:141, SEQ ID NO:143, SEQ ID NO:145, SEQ ID NO:147, SEQ ID NO:149, SEQ ID NO:151, SEQ ID NO:153, SEQ ID NO:155, SEQ ID NO:157, SEQ ID NO:159, SEQ ID NO:161, SEQ ID NO:163, SEQ ID NO:165, SEQ ID NO:167, SEQ ID NO:169, SEQ ID NO:171, SEQ ID NO:173, SEQ ID NO:175, SEQ ID NO:177, SEQ ID NO:179, SEQ ID NO:181, SEQ ID NO:183, SEQ ID NO:185, SEQ ID NO:187, SEQ ID NO:189, SEQ ID NO:191, SEQ ID NO:193, SEQ ID NO:195, SEQ ID NO:197, SEQ ID NO:199, SEQ ID NO:201, SEQ ID NO:203, SEQ ID NO:205, SEQ ID NO:207, SEQ ID NO:209, SEQ ID NO:211, SEQ ID NO:213, SEQ ID NO:215, SEQ ID NO:217, SEQ ID NO:219, SEQ ID NO:221, SEQ ID NO:223, SEQ ID NO:225, SEQ ID NO:227, SEQ ID NO:229, SEQ ID NO:231, and SEQ ID NO:233. 
     Embodiment I-45. The nucleic acid of Embodiment I-43 or I-44, wherein the nucleotide sequence is codon-optimized. 
     Embodiment I-46. A method of making a modified host cell for producing a cannabinoid or a cannabinoid derivative, the method comprising introducing one or more nucleic acids of any one of Embodiments I-43 to I-45 into a host cell. 
     Embodiment I-47. A vector comprising one or more nucleic acids of any one of Embodiments I-43 to I-45. 
     Embodiment I-48. A method of making a modified host cell for producing a cannabinoid or a cannabinoid derivative, the method comprising introducing one or more vectors of Embodiment I-47 into a host cell. 
     Embodiment I-49. A modified host cell for producing a cannabinoid or a cannabinoid derivative, wherein the modified host cell comprises one or more nucleic acids of any one of Embodiments I-43 to I-45. 
     Embodiment I-50. The modified host cell of Embodiment I-49, wherein the modified host cell comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a geranyl pyrophosphate:olivetolic acid geranyltransferase (GOT) polypeptide. 
     Embodiment I-51. The modified host cell of Embodiment I-50, wherein the GOT polypeptide comprises an amino acid sequence having at least 85% sequence identity to SEQ ID NO:17. 
     Embodiment I-52. The modified host cell of Embodiment I-50 or I-51, wherein the modified host cell comprises two or more heterologous nucleic acids comprising the nucleotide sequence encoding the GOT polypeptide. 
     Embodiment I-53. The modified host cell of Embodiment I-49, wherein the modified host cell comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a NphB polypeptide. 
     Embodiment I-54. The modified host cell of Embodiment I-53, wherein the NphB polypeptide comprises an amino acid sequence having at least 85% sequence identity to SEQ ID NO:294. 
     Embodiment I-55. The modified host cell of any one of Embodiments I-49 to I-54, wherein the modified host cell comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a tetraketide synthase (TKS) polypeptide and one or more heterologous nucleic acids comprising a nucleotide sequence encoding an olivetolic acid cyclase (OAC) polypeptide. 
     Embodiment I-56. The modified host cell of Embodiment I-55, wherein the TKS polypeptide comprises an amino acid sequence having at least 85% sequence identity to SEQ ID NO:19. 
     Embodiment I-57. The modified host cell of Embodiment I-55 or I-56, wherein the modified host cell comprises three or more heterologous nucleic acids comprising a nucleotide sequence encoding a TKS polypeptide. 
     Embodiment I-58. The modified host cell of any one of Embodiments I-55 to I-57, wherein the OAC polypeptide comprises an amino acid sequence having at least 85% sequence identity to SEQ ID NO:21 or SEQ ID NO:48. 
     Embodiment I-59. The modified host cell of any one of Embodiments I-55 to I-58, wherein the modified host cell comprises three or more heterologous nucleic acids comprising a nucleotide sequence encoding an OAC polypeptide. 
     Embodiment I-60. The modified host cell of any one of Embodiments I-49 to I-59, wherein the modified host cell comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding an acyl-activating enzyme (AAE) polypeptide. 
     Embodiment I-61. The modified host cell of Embodiment I-60, wherein the AAE polypeptide comprises an amino acid sequence having at least 85% sequence identity to SEQ ID NO:23. 
     Embodiment I-62. The modified host cell of Embodiment I-60 or I-61, wherein the modified host cell comprises two or more heterologous nucleic acids comprising a nucleotide sequence encoding an AAE polypeptide. 
     Embodiment I-63. The modified host cell of any one of Embodiments I-49 to I-62, wherein the modified host cell comprises one or more of the following: a) one or more heterologous nucleic acids comprising a nucleotide sequence encoding a HMG-CoA synthase (HMGS) polypeptide; b) one or more heterologous nucleic acids comprising a nucleotide sequence encoding a truncated 3-hydroxy-3-methyl-glutaryl-CoA reductase (tHMGR) polypeptide; c) one or more heterologous nucleic acids comprising a nucleotide sequence encoding a mevalonate kinase (MK) polypeptide; d) one or more heterologous nucleic acids comprising a nucleotide sequence encoding a phosphomevalonate kinase (PMK) polypeptide; e) one or more heterologous nucleic acids comprising a nucleotide sequence encoding a mevalonate pyrophosphate decarboxylase (MVD1) polypeptide; or f) one or more heterologous nucleic acids comprising a nucleotide sequence encoding a isopentenyl diphosphate isomerase (IDI1) polypeptide. 
     Embodiment I-64. The modified host cell of Embodiment I-63, wherein the IDI1 polypeptide comprises an amino acid sequence having at least 85% sequence identity to SEQ ID NO:25. 
     Embodiment I-65. The modified host cell of Embodiment I-63 or I-64, wherein the tHMGR polypeptide comprises an amino acid sequence having at least 85% sequence identity to SEQ ID NO:27. 
     Embodiment I-66. The modified host cell of any one of Embodiments I-63 to I-65, wherein the HMGS polypeptide comprises an amino acid sequence having at least 85% sequence identity to SEQ ID NO:29. 
     Embodiment I-67. The modified host cell of any one of Embodiments I-63 to I-66, wherein the MK polypeptide comprises an amino acid sequence having at least 85% sequence identity to SEQ ID NO:39. 
     Embodiment I-68. The modified host cell of any one of Embodiments I-63 to I-67, wherein the PMK polypeptide comprises an amino acid sequence having at least 85% sequence identity to SEQ ID NO:37. 
     Embodiment I-69. The modified host cell of any one of Embodiments I-63 to I-68, wherein the MVD1 polypeptide comprises an amino acid sequence having at least 85% sequence identity to SEQ ID NO:33. 
     Embodiment I-70. The modified host cell of any one of Embodiments I-49 to I-69, wherein the modified host cell comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding an acetoacetyl-CoA thiolase polypeptide. 
     Embodiment I-71. The modified host cell of Embodiment I-70, wherein the acetoacetyl-CoA thiolase polypeptide comprises an amino acid sequence having at least 85% sequence identity to SEQ ID NO:31. 
     Embodiment I-72. The modified host cell of any one of Embodiments I-49 to I-71, wherein the modified host cell comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a pyruvate decarboxylase (PDC) polypeptide. 
     Embodiment I-73. The modified host cell of Embodiment I-72, wherein the PDC polypeptide comprises an amino acid sequence having at least 85% sequence identity to SEQ ID NO:35. 
     Embodiment I-74. The modified host cell of any one of Embodiments I-49 to I-73, wherein the modified host cell comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a geranyl pyrophosphate synthetase (GPPS) polypeptide. 
     Embodiment I-75. The modified host cell of Embodiment I-74, wherein the GPPS polypeptide comprises an amino acid sequence having at least 85% sequence identity to SEQ ID NO:41. 
     Embodiment I-76. The modified host cell of any one of Embodiments I-49 to I-75, wherein the modified host cell comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a KAR2 polypeptide. 
     Embodiment I-77. The modified host cell of Embodiment I-76, wherein the KAR2 polypeptide comprises an amino acid sequence having at least 85% sequence identity to SEQ ID NO:5. 
     Embodiment I-78. The modified host cell of Embodiment I-76 or I-77, wherein the modified host cell comprises two or more heterologous nucleic acids comprising a nucleotide sequence encoding a KAR2 polypeptide. 
     Embodiment I-79. The modified host cell of any one of Embodiments I-49 to I-78, wherein the modified host cell comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding a PDI1 polypeptide. 
     Embodiment I-80. The modified host cell of Embodiment I-79, wherein the PDI1 polypeptide comprises an amino acid sequence having at least 85% sequence identity to SEQ ID NO:9. 
     Embodiment I-81. The modified host cell of any one of Embodiments I-49 to I-80, wherein the modified host cell comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding an IRE1 polypeptide. 
     Embodiment I-82. The modified host cell of Embodiment I-81, wherein the IRE1 polypeptide comprises an amino acid sequence having at least 85% sequence identity to SEQ ID NO:11 or SEQ ID NO:296. 
     Embodiment I-83. The modified host cell of any one of Embodiments I-49 to I-82, wherein the modified host cell comprises one or more heterologous nucleic acids comprising a nucleotide sequence encoding an ERO1 polypeptide. 
     Embodiment I-84. The modified host cell of Embodiment I-83, wherein the ERO1 polypeptide comprises an amino acid sequence having at least 85% sequence identity to SEQ ID NO:7. 
     Embodiment I-85. The modified host cell of any one of Embodiments I-49 to I-84, wherein the modified host cell comprises a deletion or downregulation of one or more genes encoding a PEP4 polypeptide. 
     Embodiment I-86. The modified host cell of Embodiment I-85, wherein the PEP4 polypeptide comprises an amino acid sequence having at least 85% sequence identity to SEQ ID NO:15. 
     Embodiment I-87. The modified host cell of any one of Embodiments I-49 to I-86, wherein the modified host cell comprises a deletion or downregulation of one or more genes encoding a ROT2 polypeptide. 
     Embodiment I-88. The modified host cell of Embodiment I-87, wherein the ROT2 polypeptide comprises an amino acid sequence having at least 85% sequence identity to SEQ ID NO:13. 
     Embodiment I-89. The modified host cell of any one of Embodiments I-49 to I-88, wherein the modified host cell is a eukaryotic cell. 
     Embodiment I-90. The modified host cell of Embodiment I-89, wherein the eukaryotic cell is a yeast cell. 
     Embodiment I-91. The modified host cell of Embodiment I-90, wherein the yeast cell is  Saccharomyces cerevisiae.    
     Embodiment I-92. The modified host cell of Embodiment I-91, wherein the  Saccharomyces cerevisiae  is a protease-deficient strain of  Saccharomyces cerevisiae.    
     Embodiment I-93. The modified host cell of any one of Embodiments I-49 to I-92, wherein at least one of the one or more nucleic acids are integrated into the chromosome of the modified host cell. 
     Embodiment I-94. The modified host cell of any one of Embodiments I-49 to I-92, wherein at least one of the one or more nucleic acids are maintained extrachromosomally. 
     Embodiment I-95. The modified host cell of any one of Embodiments I-49 to I-94, wherein at least one of the one or more nucleic acids are operably-linked to an inducible promoter. 
     Embodiment I-96. The modified host cell of any one of Embodiments I-49 to I-94, wherein at least one of the one or more nucleic acids are operably-linked to a constitutive promoter. 
     Embodiment I-97. The modified host cell of any one of Embodiments I-49 to I-96, wherein the modified host cell produces a cannabinoid or a cannabinoid derivative in an amount, as measured in mg/L or mM, greater than an amount of the cannabinoid or the cannabinoid derivative produced by a modified host cell comprising one or more nucleic acids comprising a nucleotide sequence encoding a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3, wherein the modified host cell comprising one or more nucleic acids comprising the nucleotide sequence encoding the cannabidiolic acid synthase polypeptide having the amino acid sequence of SEQ ID NO:3 lacks a nucleic acid comprising a nucleotide sequence encoding an engineered variant of any one of Embodiments I-1 to I-42, grown under similar culture conditions for the same length of time. 
     Embodiment I-98. The modified host cell of any one of Embodiments I-49 to I-97, wherein the modified host cell produces a cannabinoid or a cannabinoid derivative in an amount, as measured in mg/L or mM, at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 100%, at least 150% at least 200%, at least 500%, or at least 1000% greater than an amount of the cannabinoid or the cannabinoid derivative produced by a modified host cell comprising one or more nucleic acids comprising a nucleotide sequence encoding a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3, wherein the modified host cell comprising one or more nucleic acids comprising the nucleotide sequence encoding the cannabidiolic acid synthase polypeptide having the amino acid sequence of SEQ ID NO:3 lacks a nucleic acid comprising a nucleotide sequence encoding an engineered variant of any one of Embodiments I-1 to I-42, grown under similar culture conditions for the same length of time. 
     Embodiment I-99. The modified host cell of any one of Embodiments I-49 to I-98, wherein the modified host cell has a faster growth rate and/or higher biomass yield compared to a growth rate and/or higher biomass yield of a modified host cell comprising one or more nucleic acids comprising a nucleotide sequence encoding a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3, wherein the modified host cell comprising one or more nucleic acids comprising the nucleotide sequence encoding the cannabidiolic acid synthase polypeptide having the amino acid sequence of SEQ ID NO:3 lacks a nucleic acid comprising a nucleotide sequence encoding an engineered variant of any one of Embodiments I-1 to I-42, grown under similar culture conditions for the same length of time. 
     Embodiment I-100. The modified host cell of any one of Embodiments I-49 to I-99, wherein the modified host cell has a growth rate and/or higher biomass yield at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 100%, at least 150% at least 200%, at least 500%, or at least 1000% faster than a growth rate and/or higher biomass yield of a modified host cell comprising one or more nucleic acids comprising a nucleotide sequence encoding a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3, wherein the modified host cell comprising one or more nucleic acids comprising the nucleotide sequence encoding the cannabidiolic acid synthase polypeptide having the amino acid sequence of SEQ ID NO:3 lacks a nucleic acid comprising a nucleotide sequence encoding an engineered variant of any one of Embodiments I-1 to I-42, grown under similar culture conditions for the same length of time. 
     Embodiment I-101. The modified host cell of any one of Embodiments I-49 to I-100, wherein the modified host cell produces cannabidiolic acid (CBDA) from cannabigerolic acid (CBGA) in an increased ratio of CBDA over tetrahydrocannabinolic acid (THCA) compared to that produced by a modified host cell comprising one or more nucleic acids comprising a nucleotide sequence encoding a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3, wherein the modified host cell comprising one or more nucleic acids comprising the nucleotide sequence encoding the cannabidiolic acid synthase polypeptide having the amino acid sequence of SEQ ID NO:3 lacks a nucleic acid comprising a nucleotide sequence encoding an engineered variant of any one of Embodiments I-1 to I-42, grown under similar culture conditions for the same length of time. 
     Embodiment I-102. The modified host cell of any one of Embodiments I-49 to I-101, wherein the modified host cell produces CBDA from CBGA in a ratio of CBDA over THCA of about 11:1, about 11.5:1, about 12:1, about 12.5:1, about 13:1, about 13.5:1, about 14:1, about 14.5:1, about 15:1, about 15.5:1, about 16:1, about 16.5:1, about 17:1, about 17.5:1, about 18:1, about 18.5:1, about 19:1, about 19.5:1, about 20:1, about 25:1, about 30:1, about 35:1, about 40:1, about 45:1, about 50:1, about 60:1, about 70:1, about 80:1, about 90:1, about 100:1, about 150:1, about 200:1, about 500:1, or greater than about 500:1. 
     Embodiment I-103. A method of producing a cannabinoid or a cannabinoid derivative, the method comprising: a) culturing a modified host cell of any one of Embodiments I-49 to I-102 in a culture medium. 
     Embodiment I-104. The method of Embodiment I-103, wherein the method comprises: b) recovering the produced cannabinoid or cannabinoid derivative. 
     Embodiment I-105. The method of Embodiment I-103 or I-104, wherein the culture medium comprises a carboxylic acid. 
     Embodiment I-106. The method of Embodiment I-105, wherein the carboxylic acid is an unsubstituted or substituted C 3 -C 18  carboxylic acid. 
     Embodiment I-107. The method of Embodiment I-106, wherein the unsubstituted or substituted C 3 -C 18  carboxylic acid is an unsubstituted or substituted hexanoic acid. 
     Embodiment I-108. The method of Embodiment I-103 or I-104, wherein the culture medium comprises olivetolic acid or an olivetolic acid derivative. 
     Embodiment I-109. The method of Embodiment I-103 or I-104, wherein the cannabinoid is cannabidiolic acid, cannabidiol, cannabidivarinic acid, or cannabidivarin. 
     Embodiment I-110. The method of any one of Embodiments I-103 to I-109, wherein the culture medium comprises a fermentable sugar. 
     Embodiment I-111. The method of any one of Embodiments I-103 to I-109, wherein the culture medium comprises a pretreated cellulosic feedstock. 
     Embodiment I-112. The method of any one of Embodiments I-103 to I-109, wherein the culture medium comprises a non-fermentable carbon source. 
     Embodiment I-113. The method of Embodiment I-112, wherein the non-fermentable carbon source comprises ethanol. 
     Embodiment I-114. The method of any one of Embodiments I-103 to I-113, wherein the cannabinoid or the cannabinoid derivative is produced in an amount of more than 100 mg/L culture medium. 
     Embodiment I-115. The method of any one of Embodiments I-103 to I-113, wherein the cannabinoid or the cannabinoid derivative is produced in an amount, as measured in mg/L or mM, greater than an amount of the cannabinoid or the cannabinoid derivative produced in a method comprising culturing a modified host cell comprising one or more nucleic acids comprising a nucleotide sequence encoding a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3 instead of the modified host cell of any one of Embodiments I-49 to I-102, wherein the modified host cell comprising one or more nucleic acids comprising the nucleotide sequence encoding the cannabidiolic acid synthase polypeptide having the amino acid sequence of SEQ ID NO:3 lacks a nucleic acid comprising a nucleotide sequence encoding an engineered variant of any one of Embodiments I-1 to I-42, and wherein the modified host cell of any one of Embodiments I-49 to I-102 and the modified host cell comprising one or more nucleic acids comprising the nucleotide sequence encoding the cannabidiolic acid synthase polypeptide having the amino acid sequence of SEQ ID NO:3, but lacking a nucleic acid comprising a nucleotide sequence encoding an engineered variant of any one of Embodiments I-1 to I-42, are cultured under similar culture conditions for the same length of time. 
     Embodiment I-116. The method of any one of Embodiments I-103 to I-115, wherein the cannabinoid or the cannabinoid derivative is produced in an amount, as measured in mg/L or mM, at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 100%, at least 150% at least 200%, at least 500%, or at least 1000% greater than an amount of the cannabinoid or the cannabinoid derivative produced in a method comprising culturing a modified host cell comprising one or more nucleic acids comprising a nucleotide sequence encoding a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3 instead of the modified host cell of any one of Embodiments I-49 to I-102, wherein the modified host cell comprising one or more nucleic acids comprising the nucleotide sequence encoding the cannabidiolic acid synthase polypeptide having the amino acid sequence of SEQ ID NO:3 lacks a nucleic acid comprising a nucleotide sequence encoding an engineered variant of any one of Embodiments I-1 to I-42, and wherein the modified host cell of any one of Embodiments I-49 to I-102 and the modified host cell comprising one or more nucleic acids comprising the nucleotide sequence encoding the cannabidiolic acid synthase polypeptide having the amino acid sequence of SEQ ID NO:3, but lacking a nucleic acid comprising a nucleotide sequence encoding an engineered variant of any one of Embodiments I-1 to I-42, are cultured under similar culture conditions for the same length of time. 
     Embodiment I-117. The method of any one of Embodiments I-103 to I-116, wherein the cannabinoid is cannabidiolic acid (CBDA), and wherein the method produces CBDA in an increased ratio of CBDA over tetrahydrocannabinolic acid (THCA) compared to that produced in a method comprising culturing a modified host cell comprising one or more nucleic acids comprising a nucleotide sequence encoding a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3 instead of the modified host cell of any one of Embodiments I-49 to I-102, wherein the modified host cell comprising one or more nucleic acids comprising the nucleotide sequence encoding the cannabidiolic acid synthase polypeptide having the amino acid sequence of SEQ ID NO:3 lacks a nucleic acid comprising a nucleotide sequence encoding an engineered variant of any one of Embodiments I-1 to I-42, grown under similar culture conditions for the same length of time. 
     Embodiment I-118. The method of any one of Embodiments I-103 to I-117, wherein the method produces CBDA from CBGA in a ratio of CBDA over THCA of about 11:1, about 11.5:1, about 12:1, about 12.5:1, about 13:1, about 13.5:1, about 14:1, about 14.5:1, about 15:1, about 15.5:1, about 16:1, about 16.5:1, about 17:1, about 17.5:1, about 18:1, about 18.5:1, about 19:1, about 19.5:1, about 20:1, about 25:1, about 30:1, about 35:1, about 40:1, about 45:1, about 50:1, about 60:1, about 70:1, about 80:1, about 90:1, about 100:1, about 150:1, about 200:1, about 500:1, or greater than about 500:1. 
     Embodiment I-119. A method of producing a cannabinoid or a cannabinoid derivative, the method comprising use of an engineered variant of any one of Embodiments I-1 to I-42. 
     Embodiment I-120. The method of Embodiment I-119, wherein the method comprises recovering the produced cannabinoid or cannabinoid derivative. 
     Embodiment I-121. The method of Embodiment I-119 or I-120, wherein the cannabinoid is cannabidiolic acid, cannabidiol, cannabidivarinic acid, or cannabidivarin. 
     Embodiment I-122. The method of any one of Embodiments I-119 to I-121, wherein the cannabinoid or the cannabinoid derivative is produced in an amount, as measured in mg/L or mM, greater than an amount of the cannabinoid or the cannabinoid derivative produced in a method comprising use of a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3 instead of the engineered variant of any one of Embodiments I-1 to I-42, wherein the engineered variant of any one of Embodiments I-1 to I-42 and the cannabidiolic acid synthase polypeptide having the amino acid sequence of SEQ ID NO:3 are used under similar conditions for the same length of time. 
     Embodiment I-123. The method of any one of Embodiments I-119 to I-121, wherein the cannabinoid or the cannabinoid derivative is produced in an amount, as measured in mg/L or mM, at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 100%, at least 150% at least 200%, at least 500%, or at least 1000% greater than an amount of the cannabinoid or the cannabinoid derivative produced in a method comprising use of a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3 instead of the engineered variant of any one of Embodiments I-1 to I-42, wherein the engineered variant of any one of Embodiments I-1 to I-42 and the cannabidiolic acid synthase polypeptide having the amino acid sequence of SEQ ID NO:3 are used under similar conditions for the same length of time. 
     Embodiment I-124. The method of any one of Embodiments I-119 to I-123, wherein the cannabinoid is cannabidiolic acid (CBDA), and wherein the method produces CBDA in an increased ratio of CBDA over tetrahydrocannabinolic acid (THCA) compared to that produced in a method comprising use of a cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3 instead of the engineered variant of any one of Embodiments I-1 to I-42, wherein the engineered variant of any one of Embodiments I-1 to I-42 and the cannabidiolic acid synthase polypeptide having the amino acid sequence of SEQ ID NO:3 are used under similar conditions for the same length of time. 
     Embodiment I-125. The method of any one of Embodiments I-119 to I-124, wherein the method produces CBDA from CBGA in a ratio of CBDA over THCA of about 11:1, about 11.5:1, about 12:1, about 12.5:1, about 13:1, about 13.5:1, about 14:1, about 14.5:1, about 15:1, about 15.5:1, about 16:1, about 16.5:1, about 17:1, about 17.5:1, about 18:1, about 18.5:1, about 19:1, about 19.5:1, about 20:1, about 25:1, about 30:1, about 35:1, about 40:1, about 45:1, about 50:1, about 60:1, about 70:1, about 80:1, about 90:1, about 100:1, about 150:1, about 200:1, about 500:1, or greater than about 500:1. 
     Embodiment I-126. A method of screening an engineered variant of a cannabidiolic acid synthase (CBDAS) polypeptide comprising an amino acid sequence of SEQ ID NO:3 with one or more amino acid substitutions, the method comprising: a) dividing a population of host cells into a control population and a test population; b) co-expressing in the control population a CBDAS polypeptide having an amino acid sequence of SEQ ID NO:3 and a comparison cannabinoid synthase polypeptide, wherein the CBDAS polypeptide having an amino acid sequence of SEQ ID NO:3 can convert cannabigerolic acid (CBGA) to a first cannabinoid, cannabidiolic acid (CBDA), and the comparison cannabinoid synthase polypeptide can convert the same CBGA to a different second cannabinoid; c) co-expressing in the test population the engineered variant and the comparison cannabinoid synthase polypeptide, wherein the engineered variant may convert CBGA to the same first cannabinoid, cannabidiolic acid (CBDA), as the CBDAS polypeptide having an amino acid sequence of SEQ ID NO:3, and wherein the comparison cannabinoid synthase polypeptide can convert the same CBGA to the second cannabinoid and is expressed at similar levels in the test population and in the control population; d) measuring a ratio of the first cannabinoid, cannabidiolic acid (CBDA), over the second cannabinoid produced by both the test population and the control population; and e) measuring an amount, in mg/L or mM, of the first cannabinoid produced by both the test population and the control population. 
     Embodiment I-127. The method of Embodiment I-126, wherein the test population is identified as comprising an engineered variant having improved in vivo performance compared to the cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3, wherein improved in vivo performance is demonstrated by an increase in the ratio of the first cannabinoid over the second cannabinoid produced by the test population compared to that produced by the control population under similar culture conditions for the same length of time. 
     Embodiment I-128. The method of Embodiment I-126 or I-127, wherein the test population is identified as comprising an engineered variant having improved in vivo performance compared to the cannabidiolic acid synthase polypeptide having an amino acid sequence of SEQ ID NO:3 by producing the first cannabinoid in a greater amount, as measured in mg/L or mM, by the test population compared to the amount produced by the control population under similar culture conditions for the same length of time. 
     Embodiment I-129. The method of any one of Embodiments I-126 to I-128, wherein the cannabinoid synthase polypeptide is a tetrahydrocannabinolic acid synthase polypeptide. 
     Embodiment I-130. The method of Embodiment I-129, wherein the tetrahydrocannabinolic acid synthase polypeptide comprises an amino acid sequence having at least 85% sequence identity to SEQ ID NO:44. 
     Embodiment I-131. The method of any one of Embodiments I-126 to I-130, wherein the second cannabinoid is tetrahydrocannabinolic acid (THCA). 
     Embodiment I-132. The method of any one of Embodiments I-126 to I-131, wherein the engineered variant is an engineered variant of any one of Embodiments I-1 to I-42. 
     Provided in Table 1 are amino acid and nucleotide sequences disclosed herein. Where a genus and/or species is noted, the sequence should not be construed to be limited only to the specified genus and/or species, but also includes other genera and/or species expressing said sequence. Orthologs of the sequences disclosed in Table 1 may also be encompassed by this disclosure. Nucleotide sequences indicated as codon optimized in Table 1 are codon optimized for expression in  S. cerevisiae . In Table 1, “*” used as the end of a sequence denotes a stop codon. In reference to OAC*, “*” denotes a mutation is present in the sequence. 
     
       
         
           
               
             
               
                 TABLE 1 
               
               
                   
               
               
                 Amino acid and nucleotide sequences of the disclosure 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
            
               
                 SEQ ID NO: 1 
                 ATGAAATGCTCTACCTTTTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                 Cannabidiolic 
                 TTCTTCTTCTTCTCCTTCAACATCCAAACCTCTATCGCTAACCCT 
               
               
                 Acid 
                 CGTGAAAACTTTTTGAAATGTTTTTCCCAATACATCCCAAATAAC 
               
               
                 (CBDA) Synthase 
                 GCTACTAATTTGAAGTTGGTTTACACCCAAAACAACCCATTGTAT 
               
               
                 Codon opt 2 
                 ATGTCCGTTTTAAACTCTACTATTCACAATTTGCGTTTTACCTCT 
               
               
                 Artificial 
                 GATACTACCCCTAAACCATTGGTCATTGTTACCCCATCCCATGTT 
               
               
                 sequence 
                 TCTCATATCCAAGGTACTATCTTGTGTTCTAAAAAGGTTGGTTTG 
               
               
                 Codon optimized 
                 CAAATTAGAACTCGTTCCGGTGGTCACGATTCTGAAGGTATGTCT 
               
               
                   
                 TACATTTCTCAAGTTCCTTTCGTCATTGTCGACTTGAGAAACATG 
               
               
                   
                 AGATCCATCAAAATTGATGTTCACTCTCAAACTGCTTGGGTCGAA 
               
               
                   
                 GCCGGTGCCACTTTAGGTGAGGTCTACTATTGGGTTAACGAGAAG 
               
               
                   
                 AACGAAAACTTGTCTTTGGCTGCCGGTTACTGTCCAACTGTCTGT 
               
               
                   
                 GCTGGTGGTCATTTTGGTGGTGGTGGTTACGGTCCATTGATGAGA 
               
               
                   
                 AACTACGGTTTGGCTGCTGATAACATTATTGATGCTCACTTAGTT 
               
               
                   
                 AACGTCCACGGTAAAGTCTTGGATAGAAAGTCCATGGGTGAAGAC 
               
               
                   
                 TTGTTCTGGGCTTTAAGAGGTGGTGGTGCTGAATCCTTCGGTATT 
               
               
                   
                 ATTGTTGCTTGGAAAATCAGATTGGTCGCTGTTCCAAAATCCACC 
               
               
                   
                 ATGTTTTCTGTCAAGAAAATCATGGAAATTCATGAATTAGTTAAG 
               
               
                   
                 TTGGTCAACAAATGGCAAAACATTGCCTATAAATACGACAAGGAT 
               
               
                   
                 TTGTTGTTGATGACTCATTTCATCACTCGTAACATCACTGATAAT 
               
               
                   
                 CAAGGTAAGAACAAGACTGCTATCCATACTTACTTCTCTTCCGTC 
               
               
                   
                 TTCTTGGGTGGTGTTGACTCTTTGGTCGATTTGATGAACAAATCC 
               
               
                   
                 TTTCCAGAGTTAGGTATTAAGAAGACTGACTGTAGACAATTATCT 
               
               
                   
                 TGGATTGACACTATTATCTTCTACTCTGGTGTTGTCAATTACGAT 
               
               
                   
                 ACTGATAACTTTAACAAGGAAATTTTGTTGGACCGTTCTGCTGGT 
               
               
                   
                 CAAAACGGTGCCTTCAAGATTAAGTTAGATTACGTTAAGAAGCCA 
               
               
                   
                 ATCCCAGAATCTGTCTTCGTCCAAATTTTGGAGAAATTGTATGAA 
               
               
                   
                 GAGGACATTGGTGCTGGTATGTACGCCTTGTATCCTTACGGTGGT 
               
               
                   
                 ATCATGGACGAGATCTCCGAATCTGCCATCCCTTTTCCTCATCGT 
               
               
                   
                 GCTGGTATCTTGTACGAGTTGTGGTACATCTGTTCCTGGGAGAAG 
               
               
                   
                 CAAGAAGATAATGAAAAGCACTTGAACTGGATTAGAAATATTTAT 
               
               
                   
                 AATTTCATGACTCCATACGTTTCTAAGAACCCACGTTTGGCTTAC 
               
               
                   
                 TTAAATTACAGAGATTTGGATATTGGTATCAACGACCCTAAGAAC 
               
               
                   
                 CCTAACAACTACACTCAAGCTAGAATTTGGGGTGAGAAATATTTC 
               
               
                   
                 GGTAAGAACTTCGATAGATTGGTCAAGGTTAAAACTTTAGTTGAT 
               
               
                   
                 CCAAATAACTTTTTTAGAAACGAACAATCTATTCCACCATTGCCA 
               
               
                   
                 AGACACAGACACTAG 
               
               
                   
               
               
                 SEQ ID NO: 2 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                 Cannabidiolic 
                 TTCTTCTTCTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 Acid 
                 CGTGAGAACTTCTTGAAATGTTTTTCTCAATATATCCCAAATAAC 
               
               
                 (CBDA) Synthase 
                 GCTACTAACTTGAAGTTAGTCTATACTCAAAACAACCCATTATAT 
               
               
                 Codon opt 5 
                 ATGTCTGTCTTAAACTCTACCATTCACAACTTACGTTTCACTTCT 
               
               
                 Artificial 
                 GATACTACTCCAAAACCTTTGGTCATCGTCACCCCATCCCACGTT 
               
               
                 sequence 
                 TCTCACATCCAAGGTACCATCTTGTGTTCCAAAAAGGTTGGTTTA 
               
               
                 Codon optimized 
                 CAAATCCGTACTAGATCCGGTGGTCATGACTCCGAAGGTATGTCT 
               
               
                   
                 TACATTTCCCAAGTCCCTTTCGTCATCGTCGACTTAAGAAATATG 
               
               
                   
                 CGTTCCATCAAGATTGATGTCCATTCCCAAACTGCTTGGGTTGAA 
               
               
                   
                 GCCGGTGCCACTTTAGGTGAAGTCTATTACTGGGTTAACGAGAAG 
               
               
                   
                 AATGAGAACTTATCTTTGGCTGCCGGTTACTGTCCAACTGTTTGT 
               
               
                   
                 GCTGGTGGTCATTTCGGTGGTGGTGGTTACGGTCCATTAATGCGT 
               
               
                   
                 AACTACGGTTTGGCTGCCGATAACATCATTGATGCCCACTTAGTC 
               
               
                   
                 AACGTTCATGGTAAGGTCTTGGACCGTAAGTCTATGGGTGAGGAT 
               
               
                   
                 TTATTCTGGGCTTTGAGAGGTGGTGGTGCTGAATCTTTCGGTATT 
               
               
                   
                 ATCGTCGCTTGGAAGATTAGATTAGTTGCTGTTCCAAAGTCTACT 
               
               
                   
                 ATGTTCTCTGTTAAGAAGATCATGGAAATTCACGAGTTGGTTAAA 
               
               
                   
                 TTAGTTAACAAATGGCAAAACATTGCCTACAAGTACGATAAAGAT 
               
               
                   
                 TTGTTATTAATGACTCACTTTATCACTAGAAACATTACTGATAAC 
               
               
                   
                 CAAGGTAAGAATAAGACTGCCATTCACACTTACTTCTCTTCTGTT 
               
               
                   
                 TTCTTGGGTGGTGTTGATTCCTTGGTCGATTTGATGAACAAGTCT 
               
               
                   
                 TTTCCAGAATTAGGTATTAAGAAGACCGATTGTCGTCAATTATCT 
               
               
                   
                 TGGATTGATACCATTATTTTTTACTCCGGTGTTGTCAACTACGAC 
               
               
                   
                 ACTGATAATTTTAATAAGGAGATTTTGTTAGATAGATCTGCTGGT 
               
               
                   
                 CAAAATGGTGCCTTTAAAATCAAATTGGACTACGTTAAGAAGCCT 
               
               
                   
                 ATTCCAGAATCCGTCTTTGTTCAAATTTTGGAGAAGTTATACGAA 
               
               
                   
                 GAAGATATTGGTGCTGGTATGTACGCCTTGTATCCATATGGTGGT 
               
               
                   
                 ATTATGGATGAAATTTCTGAATCCGCCATCCCTTTCCCTCATCGT 
               
               
                   
                 GCTGGTATCTTATACGAGTTGTGGTACATCTGTTCTTGGGAAAAG 
               
               
                   
                 CAAGAAGATAATGAAAAGCATTTGAACTGGATCCGTAACATCTAT 
               
               
                   
                 AACTTCATGACTCCATACGTTTCCAAAAACCCTAGATTGGCTTAC 
               
               
                   
                 TTAAATTACAGAGACTTAGATATTGGTATTAACGACCCTAAGAAC 
               
               
                   
                 CCAAACAATTACACTCAAGCTAGAATCTGGGGTGAAAAGTACTTC 
               
               
                   
                 GGTAAGAATTTCGACAGATTAGTTAAGGTCAAGACTTTAGTTGAC 
               
               
                   
                 CCAAATAACTTCTTCAGAAACGAACAATCTATCCCACCATTGCCT 
               
               
                   
                 AGACATAGACACTAG 
               
               
                   
               
               
                 SEQ ID NO: 3 
                 MKCSTFSFWFVCKIIFFFFSFNIQTSIANPRENFLKCFSQYIPNN 
               
               
                 Cannabidiolic  
                 ATNLKLVYTQNNPLYMSVLNSTIHNLRFTSDTTPKPLVIVTPSHV 
               
               
                 Acid 
                 SHIQGTILCSKKVGLQIRTRSGGHDSEGMSYISQVPFVIVDLRNM 
               
               
                 (CBDA) 
                 RSIKIDVHSQTAWVEAGATLGEVYYWVNEKNENLSLAAGYCPTVC 
               
               
                 Synthase 
                 AGGHFGGGGYGPLMRNYGLAADNIIDAHLVNVHGKVLDRKSMGED 
               
               
                 Polypeptide 
                 LFWALRGGGAESFGIIVAWKIRLVAVPKSTMFSVKKIMEIHELVK 
               
               
                 front codon 
                 LVNKWQNIAYKYDKDLLLMTHFITRNITDNQGKNKTAIHTYFSSV 
               
               
                 opts 2 and 5 
                 FLGGVDSLVDLMNKSFPELGIKKTDCRQLSWIDTIIFYSGWNYDT 
               
               
                 
                   Cannabis sativa 
                 
                 DNFNKEILLDRSAGQNGAFKIKLDYVKKPIPESVFVQILEKLYEE 
               
               
                   
                 DIGAGMYALYPYGGIMDEISESAIPFPHRAGILYELWYICSWEKQ 
               
               
                   
                 EDNEKHLNWIRNIYNFMTPYVSKNPRLAYLNYRDLDIGINDPKNP 
               
               
                   
                 NNYTQARIWGEKYFGKNFDRLVKVKTLVDPNNFFRNEQSIPPLPR 
               
               
                   
                 HRH* 
               
               
                   
               
               
                 SEQ ID NO: 4 
                 ATGTTTTTCAACAGACTAAGCGCTGGCAAGCTGCTGGTACCACTC 
               
               
                 KAR2 
                 TCCGTGGTCCTGTACGCCCTTTTCGTGGTAATATTACCTTTACAG 
               
               
                   Saccharomyces  sp. 
                 AATTCTTTCCACTCCTCCAATGTTTTAGTTAGAGGTGCCGATGAT 
               
               
                   
                 GTAGAAAACTACGGAACTGTTATCGGTATTGACTTAGGTACTACT 
               
               
                   
                 TATTCCTGTGTTGCTGTGATGAAAAATGGTAAGACTGAAATTCTT 
               
               
                   
                 GCTAATGAGCAAGGTAACAGAATCACCCCATCTTACGTGGCATTC 
               
               
                   
                 ACCGATGATGAAAGATTGATTGGTGATGCTGCAAAGAACCAAGTT 
               
               
                   
                 GCTGCCAATCCTCAAAACACCATCTTCGACATTAAGAGATTGATC 
               
               
                   
                 GGTTTGAAATATAACGACAGATCTGTTCAGAAGGATATCAAGCAC 
               
               
                   
                 TTGCCATTTAATGTGGTTAATAAAGATGGGAAGCCCGCTGTAGAA 
               
               
                   
                 GTAAGTGTCAAAGGAGAAAAGAAGGTTTTTACTCCAGAAGAAATT 
               
               
                   
                 TCTGGTATGATCTTGGGTAAGATGAAACAAATTGCCGAAGATTAT 
               
               
                   
                 TTAGGCACTAAGGTTACCCATGCTGTCGTTACTGTTCCTGCTTAT 
               
               
                   
                 TTCAATGACGCGCAAAGACAAGCCACCAAGGATGCTGGTACCATC 
               
               
                   
                 GCTGGTTTGAACGTTTTGAGAATTGTTAATGAACCAACCGCAGCC 
               
               
                   
                 GCCATTGCCTACGGTTTGGATAAATCTGATAAGGAACATCAAATT 
               
               
                   
                 ATTGTTTATGATTTGGGTGGTGGTACTTTCGATGTCTCTCTATTG 
               
               
                   
                 TCTATTGAAAACGGTGTTTTCGAAGTCCAAGCCACTTCTGGTGAT 
               
               
                   
                 ACTCATTTAGGTGGTGAAGATTTTGACTATAAGATCGTTCGTCAA 
               
               
                   
                 TTGATAAAAGCTTTCAAGAAGAAGCATGGTATTGATGTGTCTGAC 
               
               
                   
                 AACAACAAGGCCCTAGCTAAATTGAAGAGAGAAGCTGAAAAGGCT 
               
               
                   
                 AAACGTGCCTTGTCCAGCCAAATGTCCACCCGTATTGAAATTGAC 
               
               
                   
                 TCCTTCGTTGATGGTATCGACTTAAGTGAAACCTTGACCAGAGCT 
               
               
                   
                 AAGTTTGAGGAATTAAACCTAGATCTATTCAAGAAGACCTTGAAG 
               
               
                   
                 CCTGTCGAGAAGGTTTTGCAAGATTCTGGTTTGGAAAAGAAGGAT 
               
               
                   
                 GTTGATGATATCGTTTTGGTTGGTGGTTCTACTAGAATTCCAAAG 
               
               
                   
                 GTCCAACAATTGTTAGAATCATACTTTGATGGTAAGAAGGCCTCC 
               
               
                   
                 AAGGGTATTAACCCAGATGAAGCTGTTGCATACGGTGCAGCCGTT 
               
               
                   
                 CAAGCTGGTGTCTTATCCGGTGAAGAAGGTGTCGAAGATATTGTT 
               
               
                   
                 TTATTGGATGTCAACGCTTTGACTCTTGGTATTGAAACCACTGGT 
               
               
                   
                 GGTGTCATGACTCCATTAATTAAGAGAAATACTGCTATTCCTACA 
               
               
                   
                 AAGAAATCCCAAATTTTCTCTACTGCCGTTGACAACCAACCAACC 
               
               
                   
                 GTTATGATCAAGGTATACGAGGGTGAAAGAGCCATGTCTAAGGAC 
               
               
                   
                 AACAATCTATTAGGTAAGTTTGAATTAACCGGCATTCCACCAGCA 
               
               
                   
                 CCAAGAGGTGTACCTCAAATTGAAGTCACATTTGCACTTGACGCT 
               
               
                   
                 AATGGTATTCTGAAGGTGTCTGCCACAGATAAGGGAACTGGTAAA 
               
               
                   
                 TCCGAATCTATCACCATCACTAACGATAAAGGTAGATTAACCCAA 
               
               
                   
                 GAAGAGATTGATAGAATGGTTGAAGAGGCTGAAAAATTCGCTTCT 
               
               
                   
                 GAAGACGCTTCTATCAAGGCCAAGGTTGAATCTAGAAACAAATTA 
               
               
                   
                 GAAAACTACGCTCACTCTTTGAAAAACCAAGTTAATGGTGACCTA 
               
               
                   
                 GGTGAAAAATTGGAAGAAGAAGACAAGGAAACCTTATTAGATGCT 
               
               
                   
                 GCTAACGATGTTTTAGAATGGTTAGATGATAACTTTGAAACCGCC 
               
               
                   
                 ATTGCTGAAGACTTTGATGAAAAGTTCGAATCTTTGTCCAAGGTC 
               
               
                   
                 GCTTATCCAATTACTTCTAAGTTGTACGGAGGTGCTGATGGTTCT 
               
               
                   
                 GGTGCCGCTGATTATGACGACGAAGATGAAGATGACGATGGTGAT 
               
               
                   
                 TATTTCGA 
               
               
                   
                 ACACGACGAATTGTAG 
               
               
                   
               
               
                 SEQ ID NO: 5 
                 MFFNRLSAGKLLVPLSWLYALFWILPLQNSFHSSNVLVRGADDVE 
               
               
                 KAR2 
                 NYGTVIGIDLGTTYSCVAVMKNGKTEILANEQGNRITPSYVAFTD 
               
               
                   Saccharomyces  sp. 
                 DERLIGDAAKNQVAANPQNTIFDIKRLIGLKYNDRSVQKDIKHLP 
               
               
                   
                 FNWNKDGKPAVEVSVKGEKKVFTPEEISGMILGKMKQIAEDYLGT 
               
               
                   
                 KVTHAVVTVPAYFNDAQRQATKDAGTIAGLNVLRIVNEPTAAAIA 
               
               
                   
                 YGLDKSDKEHQIIVYDLGGGTFDVSLLSIENGVFEVQATSGDTHL 
               
               
                   
                 GGEDFDYKIVRQLIKAFKKKHGIDVSDNNKALAKLKREAEKAKRA 
               
               
                   
                 LSSQMSTRIEIDSFVDGIDLSETLTRAKFEELNLDLFKKTLKPVE 
               
               
                   
                 KVLQDSGLEKKDVDDIVLVGGSTRIPKVQQLLESYFDGKKASKGI 
               
               
                   
                 NPDEAVAYGAAVQAGVLSGEEGVEDIVLLDVNALTLGIETTGGVM 
               
               
                   
                 TPLIKRNTA1PTKKSQIFSTAVDNQPTVMIKVYEGERAMSKDNNL 
               
               
                   
                 LGKFELTGIPPAPRGVPQIEVTFALDANGILKVSATDKGTGKSES 
               
               
                   
                 ITITNDKGRLTQEEIDRMVEEAEKFASEDASIKAKVESRNKLENY 
               
               
                   
                 AHSLKNQVNGDLGEKLEEEDKETLLDAANDVLEWLDDNFETAIAE 
               
               
                   
                 DFDEKFESLSKVAYPITSKLYGGADGSGAADYDDEDEDDDGDYFE 
               
               
                   
                 HDEL* 
               
               
                   
               
               
                 SEQ ID NO: 6 
                 ATGAGATTAAGAACCGCCATTGCCACACTGTGCCTCACGGCTTTT 
               
               
                 EROl 
                 ACATCTGCAACTTCAAACAATAGCTACATCGCCACCGACCAAACA 
               
               
                   Saccharomyces  sp. 
                 CAAAATGCCTTTAATGACACTCACTTTTGTAAGGTCGACAGGAAT 
               
               
                   
                 GATCACGTTAGTCCCAGTTGTAACGTAACATTCAATGAATTAAAT 
               
               
                   
                 GCCATAAATGAAAACATTAGAGATGATCTTTCGGCGTTATTAAAA 
               
               
                   
                 TCTGATTTCTTCAAATACTTTCGGCTGGATTTATACAAGCAATGT 
               
               
                   
                 TCATTTTGGGACGCCAACGATGGTCTGTGCTTAAACCGCGCTTGC 
               
               
                   
                 TCTGTTGATGTCGTAGAGGACTGGGATACACTGCCTGAGTACTGG 
               
               
                   
                 CAGCCTGAGATCTTGGGTAGTTTCAATAATGATACAATGAAGGAA 
               
               
                   
                 GCGGATGATAGCGATGACGAATGTAAGTTCTTAGATCAACTATGT 
               
               
                   
                 CAAACCAGTAAAAAACCTGTAGATATCGAAGACACCATCAACTAC 
               
               
                   
                 TGTGATGTAAATGACTTTAACGGTAAAAACGCCGTTCTGATTGAT 
               
               
                   
                 TTAACAGCAAATCCGGAACGATTTACAGGTTATGGTGGTAAGCAA 
               
               
                   
                 GCTGGTCAAATTTGGTCTACTATCTACCAAGACAACTGTTTTACA 
               
               
                   
                 ATTGGCGAAACTGGTGAATCATTGGCCAAAGATGCATTTTATAGA 
               
               
                   
                 CTTGTATCCGGTTTCCATGCCTCTATCGGTACTCACTTATCAAAG 
               
               
                   
                 GAATATTTGAACACGAAAACTGGTAAATGGGAGCCCAATCTGGAT 
               
               
                   
                 TTGTTTATGGCAAGAATCGGGAACTTTCCTGATAGAGTGACAAAC 
               
               
                   
                 ATGTATTTCAATTATGCTGTTGTAGCTAAGGCTCTCTGGAAAATT 
               
               
                   
                 CAACCATATTTACCAGAATTTTCATTCTGTGATCTAGTCAATAAA 
               
               
                   
                 GAAATCAAAAACAAAATGGATAACGTTATTTCCCAGCTGGACACA 
               
               
                   
                 AAAATTTTTAACGAAGACTTAGTTTTTGCCAACGACCTAAGTTTG 
               
               
                   
                 ACTTTGAAGGACGAATTCAGATCTCGCTTCAAGAATGTCACGAAG 
               
               
                   
                 ATTATGGATTGTGTGCAATGTGATAGATGTAGATTGTGGGGCAAA 
               
               
                   
                 ATTCAAACTACCGGTTACGCAACTGCCTTGAAAATTTTGTTTGAA 
               
               
                   
                 ATCAACGACGCTGATGAATTCACCAAACAACATATTGTTGGTAAG 
               
               
                   
                 TTAACCAAATATGAGTTGATTGCACTATTACAAACTTTCGGTAGA 
               
               
                   
                 TTATCTGAATCTATTGAATCTGTTAACATGTTCGAAAAAATGTAC 
               
               
                   
                 GGGAAAAGGTTAAACGGTTCTGAAAACAGGTTAAGCTCATTCTTC 
               
               
                   
                 CAAAATAACTTCTTCAACATTTTGAAGGAGGCAGGCAAGTCGATT 
               
               
                   
                 CGTTACACCATAGAGAACATCAATTCCACTAAAGAAGGAAAGAAA 
               
               
                   
                 AAGACTAACAATTCTCAATCACATGTATTTGATGATTTAAAAATG 
               
               
                   
                 CCCAAAGCAGAAATAGTTCCAAGGCCCTCTAACGGTACAGTAAAT 
               
               
                   
                 AAATGGAAGAAAGCTTGGAATACTGAAGTTAACAACGTTTTAGAA 
               
               
                   
                 GCATTCAGATTTATTTATAGAAGCTATTTGGATTTACCCAGGAAC 
               
               
                   
                 ATCTGGGAATTATCTTTGATGAAGGTATACAAATTTTGGAATAAA 
               
               
                   
                 TTCATCGGTGTTGCTGATTACGTTAGTGAGGAGACACGAGAGCCT 
               
               
                   
                 ATTTCCTATAAGCTAGATATACAATAA 
               
               
                   
               
               
                 SEQ ID NO: 7 
                 MRLRTAIATLCLTAFTSATSNNSYIATDQTQNAFNDTHFCKVDRN 
               
               
                 EROl 
                 DHVSPSCNVTFNELNAINENIRDDLSALLKSDFFKYFRLDLYKQC 
               
               
                   Saccharomyces  sp. 
                 SFWDANDGLCLNRACSVDVVEDWDTLPEYWQPEILGSFNNDTMKE 
               
               
                   
                 ADDSDDECKFLDQLCQTSKKPVDIEDTINYCDVNDFNGKNAVLID 
               
               
                   
                 LTANPERFTGYGGKQAGQIWSTIYQDNCFTIGETGESLAKDAFYR 
               
               
                   
                 LVSGFHASIGTHLSKEYLNTKTGKWEPNLDLFMARIGNFPDRVTN 
               
               
                   
                 MYFNYAWAKALWKIQPYLPEFSFCDLVNKEIKNKMDNVISQLDTK 
               
               
                   
                 IFNEDLVFANDLSLTLKDEFRSRFKNVTKIMDCVQCDRCRLWGKI 
               
               
                   
                 QTTGYATALKILFEINDADEFTKQHIVGKLTKYELIALLQTFGRL 
               
               
                   
                 SESIESVNMFEKMYGKRLNGSENRLSSFFQNNFFNILKEAGKSIR 
               
               
                   
                 YTIENINSTKEGKKKTNNSQSHVFDDLKMPKAEIVPRPSNGTVNK 
               
               
                   
                 WKKAWNTEVNNVLEAFRFIYRSYLDLPRNIWELSLMKVYKFWNKF 
               
               
                   
                 IGVADYVSEETREPISYKLDIQ* 
               
               
                   
               
               
                 SEQ ID NO: 8 
                 ATGAAGTTTTCTGCTGGTGCCGTCCTGTCATGGTCCTCCCTGCTG 
               
               
                 PDI1 
                 CTCGCCTCCTCTGTTTTCGCCCAACAAGAGGCTGTGGCCCCTGAA 
               
               
                   Saccharomyces  sp. 
                 GACTCCGCTGTCGTTAAGTTGGCCACCGACTCCTTCAATGAGTAC 
               
               
                   
                 ATTCAGTCGCACGACTTGGTGCTTGCGGAGTTTTTTGCTCCATGG 
               
               
                   
                 TGTGGCCACTGTAAGAACATGGCTCCTGAATACGTTAAAGCCGCC 
               
               
                   
                 GAGACTTTAGTTGAGAAAAACATTACCTTGGCCCAGATCGACTGT 
               
               
                   
                 ACTGAAAACCAGGATCTGTGTATGGAACACAACATTCCAGGGTTC 
               
               
                   
                 CCAAGCTTGAAGATTTTCAAAAACAGCGATGTTAACAACTCGATC 
               
               
                   
                 GATTACGAGGGACCTAGAACTGCCGAGGCCATTGTCCAATTCATG 
               
               
                   
                 ATCAAGCAAAGCCAACCGGCTGTCGCCGTTGTTGCTGATCTACCA 
               
               
                   
                 GCTTACCTTGCTAACGAGACTTTTGTCACTCCAGTTATCGTCCAA 
               
               
                   
                 TCCGGTAAGATTGACGCCGACTTCAACGCCACCTTTTACTCCATG 
               
               
                   
                 GCCAACAAACACTTCAACGACTACGACTTTGTCTCCGCTGAAAAC 
               
               
                   
                 GCAGACGATGATTTCAAGCTTTCTATTTACTTGCCCTCCGCCATG 
               
               
                   
                 GACGAGCCTGTAGTATACAACGGTAAGAAAGCCGATATCGCTGAC 
               
               
                   
                 GCTGATGTTTTTGAAAAATGGTTGCAAGTGGAAGCCTTGCCCTAC 
               
               
                   
                 TTTGGTGAAATCGACGGTTCCGTTTTCGCCCAATACGTCGAAAGC 
               
               
                   
                 GGTTTGCCTTTGGGTTACTTATTCTACAATGACGAGGAAGAATTG 
               
               
                   
                 GAAGAATACAAGCCTCTCTTTACCGAGTTGGCCAAAAAGAACAGA 
               
               
                   
                 GGTCTAATGAACTTTGTTAGCATCGATGCCAGAAAATTCGGCAGA 
               
               
                   
                 CACGCCGGCAACTTGAACATGAAGGAACAATTCCCTCTATTTGCC 
               
               
                   
                 ATCCACGACATGACTGAAGACTTGAAGTACGGTTTGCCTCAACTC 
               
               
                   
                 TCTGAAGAGGCGTTTGACGAATTGAGCGACAAGATCGTGTTGGAG 
               
               
                   
                 TCTAAGGCTATTGAATCTTTGGTTAAGGACTTCTTGAAAGGTGAT 
               
               
                   
                 GCCTCCCCAATCGTGAAGTCCCAAGAGATCTTCGAGAACCAAGAT 
               
               
                   
                 TCCTCTGTCTTCCAATTGGTCGGTAAGAACCATGACGAAATCGTC 
               
               
                   
                 AACGACCCAAAGAAGGACGTTCTTGTTTTGTACTATGCCCCATGG 
               
               
                   
                 TGTGGTCACTGTAAGAGATTGGCCCCAACTTACCAAGAACTAGCT 
               
               
                   
                 GATACCTACGCCAACGCCACATCCGACGTTTTGATTGCTAAACTA 
               
               
                   
                 GACCACACTGAAAACGATGTCAGAGGCGTCGTAATTGAAGGTTAC 
               
               
                   
                 CCAACAATCGTCTTATACCCAGGTGGTAAGAAGTCCGAATCTGTT 
               
               
                   
                 GTGTACCAAGGTTCAAGATCCTTGGACTCTTTATTCGACTTCATC 
               
               
                   
                 AAGGAAAACGGTCACTTCGACGTCGACGGTAAGGCCTTGTACGAA 
               
               
                   
                 GAAGCCCAGGAAAAAGCTGCTGAGGAAGCCGATGCTGACGCTGAA 
               
               
                   
                 TTGGCTGACGAAGAAGATGCCATTCACGATGAATTGTAA 
               
               
                   
               
               
                 SEQ ID NO: 9 
                 MKFSAGAVLSWSSLLLASSVFAQQEAVAPEDSAVVKLATDSFNEY 
               
               
                 PDI1 
                 IQSHDLVLAEFFAPWCGHCKNMAPEYVKAAETLVEKNITLAQIDC 
               
               
                   Saccharomyces  sp. 
                 TENQDLCMEHNIPGFPSLKIFKNSDVNNSIDYEGPRTAEAIVQFM 
               
               
                   
                 IKQSQPAVAVVADLPAYLANETFVTPVIVQSGKIDADFNATFYSM 
               
               
                   
                 ANKHFNDYDFVSAENADDDFKLSIYLPSAMDEPWYNGKKADIADA 
               
               
                   
                 DVFEKWLQVEALPYFGEIDGSVFAQYVESGLPLGYLFYNDEEELE 
               
               
                   
                 EYKPLFTELAKKNRGLMNFVSIDARKFGRHAGNLNMKEQFPLFAI 
               
               
                   
                 HDMTEDLKYGLPQLSEEAFDELSDKIVLESKAIESLVKDFLKGDA 
               
               
                   
                 SPIVKSQEIFENQDSSVFQLVGKNHDEIVNDPKKDVLVLYYAPWC 
               
               
                   
                 GHCKRLAPTYQELADTYANATSDVLIAKLDHTENDVRGWIEGYPT 
               
               
                   
                 IVLYPGGKKSESWYQGSRSLDSLFDFIKENGHFDVDGKALYEEAQ 
               
               
                   
                 EKAAEEADADAELADEEDAIHDEL* 
               
               
                   
               
               
                 SEQ ID NO: 10 
                 ATGCGTCTACTTCGAAGAAACATGTTAGTATTGACACTGCTCGTT 
               
               
                 IRE1 
                 TGTGTGTTTTCATCCATCATTTCATGCTCAATCCCATTGTCGTCT 
               
               
                   Saccharomyces  sp. 
                 CGCACCTCAAGGCGGCAGATAGTGGAAGATGAAGTTGCCTCCACT 
               
               
                   
                 AAAAAGCTCAATTTCAACTATGGTGTGGATAAAAATATAAACTCG 
               
               
                   
                 CCCATTCCTGCTCCAAGAACCACTGAAGGTTTACCAAATATGAAA 
               
               
                   
                 CTCAGCTCATATCCAACTCCTAACTTATTGAATACTGCTGATAAT 
               
               
                   
                 CGACGTGCTAACAAAAAAGGACGTAGGGCTGCCAATTCTATAAGT 
               
               
                   
                 GTACCCTATTTGGAGAATCGTTCCTTGAACGAACTGAGTTTATCA 
               
               
                   
                 GATATACTAATCGCAGCCGACGTTGAGGGTGGACTTCATGCTGTA 
               
               
                   
                 GATAGAAGAAATGGTCATATCATATGGTCAATCGAACCAGAAAAT 
               
               
                   
                 TTTCAACCTCTGATAGAAATACAAGAACCTTCGAGGTTAGAAACA 
               
               
                   
                 TATGAAACGTTGATTATAGAACCTTTCGGTGATGGGAACATTTAC 
               
               
                   
                 TACTTTAACGCCCATCAAGGGTTACAAAAACTGCCTTTATCCATA 
               
               
                   
                 CGACAACTTGTATCAACTTCCCCGCTGCACTTGAAAACAAATATT 
               
               
                   
                 GTGGTTAATGACTCTGGAAAAATTGTTGAAGATGAAAAGGTCTAC 
               
               
                   
                 ACTGGATCGATGAGAACTATAATGTATACTATAAACATGTTGAAT 
               
               
                   
                 GGTGAAATTATATCAGCGTTCGGACCTGGTTCAAAAAACGGGTAT 
               
               
                   
                 TTCGGGAGCCAGAGTGTGGATTGCTCACCTGAGGAGAAGATAAAA 
               
               
                   
                 CTTCAGGAATGTGAAAATATGATTGTAATAGGCAAAACTATTTTT 
               
               
                   
                 GAGCTGGGAATTCACTCTTATGATGGAGCAAGCTACAATGTCACT 
               
               
                   
                 TACTCTACATGGCAGCAAAATGTTTTAGATGTTCCCCTAGCGCTT 
               
               
                   
                 CAGAATACATTTTCAAAGGACGGCATGTGCATAGCGCCTTTCCGT 
               
               
                   
                 GATAAATCATTGCTAGCAAGCGATTTAGATTTTAGAATTGCTAGA 
               
               
                   
                 TGGGTTTCTCCGACATTCCCCGGAATTATTGTTGGGCTTTTCGAT 
               
               
                   
                 GTGTTTAATGATCTCCGCACCAATGAAAATATACTGGTACCGCAT 
               
               
                   
                 CCCTTTAATCCTGGTGATCATGAAAGTATATCGAGTAACAAAGTT 
               
               
                   
                 TACTTGGATCAGACTTCGAACCTCTCCTGGTTTGCATTATCTAGT 
               
               
                   
                 CAGAATTTTCCATCTTTAGTCGAATCAGCTCCCATATCAAGATAC 
               
               
                   
                 GCTTCCAGTGACCGTTGGAGGGTGTCTTCAATTTTTGAAGATGAG 
               
               
                   
                 ACTTTATTCAAGAACGCAATCATGGGTGTTCATCAGATATATAAT 
               
               
                   
                 AATGAATATGATCACCTTTATGAAAACTATGAAAAAACGAATAGT 
               
               
                   
                 TTGGACACTACGCACAAATATCCACCTCTGATGATTGATTCGTCC 
               
               
                   
                 GTTGATACAACCGATTTACATCAGAATAACGAGATGAATTCACTA 
               
               
                   
                 AAGGAATACATGTCACCAGAAGACCTTGAGGCATATAGAAAAAAG 
               
               
                   
                 ATACACGAGCAAATATCGAGAGAATTAGATGAAAAGAACCAAAAT 
               
               
                   
                 TCTTTGCTACTGAAGTTTGGAAGTCTAGTATATCGAATTATAGAG 
               
               
                   
                 ACTGGAGTTTGCCGCCACTATATGTATTATTATCCAAAATTGGAT 
               
               
                   
                 TTATGCCTGAAAAGGAAATCCCCATAGTTGAGTCGAAATCGCTAA 
               
               
                   
                 ATTGTCCCTCTTCATCGGAAAATGTAACCAAGCCATTCGATATGA 
               
               
                   
                 AATCAGGGAAGCAAGTTGTTTTTGAAGGTGCTGTGAACGATGGAA 
               
               
                   
                 GTCTAAAATCTGAAAAAGATAACGATGATGCTGATGAAGATGATG 
               
               
                   
                 AAAAATCACTAGATTTAACCACAGAAAAGAAGAAGAGGAAAAGAG 
               
               
                   
                 GTTCGAGAGGAGGCAAAAAGGGCCGAAAATCACGCATTGCAAATA 
               
               
                   
                 TACCAAACTTTGAGCAATCTTTAAAAAATTTGGTAGTATCCGAAA 
               
               
                   
                 AAATTTTAGGTTACGGTTCATCAGGAACAGTAGTTTTTCAGGGAA 
               
               
                   
                 GTTTTCAAGGAAGACCTGTTGCGGTAAAGAGAATGTTAATTGATT 
               
               
                   
                 TTTGTGACATAGCTTTAATGGAAATAAAACTTTTGACTGAAAGCG 
               
               
                   
                 ATGATCACCCTAACGTCATACGATACTACTGTTCAGAAACAACAG 
               
               
                   
                 ACAGATTTTTGTATATTGCTTTAGAGCTCTGCAATTTGAACCTTC 
               
               
                   
                 AAGATTTGGTGGAGTCTAAGAATGTATCAGATGAAAACCTGAAAT 
               
               
                   
                 TACAGAAAGAGTATAATCCAATTTCGTTATTGAGACAAATAGCGT 
               
               
                   
                 CCGGGGTAGCACATTTACATTCTTTAAAGATTATCCATCGAGATT 
               
               
                   
                 TAAAGCCTCAAAATATTCTCGTTTCTACTTCGAGTAGGTTTACTG 
               
               
                   
                 CCGATCAGCAAACAGGAGCAGAAAATCTTCGAATTTTGATATCAG 
               
               
                   
                 ACTTTGGTCTTTGCAAAAAACTAGACTCTGGTCAGTCTTCATTTA 
               
               
                   
                 GAACAAATTTGAATAACCCTTCTGGCACAAGTGGTTGGAGGGCCC 
               
               
                   
                 CAGAGCTGCTTGAAGAATCAAACAATTTGCAGTGCCAAGTCGAAA 
               
               
                   
                 CGGAACACTCTTCTAGTAGGCATACAGTAGTTTCATCTGATTCTT 
               
               
                   
                 TTTATGATCCGTTCACCAAGAGGAGGCTAACAAAGGGAAGCATCC 
               
               
                   
                 ATTTGGAGATAAATATTCACGTGAAAGCAATATCATAAGAGGAAT 
               
               
                   
                 ATTCAGTCTTGATGAAATGAAATGTCTACATGATAGATCCTTAAT 
               
               
                   
                 TGCAGAAGCTACAGATCTGATCTCCCAAATGATTGATCACGATCC 
               
               
                   
                 GTTAAAAAGACCTACTGCTATGAAAGTTCTAAGGCATCCGTTGTT 
               
               
                   
                 TTGGCCAAAGTCGAAAAAATTGGAGTTCCTTTTAAAAGTTAGTGA 
               
               
                   
                 TAGGCTTGAAATTGAAAACAGAGACCCTCCAAGTGCCCTGTTAAT 
               
               
                   
                 GAAATTTGACGCCGGTTCTGACTTTGTAATACCCAGTGGAGATTG 
               
               
                   
                 GACTGTCAAGTTTGATAAAACATTCATGGACAACCTTGAAAGGTA 
               
               
                   
                 CAGAAAATACCATTCATCAAAGTTAATGGATCTATTAAGAGCACT 
               
               
                   
                 TAGGAATAAATATCATCATTTTATGGATTTACCTGAAGATATAGC 
               
               
                   
                 AGAACTAATGGGGCCGGTACCCGATGGATTTTACGATTACTTCAC 
               
               
                   
                 CAAGCGTTTTCCAAACCTATTAATAGGTGTTTATATGATTGTCAA 
               
               
                   
                 GGAAAATTTAAGTGACGATCAAATTTTACGTGAATTTTTGTATTC 
               
               
                   
                 ATAA 
               
               
                   
               
               
                 SEQ ID NO: 11 
                 MRLLRRNMLVLTLLVCVFSSIISCSIPLSSRTSRRQIVEDEVAST 
               
               
                 IRE1 
                 KKLNFNYGVDKNINSPIPAPRTTEGLPNMKLSSYPTPNLLNTADN 
               
               
                   Saccharomyces  sp. 
                 RRANKKGRRAANSISVPYLENRSLNELSLSDILIAADVEGGLHAV 
               
               
                   
                 DRRNGHIIWSIEPENFQPLIEIQEPSRLETYETLIIEPFGDGNIY 
               
               
                   
                 YFNAHQGLQKLPLSIRQLVSTSPLHLKTNIVVNDSGKIVEDEKVY 
               
               
                   
                 TGSMRTIMYTINMLNGEIISAFGPGSKNGYFGSQSVDCSPEEKIK 
               
               
                   
                 LQECENMIVIGKTIEELGIHSYDGASYNVTYSTWQQNVLDVPLAL 
               
               
                   
                 QNTFSKDGMCIAPFRDKSLLASDLDFRIARWVSPTFPGIIVGLFD 
               
               
                   
                 VFNDLRTNENILVPHPFNPGDHESISSNKVYLDQTSNLSWFALSS 
               
               
                   
                 QNFPSLVESAPISRYASSDRWRVSSIFEDETLFKNAIMGVHQIYN 
               
               
                   
                 NEYDHLYENYEKTNSLDTTHKYPPLMIDSSVDTTDLHQNNEMNSL 
               
               
                   
                 KEYMSPEDLEAYRKKIHEQISRELDEKNQNSLLLKFGSLVYRIIE 
               
               
                   
                 TGVFLLLFLIFCAILQRFKILPPLYVLLSKIGFMPEKEIPIVESK 
               
               
                   
                 SLNCPSSSENVTKPFDMKSGKQVVFEGAVNDGSLKSEKDNDDADE 
               
               
                   
                 DDEKSLDLTTEKKKRKRGSRGGKKGRKSRIANIPNFEQSLKNLVV 
               
               
                   
                 SEKILGYGSSGTVVFQGSFQGRPVAVKRMLIDFCDIALMEIKLLT 
               
               
                   
                 ESDDHPNVIRYYCSETTDRFLYIALELCNLNLQDLVESKNVSDEN 
               
               
                   
                 LKLQKEYNPISLLRQIASGVAHLHSLKIIHRDLKPQNILVSTSSR 
               
               
                   
                 FTADQQTGAENLRILISDFGLCKKLDSGQSSFRTNLNNPSGTSGW 
               
               
                   
                 RAPELLEESNNLQCQVETEHSSSRHTVVSSDSFYDPFTKRRLTRS 
               
               
                   
                 IDIFSMGCVFYYILSKGKHPFGDKYSRESNIIRGIFSLDEMKCLH 
               
               
                   
                 DRSLIAEATDLISQMIDHDPLKRPTAMKVLRHPLFWPKSKKLEFL 
               
               
                   
                 LKVSDRLEIENRDPPSALLMKFDAGSDFVIPSGDWTVKFDKTFMD 
               
               
                   
                 NLERYRKYHSSKLMDLLRALRNKYHHFMDLPEDIAELMGPVPDGF 
               
               
                   
                 YDYFTKRFPNLLIGVYMIVKENLSDDQILREFLYS* 
               
               
                   
               
               
                 SEQ ID NO: 12 
                 ATGGTCCTTTTGAAATGGCTCGTATGCCAATTGGTCTTCTTTACC 
               
               
                 rot2 
                 GCTTTTTCGCATGCGTTTACCGACTATCTATTAAAGAAGTGTGCG 
               
               
                   Saccharomyces  sp. 
                 CAATCTGGGTTTTGCCATAGAAACAGGGTTTATGCAGAAAATATT 
               
               
                   
                 GCCAAATCTCATCACTGCTATTACAAAGTGGACGCCGAGTCTATT 
               
               
                   
                 GCACACGATCCTTTAGAGAATGTGCTTCATGCTACCATAATTAAA 
               
               
                   
                 ACTATACCAAGATTGGAGGGCGATGATATAGCCGTTCAGTTCCCA 
               
               
                   
                 TTCTCTCTCTCTTTTTTACAGGATCACTCAGTAAGGTTCACTATA 
               
               
                   
                 AATGAGAAAGAGAGAATGCCAACCAACAGCAGCGGTTTGTTGATC 
               
               
                   
                 TCTTCACAACGGTTCAATGAGACCTGGAAGTACGCATTCGACAAG 
               
               
                   
                 AAATTTCAAGAGGAGGCGAACAGGACCAGTATTCCACAATTCCAC 
               
               
                   
                 TTCCTTAAGCAAAAACAAACTGTGAACTCATTCTGGTCGAAAATA 
               
               
                   
                 TCTTCATTTTTGTCACTTTCAAACTCCACTGCAGACACATTTCAT 
               
               
                   
                 CTTCGAAACGGTGATGTATCCGTAGAAATCTTTGCTGAACCTTTT 
               
               
                   
                 CAATTGAAAGTTTACTGGCAAAATGCGCTGAAACTTATTGTAAAC 
               
               
                   
                 GAGCAAAATTTCCTGAACATTGAACATCATAGAACTAAGCAGGAA 
               
               
                   
                 AACTTCGCACACGTGCTGCCAGAAGAAACAACTTTCAACATGTTT 
               
               
                   
                 AAGGACAATTTCTTGTATTCAAAGCATGACTCTATGCCTTTGGGG 
               
               
                   
                 CCTGAATCGGTTGCGCTAGATTTCTCTTTCATGGGTTCTACTAAT 
               
               
                   
                 GTCTACGGTATACCGGAACATGCGACGTCGCTAAGGCTGATGGAC 
               
               
                   
                 ACTTCAGGTGGAAAGGAACCCTACAGGCTTTTCAACGTTGATGTC 
               
               
                   
                 TTTGAGTACAACATCGGTACCAGCCAACCAATGTACGGTTCGATC 
               
               
                   
                 CCATTCATGTTTTCATCTTCGTCCACATCTATCTTTTGGGTCAAT 
               
               
                   
                 GCAGCTGACACTTGGGTAGACATAAAGTATGACACCAGTAAAAAT 
               
               
                   
                 AAAACGATGACTCATTGGATCTCCGAAAATGGTGTCATAGATGTA 
               
               
                   
                 GTCATGTCCCTGGGGCCAGATATTCCAACTATCATTGACAAATTT 
               
               
                   
                 ACCGATTTGACTGGTAGACCCTTTTTACCGCCCATTTCCTCTATA 
               
               
                   
                 GGGTACCATCAATGTAGATGGAATTATAATGATGAGATGGACGTT 
               
               
                   
                 CTCACAGTGGACTCTCAGATGGATGCTCATATGATTCCTTACGAT 
               
               
                   
                 TTTATTTGGTTGGACTTGGAGTATACGAACGACAAAAAATATTTT 
               
               
                   
                 ACTTGGAAGCAGCACTCCTTTCCCAATCCAAAAAGGCTGTTATCC 
               
               
                   
                 AAATTAAAAAAGTTGGGTAGAAATCTTGTCGTACTAATCGATCCT 
               
               
                   
                 CATTTAAAGAAAGATTATGAAATCAGTGACAGGGTAATTAATGAA 
               
               
                   
                 AATGTAGCAGTCAAGGATCACAATGGAAATGACTATGTAGGTCAT 
               
               
                   
                 TGCTGGCCAGGTAATTCTATATGGATTGATACCATAAGCAAATAT 
               
               
                   
                 GGCCAAAAGATTTGGAAGTCCTTTTTCGAACGGTTTATGGATCTG 
               
               
                   
                 CCGGCTGATTTAACTAATTTATTCATTTGGAATGATATGAACGAG 
               
               
                   
                 CCTTCGATTTTCGATGGCCCAGAGACCACAGCTCCAAAAGATTTG 
               
               
                   
                 ATTCACGACAATTACATTGAGGAAAGATCCGTCCATAACATATAT 
               
               
                   
                 GGTCTATCAGTGCATGAAGCTACTTACGACGCAATAAAATCGATT 
               
               
                   
                 TATTCACCATCCGATAAGCGTCCTTTCCTTCTTGACAATGTGGCC 
               
               
                   
                 AATTGGGATTACTTAAAGATTTCCATTCCTATGGTTCTGTCAAAC 
               
               
                   
                 AACATTGCTGGTATGCCATTTATAGGAGCCGACATAGCTGGCTTT 
               
               
                   
                 GCTGAGGATCCTACACCTGAATTGATTGCACGTTGGTACCAAGCG 
               
               
                   
                 GGCTTATGGTACCCATTTTTTAGAGCACACGCCCATATAGACACC 
               
               
                   
                 AAGAGAAGAGAACCATACTTATTCAATGAACCTTTGAAGTCGATA 
               
               
                   
                 GTACGTGATATTATCCAATTGAGATATTTCCTGCTACCTACCTTA 
               
               
                   
                 TACACCATGTTTCATAAATCAAGTGTCACTGGATTTCCGATAATG 
               
               
                   
                 AATCCAATGTTTATTGAACACCCTGAATTTGCTGAATTGTATCAT 
               
               
                   
                 ATCGATAACCAATTTTACTGGAGTAATTCAGGTCTATTAGTCAAA 
               
               
                   
                 CCTGTCACGGAGCCTGGTCAATCAGAAACGGAAATGGTTTTCCCA 
               
               
                   
                 CCCGGTATATTCTATGAATTCGCATCTTTACACTCTTTTATAAAC 
               
               
                   
                 AATGGTACTGATTTGATAGAAAAGAATATTTCTGCACCATTGGAT 
               
               
                   
                 AAAATTCCATTATTTATTGAAGGCGGTCACATTATCACTATGAAA 
               
               
                   
                 GATAAGTATAGAAGATCTTCAATGTTAATGAAAAACGATCCATAT 
               
               
                   
                 GTAATAGTTATAGCCCCTGATACCGAGGGACGAGCCGTTGGAGAT 
               
               
                   
                 CTTTATGTTGATGATGGAGAAACTTTTGGCTACCAAAGAGGTGAG 
               
               
                   
                 TACGTAGAAACTCAGTTCATTTTCGAAAACAATACCTTAAAAAAT 
               
               
                   
                 GTTCGAAGTCATATTCCCGAGAATTTGACAGGCATTCACCACAAT 
               
               
                   
                 ACTTTGAGGAATACCAATATTGAAAAAATCATTATCGCAAAGAAT 
               
               
                   
                 AATTTACAACACAACATAACGTTGAAAGACAGTATTAAAGTCAAA 
               
               
                   
                 AAAAATGGCGAAGAAAGTTCATTGCCGACTAGATCGTCATATGAG 
               
               
                   
                 AATGATAATAAGATCACCATTCTTAACCTATCGCTTGACATAACT 
               
               
                   
                 GAAGATTGGGAAGTT 
               
               
                   
               
               
                 SEQ ID NO: 13 
                 MVLLKWLVCQLVFFTAFSHAFTDYLLKKCAQSGFCHRNRVYAENI 
               
               
                 rot2 
                 AKSHHCYYKVDAESIAHDPLENVLHATIIKTIPRLEGDDIAVQFP 
               
               
                   Saccharomyces  sp. 
                 FSLSFLQDHSVRFTINEKERMPTNSSGLLISSQRFNETWKYAFDK 
               
               
                   
                 KFQEEANRTSIPQFHFLKQKQTVNSFWSKISSFLSLSNSTADTFH 
               
               
                   
                 LRNGDVSVEIFAEPFQLKVYWQNALKLIVNEQNFLNIEHHRTKQE 
               
               
                   
                 NFAHVLPEETTFNMFKDNFLYSKHDSMPLGPESVALDFSFMGSTN 
               
               
                   
                 VYGIPEHATSLRLMDTSGGKEPYRLFNVDWEYNIGTSQPMYGSIP 
               
               
                   
                 FMFSSSSTSIFWVNAADTWVDIKYDTSKNKTMTHWISENGVIDVV 
               
               
                   
                 MSLGPDIPTIIDKFTDLTGRPFLPPISSIGYHQCRWNYNDEMDVL 
               
               
                   
                 TVDSQMDAHMIPYDFIWLDLEYTNDKKYFTWKQHSFPNPKRLLSK 
               
               
                   
                 LKKLGRNLVVLIDPHLKKDYEISDRVINENVAVKDHNGNDYVGHC 
               
               
                   
                 WPGNSIWIDTISKYGQKIWKSFFERFMDLPADLTNLFIWNDMNEP 
               
               
                   
                 SIFDGPETTAPKDLIHDNYIEERSVHNIYGLSVHEATYDAIKSIY 
               
               
                   
                 SPSDKRPFLLTRAFFAGSQRTAATWTGDNVANWDYLKISIPMVLS 
               
               
                   
                 NNIAGMPFIGADIAGFAEDPTPELIARWYQAGLWYPFFRAHAHID 
               
               
                   
                 TKRREPYLFNEPLKSIVRDIIQLRYFLLPTLYTMFHKSSVTGFPI 
               
               
                   
                 MNPMFIEHPEFAELYHIDNQFYWSNSGLLVKPVTEPGQSETEMVF 
               
               
                   
                 PPGIFYEFASLHSFINNGTDLIEKNISAPLDKIPLFIEGGHIITM 
               
               
                   
                 KDKYRRSSMLMKNDPYVIVIAPDTEGRAVGDLYVDDGETFGYQRG 
               
               
                   
                 EYVETQFIFENNTLKNVRSHIPENLTGIHHNTLRNTNIEKIIIAK 
               
               
                   
                 NNLQHNITLKJDSIKVKKNGEESSLPTRSSYENDNKITILNLSLD 
               
               
                   
                 ITEDWEVIF* 
               
               
                   
               
               
                 SEQ ID NO: 14 
                 ATGTTCAGCTTGAAAGCATTATTGCCATTGGCCTTGTTGTTGGTC 
               
               
                 Pep4 
                 AGCGCCAACCAAGTTGCTGCAAAAGTCCACAAGGCTAAAATTTAT 
               
               
                   Saccharomyces  sp. 
                 AAACACGAGTTGTCCGATGAGATGAAAGAAGTCACTTTCGAGCAA 
               
               
                   
                 CATTTAGCTCATTTAGGTAGGGAGCATCCTTTCTTCACTGAAGGT 
               
               
                   
                 GGTCACGATGTTCCATTGACAAATTACTTGAACGCACAATATTAC 
               
               
                   
                 ACTGACATTACTTTGGGTACTCCACCTCAAAACTTCAAGGTTATT 
               
               
                   
                 TTGGATACTGGTTCTTCAAACCTTTGGGTTCCAAGTAACGAATGT 
               
               
                   
                 GGTTCCTTGGCTTGTTTCCTACATTCTAAATACGATCATGAAGCT 
               
               
                   
                 TCATCAAGCTACAAAGCTAATGGTACTGAATTTGCCATTCAATAT 
               
               
                   
                 GGTACTGGTTCTTTGGAAGGTTACATTTCTCAAGACACTTTGTCC 
               
               
                   
                 ATCGGGGATTTGACCATTCCAAAACAAGACTTCGCTGAGGCTACC 
               
               
                   
                 AGCGAGCCGGGCTTAACATTTGCATTTGGCAAGTTCGATGGTATT 
               
               
                   
                 TTGGGTTTGGGTTACGATACCATTTCTGTTGATAAGGTGGTCCCT 
               
               
                   
                 CCATTTTACAACGCCATTCAACAAGATTTGTTGGACGAAAAGAGA 
               
               
                   
                 TTTGCCTTTTATTTGGGAGACACTTCAAAGGATACTGAAAATGGC 
               
               
                   
                 GGTGAAGCCACCTTTGGTGGTATTGACGAGTCTAAGTTCAAGGGC 
               
               
                   
                 GATATCACTTGGTTACCTGTTCGTCGTAAGGCTTACTGGGAAGTC 
               
               
                   
                 AAGTTTGAAGGTATCGGTTTAGGCGACGAGTACGCCGAATTGGAG 
               
               
                   
                 AGCCATGGTGCCGCCATCGATACTGGTACTTCTTTGATTACCTTG 
               
               
                   
                 CCATCAGGATTAGCTGAAATGATTAATGCTGAAATTGGGGCCAAG 
               
               
                   
                 AAGGGTTGGACCGGTCAATATACTCTAGACTGTAACACCAGAGAC 
               
               
                   
                 AATCTACCTGATCTAATTTTCAACTTCAATGGCTACAACTTCACT 
               
               
                   
                 ATTGGGCCATACGATTACACGCTTGAAGTTTCAGGCTCCTGTATC 
               
               
                   
                 TCTGCAATTACACCAATGGATTTCCCAGAACCTGTTGGCCCACTG 
               
               
                   
                 GCCATCGTTGGTGATGCCTTCTTGCGTAAATACTATTCTATTTAC 
               
               
                   
                 GATTTGGGCAACAATGCGGTTGGTTTGGCCAAAGCAATTTGA 
               
               
                   
               
               
                 SEQ ID NO: 15 
                 MFSLKALLPLALLLVSANQVAAKVHKAKIYKHELSDEMKEVTFEQ 
               
               
                 pep4 
                 HLAHLGQKYLTQFEKANPEWFSREHPFFTEGGHDVPLTNYLNAQY 
               
               
                   Saccharomyces  sp. 
                 YTDITLGTPPQNFKVILDTGSSNLWVPSNECGSLACFLHSKYDHE 
               
               
                   
                 ASSSYKANGTEFAIQYGTGSLEGYISQDTLSIGDLTIPKQDFAEA 
               
               
                   
                 TSEPGLTFAFGKFDGILGLGYDTISVDKVVPPFYNAIQQDLLDEK 
               
               
                   
                 RFAFYLGDTSKDTENGGEATFGGIDESKFKGDITWLPVRRKAYWE 
               
               
                   
                 VKFEGIGLGDEYAELESHGAAIDTGTSLITLPSGLAEMINAEIGA 
               
               
                   
                 KKGWTGQYTLDCNTRDNLPDLIFNFNGYNFTIGPYDYTLEVSGSC 
               
               
                   
                 ISAITPMDFPEPVGPLAIVGDAFLRKYYSIYDLGNNAVGLAKAI* 
               
               
                   
               
               
                 SEQ ID NO: 16 
                 ATGGGTTTATCTTTGGTCTGCACCTTCTCCTTTCAAACTAACTAC 
               
               
                 Geranyl 
                 CACACTTTATTGAATCCACATAATAAGAATCCTAAGAACTCTTTA 
               
               
                 pyrophosphate 
                 TTGTCCTACCAACACCCAAAGACTCCTATTATCAAGTCCTCTTAC 
               
               
                 olivetolic acid 
                 GATAACTTCCCATCTAAGTACTGTTTGACTAAGAATTTCCATTTG 
               
               
                 geranyltransferase 
                 TTGGGTTTGAATTCTCACAACAGAATTTCCTCCCAATCCCGTTCT 
               
               
                 CsPT4 nucleotide 
                 ATTAGAGCCGGTTCTGATCAAATCGAAGGTTCCCCTCATCATGAG 
               
               
                 sequence 
                 TCCGATAACTCCATTGCTACTAAAATTTTAAATTTCGGTCATACT 
               
               
                 (GOT) 
                 TGTTGGAAGTTGCAACGTCCTTACGTTGTCAAGGGTATGATCTCT 
               
               
                 Artificial sequence 
                 ATTGCTTGTGGTTTGTTCGGTAGAGAATTGTTTAACAACAGACAC 
               
               
                 Codon optimized 
                 TTGTTCTCTTGGGGTTTGATGTGGAAAGCTTTCTTCGCTTTGGTC 
               
               
                   
                 CCAATTTTGTCTTTCAATTTCTTCGCCGCCATCATGAACCAAATC 
               
               
                   
                 TACGATGTTGATATCGACCGTATCAACAAGCCAGACTTACCTTTA 
               
               
                   
                 GTTTCCGGTGAAATGTCCATTGAAACTGCTTGGATCTTGTCTATC 
               
               
                   
                 ATTGTTGCCTTGACTGGTTTAATTGTTACTATTAAGTTGAAGTCC 
               
               
                   
                 GCTCCATTGTTTGTCTTCATCTACATCTTCGGTATCTTCGCTGGT 
               
               
                   
                 TTCGCTTACTCCGTCCCACCTATTAGATGGAAACAATATCCTTTT 
               
               
                   
                 ACCAATTTCTTGATCACTATTTCCTCTCATGTTGGTTTGGCTTTC 
               
               
                   
                 ACTTCTTACTCTGCCACCACTTCTGCTTTAGGTTTGCCTTTCGTT 
               
               
                   
                 TGGCGTCCTGCCTTCTCTTTCATTATTGCTTTCATGACTGTCATG 
               
               
                   
                 GGTATGACTATTGCCTTTGCTAAAGACATTTCTGATATCGAAGGT 
               
               
                   
                 GATGCTAAGTACGGTGTCTCTACCGTTGCTACCAAGTTAGGTGCT 
               
               
                   
                 AGAAATATGACTTTTGTTGTTTCTGGTGTCTTATTGTTGAACTAC 
               
               
                   
                 TTGGTTTCTATCTCTATTGGTATCATTTGGCCACAAGTTTTCAAG 
               
               
                   
                 TCTAACATTATGATCTTGTCTCATGCTATTTTGGCTTTCTGTTTG 
               
               
                   
                 ATCTTTCAAACTCGTGAATTAGCCTTAGCCAATTATGCCTCTGCC 
               
               
                   
                 CCATCCCGTCAATTTTTCGAATTCATCTGGTTGTTATACTATGCC 
               
               
                   
                 GAATACTTCGTTTACGTCTTCATTTAA 
               
               
                   
               
               
                 SEQ ID NO: 17 
                 MGLSLVCTFSFQTNYHTLLNPHNKNPKNSLLSYQHPKTPIIKSSY 
               
               
                 Geranyl pyrophosphate 
                 DNFPSKYCLTKNFHLLGLNSHNRISSQSRSIRAGSDQIEGSPHHE 
               
               
                 olivetolic acid 
                 SDNSIATKILNFGHTCWKLQRPYWKGMISIACGLFGRELFNNRHL 
               
               
                 geranyltransferase 
                 FSWGLMWKAFFALVPILSFNFFAAIMNQIYDVDIDRINKPDLPLV 
               
               
                 CsPT4 
                 SGEMSIETAWILSIIVALTGLIVTIKLKSAPLFVFIYIFGIFAGF 
               
               
                 (GOT) 
                 AYSVPPIRWKQYPFTNFLITISSHVGLAFTSYSATTSALGLPFVW 
               
               
                 Cannibis sativa 
                 RPAFSFIIAFMTVMGMTIAFAKDISDIEGDAKYGVSTVATKLGAR 
               
               
                   
                 NMTFVVSGVLLLNYLVSISIGIIWPQVFKSNIMILSHAILAFCLI 
               
               
                   
                 FQTRELALANYASAPSRQFFEFIWLLYYAEYFVYVFI* 
               
               
                   
               
               
                 SEQ ID NO: 18 
                 ATGAACCATTTAAGAGCTGAGGGTCCAGCTTCCGTCTTGGCTATC 
               
               
                 Tetraketide synthase 
                 GGTACTGCTAATCCAGAGAACATTTTATTACAAGATGAGTTTCCA 
               
               
                 (TKS) nucleotide 
                 GATTACTATTTCCGTGTTACTAAGTCCGAGCATATGACCCAATTG 
               
               
                 sequence 
                 AAAGAAAAGTTCCGTAAAATCTGTGATAAATCTATGATTAGAAAA 
               
               
                 Artificial sequence 
                 AGAAACTGCTTTTTAAACGAAGAACACTTGAAGCAAAACCCAAGA 
               
               
                 Codon optimized 
                 TTAGTTGAACACGAGATGCAAACCTTGGACGCTAGACAAGATATG 
               
               
                   
                 TTGGTTGTCGAGGTTCCTAAATTGGGTAAAGACGCCTGTGCTAAA 
               
               
                   
                 GCTATCAAAGAGTGGGGTCAACCTAAGTCCAAGATCACTCACTTA 
               
               
                   
                 ATCTTCACTTCCGCTTCCACCACTGACATGCCTGGTGCTGATTAC 
               
               
                   
                 CACTGTGCCAAGTTGTTGGGTTTGTCTCCTTCTGTCAAGAGAGTT 
               
               
                   
                 ATGATGTACCAATTAGGTTGTTACGGTGGTGGTACTGTCTTAAGA 
               
               
                   
                 ATTGCTAAGGACATCGCTGAAAACAACAAAGGTGCTAGAGTTTTA 
               
               
                   
                 GCCGTTTGTTGTGACATCATGGCTTGTTTATTTCGTGGTCCATCT 
               
               
                   
                 GAATCTGACTTGGAGTTGTTGGTTGGTCAAGCTATTTTTGGTGAT 
               
               
                   
                 GGTGCCGCTGCCGTCATCGTTGGTGCTGAGCCAGATGAATCCGTT 
               
               
                   
                 GGTGAAAGACCAATTTTCGAATTAGTCTCTACTGGTCAAACTATT 
               
               
                   
                 TTGCCAAACTCCGAGGGTACTATCGGTGGTCATATTCGTGAAGCC 
               
               
                   
                 GGTTTAATCTTTGATTTGCACAAAGACGTTCCAATGTTGATCTCT 
               
               
                   
                 AACAACATCGAAAAGTGTTTAATTGAGGCTTTTACTCCAATTGGT 
               
               
                   
                 ATCTCTGACTGGAACTCTATCTTCTGGATCACTCATCCAGGTGGT 
               
               
                   
                 AAGGCTATCTTGGACAAGGTTGAAGAAAAATTACATTTAAAGTCC 
               
               
                   
                 GATAAATTCGTCGATTCTCGTCATGTTTTGTCTGAACACGGTAAC 
               
               
                   
                 ATGTCTTCCTCCACTGTCTTGTTTGTTATGGATGAATTACGTAAG 
               
               
                   
                 AGATCTTTGGAGGAGGGTAAGTCTACTACTGGTGATGGTTTCGAA 
               
               
                   
                 TGGGGTGTTTTGTTCGGTTTCGGTCCTGGTTTGACTGTTGAACGT 
               
               
                   
                 GTTGTTGTTAGATCTGTTCCAATTAAGTACTAG 
               
               
                   
               
               
                 SEQ ID NO: 19 
                 MNHLRAEGPASVLAIGTANPENILLQDEFPDYYFRVTKSEHMTQL 
               
               
                 Tetraketide 
                 KEKFRKICDKSMIRKRNCFLNEEHLKQNPRLVEHEMQTLDARQDM 
               
               
                 synthase 
                 LVVEVPKLGKDACAKAIKEWGQPKSKITHLIFTSASTTDMPGADY 
               
               
                 (TKS) 
                 HCAKLLGLSPSVKRVMMYQLGCYGGGTVLRIAKDIAENNKGARVL 
               
               
                 GenBank B1Q2B6 
                 AVCCDIMACLFRGPSESDLELLVGQAIFGDGAAAVIVGAEPDESV 
               
               
                 
                   Cannabis sativa 
                 
                 GERPIFELVSTGQTILPNSEGTIGGHIREAGLIFDLHKDVPMLIS 
               
               
                   
                 NNIEKCLIEAFTPIGISDWNSIFWITHPGGKAILDKVEEKLHLKS 
               
               
                   
                 DKFVDSRHVLSEHGNMSSSTVLFVMDELRKRSLEEGKSTTGDGFE 
               
               
                   
                 WGVLFGFGPGLTVERVVVRSVPIKY* 
               
               
                   
               
               
                 SEQ ID NO: 20 
                 ATGGCCGTCAAACACTTGATCGTCTTAAAATTCAAGGATGAAATT 
               
               
                 Olivetolic acid 
                 ACTGAAGCTCAAAAAGAAGAGTTCTTCAAAACCTATGTCAATTTA 
               
               
                 cyclase 
                 GTCAACATTATTCCTGCTATGAAGGACGTTTACTGGGGTAAGGAT 
               
               
                 (OAC) nucleotide 
                 GTCACCCAAAAGAACAAGGAAGAAGGTTACACTCACATTGTTGAA 
               
               
                 sequence 
                 GTCACTTTCGAATCTGTTGAAACTATCCAAGATTATATTATCCAC 
               
               
                 Artificial  
                 CCAGCTCATGTCGGTTTTGGTGATGTTTACAGATCTTTTTGGGAA 
               
               
                 Sequence 
                 AAATTGTTGATCTTTGACTATACTCCAAGAAAATAA 
               
               
                 Codon optimized 
                   
               
               
                   
               
               
                 SEQ ID NO: 21 
                 MAVKHLIVLKFKDEITEAQKEEFFKTYVNLVNIIPAMKDVYWGKD 
               
               
                 Olivetolic acid 
                 VTQKNKEEGYTHIVEVTFESVETIQDYIIHPAHVGFGDVYRSFWE 
               
               
                 cyclase 
                 KLLIFDYTPRK* 
               
               
                 (OAC) 
                   
               
               
                 GenBank AFN42527 
                   
               
               
                 
                   Cannabis sativa 
                 
                   
               
               
                   
               
               
                 SEQ ID NO: 22 
                 ATGGGTAAGAATTACAAGTCCTTAGACTCTGTTGTTGCTTCTGAC 
               
               
                 Acyl-activating 
                 TTTATTGCTTTAGGTATTACTTCCGAAGTTGCTGAAACCTTACAC 
               
               
                 enzyme 
                 GGTAGATTGGCTGAAATTGTTTGCAACTACGGTGCTGCTACCCCT 
               
               
                 Cs_AAE1  
                 CAAACTTGGATTAACATTGCTAATCATATTTTGTCTCCAGATTTG 
               
               
                 nucleotide 
                 CCATTTTCTTTACACCAAATGTTGTTCTACGGTTGTTACAAGGAT 
               
               
                 sequence 
                 TTCGGTCCTGCTCCTCCAGCTTGGATTCCTGATCCAGAAAAAGTC 
               
               
                 Artificial 
                 AAATCTACTAACTTGGGTGCTTTGTTGGAAAAGAGAGGTAAGGAG 
               
               
                 sequence 
                 TTTTTGGGTGTTAAGTACAAGGACCCAATTTCTTCTTTCTCTCAC 
               
               
                 Codon optimized 
                 TTCCAAGAATTCTCTGTTAGAAACCCTGAAGTTTACTGGAGAACT 
               
               
                   
                 GTTTTGATGGATGAGATGAAGATTTCTTTTTCTAAGGACCCAGAG 
               
               
                   
                 TGTATCTTAAGAAGAGACGACATTAACAATCCAGGTGGTTCTGAG 
               
               
                   
                 TGGTTACCAGGTGGTTACTTGAACTCTGCCAAAAATTGCTTGAAC 
               
               
                   
                 GTTAACTCTAACAAGAAATTGAATGACACTATGATTGTCTGGAGA 
               
               
                   
                 GATGAGGGTAACGATGATTTGCCTTTGAATAAATTGACTTTGGAT 
               
               
                   
                 CAATTGAGAAAAAGAGTCTGGTTGGTTGGTTACGCTTTGGAAGAA 
               
               
                   
                 ATGGGTTTAGAAAAAGGTTGTGCTATCGCCATCGATATGCCTATG 
               
               
                   
                 CACGTTGATGCTGTTGTTATTTATTTGGCTATTGTTTTAGCTGGT 
               
               
                   
                 TATGTTGTTGTTTCCATCGCCGACTCCTTCTCTGCTCCAGAAATC 
               
               
                   
                 TCCACCAGATTGAGATTGTCTAAAGCCAAAGCCATTTTCACCCAA 
               
               
                   
                 GACCACATCATTAGAGGTAAGAAGCGTATTCCATTGTATTCTCGT 
               
               
                   
                 GTTGTTGAAGCTAAATCTCCTATGGCTATCGTCATCCCATGCTCT 
               
               
                   
                 GGTTCTAACATCGGTGCTGAATTAAGAGACGGTGATATTTCTTGG 
               
               
                   
                 GACTACTTTTTAGAAAGAGCTAAAGAATTCAAAAACTGCGAGTTT 
               
               
                   
                 ACTGCTAGAGAACAACCTGTCGACGCTTATACTAATATTTTATTC 
               
               
                   
                 TCTTCTGGTACTACTGGTGAACCTAAGGCTATTCCATGGACCCAA 
               
               
                   
                 GCTACTCCTTTGAAAGCCGCTGCTGATGGTTGGTCCCATTTAGAC 
               
               
                   
                 ATCAGAAAAGGTGATGTCATCGTCTGGCCAACTAACTTAGGTTGG 
               
               
                   
                 ATGATGGGTCCATGGTTAGTCTACGCTTCTTTGTTGAATGGTGCC 
               
               
                   
                 TCTATCGCCTTATATAATGGTTCCCCTTTAGTCTCTGGTTTTGCT 
               
               
                   
                 AAATTCGTTCAAGATGCTAAGGTTACCATGTTAGGTGTTGTCCCT 
               
               
                   
                 TCTATCGTTAGATCTTGGAAATCTACTAACTGTGTTTCTGGTTAC 
               
               
                   
                 GACTGGTCCACTATTCGTTGTTTCTCTTCTTCTGGTGAAGCTTCC 
               
               
                   
                 AATGTCGATGAGTACTTATGGTTAATGGGTCGTGCTAACTACAAG 
               
               
                   
                 CCAGTCATCGAAATGTGCGGTGGTACTGAAATTGGTGGTGCTTTT 
               
               
                   
                 TCCGCTGGTTACTTTATATATCTTAGATAAGAATGGTTACCCTAT 
               
               
                   
                 GCCTAAAAACAAGCCAGGTATTGGTGAATTAGCTTTGGGTCCTGT 
               
               
                   
                 TATGTTTGGTGCTTCTAAAACCTTGTTAAATGGTAATCATCACGA 
               
               
                   
                 CGTTTACTTCAAAGGTATGCCTACTTTGAACGGTGAGGTTTTGAG 
               
               
                   
                 ACGTCATGGTGATATTTTCGAATTAACTTCCAACGGTTATTATCA 
               
               
                   
                 CGCTCACGGTAGAGCTGATGATACTATGAACATTGGTGGTATTAA 
               
               
                   
                 GATCTCTTCCATCGAAATTGAGAGAGTTTGTAACGAGGTTGACGA 
               
               
                   
                 TCGTGTTTTCGAAACTACTGCTATTGGTGTCCCTCCTTTAGGTGG 
               
               
                   
                 TGGTCCAGAACAATTGGTTATCTTTTTCGTCTTGAAGGACTCCAA 
               
               
                   
                 CGACACCACTATCGACTTAAACCAATTAAGATTGTCTTTCAACTT 
               
               
                   
                 GGGTTTGCAAAAGAAGTTGAATCCATTATTTAAGGTTACTCGTGT 
               
               
                   
                 CGTTCCATTGTCCTCCTTGCCAAGAACTGCTACCAACAAGATTAT 
               
               
                   
                 GCGTAGAGTCTTGAGACAACAATTCTCTCACTTTGAGTAA 
               
               
                   
               
               
                 SEQ ID NO: 23 
                 MGKNYKSLDSWASDFIALGITSEVAETLHGRLAETVCNYGAATP 
               
               
                 Acyl-activating 
                 QTWINIANHILSPDLPFSLHQMLFYGCYKDFGPAPP 
               
               
                 enzyme 
                 AWIPDPEKVKSTNLGALLEKRGKEFLGVKYKDPISSFSHFQEFSV 
               
               
                 (CsAAE1) 
                 RNPEVYWRTVLMDEMKISFSKDPECILRRDDINNPGGSEWLPGGY 
               
               
                 
                   Cannabis sativa 
                 
                 LNSAKNCLNVNSNKKLNDTMIVWRDEGNDDLPLNKLTLDQLRKRV 
               
               
                   
                 WLVGYALEEMGLEKGCAIAIDMPMHVDAWIYLAIVLAGYWVSIAD 
               
               
                   
                 SFSAPEISTRJLRLSKAKAIFTQDHIIRGKKRIPLYSRVVEAKSP 
               
               
                   
                 MAIVIPCSGSNIGAELRDGDISWDYFLERAKEFKNCEFTAREQPV 
               
               
                   
                 DAYTNILFSSGTTGEPKAIPWTQATPLKAAADGWSHLDIRKGDVI 
               
               
                   
                 VWPTNLGWMMGPWLVYASLLNGASIALYNGSPLVSGFAKFVQDAK 
               
               
                   
                 VTMLGWPSIVRSWKSTNCVSGYDWSTIRCFSSSGE 
               
               
                   
                 ASNVDEYLWLMGRANYKPVIEMCGGTEIGGAFSAGSFLQAQSLSS 
               
               
                   
                 FSSQCMGCTLYILDKNGYPMPKNKPGIGELALGPVMFGASKTLLN 
               
               
                   
                 GNHHDVYFKGMPTLNGEVLRRHGDIFELTSNGYYHAHGRADDTMN 
               
               
                   
                 IGGIKISSIEIERVCNEVDDRVFETTAIGWPLGGGPEQLVIFFVL 
               
               
                   
                 KDSNDTTIDLNQLRLSFNLGLQKKLNPLFKVTRVVPLSSLPRTAT 
               
               
                   
                 NKiMRRVLRQQFSHFE* 
               
               
                   
               
               
                 SEQ ID NO: 24 
                 ATGACTGCCGACAACAATAGTATGCCCCATGGTGCAGTATCTAGT 
               
               
                 Isopentenyl 
                 TACGCCAAATTAGTGCAAAACCAAACACCTGAAGACATTTTGGAA 
               
               
                 pyrophosphate 
                 GAGTTTCCTGAAATTATTCCATTACAACAAAGACCTAATACCCGA 
               
               
                 isomerase 
                 TCTAGTGAGACGTCAAATGACGAAAGCGGAGAAACATGTTTTTCT 
               
               
                 (Sc_IDI1) 
                 GGTCATGATGAGGAGCAAATTAAGTTAATGAATGAAAATTGTATT 
               
               
                   Saccharomyces  sp. 
                 GTTTTGGATTGGGACGATAATGCTATTGGTGCCGGTACCAAGAAA 
               
               
                   
                 GTTTGTCATTTAATGGAAAATATTGAAAAGGGTTTACTACATCGT 
               
               
                   
                 GCATTCTCCGTCTTTATTTTCAATGAACAAGGTGAATTACTTTTA 
               
               
                   
                 CAACAAAGAGCCACTGAAAAAATAACTTTCCCTGATCTTTGGACT 
               
               
                   
                 AACACATGCTGCTCTCATCCACTATGTATTGATGACGAATTAGGT 
               
               
                   
                 TTGAAGGGTAAGCTAGACGATAAGATTAAGGGCGCTATTACTGCG 
               
               
                   
                 GCGGTGAGAAAACTAGATCATGAATTAGGTATTCCAGAAGATGAA 
               
               
                   
                 ACTAAGACAAGGGGTAAGTTTCACTTTTTAAACAGAATCCATTAC 
               
               
                   
                 ATGGCACCAAGCAATGAACCATGGGGTGAACATGAAATTGATTAC 
               
               
                   
                 ATCCTATTTTATAAGATCAACGCTAAAGAAAACTTGACTGTCAAC 
               
               
                   
                 CCAAACGTCAATGAAGTTAGAGACTTCAAATGGGTTTCACCAAAT 
               
               
                   
                 GATTTGAAAACTATGTTTGCTGACCCAAGTTACAAGTTTACGCCT 
               
               
                   
                 TGGTTTAAGATTATTTGCGAGAATTACTTATTCAACTGGTGGGAG 
               
               
                   
                 CAATTAGATGACCTTTCTGAAGTGGAAAATGACAGGCAAATTCAT 
               
               
                   
                 AGAATGCTATAA 
               
               
                   
               
               
                 SEQ ID NO: 25 
                 MTADNNSMPHGAVSSYAKLVQNQTPEDILEEFPEIIPLQQRPNTR 
               
               
                 Isopentenyl 
                 SSETSNDESGETCFSGHDEEQIKLMNENCIVLDWDDNAIGAGTKK 
               
               
                 pyrophosphate 
                 VCHLMENIEKGLLHRAFSWIFNEQGELLLQQRATEKITFPDLWTN 
               
               
                 isomerase 
                 TCCSHPLCIDDELGLKGKLDDKIKGAITAAVRKLDHELGIPEDET 
               
               
                 (Sc_IDI1) 
                 KTRGKFHFLNRIHYMAPSNEPWGEHEIDYILFYKINAKENLTVNP 
               
               
                   Saccharomyces  sp. 
                 NVNEVRDFKWVSPNDLKTMFADPSYKFTPWFKIICENYLFNWWEQ 
               
               
                   
                 LDDLSEVENDRQIHRML* 
               
               
                   
               
               
                 SEQ ID NO: 26 
                 ATGCAATTGGTGAAGACTGAAGTCACCAAGAAGTCTTTTACTGCT 
               
               
                 Truncated 
                 CCTGTACAAAAGGCTTCTACACCAGTTTTAACCAATAAAACAGTC 
               
               
                 3-hydroxy-3- 
                 ATTTCTGGATCGAAAGTCAAAAGTTTATCATCTGCGCAATCGAGC 
               
               
                 methyl-glutaryl- 
                 TCATCAGGACCTTCATCATCTAGTGAGGAAGATGATTCCCGCGAT 
               
               
                 CoA 
                 ATTGAAAGCTTGGATAAGAAAATACGTCCTTTAGAAGAATTAGAA 
               
               
                 reductase 
                 GCATTATTAAGTAGTGGAAATACAAAACAATTGAAGAACAAAGAG 
               
               
                 (tHMG1, 
                 GTCGCTGCCTTGGTTATTCACGGTAAGTTACCTTTGTACGCTTTG 
               
               
                 tHMGR) 
                 GAGAAAAAATTAGGTGATACTACGAGAGCGGTTGCGGTACGTAGG 
               
               
                 Artificial 
                 AAGGCTCTTTCAATTTTGGCAGAAGCTCCTGTATTAGCATCTGAT 
               
               
                 sequence 
                 CGTTTACCATATAAAAATTATGACTACGACCGCGTATTTGGCGCT 
               
               
                   
                 TGTTGTGAAAATGTTATAGGTTACATGCCTTTGCCCGTTGGTGTT 
               
               
                   
                 ATAGGCCCCTTGGTTATCGATGGTACATCTTATCATATACCAATG 
               
               
                   
                 GCAACTACAGAGGGTTGTTTGGTAGCTTCTGCCATGCGTGGCTGT 
               
               
                   
                 AAGGCAATCAATGCTGGCGGTGGTGCAACAACTGTTTTAACTAAG 
               
               
                   
                 GATGGTATGACAAGAGGCCCAGTAGTCCGTTTCCCAACTTTGAAA 
               
               
                   
                 AGATCTGGTGCCTGTAAGATATGGTTAGACTCAGAAGAGGGACAA 
               
               
                   
                 AACGCAATTAAAAAAGCTTTTAACTCTACATCAAGATTTGCACGT 
               
               
                   
                 CTGCAACATATTCAAACTTGTCTAGCAGGAGATTTACTCTTCATG 
               
               
                   
                 AGATTTAGAACAACTACTGGTGACGCAATGGGTATGAATATGATT 
               
               
                   
                 TCTAAGGGTGTCGAATACTCATTAAAGCAAATGGTAGAAGAGTAT 
               
               
                   
                 GGCTGGGAAGATATGGAGGTTGTCTCCGTTTCTGGTAACTACTGT 
               
               
                   
                 ACCGACAAAAAACCAGCTGCCATCAACTGGATCGAAGGTCGTGGT 
               
               
                   
                 AAGAGTGTCGTCGCAGAAGCTACTATTCCTGGTGATGTTGTCAGA 
               
               
                   
                 AAAGTGTTAAAAAGTGATGTTTCCGCATTGGTTGAGTTGAACATT 
               
               
                   
                 GCTAAGAATTTGGTTGGATCTGCAATGGCTGGGTCTGTTGGTGGA 
               
               
                   
                 TTTAACGCACATGCAGCTAATTTAGTGACAGCTGTTTTCTTGGCA 
               
               
                   
                 TTAGGACAAGATCCTGCACAAAATGTCGAAAGTTCCAACTGTATA 
               
               
                   
                 ACATTGATGAAAGAAGTGGACGGTGATTTGAGAATTTCCGTATCC 
               
               
                   
                 ATGCCATCCATCGAAGTAGGTACCATCGGTGGTGGTACTGTTCTA 
               
               
                   
                 GAACCACAAGGTGCCATGTTGGACTTATTAGGTGTAAGAGGCCCA 
               
               
                   
                 CATGCTACCGCTCCTGGTACCAACGCACGTCAATTAGCAAGAATA 
               
               
                   
                 GTTGCCTGTGCCGTCTTGGCAGGTGAATTATCCTTATGTGCTGCC 
               
               
                   
                 CTAGCAGCCGGCCATTTGGTTCAAAGTCATATGACCCACAACAGG 
               
               
                   
                 AAACCTGCTGAACCAACAAAACCTAACAATTTGGACGCCACTGAT 
               
               
                   
                 ATAAATCGTTTGAAAGATGGGTCCGTCACCTGCATTAAATCCTAA 
               
               
                   
               
               
                 SEQ ID NO: 27 
                 MQLVKTEVTKKSFTAPVQKASTPVLTNKTVISGSKVKSLSSAQSS 
               
               
                 Truncated 
                 SSGPSSSSEEDDSRDIESLDKKIRPLEELEAJLLSSGNTKQLKNK 
               
               
                 3-hydroxy-3- 
                 EVAALVIHGKLPLYALEKKLGDTTRAVAVRRKALSILAEAPVLAS 
               
               
                 methyl-glutaryl-CoA 
                 DRLPYKNYDYDRVFGACCENVIGYMPLPVGVIGPLVIDGTSYHIP 
               
               
                 reductase 
                 MATTEGCLVASAMRGCKAINAGGGATTVLTKDGMTRGPWRFPTLK 
               
               
                 (Sc_tHMG1, 
                 RSGACKIWLDSEEGQNAIKKAFNSTSRFARLQHIQTCLAGDLLFM 
               
               
                 tHMGR) 
                 RFRTTTGDAMGMNMISKGVEYSLKQMVEEYGWEDMEVVSVSGNYC 
               
               
                 Artificial sequence 
                 TDKKPAAINWIEGRGKSWAEATIPGDVVRKVLKSDVSALVELNIA 
               
               
                   
                 KNLVGSAMAGSVGGFNAHAANLVTAWLALGQDPAQNVESSNCITL 
               
               
                   
                 MKEVDGDLRISVSMPSIEVGTIGGGTVLEPQGAMLDLLGVRGPHA 
               
               
                   
                 TAPGTNARQLARIVACAVLAGELSLCAALAAGHLVQSHMTHNRKP 
               
               
                   
                 AEPTKPNNLDATDINRLKDGSVTCIKS* 
               
               
                   
               
               
                 SEQ ID NO: 28 
                 ATGACTGAACTAAAAAAACAAAAGACCGCTGAACAAAAAACCAGA 
               
               
                 HMG-CoA synthase 
                 CCTCAAAATGTCGGTATTAAAGGTATCCAAATTTACATCCCAACT 
               
               
                 (Sc_ERG13, HMGS) 
                 CAATGTGTCAACCAATCTGAGCTAGAGAAATTTGATGGCGTTTCT 
               
               
                   Saccharomyces  sp. 
                 CAAGGTAAATACACAATTGGTCTGGGCCAAACCAACATGTCTTTT 
               
               
                   
                 GTCAATGACAGAGAAGATATCTACTCGATGTCCCTAACTGTTTTG 
               
               
                   
                 TCTAAGTTGATCAAGAGTTACAACATCGACACCAACAAAATTGGT 
               
               
                   
                 AGATTAGAAGTCGGTACTGAAACTCTGATTGACAAGTCCAAGTCT 
               
               
                   
                 GTCAAGTCTGTCTTGATGCAATTGTTTGGTGAAAACACTGACGTC 
               
               
                   
                 GAAGGTATTGACACGCTTAATGCCTGTTACGGTGGTACCAACGCG 
               
               
                   
                 TTGTTCAACTCTTTGAACTGGATTGAATCTAACGCATGGGATGGT 
               
               
                   
                 AGAGACGCCATTGTAGTTTGCGGTGATATTGCCATCTACGATAAG 
               
               
                   
                 GGTGCCGCAAGACCAACCGGTGGTGCCGGTACTGTTGCTATGTGG 
               
               
                   
                 ATCGGTCCTGATGCTCCAATTGTATTTGACTCTGTAAGAGCTTCT 
               
               
                   
                 TACATGGAACACGCCTACGATTTTTACAAGCCAGATTTCACCAGC 
               
               
                   
                 GAATATCCTTACGTCGATGGTCATTTTTCATTAACTTGTTACGTC 
               
               
                   
                 AAGGCTCTTGATCAAGTTTACAAGAGTTATTCCAAGAAGGCTATT 
               
               
                   
                 TCTAAAGGGTTGGTTAGCGATCCCGCTGGTTCGGATGCTTTGAAC 
               
               
                   
                 GTTTTGAAATATTTCGACTACAACGTTTTCCATGTTCCAACCTGT 
               
               
                   
                 AAATTGGTCACAAAATCATACGGTAGATTACTATATAACGATTTC 
               
               
                   
                 AGAGCCAATCCTCAATTGTTCCCAGAAGTTGACGCCGAATTAGCT 
               
               
                   
                 ACTCGCGATTATGACGAATCTTTAACCGATAAGAACATTGAAAAA 
               
               
                   
                 ACTTTTGTTAATGTTGCTAAGCCATTCCACAAAGAGAGAGTTGCC 
               
               
                   
                 CAATCTTTGATTGTTCCAACAAACACAGGTAACATGTACACCGCA 
               
               
                   
                 TCTGTTTATGCCGCCTTTGCATCTCTATTAAACTATGTTGGATCT 
               
               
                   
                 GACGACTTACAAGGCAAGCGTGTTGGTTTATTTTCTTACGGTTCC 
               
               
                   
                 GGTTTAGCTGCATCTCTATATTCTTGCAAAATTGTTGGTGACGTC 
               
               
                   
                 CAACATATTATCAAGGAATTAGATATTACTAACAAATTAGCCAAG 
               
               
                   
                 AGAATCACCGAAACTCCAAAGGATTACGAAGCTGCCATCGAATTG 
               
               
                   
                 AGAGAAAATGCCCATTTGAAGAAGAACTTCAAACCTCAAGGTTCC 
               
               
                   
                 ATTGAGCATTTGCAAAGTGGTGTTTACTACTTGACCAACATCGAT 
               
               
                   
                 GACAAATTTAGAAGATCTTACGATGTTAAAAAATAAT 
               
               
                   
               
               
                 SEQ ID NO: 29 
                 MTELKKQKTAEQKTRPQNVGIKGIQIYIPTQCVNQSELEKFDGVS 
               
               
                 HMG-CoA synthase 
                 QGKYTIGLGQTNMSFVNDREDIYSMSLTVLSKLIKSYNIDTNKIG 
               
               
                 (Sc_ERG13, HMGS) 
                 RLEVGTETLIDKSKSVKSVLMQLFGENTDVEGIDTLNACYGGTNA 
               
               
                   Saccharomyces  sp. 
                 LFNSLNWIESNAWDGRDAIWCGDIAIYDKGAARPTGGAGTVAMWI 
               
               
                   
                 GPDAPIVFDSVRASYMEHAYDFYKPDFTSEYPYVDGHFSLTCYVK 
               
               
                   
                 ALDQVYKSYSKKAISKGLVSDPAGSDALNVLKYFDYNVFHVPTCK 
               
               
                   
                 LVTKSYGRLLYNDFRANPQLFPEVDAELATRDYDESLTDKNIEKT 
               
               
                   
                 FVNVAKPFHKERVAQSLIVPTNTGNMYTASVYAAFASLLNYVGSD 
               
               
                   
                 DLQGKRVGLFSYGSGLAASLYSCKIVGDVQHIIKELDITNKLAKR 
               
               
                   
                 ITETPKDYEAAIELRENAHLKKNFKPQGSIEHLQSGVYYLTNIDD 
               
               
                   
                 KFRRSYDVKK* 
               
               
                   
               
               
                 SEQ ID NO: 30 
                 ATGTCTCAGAACGTTTACATTGTATCGACTGCCAGAACCCCAATT 
               
               
                 Acctoacctyl CoA 
                 GGTTCATTCCAGGGTTCTCTATCCTCCAAGACAGCAGTGGAATTG 
               
               
                 thiolase (ERG 10) 
                 GGTGCTGTTGCTTTAAAAGGCGCCTTGGCTAAGGTTCCAGAATTG 
               
               
                 
                   Saccharomyces 
                 
                 GATGCATCCAAGGATTTTGACGAAATTATTTTTGGTAACGTTCTT 
               
               
                 
                   cerevisiae 
                 
                 TCTGCCAATTTGGGCCAAGCTCCGGCCAGACAAGTTGCTTTGGCT 
               
               
                   
                 GCCGGTTTGAGTAATCATATCGTTGCAAGCACAGTTAACAAGGTC 
               
               
                   
                 TGTGCATCCGCTATGAAGGCAATCATTTTGGGTGCTCAATCCATC 
               
               
                   
                 AAATGTGGTAATGCTGATGTTGTCGTAGCTGGTGGTTGTGAATCT 
               
               
                   
                 ATGACTAACGCACCATACTACATGCCAGCAGCCCGTGCGGGTGCC 
               
               
                   
                 AAATTTGGCCAAACTGTTCTTGTTGATGGTGTCGAAAGAGATGGG 
               
               
                   
                 TTGAACGATGCGTACGATGGTCTAGCCATGGGTGTACACGCAGAA 
               
               
                   
                 AAGTGTGCCCGTGATTGGGATATTACTAGAGAACAACAAGACAAT 
               
               
                   
                 TTTGCCATCGAATCCTACCAAAAATCTCAAAAATCTCAAAAGGAA 
               
               
                   
                 GGTAAATTCGACAATGAAATTGTACCTGTTACCATTAAGGGATTT 
               
               
                   
                 AGAGGTAAGCCTGATACTCAAGTCACGAAGGACGAGGAACCTGCT 
               
               
                   
                 AGATTACACGTTGAAAAATTGAGATCTGCAAGGACTGTTTTCCAA 
               
               
                   
                 AAAGAAAACGGTACTGTTACTGCCGCTAACGCTTCTCCAATCAAC 
               
               
                   
                 GATGGTGCTGCAGCCGTCATCTTGGTTTCCGAAAAAGTTTTGAAG 
               
               
                   
                 GAAAAGAATTTGAAGCCTTTGGCTATTATCAAAGGTTGGGGTGAG 
               
               
                   
                 GCCGCTCATCAACCAGCTGATTTTACATGGGCTCCATCTCTTGCA 
               
               
                   
                 GTTCCAAAGGCTTTGAAACATGCTGGCATCGAAGACATCAATTCT 
               
               
                   
                 GTTGATTACTTTGAATTCAATGAAGCCTTTTCGGTTGTCGGTTTG 
               
               
                   
                 GTGAACACTAAGATTTTGAAGCTAGACCCATCTAAGGTTAATGTA 
               
               
                   
                 TATGGTGGTGCTGTTGCTCTAGGTCACCCATTGGGTTGTTCTGGT 
               
               
                   
                 GCTAGAGTGGTTGTTACACTGCTATCCATCTTACAGCAAGAAGGA 
               
               
                   
                 GGTAAGATCGGTGTTGCCGCCATTTGTAATGGTGGTGGTGGTGCT 
               
               
                   
                 TCCTCTATTGTCATTGAAAAGATATGA 
               
               
                   
               
               
                 SEQ ID NO: 31 
                 MSQNVYIVSTARTPIGSFQGSLSSKTAVELGAVALKGALAKVPEL 
               
               
                 Acetoacetyl CoA 
                 DASKDFDEIIFGNVLSANLGQAPARQVALAAGLSNHIVASTVNKV 
               
               
                 thiolase (ERG10) 
                 CASAMKAIILGAQSIKCGNADVWAGGCESMTNAPYYMPAARAGAK 
               
               
                 
                   Saccharomyces 
                 
                 FGQTVLVDGVERDGLNDAYDGLAMGVHAEKCARDWDITREQQDNF 
               
               
                 
                   cerevisiae 
                 
                 AIESYQKSQKSQKEGKFDNEIVPVTIKGFRGKPDTQVTKDEEPAR 
               
               
                   
                 LHVEKLRSARTVFQKENGTVTAANASPINDGAAAVILVSEKVLKE 
               
               
                   
                 KNLKPLAIIKGWGEAAHQPADFTWAPSLAVPKALKHAGIEDINSV 
               
               
                   
                 DYFEFNEAFSWGLVNTKILKLDPSKVNVYGGAVALGHPLGCSGAR 
               
               
                   
                 WVTLLSILQQEGGKIGVAAICNGGGGASSIVIEKI* 
               
               
                   
               
               
                 SEQ ID NO: 32 
                 ATGACCGTTTACACAGCATCCGTTACCGCACCCGTCAACATCGCA 
               
               
                 Mevalonate 
                 ACCCTTAAGTATTGGGGGAAAAGGGACACGAAGTTGAATCTGCCC 
               
               
                 pyrophosphate 
                 ACCAATTCGTCCATATCAGTGACTTTATCGCAAGATGACCTCAGA 
               
               
                 decarboxylase 
                 ACGTTGACCTCTGCGGCTACTGCACCTGAGTTTGAACGCGACACT 
               
               
                 (Sc_ERG19, MVD1) 
                 TTGTGGTTAAATGGAGAACCACACAGCATCGACAATGAAAGAACT 
               
               
                   Saccharomyces  sp. 
                 CAAAATTGTCTGCGCGACCTACGCCAATTAAGAAAGGAAATGGAA 
               
               
                   
                 TCGAAGGACGCCTCATTGCCCACATTATCTCAATGGAAACTCCAC 
               
               
                   
                 ATTGTCTCCGAAAATAACTTTCCTACAGCAGCTGGTTTAGCTTCC 
               
               
                   
                 TCCGCTGCTGGCTTTGCTGCATTGGTCTCTGCAATTGCTAAGTTA 
               
               
                   
                 TACCAATTACCACAGTCAACTTCAGAAATATCTAGAATAGCAAGA 
               
               
                   
                 AAGGGGTCTGGTTCAGCTTGTAGATCGTTGTTTGGCGGATACGTG 
               
               
                   
                 GCCTGGGAAATGGGAAAAGCTGAAGATGGTCATGATTCCATGGCA 
               
               
                   
                 GTACAAATCGCAGACAGCTCTGACTGGCCTCAGATGAAAGCTTGT 
               
               
                   
                 GTCCTAGTTGTCAGCGATATTAAAAAGGATGTGAGTTCCACTCAG 
               
               
                   
                 GGTATGCAATTGACCGTGGCAACCTCCGAACTATTTAAAGAAAGA 
               
               
                   
                 ATTGAACATGTCGTACCAAAGAGATTTGAAGTCATGCGTAAAGCC 
               
               
                   
                 ATTGTTGAAAAAGATTTCGCCACCTTTGCAAAGGAAACAATGATG 
               
               
                   
                 GATTCCAACTCTTTCCATGCCACATGTTTGGACTCTTTCCCTCCA 
               
               
                   
                 ATATTCTACATGAATGACACTTCCAAGCGTATCATCAGTTGGTGC 
               
               
                   
                 CACACCATTAATCAGTTTTACGGAGAAACAATCGTTGCATACACG 
               
               
                   
                 TTTGATGCAGGTCCAAATGCTGTGTTGTACTACTTAGCTGAAAAT 
               
               
                   
                 GAGTCGAAACTCTTTGCATTTATCTATAAATTGTTTGGCTCTGTT 
               
               
                   
                 CCTGGATGGGACAAGAAATTTACTACTGAGCAGCTTGAGGCTTTC 
               
               
                   
                 AACCATCAATTTGAATCATCTAACTTTACTGCACGTGAATTGGAT 
               
               
                   
                 CTTGAGTTGCAAAAGGATGTTGCCAGAGTGATTTTAACTCAAGTC 
               
               
                   
                 GGTTCAGGCCCACAAGAAACAAACGAATCTTTGATTGACGCAAAG 
               
               
                   
                 ACTGGTCTACCAAAGGAATAA 
               
               
                   
               
               
                 SEQ ID NO: 33 
                 MTVYTASVTAPVNIATLKYWGKRDTKLNLPTNSSISVTLSQDDLR 
               
               
                 Mevalonate 
                 TLTSAATAPEFERDTLWLNGEPHSIDNERTQNCLRDLRQLRKEME 
               
               
                 pyrophosphate 
                 SKDASLPTLSQWKLHIVSENNFPTAAGLASSAAGFAALVSAIAKL 
               
               
                 decarboxylase 
                 YQLPQSTSEISRIARKGSGSACRSLFGGYVAWEMGKAEDGHDSMA 
               
               
                 (Sc_ERG19, MVD1) 
                 VQIADSSDWPQMKACVLWSDIKKDVSSTQGMQLTVATSELFKERI 
               
               
                   Saccharomyces  sp. 
                 EHVWKRFEVMRKAIVEKDFATFAKETMMDSNSFHATCLDSFPPIF 
               
               
                   
                 YMNDTSKRIISWCHTINQFYGETIVAYTFDAGPNAVLYYLAENES 
               
               
                   
                 KLFAFIYKLFGSVPGWDKKFTTEQLEAFNHQFESSNFTARELDLE 
               
               
                   
                 LQKDVARVILTQVGSGPQETNESLIDAKTGLPKE* 
               
               
                   
               
               
                 SEQ ID NO: 34 
                 ATGTCCTACACCGTTGGTACCTACTTAGCTGAGCGTTTGGTCCAA 
               
               
                 Pyruvate decarboxy 
                 ATCGGTTTGAAGCACCATTTCGCCGTTGCTGGTGATTACAACTTG 
               
               
                 lase (Zm_PDC) 
                 GTCTTGTTAGATAATTTATTATTGAACAAGAACATGGAACAAGTC 
               
               
                 Artificial sequence 
                 TACTGCTGTAATGAATTGAACTGTGGTTTCTCTGCTGAAGGTTAT 
               
               
                 Codon optimized 
                 GCTAGAGCTAAAGGTGCCGCTGCCGCTGTTGTCACTTACTCTGTT 
               
               
                   
                 GGTGCTTTGTCTGCCTTCGACGCTATTGGTGGTGCTTACGCCGAG 
               
               
                   
                 AATTTACCTGTTATTTTAATTTCTGGTGCCCCTAACAATAACGAT 
               
               
                   
                 CATGCTGCTGGTCATGTTTTACACCACGCTTTGGGTAAAACTGAC 
               
               
                   
                 TACCATTATCAATTAGAGATGGCCAAAAACATCACCGCCGCTGCC 
               
               
                   
                 GAGGCCATTTACACTCCAGAAGAAGCCCCAGCCAAAATTGATCAC 
               
               
                   
                 GTCATCAAAACCGCCTTGAGAGAGAAAAAACCTGTTTACTTGGAA 
               
               
                   
                 ATCGCCTGTAATATCGCCTCTATGCCTTGCGCCGCTCCTGGTCCT 
               
               
                   
                 GCTTCCGCCTTATTCAACGATGA 
               
               
                   
                 GGCTTCTGATGAAGCTTCCTTAAACGCTGCTGTTGAGGAGACTTT 
               
               
                   
                 AAAGTTCATCGCTAATAGAGATAAGGTCGCTGTTTTAGTCGGTTC 
               
               
                   
                 TAAGTTGCGTGCTGCCGGTGCCGAGGAAGCTGCTGTTAAATTCGC 
               
               
                   
                 CGATGCTTTAGGTGGTGCTGTCGCCACCATGGCCGCCGCCAAATC 
               
               
                   
                 CTTTTTCCCTGAAGAAAACCCACACTACATCGGTACTTCTTGGGG 
               
               
                   
                 TGAAGTCTCTTACCCAGGTGTCGAAAAGACTATGAAGGAAGCCGA 
               
               
                   
                 TGCCGTCATCGCCTTGGCCCCAGTTTTTAATGATTATTCCACCAC 
               
               
                   
                 TGGTTGGACTGATATCCCAGATCCTAAAAAGTTAGTTTTAGCCGA 
               
               
                   
                 GCCTAGATCCGTTGTTGTTAACGGTATTAGATTCCCTTCCGTTCA 
               
               
                   
                 CTTGAAGGATTACTTAACTAGATTGGCTCAAAAGGTTTCCAAGAA 
               
               
                   
                 GACCGGTGCTTTGGACTTTTTCAAATCTTTGAACGCCGGTGAGTT 
               
               
                   
                 AAAGAAGGCCGCCCCTGCTGACCCATCTGCTCCATTGGTTAACGC 
               
               
                   
                 TGAGATTGCTAGACAAGTCGAAGCTTTATTGACCCCAAACACTAC 
               
               
                   
                 CGTTATCGCCGAAACTGGTGACTCTTGGTTTAATGCTCAAAGAAT 
               
               
                   
                 GAAGTTACCAAATGGTGCCAGAGTTGAGTACGAAATGCAATGGGG 
               
               
                   
                 TCATATCGGTTGGTCTGTCCCAGCTGCTTTTGGTTATGCTGTTGG 
               
               
                   
                 TGCCCCTGAGAGAAGAAACATCTTGATGGTTGGTGACGGTTCCTT 
               
               
                   
                 CCAATTGACTGCTCAAGAAGTCGCTCAAATGGTTAGATTAAAATT 
               
               
                   
                 ACCAGTCATCATCTTCTTGATCAATAACTACGGTTACACTATCGA 
               
               
                   
                 AGTCATGATTCACGATGGTCCTTACAATAATATTAAGAACTGGGA 
               
               
                   
                 CTATGCTGGTTTGATGGAAGTCTTTAATGGTAACGGTGGTTACGA 
               
               
                   
                 TTCCGGTGCTGGTAAGGGTTTAAAGGCTAAGACTGGTGGTGAATT 
               
               
                   
                 AGCTGAAGCCATTAAGGTTGCCTTGGCTAACACCGACGGTCCTAC 
               
               
                   
                 TTTAATCGAATGTTTCATTGGTAGAGAGGATTGTACCGAAGAGTT 
               
               
                   
                 AGTTAAGTGGGGTAAGAGAGTTGCCGCTGCTAATTCCCGTAAGCC 
               
               
                   
                 TGTCAATAAATTGTTATAA 
               
               
                   
               
               
                 SEQ ID NO: 35 
                 MSYTVGTYLAERLVQIGLKHHFAVAGDYNLVLLDNLLLNKNMEQV 
               
               
                 Pyruvate 
                 YCCNELNCGFSAEGYARAKGAAAAVVTYSVGAJLSAFDAIGGAYA 
               
               
                 decarboxylase 
                 ENLPVILISGAPNNNDHAAGHVLHHALGKTDYHYQLEMAKNITAA 
               
               
                 (ZmPDC) 
                 AEAIYTPEEAPAKIDHVIKTALREKKPVYLEIACNIASMPCAAPG 
               
               
                 
                   Zymomonas mobilis 
                 
                 PASALFNDEASDEASLNAAVEETLKFIANRDKVAVLVGSKLRAAG 
               
               
                   
                 AEEAAVKFADALGGAVATMAAAKSFFPEENPHYIGTSWGEVSYPG 
               
               
                   
                 VEKTMKEADAVIALAPVFNDYSTTGWTDIPDPKKLVLAEPRSVWN 
               
               
                   
                 GIRFPSVHLKDYLTRLAQKVSKKTGALDFFKSLNAGELKKAAPAD 
               
               
                   
                 PSAPLVNAEIARQVEALLTPNTTVIAETGDSWFNAQRMKLPNGAR 
               
               
                   
                 VEYEMQWGHIGWSVPAAFGYAVGAPERRNILMVGDGSFQLTAQEV 
               
               
                   
                 AQMVRLKLPVIIFLINNYGYTIEVMIHDGPYNNIKNWDYAGLMEV 
               
               
                   
                 FNGNGGYDSGAGKGLKAKTGGELAEAIKVALANTDGPTLIECFIG 
               
               
                   
                 REDCTEELVKWGKRVAAANSRKPVNKLL* 
               
               
                   
               
               
                 SEQ ID NO: 36 
                 ATGTCAGAGTTGAGAGCCTTCAGTGCCCCAGGGAAAGCGTTACTA 
               
               
                 Phosphomevalonate 
                 GCTGGTGGATATTTAGTTTTAGATCCGAAATATGAAGCATTTGTA 
               
               
                 kinase 
                 GTCGGATTATCGGCAAGAATGCATGCTGTAGCCCATCCTTACGGT 
               
               
                 (Sc_ERG8, PMK) 
                 TCATTGCAAGAGTCTGATAAGTTTGAAGTGCGTGTGAAAAGTAAA 
               
               
                 
                   Saccharomyces 
                 
                 CAATTTAAAGATGGGGAGTGGCTGTACCATATAAGTCCTAAAACT 
               
               
                 
                   cerevisiae 
                 
                 GGCTTCATTCCTGTTTCGATAGGCGGATCTAAGAACCCTTTCATT 
               
               
                   
                 GAAAAAGTTATCGCTAACGTATTTAGCTACTTTAAGCCTAACATG 
               
               
                   
                 GACGACTACTGCAATAGAAACTTGTTCGTTATTGATATTTTCTCT 
               
               
                   
                 GATGATGCCTACCATTCTCAGGAGGACAGCGTTACCGAACATCGT 
               
               
                   
                 GGCAACAGAAGATTGAGTTTTCATTCGCACAGAATTGAAGAAGTT 
               
               
                   
                 CCCAAAACAGGGCTGGGCTCCTCGGCAGGTTTAGTCACAGTTTTA 
               
               
                   
                 ACTACAGCTTTGGTTATTCATAATTTATCACAAGTTGCTCATTGT 
               
               
                   
                 CAAGCTCAGGGTAAAATTGGAAGCGGGTTTGATGTAGCGGCGGCA 
               
               
                   
                 GCATATGGATCTATCAGATATAGAAGATTCCCACCCGCATTAATC 
               
               
                   
                 TCTAATTTGCCAGATATTGGAAGTGCTACTTACGGCAGTAAACTG 
               
               
                   
                 GCGCATTTGGTTAATGAAGAAGACTGGAATATAACGATTAAAAGT 
               
               
                   
                 AACCATTTACCTTCGGGATTAACTTTATGGATGGGCGATATTAAG 
               
               
                   
                 AATGGTTCAGAAACAGTAAAACTGGTCCAGAAGGTAAAAAATTGG 
               
               
                   
                 TATGATTCGCATATGCCGGAAAGCTTGAAAATATATACAGAACTC 
               
               
                   
                 GATCATGCAAATTCTAGATTTATGGATGGACTATCTAAACTAGAT 
               
               
                   
                 CGCTTACACGAGACTCATGACGATTACAGCGATCAGATATTTGAG 
               
               
                   
                 TCTCTTGAGAGGAATGACTGTACCTGTCAAAAGTATCCTGAGATC 
               
               
                   
                 ACAGAAGTTAGAGATGCAGTTGCCACAATTAGACGTTCCTTTAGA 
               
               
                   
                 AAAATAACTAAAGAATCTGGTGCCGATATCGAACCTCCCGTACAA 
               
               
                   
                 ACTAGCTTATTGGATGATTGCCAGACCTTAAAAGGAGTTCTTACT 
               
               
                   
                 TGCTTAATACCTGGTGCTGGTGGTTATGACGCCATTGCAGTGATT 
               
               
                   
                 GCTAAGCAAGATGTTGATCTTAGGGCTCAAACCGCTGATGACAAA 
               
               
                   
                 AGATTTTCTAAGGTTCAATGGCTGGATGTAACTCAGGCTGACTGG 
               
               
                   
                 GGTGTTAGGAAAGAAAAAGATCCGGAAACTTATCTTGATAAATAA 
               
               
                   
               
               
                 SEQ ID NO: 37 
                 MSELRAFSAPGKALLAGGYLVLDPKYEAFVVGLSARMHAVAHPYG 
               
               
                 Phosphomevalonate 
                 SLQESDKFEVRVKSKQFKDGEWLYHISPKTGFIPVSIGGSKNPFI 
               
               
                 kinase 
                 EKVIANVFSYFKPNMDDYCNRNLFVIDIFSDDAYHSQEDSVTEHR 
               
               
                 (Sc_ERG8, PMK) 
                 GNRRLSFHSHRIEEVPKTGLGSSAGLVTVLTTALASFFVSDLENN 
               
               
                 
                   Saccharomyces 
                 
                 VDKYREVIHNLSQVAHCQAQGKIGSGFDVAAAAYGSIRYRRFPPA 
               
               
                 
                   cerevisiae 
                 
                 LISNLPDIGSATYGSKLAHLVNEEDWNITIKSNHLPSGLTLWMGD 
               
               
                   
                 IKNGSETVKLVQKVKNWYDSHMPESLKIYTELDHANSRFMDGLSK 
               
               
                   
                 LDRLHETHDDYSDQIFESLERNDCTCQKYPEITEVRDAVATIRRS 
               
               
                   
                 FRKITKESGADIEPPVQTSLLDDCQTLKGVLTCLIPGAGGYDAIA 
               
               
                   
                 VIAKQDVDLRAQTADDKRFSKVQWLDVTQADWGVRKEKDPETYLD 
               
               
                   
                 K* 
               
               
                   
               
               
                 SEQ ID NO: 38 
                 ATGTCATTACCGTTCTTAACTTCTGCACCGGGAAAGGTTATTATT 
               
               
                 Mevalonate kinase 
                 TTTGGTGAACACTCTGCTGTGTACAACAAGCCTGCCGTCGCTGCT 
               
               
                 (ERG12, MK) 
                 AGTGTGTCTGCGTTGAGAACCTACCTGCTAATAAGCGAGTCATCT 
               
               
                   Saccharomyces  sp. 
                 GCACCAGATACTATTGAATTGGACTTCCCGGACATTAGCTTTAAT 
               
               
                   
                 CATAAGTGGTCCATCAATGATTTCAATGCCATCACCGAGGATCAA 
               
               
                   
                 GTAAACTCCCAAAAATTGGCCAAGGCTCAACAAGCCACCGATGGC 
               
               
                   
                 TTGTCTCAGGAACTCGTTAGTCTTTTGGATCCGTTGTTAGCTCAA 
               
               
                   
                 CTATCCGAATCCTTCCACTACCATGCAGCGTTTTGTTTCCTGTAT 
               
               
                   
                 ATGTTTGTTTGCCTATGCCCCCATGCCAAGAATATTAAGTTTTCT 
               
               
                   
                 TTAAAGTCTACTTTACCCATCGGTGCTGGGTTGGGCTCAAGCGCC 
               
               
                   
                 TCTATTTCTGTATCACTGGCCTTAGCTATGGCCTACTTGGGGGGG 
               
               
                   
                 TTAATAGGATCTAATGACTTGGAAAAGCTGTCAGAAAACGATAAG 
               
               
                   
                 CATATAGTGAATCAATGGGCCTTCATAGGTGAAAAGTGTATTCAC 
               
               
                   
                 GGTACCCCTTCAGGAATAGATAACGCTGTGGCCACTTATGGTAAT 
               
               
                   
                 GCCCTGCTATTTGAAAAAGACTCACATAATGGAACAATAAACACA 
               
               
                   
                 AACAATTTTAAGTTCTTAGATGATTTCCCAGCCATTCCAATGATC 
               
               
                   
                 CTAACCTATACTAGAATTCCAAGGTCTACAAAAGATCTTGTTGCT 
               
               
                   
                 CGCGTTCGTGTGTTGGTCACCGAGAAATTTCCTGAAGTTATGAAG 
               
               
                   
                 CCAATTCTAGATGCCATGGGTGAATGTGCCCTACAAGGCTTAGAG 
               
               
                   
                 ATCATGACTAAGTTAAGTAAATGTAAAGGCACCGATGACGAGGCT 
               
               
                   
                 GTAGAAACTAATAATGAACTGTATGAACAACTATTGGAATTGATA 
               
               
                   
                 AGAATAAATCATGGACTGCTTGTCTCAATCGGTGTTTCTCATCCT 
               
               
                   
                 GGATTAGAACTTATTAAAAATCTGAGCGATGATTTGAGAATTGGC 
               
               
                   
                 TCCACAAAACTTACCGGTGCTGGTGGCGGCGGTTGCTCTTTGACT 
               
               
                   
                 TTGTTACGAAGAGACATTACTCAAGAGCAAATTGACAGTTTCAAA 
               
               
                   
                 AAGAAATTGCAAGATGATTTTAGTTACGAGACATTTGAAACAGAC 
               
               
                   
                 TTGGGTGGGACTGGCTGCTGTTTGTTAAGCGCAAAAAATTTGAAT 
               
               
                   
                 AAAGATCTTAAAATCAAATCCCTAGTATTCCAATTATTTGAAAAT 
               
               
                   
                 AAAACTACCACAAAGCAACAAATTGACGATCTATTATTGCCAGGA 
               
               
                   
                 AACACGAATTTACCATGGACTTCATAA 
               
               
                   
               
               
                 SEQ ID NO: 39 
                 MSLPFLTSAPGKVIIFGEHSAVYNKPAVAASVSALRTYLLISESS 
               
               
                 Mevalonate kinase 
                 APDTIELDFPDISFNHKWSINDFNAITEDQVNSQKLAKAQQATDG 
               
               
                 (ERG12, MK) 
                 LSQELVSLLDPLLAQLSESFHYHAAFCFLYMFVCLCPHAKNIKFS 
               
               
                   Saccharomyces  sp. 
                 LKSTLPIGAGLGSSASISVSLALAMAYLGGLIGSNDLEKLSENDK 
               
               
                   
                 HIVNQWAFIGEKCIHGTPSGIDNAVATYGNALLFEKDSHNGTINT 
               
               
                   
                 NNFKFLDDFPAIPMILTYTRIPRSTKDLVARVRVLVTEKFPEVMK 
               
               
                   
                 PILDAMGECALQGLEIMTKLSKCKGTDDEAVETNNELYEQLLELI 
               
               
                   
                 RINHGLLVSIGVSHPGLELIKNLSDDLRIGSTKLTGAGGGGCSLT 
               
               
                   
                 LLRRDITQEQIDSFKKKLQDDFSYETFETDLGGTGCCLLSAKNLN 
               
               
                   
                 KDLKIKSLVFQLFENKTTTKQQIDDLLLPGNTNLPWTS* 
               
               
                   
               
               
                 SEQ ID NO: 40 
                 ATGGCTTCTGAGAAGGAGATTCGTCGTGAGAGATTCTTGAATGTT 
               
               
                 Variant farnesyl 
                 TTTCCTAAATTAGTCGAGGAATTGAACGCTTCTTTGTTGGCTTAT 
               
               
                 pyrophosphate synthase 
                 GGTATGCCTAAGGAAGCTTGTGATTGGTATGCTCACTCCTTGAAT 
               
               
                 (ERG20mut, F96W, 
                 TATAATACTCCAGGTGGTAAATTGAACCGTGGTTTGTCTGTTGTT 
               
               
                 N127W; GPPS) 
                 GACACTTACGCTATTTTATCTAACAAGACCGTCGAGCAATTGGGT 
               
               
                 Artificial sequence 
                 CAAGAAGAGTATGAAAAGGTCGCTATTTTAGGTTGGTGTATTGAA 
               
               
                 Codon optimized 
                 TTGTTGCAAGCTTACTGGTTGGTTGCCGATGACATGATGGACAAG 
               
               
                   
                 TCTATTACTCGTCGTGGTCAACCTTGCTGGTATAAGGTCCCAGAG 
               
               
                   
                 GTTGGTGAAATTGCTATCTGGGACGCTTTCATGTTGGAAGCTGCT 
               
               
                   
                 ATCTATAAATTGTTGAAATCCCACTTCAGAAACGAGAAATACTAC 
               
               
                   
                 ATTGACATCACCGAGTTGTTCCACGAAGTCACTTTCCAAACTGAG 
               
               
                   
                 TTAGGTCAATTAATGGACTTGATCACCGCTCCAGAAGACAAAGTT 
               
               
                   
                 GACTTGTCCAAGTTTTCCTTGAAAAAGCACTCTTTCATCGTTACT 
               
               
                   
                 TTCAAGACTGCTTATTACTCTTTCTACTTACCAGTTGCCTTGGCT 
               
               
                   
                 ATGTACGTCGCCGGTATCACTGACGAAAAGGACTTGAAGCAAGCT 
               
               
                   
                 CGTGACGTTTTGATTCCATTAGGTGAATATTTCCAAATCCAAGAT 
               
               
                   
                 GACTACTTAGACTGTTTTGGTACCCCTGAACAAATCGGTAAGATC 
               
               
                   
                 GGTACTGATATTCAAGATAACAAGTGCTCTTGGGTTATCAACAAG 
               
               
                   
                 GCTTTAGAGTTAGCCTCCGCCGAACAACGTAAAACTTTAGATGAA 
               
               
                   
                 AACTACGGTAAAAAAGACTCTGTTGCTGAGGCCAAGTGTAAGAAG 
               
               
                   
                 ATTTTTAACGATTTAAAAATCGAACAATTGTATCACGAATATGAA 
               
               
                   
                 GAGTCCATTGCTAAGGATTTGAAGGCTAAAATTTCTCAAGTTGAC 
               
               
                   
                 GAATCCCGTGGTTTCAAAGCTGACGTTTTG 
               
               
                   
               
               
                 SEQ ID NO: 41 
                 MASEKEIRRERFLNVFPKLVEELNASLLAYGMPKEACDWYAHSLN 
               
               
                 Variant farnesyl 
                 YNTPGGKLNRGLSWDTYAILSNKTVEQLGQEEYEKVAILGWCIEL 
               
               
                 pyrophosphate synthase 
                 LQAYWLVADDMMDKSITRRGQPCWYKVPEVGEIAIWDAFMLEAAI 
               
               
                 (ERG20mut, F96W, 
                 YKLLKSHFRNEKYYIDITELFHEVTFQTELGQLMDLITAPEDKVD 
               
               
                 N127W; GPPS) 
                 LSKFSLKKHSFIVTFKTAYYSFYLPVALAMYVAGITDEKDLKQAR 
               
               
                 Artificial sequence 
                 DVLIPLGEYFQIQDDYLDCFGTPEQIGKIGTDIQDNKCSWVINKA 
               
               
                   
                 LELASAEQRKTLDENYGKKDSVAEAKCKKIFNDLKIEQLYHEYEE 
               
               
                   
                 SIAKDLKAKISQVDESRGFKADVLTAFLNKVYKRSK* 
               
               
                   
               
               
                 SEQ ID NO: 42 
                 ATGTCTACCGCACTAACAGAAGGAGCTAAACTATTCGAAAAGGAG 
               
               
                 GFP 
                 ATTCCTTACATTACAGAATTAGAGGGTGATGTCGAAGGAATGAAA 
               
               
                 Artificial sequence 
                 TTCATTATCAAGGGCGAGGGTACTGGTGACGCTACTACCGGTACG 
               
               
                   
                 ATTAAAGCAAAGTACATCTGTACAACAGGTGACCTTCCTGTTCCG 
               
               
                   
                 TGGGCTACTCTGGTGAGCACTTTGTCTTATGGAGTTCAATGTTTT 
               
               
                   
                 GCTAAATACCCTTCGCACATTAAAGACTTTTTCAAAAGTGCAATG 
               
               
                   
                 CCTGAGGGCTATACTCAGGAGAGAACAATATCTTTCGAAGGAGAT 
               
               
                   
                 GGTGTGTATAAGACTAGGGCTATGGTCACGTATGAAAGAGGATCC 
               
               
                   
                 ATCTACAATAGAGTAACTTTAACTGGTGAAAACTTCAAAAAGGAC 
               
               
                   
                 GGTCACATCCTTAGAAAGAATGTTGCCTTTCAATGCCCACCATCC 
               
               
                   
                 ATCTTGTACATTTTGCCAGACACAGTTAACAATGGTATCAGAGTT 
               
               
                   
                 GAGTTTAACCAAGCTTATGACATAGAGGGTGTCACCGAAAAGTTG 
               
               
                   
                 GTTACAAAATGTTCACAGATGAATCGTCCCCTGGCAGGATCAGCT 
               
               
                   
                 GCCGTCCATATCCCACGTTACCATCATATCACTTATCATACCAAG 
               
               
                   
                 CTGTCCAAAGATCGTGATGAGAGAAGGGATCACATGTGTTTGGTT 
               
               
                   
                 GAAGTGGTAAAGGCCGTGGATTTGGATACTTACCAAGGTTGA 
               
               
                   
               
               
                 SEQ ID NO: 43 
                 MSTALTEGAKLFEKEIPYITELEGDVEGMKFIIKGEGTGDATTGT 
               
               
                 GFP 
                 IKAKYICTTGDLPVPWATLVSTLSYGVQCFAKYPSHIKDFFKSAM 
               
               
                 Artificial sequence 
                 PEGYTQERTISFEGDGVYKTRAMVTYERGSIYNRVTLTGENFKKD 
               
               
                   
                 GHILRKNVAFQCPPSILYILPDTVNNGIRVEFNQAYDIEGVTEKL 
               
               
                   
                 VTKCSQMNRPLAGSAAVHIPRYHHITYHTKLSKDRDERRDHMCLV 
               
               
                   
                 EVVKAVDLDTYQG* 
               
               
                   
               
               
                 SEQ ID NO: 44 
                 MNCSAFSFWFVCKIIFFFLSFHIQISIANPRENFLKCFSKHIPNN 
               
               
                 THCA synthase 
                 VANPKLVYTQHDQLYMSILNSTIQNLRFISDTTPKPLVIVTPSNN 
               
               
                 
                   Cannabis sativa 
                 
                 SHIQATILCSKKVGLQIRTRSGGHDAEGMSYISQVPFVWDLRNMH 
               
               
                   
                 SIKIDVHSQTAWVEAGATLGEVYYWINEKNENLSFPGGYCPTVGV 
               
               
                   
                 GGHFSGGGYGALMRNYGLAADNIIDAHLVNVDGKVLDRKSMGEDL 
               
               
                   
                 FWAIRGGGGENFGIIAAWKIKLVAVPSKSTIFSVKKNMEIHGLVK 
               
               
                   
                 LFNKWQNIAYKYDKDLVLMTHFITKNITDNHGKNKTTVHGYFSSI 
               
               
                   
                 FHGGVDSLVDLMNKSFPELGIKKTDCKEFSWIDTTIFYSGWNFNT 
               
               
                   
                 ANFKKEILLDRSAGKKTAFSIKLDYVKKPIPETAMVKILEKLYEE 
               
               
                   
                 DVGAGMYVLYPYGGIMEEISESAIPFPHRAGIMYELWYTASWEKQ 
               
               
                   
                 EDNEKHINWVRSVYNFTTPYVSQNPRLAYLNYRDLDLGKTNHASP 
               
               
                   
                 NNYTQARIWGEKYFGKNFNRLVKVKTKVDPNNFFRNEQSIPPLPP 
               
               
                   
                 HHH* 
               
               
                   
               
               
                 SEQ ID NO: 45 
                 ATGAATTGTTCTGCTTTCTCTTTCTGGTTCGTTTGTAAGATCATC 
               
               
                 THCA synthase 
                 TTTTTCTTCTTATCTTTCCATATTCAAATCTCTATCGCTAACCCT 
               
               
                 Artificial sequence 
                 CGTGAGAACTTCTTGAAATGTTTCTCCAAACATATCCCAAACAAT 
               
               
                 Codon optimized 
                 GTCGCTAACCCTAAGTTAGTTTACACTCAACATGATCAATTATAT 
               
               
                 sequence 1 
                 ATGTCTATCTTGAACTCTACCATCCAAAACTTGAGATTCATCTCC 
               
               
                   
                 GATACCACCCCAAAACCATTGGTTATTGTTACCCCATCCAACAAT 
               
               
                   
                 TCTCATATTCAAGCTACCATTTTGTGCTCCAAAAAGGTCGGTTTG 
               
               
                   
                 CAAATCCGTACTAGATCTGGTGGTCACGATGCTGAAGGTATGTCT 
               
               
                   
                 TACATTTCCCAAGTCCCATTCGTTGTTGTCGATTTAAGAAATATG 
               
               
                   
                 CACTCTATCAAAATCGACGTTCACTCTCAAACTGCTTGGGTTGAA 
               
               
                   
                 GCCGGTGCCACTTTAGGTGAGGTTTACTACTGGATTAACGAAAAG 
               
               
                   
                 AATGAAAACTTATCCTTTCCAGGTGGTTACTGTCCAACTGTTGGT 
               
               
                   
                 GTTGGTGGTCACTTCTCTGGTGGTGGTTATGGTGCCTTGATGAGA 
               
               
                   
                 AACTACGGTTTAGCTGCTGATAATATTATCGACGCTCACTTGGTT 
               
               
                   
                 AATGTCGACGGTAAGGTTTTGGACAGAAAATCCATGGGTGAAGAT 
               
               
                   
                 TTATTCTGGGCCATTAGAGGTGGTGGTGGTGAAAACTTCGGTATC 
               
               
                   
                 ATTGCTGCTTGGAAAATTAAATTGGTCGCTGTCCCATCCAAGTCT 
               
               
                   
                 ACTATTTTCTCCGTCAAGAAAAACATGGAAATTCATGGTTTGGTT 
               
               
                   
                 AAATTATTCAACAAGTGGCAAAACATTGCTTACAAATACGACAAA 
               
               
                   
                 GACTTAGTTTTGATGACCCACTTCATTACTAAAAACATTACCGAC 
               
               
                   
                 AACCATGGTAAAAATAAAACTACTGTTCACGGTTACTTCTCTTCC 
               
               
                   
                 ATTTTTCATGGTGGTGTCGACTCCTTGGTCGATTTAATGAACAAA 
               
               
                   
                 TCTTTCCCTGAGTTGGGTATCAAGAAGACCGACTGTAAAGAATTC 
               
               
                   
                 TCTTGGATCGACACTACTATTTTCTACTCTGGTGTCGTTAACTTC 
               
               
                   
                 AACACCGCTAATTTCAAGAAGGAAATTTTATTAGATAGATCCGCT 
               
               
                   
                 GGTAAAAAGACCGCTTTCTCTATCAAATTAGACTACGTTAAAAAA 
               
               
                   
                 CCAATCCCAGAAACCGCTATGGTCAAAATCTTGGAAAAATTATAT 
               
               
                   
                 GAAGAAGACGTTGGTGCCGGTATGTACGTCTTATATCCATATGGT 
               
               
                   
                 GGTATTATGGAAGAGATCTCTGAATCCGCTATCCCTTTTCCACAC 
               
               
                   
                 AGAGCCGGTATTATGTACGAATTATGGTACACTGCTTCCTGGGAG 
               
               
                   
                 AAACAAGAAGATAATGAAAAGCACATTAACTGGGTTAGATCTGTT 
               
               
                   
                 TACAACTTCACTACTCCATACGTCTCTCAAAACCCAAGATTAGCC 
               
               
                   
                 TACTTAAACTACCGTGATTTGGATTTAGGTAAAACTAATCACGCT 
               
               
                   
                 TCCCCAAACAACTACACCCAAGCTAGAATTTGGGGTGAGAAGTAC 
               
               
                   
                 TTTGGTAAGAACTTCAACCGTTTAGTCAAGGTCAAGACTAAAGTT 
               
               
                   
                 GATCCAAACAATTTTTTCAGAAACGAACAATCTATCCCACCTTTA 
               
               
                   
                 CCACCACACCACCATTAG 
               
               
                   
               
               
                 SEQ ID NO: 46 
                 TGTTGTGGAAATGTAAAGAGCCCCATTATCTTAGCCTAAAAAAAC 
               
               
                 pGAL1_tTDH1 
                 CTTCTCTTTGGAACTTTCAGTAATACGCTTAACTGCTCATTGCTA 
               
               
                   Saccharomyces  sp. 
                 TATTGAAGTACGGATTAGAAGCCGCCGAGCGGGCGACAGCCCTCC 
               
               
                   
                 GACGGAAGACTCTCCTCCGTGCGTCCTGGTCTTCACCGGTCGCGT 
               
               
                   
                 TCCTGAAACGCAGATGTGCCTCGCGCCGCACTGCTCCGAACAATA 
               
               
                   
                 AAGATTCTACAATACTAGCTTTTATGGTTATGAAGAGGAAAAATT 
               
               
                   
                 GGCAGTAACCTGGCCCCACAAACCTTCAAATCAAATTTCTGGGGT 
               
               
                   
                 AATTAATCAGCGAAGCGATGATTTTTGATCTATTAACAGATAT 
               
               
                   
                 ATAAATGCAAAAGCTGCATAACCACTTTAACT 
               
               
                   
                 AATACTTTCAACATTTTCGGTTTGTATTACTTCTTATTCA 
               
               
                   
                 AATGTCATAAAAGTATCAACAAAAAATTGTTAATATACCTCT 
               
               
                   
                 ATACTTTAACGTCAAGGAGAAAAAACTATAC 
               
               
                   
                 TCTTATTACCCTATCCTATGGATAAAGCAATCTTGATGAGGATA 
               
               
                   
                 ATGATTTTTTTTTGAATATACATAAATACTACCGTTTTTCTGCTA 
               
               
                   
                 GATTTTGTGAAGACGTAAATAAGTACATATTACTTTTTAAGCCAA 
               
               
                   
                 GACAAGATTAAGCATTAACTTTACCCTTTTCTCTTCTAAGTTT 
               
               
                   
                 CAATACTAGTTATCACTGTTTAAAAGTTATGGCGA 
               
               
                   
                 GAACGTCGGCGGTTAAAATATATTACCCTGAACGTGGTGAATTGA 
               
               
                   
                 AGTTCTAGGATGGTTTAAAGATTTTTCCTTTTTGGGA 
               
               
                   
                 AATAAGTAAACAATATATTGCTGCCTTTGC 
               
               
                   
               
               
                 SEQ ID NO: 47 
                 ATGGCCGTCAAACACTTGATCGTCTTAAAATTCAAGGATGAAATT 
               
               
                 OAC Y27F variant 
                 ACTGAAGCTCAAAAAGAAGAGTTCTTCAAAA 
               
               
                 (OAC*) 
                 CCTTCGTCAATTTAGTCAACATTATTCCTGCTATG 
               
               
                 Artificial sequence 
                 AAGGACGTTTACTGGGGTAAGGATGTCACCCAAAAGAACAAGGAA 
               
               
                 Codon optimized 
                 GAAGGTTACACTCACATTGTTGAAGTCACTTTCGAATCTGTTGAA 
               
               
                   
                 ACTATCCAAGATTATATTATCCACCCAGCTCATGTCGGTTTTGGT 
               
               
                   
                 GATGTTTACAGATCTTTTTGGGAAAAATTGTTGATCTTTGACTAT 
               
               
                   
                 ACTCCAAGAAAATAA 
               
               
                   
               
               
                 SEQ ID NO: 48 
                 MAVKHLIVLKFKDEITEAQKEEFFKTFVNLVNIIPAMKDVYWGKD 
               
               
                 OAC Y27F variant 
                 VTQKNKEEGYTHIVEVTFESVETIQDYIIHPAHVGFGDVYRSFWE 
               
               
                 (OAC*) 
                 KLLIFDYTPRK* 
               
               
                 Artificial sequence 
                   
               
               
                   
               
               
                 SEQ ID NO: 49 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTtttAAGATTATC 
               
               
                 CBDA Synthase, C12F 
                 TTCTTCTTCTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 variant 
                 CGTGAGAACTTCTTGAAATGTTTTTCTCAATATATCCCAAATAAC 
               
               
                 Artificial sequence 
                 GCTACTAACTTGAAGTTAGTCTATACTCAAAACAACCCATTATAT 
               
               
                 Codon optimized 
                 ATGTCTGTCTTAAACTCTACCATTCACAACTTACGTTTCACTTCT 
               
               
                   
                 GATACTACTCCAAAACCTTTGGTCATCGTCACCCCATCCCACGTT 
               
               
                   
                 TCTCACATCCAAGGTACCATCTTGTGTTCCAAAAAGGTTGGTTTA 
               
               
                   
                 CAAATCCGTACTAGATCCGGTGGTCATGACTCCGAAGGTATGTCT 
               
               
                   
                 TACATTTCCCAAGTCCCTTTCGTCATCGTCGACTTAAGAA 
               
               
                   
                 ATATGCGTTCCATCAAGATTGATGTCCATTCCCAAACTGCTT 
               
               
                   
                 GGGTTGAAGCCGGTGCCACTTTAGGTGAAGTCTATTACTGGGTTA 
               
               
                   
                 ACGAGAAGAATGAGAACTTATCTTTGGCTGCCGGTTACTGTCCAA 
               
               
                   
                 CTGTTTGTGCTGGTGGTCATTTCGGTGGTGGTGGTTACGGTCCAT 
               
               
                   
                 TAATGCGTAACTACGGTTTGGCTGCCGATAACATCATTGATGCC 
               
               
                   
                 CACTTAGTCAACGTTCATGGTAAGGTCTTGGACCGTAAGTCTATG 
               
               
                   
                 GGTGAGGATTTATTCTGGGCTTTGAGAGGTGGTGGTGCTGAATC 
               
               
                   
                 TTTCGGTATTATCGTCGCTTGGAAGATTAGATTAGTTGCTGTT 
               
               
                   
                 CCAAAGTCTACTATGTTCTCTGTTAAGAAGATCATGGAAATTCAC 
               
               
                   
                 GAGTTGGTTAAATTAGTTAACAAATGGC 
               
               
                   
                 AAAACATTGCCTACAAGTACGATAAAGATTTGTTATTAATGACTC 
               
               
                   
                 ACTTTATCACTAGAAACATTACTGATAACCAAGGTAAGAATAAGA 
               
               
                   
                 CTGCCATTCACACTTACTTCTCTTCTGTTTTCTTGGGTGGTGTTG 
               
               
                   
                 ATTCCTTGGTCGATTTGATGAACAAGTCTTTTCCAGAATTAGGTA 
               
               
                   
                 TTAAGAAGACCGATTGTCGTCAATTGATAATTTTAATAAG 
               
               
                   
                 GAGATTTTGTTAGATAGATCTGCTGGTCAAAAT 
               
               
                   
                 GGTGCCTTTAAAATCAAATTGGACTACGTTAAGAAGCCTATTCCA 
               
               
                   
                 GAATCCGTCTTTGTTCAAATTTTGGAGAAGTTATACGAAGAAGAT 
               
               
                   
                 ATTGGTGCTGGTATGTACGCCTTGTATCCATATGGTGGTATTATG 
               
               
                   
                 GATGAAATTTCTGAATCCGCCATCCCTTTCCCTCATCGTGCTGGT 
               
               
                   
                 ATCTTATACGAGTTGTGGTACATCTGTTCTTGGGAAAAGCAAGAA 
               
               
                   
                 GATAATGAAAAGCATTTGAACTGGATCCGTAACATCTATAAC 
               
               
                   
                 TTCATGACTCCATACGTTTCCAAAAACCCTAG 
               
               
                   
                 ATTGGCTTACTTAAATTACAGAGACTTAGATATTG 
               
               
                   
                 GTATTAACGACCCTAAGAACCCAAACAATTACAC 
               
               
                   
                 TCAAGCTAGAATCTGGGGTGAAAAGTACTTCGGTAAGAATTTCGA 
               
               
                   
                 CAGATTAGTTAAGGTCAAGACTTTAGTTGACCCAAATAACTTCTT 
               
               
                   
                 CAGAAACGAACAATCTATCCCACCATTGCCTAGACATAGACACTA 
               
               
                   
                 G 
               
               
                   
               
               
                 SEQ ID NO: 50 
                 MKCSTFSFWFVFKIIFFFFSFNIQTSIANPRENFLKCFSQYIPNN 
               
               
                 CBDA Synthase, C12F 
                 ATNLKLVYTQNNPLYMSVLNSTIHNLRFTSDTTPKPLVIVTPSHV 
               
               
                 variant 
                 SHIQGTILCSKKVGLQIRTRSGGHDSEGMSYISQVPFVIVDLRNM 
               
               
                 Artificial sequence 
                 RSIKIDVHSQTAWVEAGATLGEVYYWVNEKNENLSLAAGYCPTVC 
               
               
                   
                 AGGHFGGGGYGPLMRNYGLAADNIIDAHLVNVHGKVLDRKSMGED 
               
               
                   
                 LFWALRGGGAESFGIIVAWKIRLVAVPKSTMFSVKKIMEIHELVK 
               
               
                   
                 LVNKWQNIAYKYDKDLLLMTHFITRNITDNQGKNKTAIHTYF 
               
               
                   
                 SSVFLGGVDSLVDLMNKSFPELGIKKTDCRQLSWIDTIIFYSGW 
               
               
                   
                 NYDTDNFNKEILLDRSAGQNGAFKIKLDYVKKPIPESVFVQILEK 
               
               
                   
                 LYEEDIGAGMYALYPYGGIMDEISESAIPFPHRAGILYELWYICS 
               
               
                   
                 WEKQEDNEKHLNWIRNIYNFMTPYVSKNPRLAYLNYRDLDIGIN 
               
               
                   
                 DPKNPNNYTQARIWGEKYFGKNFDRLVKVKTLVDPNNFF 
               
               
                   
                 RNEQSIPPLPRHRH* 
               
               
                   
               
               
                 SEQ ID NO: 51 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                 CBDA Synthase, F17M 
                 TTCatgTTCTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 variant 
                 CGTGAGAACTTCTTGAAATGTTTTTCTCAATATATCCCA 
               
               
                 Artificial Sequence 
                 AATAACGCTACTAACTTGAAGTTAGTCTATACTCA 
               
               
                 Codon optimized 
                 AAACAACCCATTATATATGTCTGTCTTAAACTCTACCATTCACAA 
               
               
                   
                 CTTACGTTTCACTTCTGATACTACTCCAAAACCTTTGGTCATCGT 
               
               
                   
                 CACCCCATCCCACGTTTCTCACATCCAAGGTACCATCTTGTGTTC 
               
               
                   
                 CAAAAAGGTTGGTTTACAAATCCGTACTAGATCCGGTGGTCATGA 
               
               
                   
                 CTCCGAAGGTATGTCTTACATTTCCCAAGTCCCTTTCGTCATCGT 
               
               
                   
                 CGACTTAAGAAATATGCGTTCCATCAAGATTGATGTCCATTCCCA 
               
               
                   
                 AACTGCTTGGGTTGAAGCCGGTGCCACTTTAGGTGAAGTCTATTA 
               
               
                   
                 CTGGGTTAACGAGAAGAATGAGAACTTATCTTTGGCTGCCGGTTA 
               
               
                   
                 CTGTCCAACTGTTTGTGCTGGTGGTCATTTCGGTGGTGGTGGTTA 
               
               
                   
                 CGGTCCATTAATGCGTAACTACGGTTTGGCTGCCGATAACATCAT 
               
               
                   
                 TGATGCCCACTTAGTCAACGTTCATGGTAAGGTCTTGGACCGTAA 
               
               
                   
                 GTCTATGGGTGAGGATTTATTCTGGGCTTTGAGAGGTGGTGGTGC 
               
               
                   
                 TGAATCTTTCGGTATTATCGTCGCTTGGAAGATTAGATTAGTT 
               
               
                   
                 GCTGTTCCAAAGTCTACTATGTTCTCTGTTAAGAAGATCATGGAA 
               
               
                   
                 ATTCACGAGTTGGTTAAATTAGTTAACAAATGGCAAAACAT 
               
               
                   
                 TGCCTACAAGTACGATAAAGATTTGTTATTAAT 
               
               
                   
                 GACTCACTTTATCACTAGAAACATTACTGATAACCAAGGTAA 
               
               
                   
                 GAATAAGACTGCCATTCACACTTACTTCTCTTCTGTTTTCTTGGG 
               
               
                   
                 TGGTGTTGATTCCTTGGTCGATTTGATGAACAAGTCTTTTC 
               
               
                   
                 CAGAATTAGGTATTAAGAAGACCGATTGTCGTCA 
               
               
                   
                 ATTATCTTGGATTGATACCATTATTTTTTACTCCGGTGTTGTCAA 
               
               
                   
                 CTACGACACTGATAATTTTAATAAGGAGATTTTGTT 
               
               
                   
                 AGATAGATCTGCTGGTCAAAATGGTGCCTTTAAAATCAA 
               
               
                   
                 ATTGGACTACGTTAAGAAGCCTATTCCAGAATCCGTCTTTGTTC 
               
               
                   
                 AAATTTTGGAGAAGTTATACGAAGAAGATAT 
               
               
                   
                 TGGTGCTGGTATGTACGCCTTGTATCCATATGGTGGTATTA 
               
               
                   
                 TGGATGAAATTTCTGAATCCGCCATCCCTTTCCCTCATCGTGCTG 
               
               
                   
                 GTATCTTATACGAGTTGTGGTACATCTGTTCTTGGGAAAAGCAAG 
               
               
                   
                 AAGATAATGAAAAGCATTTGAACTGGATCCGTAACATCTATAA 
               
               
                   
                 CTTCATGACTCCATACGTTTCCAAAAACCCTAGA 
               
               
                   
                 TTGGCTTACTTAAATTACAGAGACTTAGATATTGGTATTAACGA 
               
               
                   
                 CCCTAAGAACCCAAACAATTACACTCAAGCTAGAATCTGGGGTGA 
               
               
                   
                 AAAGTACTTCGGTAAGAATTTCGACAGATTAGTTAAGGTCAAGAC 
               
               
                   
                 TTTAGTTGACCCAAATAACTTCTTCAGAAACGAACAATCTATCCC 
               
               
                   
                 ACCATTGCCTAGACATAGACACTAG 
               
               
                   
               
               
                 SEQ ID NO: 52 
                 MKCSTFSFWFVCKIIFMFFSFNIQTSIANPRENFLKCFSQYIPNN 
               
               
                 CBDA Synthase, F17M 
                 ATNLKLVYTQNNPLYMSVLNSTIHNLRFTSDTTPKPLVIVTPSHV 
               
               
                 variant 
                 SHIQGTILCSKKVGLQIRTRSGGHDSEGMSYISQVPFVIVDLRNM 
               
               
                 Artificial Sequence 
                 RSIKIDVHSQTAWVEAGATLGEVYYWVNEKNENLSLAAGYCPTVC 
               
               
                   
                 AGGHFGGGGYGPLMRNYGLAADNIIDAHLVNVHGKVLDRKSMGED 
               
               
                   
                 LFWALRGGGAESFGIIVAWKIRLVAWKSTMFSVKKIMEIHELVKL 
               
               
                   
                 VNKWQNIAYKYDKDLLLMTHFITRNITDNQGKNKTAIHTYFSSWL 
               
               
                   
                 GGVDSLVDLMNKSFPELGIKKTDCRQLSWIDTIIFYSGWNYDTDN 
               
               
                   
                 FNKEILLDRSAGQNGAFKIKLDYVKKPIPESVFVQILEKLYEEDI 
               
               
                   
                 GAGMYALYPYGGIMDEISESAIPFPHRAGILYELWYICSWEKQED 
               
               
                   
                 NEKHLNWIRNIYNFMTPYVSKNPRLAYLNYRDLDIGINDPKNPNN 
               
               
                   
                 YTQARIWGEKYFGKNFDRLVKVKTLVDPNNFFRNEQSIPPLPRHR 
               
               
                   
                 H* 
               
               
                   
               
               
                 SEQ ID NO: 53 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                 CBDA Synthase, F18T 
                 TTCTTCactTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 variant 
                 CGTGAGAACTTCTTGAAATGTTTTTCTCAATATATCCCAAATAAC 
               
               
                 Artificial Sequence 
                 GCTACTAACTTGAAGTTAGTCTATACTCAAAACAACCCATTATAT 
               
               
                 Codon optimized 
                 ATGTCTGTCTTAAACTCTACCATTCACAACTTACGTTTCACTTCT 
               
               
                   
                 GATACTACTCCAAAACCTTTGGTCATCGTCACCCCATCCCACGTT 
               
               
                   
                 TCTCACATCCAAGGTACCATCTTGTGTTCCAAAAAGGTTGGTTTA 
               
               
                   
                 CAAATCCGTACTAGATCCGGTGGTCATGACTCCGAAGGTATGTCT 
               
               
                   
                 TACATTTCCCAAGTCCCTTTCGTCATCGTCGACTTAAGA 
               
               
                   
                 AATATGCGTTCCATCAAGATTGATGTCCATTCCCAAACTGC 
               
               
                   
                 TTGGGTTGAAGCCGGTGCCACTTTAGGTGAAGTCTATTACTGGGT 
               
               
                   
                 TAACGAGAAGAATGAGAACTTATCTTTGGCTGCCGGTTACTGTC 
               
               
                   
                 CAACTGTTTGTGCTGGTGGTCATTTCGGTGGTGGTGGTTA 
               
               
                   
                 CGGTCCATTAATGCGTAACTACGGTTTGGCTGCCGATAACATCAT 
               
               
                   
                 TGATGCCCACTTAGTCAACGTTCATGGTAAGGTCTTGGACCGTAA 
               
               
                   
                 GTCTATGGGTGAGGATTTATTCTGGGCTTTGAGAGGTGGTGGTGC 
               
               
                   
                 TGAATCTTTCGGTATTATCGTCGCTTGGAAGATTAGATT 
               
               
                   
                 AGTTGCTGTTCCAAAGTCTACTATGTTCTCTGTTAAG 
               
               
                   
                 AAGATCATGGAAATTCACGAGTTGGTTAAA 
               
               
                   
                 TTAGTTAACAAATGGCAAAACATTGCCTACAAGTACGAT 
               
               
                   
                 AAAGATTTGTTATTAATGACTCACTTTATCACTAGAAACATTACT 
               
               
                   
                 GATAACCAAGGTAAGAATAAGACTGCCATTCACACTTACTTCTCT 
               
               
                   
                 TCTGTTTTCTTGGGTGGTGTTGATTCCTTGGTCGATTTGATGAAC 
               
               
                   
                 AAGTCTTTTCCAGAATTAGGTATTAAGAAGACCGATTGTCGTCAA 
               
               
                   
                 TTATCTTGGATTGATACCATTATTTTTTACTCCGGTGTTGTCAAC 
               
               
                   
                 TACGACACTGATAATTTTAATAAGGAGATTTTGTTA 
               
               
                   
                 GATAGATCTGCTGGTCAAAATGGTGCCTTTAAAATCA 
               
               
                   
                 AATTGGACTACGTTAAGAAGCCTATTCCAGAATCCGTCTTTGTTC 
               
               
                   
                 AAATTTTGGAGAAGTTATACGAAGAAGATATTGGTGCTGGTATGT 
               
               
                   
                 ACGCCTTGTATCCATATGGTGGTATTATGGATGAAATT 
               
               
                   
                 TCTGAATCCGCCATCCCTTTCCCTCATCGTGCTGGTATCTTATA 
               
               
                   
                 CGAGTTGTGGTACATCTGTTCTTGGGAAAAGCAAGAAGATAATGA 
               
               
                   
                 AAAGCATTTGAACTGGATCCGTAACATCTATAACTTCATGACTCC 
               
               
                   
                 ATACGTTTCCAAAAACCCTAGATTGGCTTACTTAAATTACAG 
               
               
                   
                 AGACTTAGATATTGGTATTAACGACCCTAAGAACCC 
               
               
                   
                 AAACAATTACACTCAAGCTAGAATCTGGGGTGAAAAGTACTTC 
               
               
                   
                 GGTAAGAATTTCGACAGATTAGTTAAGGTCAAGACTTTAGTTGAC 
               
               
                   
                 CCAAATAACTTCTTCAGAAACGAACAATCTATCCCACCATTGCCT 
               
               
                   
                 AGACATAGACACTAG 
               
               
                   
               
               
                 SEQ ID NO: 54 
                 MKCSTFSFWFVCKIIFFTFSFNIQTSIANPRENFLKCFSQYIPNN 
               
               
                 CBDA Synthase, F18T 
                 ATNLKJLVYTQNNPLYMSVLNSTIHNLRFTSDTTPKPLVIVTPSH 
               
               
                 variant 
                 VSHIQGTILCSKKVGLQIRTRSGGHDSEGMSYISQVPFVIVDLRN 
               
               
                 Artificial Sequence 
                 MRSIKIDVHSQTAWVEAGATLGEVYYWVNEKNENLSLAAGYCPTV 
               
               
                   
                 CAGGHFGGGGYGPLMRNYGLAADNIIDAHLVNVHGKVLDRKSMGE 
               
               
                   
                 DLFWALRGGGAESFGIIVAWKIRLVAVPKSTMFSVKKIMEIHELV 
               
               
                   
                 KLVNKWQNIAYKYDKDLLLMTHFITRNITDNQGKNKTAIHTYFSS 
               
               
                   
                 VFLGGVDSLVDLMNKSFPELGIKKTDCRQLSWIDTIIFYSGVVNY 
               
               
                   
                 DTDNFNKEILLDRSAGQNGAFKIKLDYVKKPIPESVFVQILEKLY 
               
               
                   
                 EEDIGAGMYALYPYGGIMDEISESAIPFPHRAGILYELWYICSWE 
               
               
                   
                 KQEDNEKHLNWIRNIYNFMTPYVSKNPRLAYLNYRDLDIGINDPK 
               
               
                   
                 NPNNYTQARIWGEKYFGKNFDRLVKVKTLVDPNNFFRN 
               
               
                   
                 EQSIPPLPRHRH* 
               
               
                   
               
               
                 SEQ ID NO: 55 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                 CBDA Synthase, F18W 
                 TTCTTCtggTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 variant 
                 CGTGAGAACTTCTTGAAATGTTTTTCTCAATATATCCCAAATAAC 
               
               
                 Artificial Sequence 
                 GCTACTAACTTGAAGTTAGTCTATACTCAAAACAACCCATTATAT 
               
               
                 Codon optimized 
                 ATGTCTGTCTTAAACTCTACCATTCACAACTTACGTTTCACTTCT 
               
               
                   
                 GATACTACTCCAAAACCTTTGGTCATCGTCACCCCATCCCACGTT 
               
               
                   
                 TCTCACATCCAAGGTACCATCTTGTGTTCCAAAAAGGTTGGTTT 
               
               
                   
                 ACAAATCCGTACTAGATCCGGTGGTCATGACTCCGAAGGT 
               
               
                   
                 ATGTCTTACATTTCCCAAGTCCCTTTCGTCATCGTCGACTTAAG 
               
               
                   
                 AAATATGCGTTCCATCAAGATTGATGTCCATTCCCAAACTGCTTG 
               
               
                   
                 GGTTGAAGCCGGTGCCACTTTAGGTGAAGTCTATTACTGGGTTAA 
               
               
                   
                 CGAGAAGAATGAGAACTTATCTTTGGCTGCCGGTTACTGTCCAAC 
               
               
                   
                 TGTTTGTGCTGGTGGTCATTTCGGTGGTGGTGGTTACGGTCCATT 
               
               
                   
                 AATGCGTAACTACGGTTTGGCTGCCGATAACATCATTGATGCCCA 
               
               
                   
                 CTTAGTCAACGTTCATGGTAAGGTCTTGGACCGTAAGTCTATGGG 
               
               
                   
                 TGAGGATTTATTCTGGGCTTTGAGAGGTGGTGGTGCTGAATCTTT 
               
               
                   
                 CGGTATTATCGTCGCTTGGAAGATTAGATTAGTTGCTGTTCCAAA 
               
               
                   
                 GTCTACTATGTTCTCTGTTAAGAAGATCATGGAAATTCACGAGTT 
               
               
                   
                 GGTTAAATTAGTTAACAAATGGCAAAACATTGCCTACA 
               
               
                   
                 AGTACGATAAAGATTTGTTATTAATGACTCACT 
               
               
                   
                 TTATCACTAGAAACATTACTGATAACCAAGGTAAGAATAAGACT 
               
               
                   
                 GCCATTCACACTTACTTCTCTTCTGTTTTCTTGGGTGGTGTTGAT 
               
               
                   
                 TCCTTGGTCGATTTGATGAACAAGTCTTTTCCAGAATTAGGTATT 
               
               
                   
                 AAGAAGACCGATTGTCGTCAATTATCTTGGATTGATACCATTATT 
               
               
                   
                 TTTTACTCCGGTGTTGTCAACTACGACACTGATAATTTTAATAAG 
               
               
                   
                 GAGATTTTGTTAGATAGATCTGCTGGTCAAAATGGTGCCTTTAAA 
               
               
                   
                 ATCAAATTGGACTACGTTAAGAAGCCTATTCCAGAATCCGTCTTT 
               
               
                   
                 GTTCAAATTTTGGAGAAGTTATACGAAGAAGATATTGGTGCTGGT 
               
               
                   
                 ATGTACGCCTTGTATCCATATGGTGGTATTATGGATGAAATTTCT 
               
               
                   
                 GAATCCGCCATCCCTTTCCCTCATCGTGCTGGTATCTTATACGAG 
               
               
                   
                 TTGTGGTACATCTGTTCTTGGGAAAAGCAAGAAGATAATGAAAAG 
               
               
                   
                 CATTTGAACTGGATCCGTAACATCTATAACTTCATGACTC 
               
               
                   
                 CATACGTTTCCAAAAACCCTAGATTGGCTTACTTAAA 
               
               
                   
                 TTACAGAGACTTAGATATTGGTATTAACGACCCTAAGAACCCAAA 
               
               
                   
                 CAATTACACTCAAGCTAGAATCTGGGGTGAAAAGTACTTCGGTAA 
               
               
                   
                 GAATTTCGACAGATTAGTTAAGGTCAAGACTTTAGTTGACCCAAA 
               
               
                   
                 TAACTTCTTCAGAAACGAACAATCTATCCCACCATTGCCTAGACA 
               
               
                   
                 TAGACACTAG 
               
               
                   
               
               
                 SEQ ID NO: 56 
                 MKCSTFSFWFVCKIIFFWFSFNIQTSIANPRENFLKCFSQYIPNN 
               
               
                 CBDA Synthase, 
                 ATNLKLVYTQNNPLYMSVLNSTIHNLRFTSDTTPKPLVIVTPSHV 
               
               
                 F18W 
                 SHIQGTILCSKKVGLQIRTRSGGHDSEGMSYISQVPFVIVDLRNM 
               
               
                 variant 
                 RSIKIDVHSQTAWVEAGATLGEVYYWVNEKNENLSLAAGYCP 
               
               
                 Artificial  
                 TVCAGGHFGGGGYGPLMRNYGLAADNIIDAHLVNVHGKVL 
               
               
                 Sequence 
                 DRKSMGEDLFWALRGGGAESFGIIVAWKIRLVAVPKSTMFSVKKI 
               
               
                   
                 MEIHELVKLVNKWQNIAYKYDKDLLLMTHFITRNITDNQGKNKTA 
               
               
                   
                 IHTYFSSVFLGGVDSLVDLMNKSFPELGIKKTDCRQLSWIDTHFY 
               
               
                   
                 SGWNYDTDNFNKEILLDRSAGQNGAFKIKLDYVKKPIPESVFVQI 
               
               
                   
                 LEKLYEEDIGAGMYALYPYGGIMDEISESAIPFPHRAGILYELWY 
               
               
                   
                 ICSWEKQEDNEKHLNWIRNIYNFMTPYVSKNPRLAYLNYRDLDIG 
               
               
                   
                 INDPKNPNNYTQARIWGEKYFGKNFDRLVKVKTLVDPNNFFRNEQ 
               
               
                   
                 SIPPLPRHRH* 
               
               
                   
               
               
                 SEQ ID NO: 57 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                 CBDA Synthase, 
                 TTCTTCTTCTTTggtTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 S20G 
                 CGTGAGAACTTCTTGAAATGTTTTTCTCAATATATCCCAAATAAC 
               
               
                 variant 
                 GCTACTAACTTGAAGTTAGTCTATACTCAAAACAACCCATTATAT 
               
               
                 Artificial 
                 ATGTCTGTCTTAAACTCTACCATTCACAACTTACGTTTCACTTCT 
               
               
                 Sequence 
                 GATACTACTCCAAAACCTTTGGTCATCGTCACCCCATCCCACGTT 
               
               
                 Codon optimized 
                 TCTCACATCCAAGGTACCATCTTGTGTTCCAAAAAGGTTGGTTT 
               
               
                   
                 ACAAATCCGTACTAGATCCGGTGGTCATGACTCCGA 
               
               
                   
                 AGGTATGTCTTACATTTCCCAAGTCCCTTTCGTCATCGTCGA 
               
               
                   
                 CTTAAGAAATATGCGTTCCATCAAGATTGATGTCCATTCCCAAAC 
               
               
                   
                 TGCTTGGGTTGAAGCCGGTGCCACTTTAGGTGAAGTCTATTACTG 
               
               
                   
                 GGTTAACGAGAAGAATGAGAACTTATCTTTGGCTGCCGGTTACTG 
               
               
                   
                 TCCAACTGTTTGTGCTGGTGGTCATTTCGGTGGTGGTGGTTACGG 
               
               
                   
                 TCCATTAATGCGTAACTACGGTTTGGCTGCCGATAACATCATTG 
               
               
                   
                 ATGCCCACTTAGTCAACGTTCATGGTAAGGTCTTGGACCGTAAGT 
               
               
                   
                 CTATGGGTGAGGATTTATTCTGGGCTTTGAGAGGTGGTGGTG 
               
               
                   
                 CTGAATCTTTCGGTATTATCGTCGCTTGGAAGATTAGATTAGT 
               
               
                   
                 TGCTGTTCCAAAGTCTACTATGTTCTCTGTTAAGAAGATCATG 
               
               
                   
                 GAAATTCACGAGTTGGTTAAATTAGTTAACAAAT 
               
               
                   
                 GGCAAAACATTGCCTACAAGTACGATAAAGATTTGTTATTAATGA 
               
               
                   
                 CTCACTTTATCACTAGAAACATTACTGATAACCAAGGTAAGAATA 
               
               
                   
                 AGACTGCCATTCACACTTACTTCTCTTCTGTTTTCTTGGGTGGTG 
               
               
                   
                 TTGATTCCTTGGTCGATTTGATGAACAAGTCTTTTCCAGAATTAG 
               
               
                   
                 GTATTAAGAAGACCGATTGTCGTCAATTGATAATTTTAATAAGGA 
               
               
                   
                 GATTTTGTTAGATAGATCTGCTGGTCAAAATGGTGCCTTTAAAAT 
               
               
                   
                 CAAATTGGACTACGTTAAGAAGCCTATTCCAGAATCCGTCTTTGT 
               
               
                   
                 TCAAATTTTGGAGAAGTTATACGAAGAAGATATTGGTGCTGGTAT 
               
               
                   
                 GTACGCCTTGTATCCATATGGTGGTATTATGGATGAAATTTCTGA 
               
               
                   
                 ATCCGCCATCCCTTTCCCTCATCGTGCTGGTATCTTATACGAGTT 
               
               
                   
                 GTGGTACATCTGTTCTTGGGAAAAGCAAGAAGATAATGAAAAGCA 
               
               
                   
                 TTTGAACTGGATCCGTAAC 
               
               
                   
                 ATCTATAACTTCATGACTCCATACGTTTCCAAAAACCCTAGATTG 
               
               
                   
                 GCTTACTTAAATTACAGAGACTTAGATATTGGTATTAACGACCCT 
               
               
                   
                 AAGAACCCAAACAATTACACTCAAGCTAGAATCTGGGGTGAAAAG 
               
               
                   
                 TACTTCGGTAAGAATTTCGACAGATTAGTTAAGGTCAAGACTTTA 
               
               
                   
                 GTTGACCCAAATAACTTCTTCAGAAACGAACAATCTATCCCACCA 
               
               
                   
                 TTGCCTAGACATAGACACTAG 
               
               
                   
               
               
                 SEQ ID NO: 58 
                 MKCSTFSFWFVCKIIFFFFGFNIQTSIANPRENFLKCFSQYIPNN 
               
               
                 CBDA Synthase, S20G 
                 ATNLKLVYTQNNPLYMSVLNSTIHNLRFTSDTTPKPLVIVTPSHV 
               
               
                 variant 
                 SHIQGTILCSKKVGLQIRTRSGGHDSEGMSYISQVPFVIVDLRNM 
               
               
                 Artificial Sequence 
                 RSIKIDVHSQTAWVEAGATLGEVYYWVNEKNENLSLAAGYCPTVC 
               
               
                   
                 AGGHFGGGGYGPLMRNYGLAADNIIDAHLVNVHGKVLDRKSMGED 
               
               
                   
                 LFWALRGGGAESFGIIVAWKIRLVAVPKSTMFSVKKIMEIHELVK 
               
               
                   
                 LVNKWQNIAYKYDKDLLLMTHFITRNITDNQGKNKTAIHTYFSSV 
               
               
                   
                 FLGGVDSLVDLMNKSFPELGIKKTDCRQLSWIDTIIFYSGVVNYD 
               
               
                   
                 TDNFNKEILLDRSAGQNGAFKIKLDYVKKPIPESVFVQILEKLYE 
               
               
                   
                 EDIGAGMYALYPYGGIMDEISESAIPFPHRAGILYELWYICSWEK 
               
               
                   
                 QEDNEKHLNWIRNIYNFMTPYVSKNPRLAYLNYRDLDIGINDPKN 
               
               
                   
                 PNNYTQARIWGEKYFGKNFDRLVKVKTLVDPNNFFRNEQSIPPLP 
               
               
                   
                 RHRH* 
               
               
                   
               
               
                 SEQ ID NO: 59 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                 CBDA Synthase, R31Q 
                 TTCTTCTTCTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 variant 
                 caaGAGAACTTCTTGAAATGTTTTTCTCAATATATCCCAAATAAC 
               
               
                 Artificial Sequence 
                 GCTACTAACTTGAAGTTAGTCTATACTCAAAACAACCCATTATAT 
               
               
                 Codon optimized 
                 ATGTCTGTCTTAAACTCTACCATTCACAACTTACGTTTCACTTCT 
               
               
                   
                 GATACTACTCCAAAACCTTTGGTCATCGTCACCCCATCCCACGTT 
               
               
                   
                 TCTCACATCCAAGGTACCATCTTGTGTTCCAAAAAGGTTGGTTT 
               
               
                   
                 ACAAATCCGTACTAGATCCGGTGGTCATGACTCCGAAGGT 
               
               
                   
                 ATGTCTTACATTTCCCAAGTCCCTTTCGTCATCGTCGACTTAAG 
               
               
                   
                 AAATATGCGTTCCATCAAGATTGATGTCCATTCCCAAACTGCTTG 
               
               
                   
                 GGTTGAAGCCGGTGCCACTTTAGGTGAAGTCTATTACTGGGTTAA 
               
               
                   
                 CGAGAAGAATGAGAACTTATCTTTGGCTGCCGGTTACTGTCCAAC 
               
               
                   
                 TGTTTGTGCTGGTGGTCATTTCGGTGGTGGTGGTTACGGTCCATT 
               
               
                   
                 AATGCGTAACTACGGTTTGGCTGCCGATAACATCATTGATGCCCA 
               
               
                   
                 CTTAGTCAACGTTCATGGTAAGGTCTTGGACCGTAAGTCTATGGG 
               
               
                   
                 TGAGGATTTATTCTGGGCTTTGAGAGGTGGTGGTGCTGAATCTTT 
               
               
                   
                 CGGTATTATCGTCGCTTGGAAGATTAGATTAGTTGCTGTTCCAAA 
               
               
                   
                 GTCTACTATGTTCTCTGTTAAGAAGATCATGGAAATTCACGAGTT 
               
               
                   
                 GGTTAAATTAGTTAACAAATGGCAAAACATTGCCTACAAGTACGA 
               
               
                   
                 TAAAGATTTGTTATTAATGACTCACTTTATCACTAGAAACATTAC 
               
               
                   
                 TGATAACCAAGGTAAGAATAAGACTGCCATTCACACTTACTTCTC 
               
               
                   
                 TTCTGTTTTCTTGGGTGGTGTTGATTCCTTGGTCGATTTGATGA 
               
               
                   
                 ACAAGTCTTTTCCAGAATTAGGTATTAAGAAGACCG 
               
               
                   
                 ATTGTCGTCAATTATCTTGGATTGATACCATTATTTTTTACTCC 
               
               
                   
                 GGTGTTGTCAACTACGACACTGATAATTTTAATAAGGAG 
               
               
                   
                 ATTTTGTTAGATAGATCTGCTGGTCAAAATGGTG 
               
               
                   
                 CCTTTAAAATCAAATTGGACTACGTTAAGAAGCCTATTCCAGAAT 
               
               
                   
                 CCGTCTTTGTTCAAATTTTGGAGAAGTTATACGAAGAAGATATTG 
               
               
                   
                 GTGCTGGTATGTACGCCTTGTATCCATATGGTGGTATTATGGATG 
               
               
                   
                 AAATTTCTGAATCCGCCATCCCTTTCCCTCATCGTGCTGGTATCT 
               
               
                   
                 TATACGAGTTGTGGTACATCTGTTCTTGGGAAAAGCAAGAAGATA 
               
               
                   
                 ATGAAAAGCATTTGAACTGGATCCGTAACATCTATAACTTC 
               
               
                   
                 ATGACTCCATACGTTTCCAAAAACCCTAGATTG 
               
               
                   
                 GCTTACTTAAATTACAGAGACTTAGATATTGGT 
               
               
                   
                 ATTAACGACCCTAAGAACCCAAACAATTACACTCAAGCTAGAA 
               
               
                   
                 TCTGGGGTGAAAAGTACTTCGGTAAGAATTTCGACAGATTAGTTA 
               
               
                   
                 AGGTCAAGACTTTAGTTGACCCAAATAACTTCTTCAGAAACGAAC 
               
               
                   
                 AATCTATCCCACCATTGCCTAGACATAGACACTAG 
               
               
                   
               
               
                 SEQ ID NO: 60 
                 MKCSTFSFWFVCKIIFFFFSFNIQTSIANPQENFLKCFSQYIPNN 
               
               
                 CBDA Synthase, R31Q 
                 ATNLKLVYTQNNPLYMSVLNSTIHNLRFTSDTTPKPLVIVTPSHV 
               
               
                 variant 
                 SHIQGTILCSKKVGLQIRTRSGGHDSEGMSYISQVPFVIVDLRNM 
               
               
                 Artificial Sequence 
                 RSIKIDVHSQTAWVEAGATLGEVYYWVNEKNENLSLAAGYCPTVC 
               
               
                   
                 AGGHFGGGGYGPLMRNYGLAADNIIDAHLVNVHGKVLDRKSMGED 
               
               
                   
                 LFWALRGGGAESFGIIVAWKIRLVAVPKSTMFSVKKIMEIHELVK 
               
               
                   
                 LVNKWQNIAYKYDKDLLLMTHFITRNITDNQGKNKTAIHTYFSSW 
               
               
                   
                 LGGVDSLVDLMNKSFPELGIKKTDCRQLSWIDTIIFYSGWNYDTD 
               
               
                   
                 NFNKEILLDRSAGQNGAFKIKLDYVKKPIPESVFVQILEKLYEED 
               
               
                   
                 IGAGMYALYPYGGIMDEISESAIPFPHRAGILYELWYICSWEKQE 
               
               
                   
                 DNEKHLNWIRNIYNFMTPYVSKNPRLAYLNYRDLDIGINDPKNPN 
               
               
                   
                 NYTQARIWGEKYFGKNFDRLVKVKTLVDPNNFFRNEQSIPPLPRH 
               
               
                   
                 RH* 
               
               
                   
               
               
                 SEQ ID NO: 61 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                 CBDA Synthase, N33K 
                 TTCTTCTTCTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 variant 
                 CGTGAGaaaTTCTTGAAATGTTTTTCTCAATATATCCCA 
               
               
                 Artificial Sequence 
                 AATAACGCTACTAACTTGAAGTTAGTCTATACTCAAAA 
               
               
                 Codon optimized 
                 CAACCCATTATATATGTCTGTCTTAAACTCTACCATTCACAACTT 
               
               
                   
                 ACGTTTCACTTCTGATACTACTCCAAAACCTTTGGTCATCGTCAC 
               
               
                   
                 CCCATCCCACGTTTCTCACATCCAAGGTACCATCTTGTGTTCCAA 
               
               
                   
                 AAAGGTTGGTTTACAAATCCGTACTAGATCCGGTGGTCA 
               
               
                   
                 TGACTCCGAAGGTATGTCTTACATTTCCCAAGTCCCTTTCG 
               
               
                   
                 TCATCGTCGACTTAAGAAATATGCGTTCCATCAAGATTGATGTCC 
               
               
                   
                 ATTCCCAAACTGCTTGGGTTGAAGCCGGTGCCACTTTAGGTGAAG 
               
               
                   
                 TCTATTACTGGGTTAACGAGAAGAATGAGAACTTATCTTTGGCTG 
               
               
                   
                 CCGGTTACTGTCCAACTGTTTGTGCTGGTGGTCATTTCGGTGGTG 
               
               
                   
                 GTGGTTACGGTCCATTAATGCGTAACTACGGTTTGGCTGCCGATA 
               
               
                   
                 ACATCATTGATGCCCACTTAGTCAACGTTCATGGTAAGGTCTTGG 
               
               
                   
                 ACCGTAAGTCTATGGGTGAGGATTTATTCTGGGCTTTGAGAGGTG 
               
               
                   
                 GTGGTGCTGAATCTTTCGGTATTATCGTCGCTTGGAAGATTAG 
               
               
                   
                 ATTAGTTGCTGTTCCAAAGTCTACTATGTTCTCTGTTAAGAAGAT 
               
               
                   
                 CATGGAAATTCACGAGTTGGTTAAATTAGTTAACAAA 
               
               
                   
                 TGGCAAAACATTGCCTACAAGTACGATAAAGA 
               
               
                   
                 TTTGTTATTAATGACTCACTTTATCACTAGAAACATTAC 
               
               
                   
                 TGATAACCAAGGTAAGAATAAGACTGCCATTCACACTTACTTCTC 
               
               
                   
                 TTCTGTTTTCTTGGGTGGTGTTGATTCCTTGGTCGATTTGATGAA 
               
               
                   
                 CAAGTCTTTTCCAGAATTAGGTATTAAGAAGACCGATTGTCGTCA 
               
               
                   
                 ATTATCTTGGATTGATACCATTATTTTTTACTCCGGTGTTGTCAA 
               
               
                   
                 CTACGACACTGATAATTTTAATAAGGAGATTTTGTTA 
               
               
                   
                 GATAGATCTGCTGGTCAAAATGGTGCCTTTAAAATCAA 
               
               
                   
                 ATTGGACTACGTTAAGAAGCCTATTCCAGAATCCGTCTTTGTTC 
               
               
                   
                 AAATTTTGGAGAAGTTATACGAAGAAGATATTGG 
               
               
                   
                 TGCTGGTATGTACGCCTTGTATCCATATGGTGGTATTA 
               
               
                   
                 TGGATGAAATTTCTGAATCCGCCATCCCTTTCCCTCATC 
               
               
                   
                 GTGCTGGTATCTTATACGAGTTGTGGTACATCTGTTCTTGGGAAA 
               
               
                   
                 AGCAAGAAGATAATGAAAAGCATTTGAACTGGATCCGTAACATCT 
               
               
                   
                 ATAACTTCATGACTCCATACGTTTCCAAAAACC 
               
               
                   
                 CTAGATTGGCTTACTTAAATTACAGAGACTTAGATATTGGTA 
               
               
                   
                 TTAACGACCCTAAGAACCCAAACAATTACACTCAAGCTAGAATCT 
               
               
                   
                 GGGGTGAAAAGTACTTCGGTAAGAATTTCGACAGATTAGTTAAGG 
               
               
                   
                 TCAAGACTTTAGTTGACCCAAATAACTTCTTCAGAAACGAACAAT 
               
               
                   
                 CTATCCCACCATTGCCTAGACATAGACACTAG 
               
               
                   
               
               
                 SEQ ID NO: 62 
                 MKCSTFSFWFVCKIIFFFFSFNIQTSIANPREKFLKCFSQYIPNN 
               
               
                 CBDA Synthase, N33K 
                 ATNLKLVYTQNNPLYMSVLNSTIHNLRFTSDTTPKPLVIVTPSHV 
               
               
                 variant 
                 SHIQGTILCSKKVGLQIRTRSGGHDSEGMSYISQVPFVIVDLRNM 
               
               
                 Artificial Sequence 
                 RSIKIDVHSQTAWVEAGATLGEVYYWVNEKNENLSLAAGYCPTVC 
               
               
                   
                 AGGHFGGGGYGPLMRNYGLAADNIIDAHLVNVHGKVLDRKSMGED 
               
               
                   
                 LFWALRGGGAESFGIIVAWKIRLVAVPKSTMFSVKKIMEIHELVK 
               
               
                   
                 LVNKWQNIAYKYDKDLLLMTHFITRNITDNQGKNKTAIHTYFSSV 
               
               
                   
                 FLGGVDSLVDLMNKSFPELGIKKTDCRQLSWIDTIIFYSGWNYDT 
               
               
                   
                 DNFNKEILLDRSAGQNGAFKIKLDYVKKPIPESVFVQILEKLYEE 
               
               
                   
                 DIGAGMYALYPYGGIMDEISESAIPFPHRAGILYELWYICSWEKQ 
               
               
                   
                 EDNEKHLNWIRNIYNFMTPYVSKNPRLAYLNYRDLDIGINDPKNP 
               
               
                   
                 NNYTQARIWGEKYFGKNFDRLVKVKTLVDPNNFFRNEQSIPPLPR 
               
               
                   
                 HRH* 
               
               
                   
               
               
                 SEQ ID NO: 63 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                 CBDA Synthase, P43E 
                 TTCTTCTTCTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 variant 
                 CGTGAGAACTTCTTGAAATGTTTTTCTCAATATATCgaaAATAAC 
               
               
                 Artificial Sequence 
                 GCTACTAACTTGAAGTTAGTCTATACTCAAAACAACCCATTATAT 
               
               
                 Codon optimized 
                 ATGTCTGTCTTAAACTCTACCATTCACAACTTACGTTTCACTTCT 
               
               
                   
                 GATACTACTCCAAAACCTTTGGTCATCGTCACCCCATCCCACGTT 
               
               
                   
                 TCTCACATCCAAGGTACCATCTTGTGTTCCAAAAAGGTTGGTTTA 
               
               
                   
                 CAAATCCGTACTAGATCCGGTGGTCATGACTCCGAAGGTATGTCT 
               
               
                   
                 TACATTTCCCAAGTCCCTTTCGTCATCGTCGACTTAAGAAATATG 
               
               
                   
                 CGTTCCATCAAGATTGATGTCCATTCCCAAACTGCTTGGGTTGAA 
               
               
                   
                 GCCGGTGCCACTTTAGGTGAAGTCTATTACTGGGTTAACGAGAAG 
               
               
                   
                 AATGAGAACTTATCTTTGGCTGCCGGTTACTGTCCAACTGTTTGT 
               
               
                   
                 GCTGGTGGTCATTTCGGTGGTGGTGGTTACGGTCCATTAATGCGT 
               
               
                   
                 AACTACGGTTTGGCTGCCGATAACATCATTGATGCCCACTTAGTC 
               
               
                   
                 AACGTTCATGGTAAGGTCTTGGACCGTAAGTCTATGGGTGAGGAT 
               
               
                   
                 TTATTCTGGGCTTTGAGAGGTGGTGGTGCTGAATCTTTCGGTATT 
               
               
                   
                 ATCGTCGCTTGGAAGATTAGATTAGTTGCTGTTCCAAAGTCTACT 
               
               
                   
                 ATGTTCTCTGTTAAGAAGATCATGGAAATTCACGAGT 
               
               
                   
                 TGGTTAAATTAGTTAACAAATGGCAAAACATTGCCTA 
               
               
                   
                 CAAGTACGATAAAGATTTGTTATTAATGACTCAC 
               
               
                   
                 TTTATCACTAGAAACATTACTGATAACCAAGGTAA 
               
               
                   
                 GAATAAGACTGCCATTCACACTTACTTCTCTTCTGTTTTCT 
               
               
                   
                 TGGGTGGTGTTGATTCCTTGGTCGATTTGATGAACAAGTCTTTTC 
               
               
                   
                 CAGAATTAGGTATTAAGAAGACCGATTGTCGTCAACTGATAATTT 
               
               
                   
                 TAATAAGGAGATTTTGTTAGATAGATCTGCTGGTCAAAATGGTGC 
               
               
                   
                 CTTTAAAATCAAATTGGACTACGTTAAGAAGCCTATTCCAGAATC 
               
               
                   
                 CGTCTTTGTTCAAATTTTGGAGAAGTTATACGAAGAAGATATTGG 
               
               
                   
                 TGCTGGTATGTACGCCTTGTATCCATATGGTGGTATTATGGATGA 
               
               
                   
                 AATTTCTGAATCCGCCATCCCTTTCCCTCATCGTGCTGGTATCTT 
               
               
                   
                 ATACGAGTTGTGGTACATCTGTTCTTGGGAAAAGCAAGAAGATAA 
               
               
                   
                 TGAAAAGCATTTGAACTGGATCCGTAACATCTATAACTTCATGAC 
               
               
                   
                 TCCATACGTTTCCAAAAACCCTAGATTGGCTTACTTAAATTAC 
               
               
                   
                 AGAGACTTAGATATTGGTATTAACGACCCTAAGAAC 
               
               
                   
                 CCAAACAATTACACTCAAGCTAGAATCTGGGGTGAAAAGTACTT 
               
               
                   
                 CGGTAAGAATTTCGACAGATTAGTTAAGGTCAAGACTTTAGTTGA 
               
               
                   
                 CCCAAATAACTTCTTCAGAAACGAACAATCTATCCCACCATTGCC 
               
               
                   
                 TAGACATAGACACTAG 
               
               
                   
               
               
                 SEQ ID NO: 64 
                 MKCSTFSFWFVCKIIFFFFSFNIQTSIANPRENFLKCFSQYIENN 
               
               
                 CBDA Synthase, P43E 
                 ATNLKLVYTQNNPLYMSVLNSTIHNLRFTSDTTPKPLVIVTPSHV 
               
               
                 variant 
                 SHIQGTILCSKKVGLQIRTRSGGHDSEGMSYISQVPFVIVDLRNM 
               
               
                 Artificial Sequence 
                 RSIKIDVHSQTAWVEAGATLGEVYYWVNEKNENLSLAAGYCPTV 
               
               
                   
                 CAGGHFGGGGYGPLMRNYGLAADNIIDAHLVNVHGKVLDRK 
               
               
                   
                 SMGEDLFWALRGGGAESFGIIVAWKIRLVAVPKSTMFSVKKIMEI 
               
               
                   
                 HELVKLVNKWQNIAYKYDKDLLLMTHFITRNITDNQGKNKTAIHT 
               
               
                   
                 YFSSWLGGVDSLVDLMNKSFPELGIKKTDCRQLSWIDTIIFYSGV 
               
               
                   
                 VNYDTDNFNKEILLDRSAGQNGAFKKLDYVKKPIPESVFVQILEK 
               
               
                   
                 LYEEDIGAGMYALYPYGGIMDEISESAIPFPHRAGILYELWYICS 
               
               
                   
                 WEKQEDNEKHLNWIRNIYNFMTPYVSKNPRLAYLNYRDLDIGIND 
               
               
                   
                 PKNPNNYTQARIWGEKYFGKNFDRLVKVKTLVDPNNFFRNE 
               
               
                   
                 QSIPPLPRHRH* 
               
               
                   
               
               
                 SEQ ID NO: 65 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                 CBDA Synthase, L49E 
                 TTCTTCTTCTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 variant 
                 CGTGAGAACTTCTTGATACTCAAAACAACCCATTATATATGTCTG 
               
               
                 Artificial Sequence 
                 TCTTAAACTCTACCATTCACAACTTACGTTTCACTTCTGATACTA 
               
               
                 Codon optimized 
                 CTCCAAAACCTTTGGTCATCGTCACCCCATCCCACGTTTCTCACA 
               
               
                   
                 TCCAAGGTACCATCTTGTGTTCCAAAAAGGTTGGTTTACAAATC 
               
               
                   
                 CGTACTAGATCCGGTGGTCATGACTCCGAAGGTATGTCTTACATT 
               
               
                   
                 TCCCAAGTCCCTTTCGTCATCGTCGACTTAAGAAATATGCGTTCC 
               
               
                   
                 ATCAAGATTGATGTCCATTCCCAAACTGCTTGGGTTGAAGCCGGT 
               
               
                   
                 GCCACTTTAGGTGAAGTCTATTACTGGGTTAACGAGAAGAATGAG 
               
               
                   
                 AACTTATCTTTGGCTGCCGGTTACTGTCCAACTGTTTGTGCTGGT 
               
               
                   
                 GGTCATTTCGGTGGTGGTGGTTACGGTCCATTAATGCGTAACTAC 
               
               
                   
                 GGTTTGGCTGCCGATAACATCATTGATGCCCACTTAGTCAAC 
               
               
                   
                 GTTCATGGTAAGGTCTTGGACCGTAAGTCTATGGGTGAGGA 
               
               
                   
                 TTTATTCTGGGCTTTGAGAGGTGGTGGTGCTGAATCTTTCGGTAT 
               
               
                   
                 TATCGTCGCTTGGAAGATTAGATTAGTTGCTGTTCCAAAGTCTAC 
               
               
                   
                 TATGTTCTCTGTTAAGAAGATCATGGAAATTCACGAGTTGGTTAA 
               
               
                   
                 ATTAGTTAACAAATGGCAAAACATTGCCTACAAGTACGATAAAGA 
               
               
                   
                 TTTGTTATTAATGACTCACTTTATCACTAGAAACATT 
               
               
                   
                 ACTGATAACCAAGGTAAGAATAAGACTGCCATTCAC 
               
               
                   
                 ACTTACTTCTCTTCTGTTTTCTTGGGTGGTGTTGATTCCTTGGTC 
               
               
                   
                 GATTTGATGAACAAGTCTTTTCCAGAATTAGGTATTAAGAAGACC 
               
               
                   
                 GATTGTCGTCAACTGATAATTTTAATAAGGAGATTTT 
               
               
                   
                 GTTAGATAGATCTGCTGGTCAAAATGGTGCCTTTAAAA 
               
               
                   
                 TCAAATTGGACTACGTTAAGAAGCCTATTCCAGAATCCGTCTTTG 
               
               
                   
                 TTCAAATTTTGGAGAAGTTATACGAAGAAGATATTGGTGCTGGTA 
               
               
                   
                 TGTACGCCTTGTATCCATATGGTGGTATTATGGATGAAATTTCTG 
               
               
                   
                 AATCCGCCATCCCTTTCCCTCATCGTGCTGGTATCTT 
               
               
                   
                 ATACGAGTTGTGGTACATCTGTTCTTGGGAAAAGCAAGA 
               
               
                   
                 AGATAATGAAAAGCATTTGAACTGGATCCGTAACATCTATAACTT 
               
               
                   
                 CATGACTCCATACGTTTCCAAAAACCCTAGATTGGCTTACTTAA 
               
               
                   
                 ATTACAGAGACTTAGATATTGGTATTAACGACCCT 
               
               
                   
                 AAGAACCCAAACAATTACACTCAAGCTAGAATCTGGGGT 
               
               
                   
                 GAAAAGTACTTCGGTAAGAATTTCGACAGATTAGTTAAGGTCAAG 
               
               
                   
                 ACTTTAGTTGACCCAAATAACTTCTTCAGAAACGAACAATC 
               
               
                   
                 TATCCCACCATTGCCTAGACATAGACACTAG 
               
               
                   
               
               
                 SEQ ID NO: 66 
                 MKCSTFSFWFVCKIIFFFFSFNIQTSIANPRENFLKCFSQYIPNN 
               
               
                 CBDA Synthase, L49E 
                 ATNEKLVYTQNNPLYMSVLNSTIHNLRFTSDTTPKPLVIVTPSHV 
               
               
                 variant 
                 SHIQGTILCSKKVGLQIRTRSGGHDSEGMSYISQVPFVIVDLRNM 
               
               
                 Artificial Sequence 
                 RSIKIDVHSQTAWVEAGATLGEVYYWVNEKNENLSLAAGYCPT 
               
               
                   
                 VCAGGHFGGGGYGPLMRNYGLAADNIIDAHLVNVHGKVLDRKSM 
               
               
                   
                 GEDLFWALRGGGAESFGIIVAWKIRLVAVPKSTMFSVKKIMEIHE 
               
               
                   
                 LVKLVNKWQNIAYKYDKDLLLMTHFITRNITDNQGKNKTAIHTYF 
               
               
                   
                 SSVFLGGVDSLVDLMNKSFPELGIKKTDCRQLSWIDTIIFYSGWN 
               
               
                   
                 YDTDNFNKEILLDRSAGQNGAFKIKLDYVKKPIPESVFVQILEKL 
               
               
                   
                 YEEDIGAGMYALYPYGGIMDEISESAIPFPHRAGILYELWYICSW 
               
               
                   
                 EKQEDNEKHLNWIRNIYNFMTPYVSKNPRLAYLNYRDLDIGINDP 
               
               
                   
                 KNPNNYTQARIWGEKYFGKNFDRLVKVKTLVDPNNFFRNEQSIPP 
               
               
                   
                 LPRHRH* 
               
               
                   
               
               
                 SEQ ID NO: 67 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                 CBDA Synthase, L49K 
                 TTCTTCTTCTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 variant 
                 CGTGAGAACTTCTTGAAATGTTTTTCTCAATATATCCCAAATAAC 
               
               
                 Artificial Sequence 
                 GCTACTAACaaaAAGTTAGTCTATACTCAAAACAACCCATTATA 
               
               
                 Codon optimized 
                 TATGTCTGTCTTAAACTCTACCATTCACAACTTACGTTTCACTTC 
               
               
                   
                 TGATACTACTCCAAAACCTTTGGTCATCGTCACCCCATCCCACGT 
               
               
                   
                 TTCTCACATCCAAGGTACCATCTTGTGTTCCAAAAAGGTTGGTTT 
               
               
                   
                 ACAAATCCGTACTAGATCCGGTGGTCATGACTCCGAAGGTATGTC 
               
               
                   
                 TTACATTTCCCAAGTCCCTTTCGTCATCGTCGACTTAAGAAATAT 
               
               
                   
                 GCGTTCCATCAAGATTGATGTCCATTCCCAAACTGCTTGGGTTGA 
               
               
                   
                 AGCCGGTGCCACTTTAGGTGAAGTCTATTACTGGGTTAACGAGAA 
               
               
                   
                 GAATGAGAACTTATCTTTGGCTGCCGGTTACTGTCCAACTGTTTG 
               
               
                   
                 TGCTGGTGGTCATTTCGGTGGTGGTGGTTACGGTCCATTAATGCG 
               
               
                   
                 TAACTACGGTTTGGCTGCCGATAACATCATTGATGCCCACTTAGT 
               
               
                   
                 CAACGTTCATGGTAAGGTCTTGGACCGTAAGTCTATGGGTGAGGA 
               
               
                   
                 TTTATTCTGGGCTTTGAGAGGTGGTGGTGCTGAATCTTTCGGTAT 
               
               
                   
                 TATCGTCGCTTGGAAGATTAGATTAGTTGCTGTTCCAAAGTCTAC 
               
               
                   
                 TATGTTCTCTGTTAAGAAGATCATGGAAATTCACGAGTTGGTTA 
               
               
                   
                 AATTAGTTAACAAATGGCAAAACATTGCCTACAAG 
               
               
                   
                 TACGATAAAGATTTGTTATTAATGACTCACTTTATC 
               
               
                   
                 ACTAGAAACATTACTGATAACCAAGGTAAGAATAAGACTGC 
               
               
                   
                 CATTCACACTTACTTCTCTTCTGTTTTCTTGGGTGGTGTTGATTC 
               
               
                   
                 CTTGGTCGATTTGATGAACAAGTCTTTTCCAGAATTAGGTATTAA 
               
               
                   
                 GAAGACCGATTGTCGTCAACTGATAATTTTAATAAGGAGATTTTG 
               
               
                   
                 TTAGATAGATCTGCTGGTCAAAATGGTGCCTTTAAAATCAAATTG 
               
               
                   
                 GACTACGTTAAGAAGCCTATTCCAGAATCCGTCTTTGTTCAAATT 
               
               
                   
                 TTGGAGAAGTTATACGAAGAAGATATTGGTGCTGGTATGTACGCC 
               
               
                   
                 TTGTATCCATATGGTGGTATTATGGATGAAATTTCTGAATCCGCC 
               
               
                   
                 ATCCCTTTCCCTCATCGTGCTGGTATCTTATACGAGTTGTGGTAC 
               
               
                   
                 ATCTGTTCTTGGGAAAAGCAAGAAGATAATGAAAAGCATTTGAAC 
               
               
                   
                 TGGATCCGTAACATCTATAACTTCATGACTCCATACGTTTCCAAA 
               
               
                   
                 AACCCTAGATTGGCTTACTTAAATTACAGAGACTTAGATA 
               
               
                   
                 TTGGTATTAACGACCCTAAGAACCCAAACAATTACACTC 
               
               
                   
                 AAGCTAGAATCTGGGGTGAAAAGTACTTCGGTAAGAATTTCGAC 
               
               
                   
                 AGATTAGTTAAGGTCAAGACTTTAGTTGACCCAA 
               
               
                   
                 ATAACTTCTTCAGAAACGAACAATCTATCCCACCATTGCCTAG 
               
               
                   
                 ACATAGACACTAG 
               
               
                   
               
               
                 SEQ ID NO: 68 
                 MKCSTFSFWFVCKIIFFFFSFNIQTSIANPRENFLKCFSQYIPNN 
               
               
                 CBDA Synthase, L49K 
                 ATNKKLVYTQNNPLYMSVLNSTIHNLRFTSDTTPKPLVIVTPSHV 
               
               
                 variant 
                 SHIQGTILCSKKVGLQIRTRSGGHDSEGMSYISQVPFVIVDLRNM 
               
               
                 Artificial Sequence 
                 RSIKIDVHSQTAWVEAGATLGEVYYWVNEKNENLSLAAGYCP 
               
               
                   
                 TVCAGGHFGGGGYGPLMRNYGLAADNIIDAHLVNVHGKVLDR 
               
               
                   
                 KSMGEDLFWALRGGGAESFGIIVAWKIRLVAVPKSTMFSVKKIME 
               
               
                   
                 IHELVKLVNKWQNIAYKYDKDLLLMTHFITRNITDNQGKNKT 
               
               
                   
                 AIHTYFSSVFLGGVDSLVDLMNKSFPELGIKKTDCRQLSWID 
               
               
                   
                 TIIFYSGVVNYDTDNFNKEILLDRSAGQNGAFKIKLDYVKKPIPE 
               
               
                   
                 SVFVQILEKLYEEDIGAGMYALYPYGGIMDEISESAIPFPHRAGI 
               
               
                   
                 LYELWYICSWEKQEDNEKHLNWIRNIYNFMTPYVSKNPRLAYLNY 
               
               
                   
                 RDLDIGINDPKNPNNYTQARIWGEKYFGKNFDRLVKVKTLVDPNN 
               
               
                   
                 FFRNEQSIPPLPRHRH* 
               
               
                   
               
               
                 SEQ ID NO: 69 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                 CBDA Synthase, L49Q 
                 TTCTTCTTCTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 variant 
                 CGTGAGAACTTCTTGAAATGTTTTTCTCAATATATCCCAAATAA 
               
               
                 Artificial Sequence 
                 CGCTACTAACcaaAAGTTAGTCTATACTCAAAACAACCCATTATA 
               
               
                 Codon optimized 
                 TATGTCTGTCTTAAACTCTACCATTCACAACTTACGTTTCACTTC 
               
               
                   
                 TGATACTACTCCAAAACCTTTGGTCATCGTCACCCCATCCCACGT 
               
               
                   
                 TTCTCACATCCAAGGTACCATCTTGTGTTCCAAAAAGGTTGGTTT 
               
               
                   
                 ACAAATCCGTACTAGATCCGGTGGTCATGACTCCGAAGGTATGTC 
               
               
                   
                 TTACATTTCCCAAGTCCCTTTCGTCATCGTCGACTTAAGAAATAT 
               
               
                   
                 GCGTTCCATCAAGATTGATGTCCATTCCCAAACTGCTTGGGTTGA 
               
               
                   
                 AGCCGGTGCCACTTTAGGTGAAGTCTATTACTGGGTTAACGAGAA 
               
               
                   
                 GAATGAGAACTTATCTTTGGCTGCCGGTTACTGTCCAACTGTTTG 
               
               
                   
                 TGCTGGTGGTCATTTCGGTGGTGGTGGTTACGGTCCATTAATGCG 
               
               
                   
                 TAACTACGGTTTGGCTGCCGATAACATCATTGATGCCCACTTAGT 
               
               
                   
                 CAACGTTCATGGTAAGGTCTTGGACCGTAAGTCTATGGGTG 
               
               
                   
                 AGGATTTATTCTGGGCTTTGAGAGGTGGTGGTGCTGAATCTTTCG 
               
               
                   
                 GTATTATCGTCGCTTGGAAGATTAGATTAGTTGCTGTTCCAAAGT 
               
               
                   
                 CTACTATGTTCTCTGTTAAGAAGATCATGGAAATTCACGAGTTGG 
               
               
                   
                 TTAAATTAGTTAACAAATGGCAAAACATTGCCTACAAGTACGATA 
               
               
                   
                 AAGATTTGTTATTAATGACTCACTTTATCACTAGAAACATTACTG 
               
               
                   
                 ATAACCAAGGTAAGAATAAGACTGCCATTCACACTTACTTCTCTT 
               
               
                   
                 CTGTTTTCTTGGGTGGTGTTGATTCCTTGGTCGATTTGATGAACA 
               
               
                   
                 AGTCTTTTCCAGAATTAGGTATTAAGAAGACCGATTGTCGTCAAC 
               
               
                   
                 TGATAATTTTAATAAGGAGATTTTGTTAGATAGATCTGCTGGTCA 
               
               
                   
                 AAATGGTGCCTTTAAAATCAAATTGGACTACGTTAAGAAGCCTAT 
               
               
                   
                 TCCAGAATCCGTCTTTGTTCAAATTTTGGAGAAGTTATACGAAGA 
               
               
                   
                 AGATATTGGTGCTGGTATGTACGCCTTGTATCCATATGGTGGTAT 
               
               
                   
                 TATGGATGAAATTTCTGAATCCGCCATCCCTTTCCCTCATCGTGC 
               
               
                   
                 TGGTATCTTATACGAGTTGTGGTACATCTGTTCTTGGGAAAAGCA 
               
               
                   
                 AGAAGATAATGAAAAGCATTTGAACTGGATCCGTAACATCTATAA 
               
               
                   
                 CTTCATGACTCCATACGTTTCCAAAAACCCTAGATTGGCTTACTT 
               
               
                   
                 AAATTACAGAGACTTAGATATTGGTATTAACGACCCTAAGAACCC 
               
               
                   
                 AAACAATTACACTCAAGCTAGAATCTGGGGTGAAAAGTACTTCGG 
               
               
                   
                 TAAGAATTTCGACAGATTAGTTAAGGTCAAGACTTTAGTTGACCC 
               
               
                   
                 AAATAACTTCTTCAGAAACGAACAATCTATCCCACCATTGCCTAG 
               
               
                   
                 ACATAGACACTAG 
               
               
                   
               
               
                 SEQ ID NO: 70 
                 MKCSTFSFWFVCKIIFFFFSFNIQTSIANPRENFLKCFSQYIPNN 
               
               
                 CBDA Synthase, L49Q 
                 ATNQKLVYTQNNPLYMSVLNSTIHNLRFTSDTTPKPLVIVTPSHV 
               
               
                 variant 
                 SHIQGTILCSKKVGLQIRTRSGGHDSEGMSYISQVPFVIVDLRNM 
               
               
                 Artificial Sequence 
                 RSIKIDVHSQTAWVEAGATLGEVYYWVNEKNENLSLAAGYCPTVC 
               
               
                   
                 AGGHFGGGGYGPLMRNYGLAADNIIDAHLVNVHGKVLDRKSMGED 
               
               
                   
                 LFWALRGGGAESFGIIVAWKIRLVAVPKSTMFSVKKIMEIHELVK 
               
               
                   
                 LVNKWQNIAYKYDKDLLLMTHFITRNITDNQGKNKTAIHTYFSSV 
               
               
                   
                 FLGGVDSLVDLMNKSFPELGIKKTDCRQLSWIDTIIFYSGVVNYD 
               
               
                   
                 TDNFNKEILLDRSAGQNGAFKKLDYVKKPIPESVFVQILEKLYEE 
               
               
                   
                 DIGAGMYALYPYGGIMDEISESAIPFPHRAGILYELWYICSWEKQ 
               
               
                   
                 EDNEKHLNWIRNIYNFMTPYVSKNPRLAYLNYRDLDIGINDPKNP 
               
               
                   
                 NNYTQARIWGEKYFGKNFDRLVKVKTLVDPNNFFRNEQSIPPLPR 
               
               
                   
                 HRH* 
               
               
                   
               
               
                 SEQ ID NO: 71 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                 CBDA Synthase, K50T 
                 TTCTTCTTCTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 variant 
                 CGTGAGAACTTCTTGAAATGTTTTTCTCAATATATCCCAAATAAC 
               
               
                 Artificial Sequence 
                 GCTACTAACTTGactTTAGTCTATACTCAAAACAACCCATTATAT 
               
               
                 Codon optimized 
                 ATGTCTGTCTTAAACTCTACCATTCACAACTTACGTTTCACTTCT 
               
               
                   
                 GATACTACTCCAAAACCTTTGGTCATCGTCACCCCATCCCACGTT 
               
               
                   
                 TCTCACATCCAAGGTACCATCTTGTGTTCCAAAAAGGTTGGTTTA 
               
               
                   
                 CAAATCCGTACTAGATCCGGTGGTCATGACTCCGAAGGTATGTCT 
               
               
                   
                 TACATTTCCCAAGTCCCTTTCGTCATCGTCGACTTAAGAAATATG 
               
               
                   
                 CGTTCCATCAAGATTGATGTCCATTCCCAAACTGCTTGGGTTGAA 
               
               
                   
                 GCCGGTGCCACTTTAGGTGAAGTCTATTACTGGGTTAACGAGAAG 
               
               
                   
                 AATGAGAACTTATCTTTGGCTGCCGGTTACTGTCCAACTGTTTGT 
               
               
                   
                 GCTGGTGGTCATTTCGGTGGTGGTGGTTACGGTCCATTAATGCGT 
               
               
                   
                 AACTACGGTTTGGCTGCCGATAACATCATTGATGCCCACTTAGTC 
               
               
                   
                 AACGTTCATGGTAAGGTCTTGGACCGTAAGTCTATGGGTGAGGAT 
               
               
                   
                 TTATTCTGGGCTTTGAGAGGTGGTGGTGCTGAATCTTTCGGTATT 
               
               
                   
                 ATCGTCGCTTGGAAGATTAGATTAGTTGCTGTTCCAAAGTCTACT 
               
               
                   
                 ATGTTCTCTGTTAAGAAGATCATGGAAATTCACGAGTTGGTTAAA 
               
               
                   
                 TTAGTTAACAAATGGCAAAACATTGCCTACAAGTACGATAAAGAT 
               
               
                   
                 TTGTTATTAATGACTCACTTTATCACTAGAAACATTACTGATAAC 
               
               
                   
                 CAAGGTAAGAATAAGACTGCCATTCACACTTACTTCTCTTCTGTT 
               
               
                   
                 TTCTTGGGTGGTGTTGATTCCTTGGTCGATTTGATGAACAAGTCT 
               
               
                   
                 TTTCCAGAATTAGGTATTAAGAAGACCGATTGTCGTCAATTGATA 
               
               
                   
                 ATTTTAATAAGGAGATTTTGTTAGATAGATCTGCTGGTCAAAATG 
               
               
                   
                 GTGCCTTTAAAATCAAATTGGACTACGTTAAGAAGCCTATTCCAG 
               
               
                   
                 AATCCGTCTTTGTTCAAATTTTGGAGAAGTTATACGAAGAAGATA 
               
               
                   
                 TTGGTGCTGGTATGTACGCCTTGTATCCATATGGTGGTATTATGG 
               
               
                   
                 ATGAAATTTCTGAATCCGCCATCCCTTTCCCTCATCGTGCTGGTA 
               
               
                   
                 TCTTATACGAGTTGTGGTACATCTGTTCTTGGGAAAAGCAAGAAG 
               
               
                   
                 ATAATGAAAAGCATTTGAACTGGATCCGTAACATCTATAACTTCA 
               
               
                   
                 TGACTCCATACGTTTCCAAAAACCCTAGATTGGCTTACTTAAATT 
               
               
                   
                 ACAGAGACTTAGATATTGGTATTAACGACCCTAAGAACCCAAACA 
               
               
                   
                 ATTACACTCAAGCTAGAATCTGGGGTGAAAAGTACTTCGGTAAGA 
               
               
                   
                 ATTTC 
               
               
                   
                 GACAGATTAGTTAAGGTCAAGACTTTAGTTGACCCAAATAACTTC 
               
               
                   
                 TTCAGAAACGAACAATCTATCCCACCATTGCCTAGACATAGACAC 
               
               
                   
                 TAG 
               
               
                   
               
               
                 SEQ ID NO: 72 
                 MKCSTFSFWFVCKIIFFFFSFNIQTSIANPRENFLKCFSQYIPNN 
               
               
                 CBDA Synthase, K50T 
                 ATNLTLVYTQNNPLYMSVLNSTIHNLRFTSDTTPKPLVIVTPSHV 
               
               
                 variant 
                 SHIQGTILCSKKVGLQTRTRSGGHDSEGMSYISQVPFVIVDLRNM 
               
               
                 Artificial Sequence 
                 RSIKIDVHSQTAWVEAGATLGEVYYWVNEKNENLSLAAGYCPTVC 
               
               
                   
                 AGGHFGGGGYGPLMRNYGLAADNIIDAHLVNVHGKVLDRKSMGED 
               
               
                   
                 LFWALRGGGAESFGIIVAWKIRLVAVPKSTMFSVKKIMEIHELVK 
               
               
                   
                 LVNKWQNIAYKYDKDLLLMTHFITRNITDNQGKNKTAIHTYFSSW 
               
               
                   
                 LGGVDSLVDLMNKSFPELGIKKTDCRQLSWIDTHFYSGWNYDTDN 
               
               
                   
                 FNKEILLDRSAGQNGAFKKLDYVKKPIPESVFVQILEKLYEEDIG 
               
               
                   
                 AGMYALYPYGGIMDEISESAIPFPHRAGILYELWYICSWEKQEDN 
               
               
                   
                 EKHLNWIRNIYNFMTPYVSKNPRLAYLNYRDLDIGINDPKNPNNY 
               
               
                   
                 TQARIWGEKYFGKNFDRLVKVKTLVDPNNFFRNEQSIPPLPRHRH 
               
               
                   
                 * 
               
               
                   
               
               
                 SEQ ID NO: 73 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                 CBDA Synthase, L51I 
                 TTCTTCTTCTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 variant 
                 CGTGAGAACTTCTTGAAATGTTTTTCTCAATATATCCCAAATAAC 
               
               
                 Artificial Sequence 
                 GCTACTAACTTGAAGattGTCTATACTCAAAACAACCCATTATAT 
               
               
                 Codon optimized 
                 ATGTCTGTCTTAAACTCTACCATTCACAACTTACGTTTCACTTCT 
               
               
                   
                 GATACTACTCCAAAACCTTTGGTCATCGTCACCCCATCCCACGTT 
               
               
                   
                 TCTCACATCCAAGGTACCATCTTGTGTTCCAAAAAGGTTGGTTTA 
               
               
                   
                 CAAATCCGTACTAGATCCGGTGGTCATGACTCCGAAGGTATGTCT 
               
               
                   
                 TACATTTCCCAAGTCCCTTTCGTCATCGTCGACTTAAGAAATATG 
               
               
                   
                 CGTTCCATCAAGATTGATGTCCATTCCCAAACTGCTTGGGTTGAA 
               
               
                   
                 GCCGGTGCCACTTTAGGTGAAGTCTATTACTGGGTTAACGAGAAG 
               
               
                   
                 AATGAGAACTTATCTTTGGCTGCCGGTTACTGTCCAACTGTTTGT 
               
               
                   
                 GCTGGTGGTCATTTCGGTGGTGGTGGTTACGGTCCATTAATGCGT 
               
               
                   
                 AACTACGGTTTGGCTGCCGATAACATCATTGATGCCCACTTAGTC 
               
               
                   
                 AACGTTCATGGTAAGGTCTTGGACCGTAAGTCTATGGGTGAGGAT 
               
               
                   
                 TTATTCTGGGCTTTGAGAGGTGGTGGTGCTGAATCTTTCGGTATT 
               
               
                   
                 ATCGTCGCTTGGAAGATTAGATTAGTTGCTGTTCCAAAGTCTACT 
               
               
                   
                 ATGTTCTCTGTTAAGAAGATCATGGAAATTCACGAGTTGGTTAAA 
               
               
                   
                 TTAGTTAACAAATGGCAAAACATTGCCTACAAGTACGATAAAGAT 
               
               
                   
                 TTGTTATTAATGACTCACTTTATCACTAGAAACATTACTGATAAC 
               
               
                   
                 CAAGGTAAGAATAAGACTGCCATTCACACTTACTTCTCTTCTGTT 
               
               
                   
                 TTCTTGGGTGGTGTTGATTCCTTGGTCGATTTGATGAACAAGTCT 
               
               
                   
                 TTTCCAGAATTAGGTATTAAGAAGACCGATTGTCGTCAATTGATA 
               
               
                   
                 ATTTTAATAAGGAGATTTTGTTAGATAGATCTGCTGGTCAAAATG 
               
               
                   
                 GTGCCTTTAAAATCAAATTGGACTACGTTAAGAAGCCTATTCCAG 
               
               
                   
                 AATCCGTCTTTGTTCAAATTTTGGAGAAGTTATACGAAGAAGATA 
               
               
                   
                 TTGGTGCTGGTATGTACGCCTTGTATCCATATGGTGGTATTATGG 
               
               
                   
                 ATGAAATTTCTGAATCCGCCATCCCTTTCCCTCATCGTGCTGGTA 
               
               
                   
                 TCTTATACGAGTTGTGGTACATCTGTTCTTGGGAAAAGCAAGAAG 
               
               
                   
                 ATAATGAAAAGCATTTGAACTGGATCCGTAACATCTATAACTTCA 
               
               
                   
                 TGACTCCATACGTTTCCAAAAACCCTAGATTGGCTTACTTAAATT 
               
               
                   
                 ACAGAGACTTAGATATTGGTATTAACGACCCTAAGAACCCAAACA 
               
               
                   
                 ATTACACTCAAGCTAGAATCTGGGGTGAAAAGTACTTCGGTAAGA 
               
               
                   
                 ATTTCGACAGATTAGTTAAGGTCAAGACTTTAGTTGACCCAAATA 
               
               
                   
                 ACTTCTTCAGAAACGAACAATCTATCCCACCATTGCCTAGACATA 
               
               
                   
                 GACACTAG 
               
               
                   
               
               
                 SEQ ID NO: 74 
                 MKCSTFSFWFVCKIIFFFFSFNIQTSIANPRENFLKCFSQYTPNN 
               
               
                 CBDA Synthase, L51I 
                 ATNLKIVYTQNNPLYMSVLNSTIHNLRFTSDTTPKPLVIVTPSHV 
               
               
                 variant 
                 SHIQGTILCSKKVGLQIRTRSGGHDSEGMSYISQVPFVIVDLRNM 
               
               
                 Artificial Sequence 
                 RSIKIDVHSQTAWVEAGATLGEVYYWVNEKNENLSLAAGYCPTVC 
               
               
                   
                 AGGHFGGGGYGPLMRNYGLAADNIIDAHLVNVHGKVLDRKSMGED 
               
               
                   
                 LFWALRGGGAESFGIIVAWKIRLVAWKSTMFSVKKIMEIHELVKL 
               
               
                   
                 VNKWQNIAYKYDKDLLLMTHFITRNITDNQGKNKTAIHTYFSSWL 
               
               
                   
                 GGVDSLVDLMNKSFPELGIKKTDCRQLSWIDTIIFYSGVVNYDTD 
               
               
                   
                 NFNKEILLDRSAGQNGAFKIKLDYVKKPIPESVFVQILEKLYEED 
               
               
                   
                 IGAGMYALYPYGGIMDEISESAIPFPHRAGILYELWYICSWEKQE 
               
               
                   
                 DNEKHLNWIRNIYNFMTPYVSKNPRLAYLNYRDLDIGINDPKNPN 
               
               
                   
                 NYTQARIWGEKYFGKNFDRLVKVKTLVDPNNFFRNEQSIPPLPRH 
               
               
                   
                 RH* 
               
               
                   
               
               
                 SEQ ID NO: 75 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                 CBDA Synthase, Q55E 
                 TTCTTCTTCTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 variant 
                 CGTGAGAACTTCTTGAAATGTTTTTCTCAATATATCCCAAATAAC 
               
               
                 Artificial Sequence 
                 GCTACTAACTTGAAGTTAGTCTATACTgaaAACAACCCATTATAT 
               
               
                 Codon optimized 
                 ATGTCTGTCTTAAACTCTACCATTCACAACTTACGTTTCACTTCT 
               
               
                   
                 GATACTACTCCAAAACCTTTGGTCATCGTCACCCCATCCCACGTT 
               
               
                   
                 TCTCACATCCAAGGTACCATCTTGTGTTCCAAAAAGGTTGGTTTA 
               
               
                   
                 CAAATCCGTACTAGATCCGGTGGTCATGACTCCGAAGGTATGTCT 
               
               
                   
                 TACATTTCCCAAGTCCCTTTCGTCATCGTCGACTTAAGAAATATG 
               
               
                   
                 CGTTCCATCAAGATTGATGTCCATTCCCAAACTGCTTGGGTTGAA 
               
               
                   
                 GCCGGTGCCACTTTAGGTGAAGTCTATTACTGGGTTAACGAGAAG 
               
               
                   
                 AATGAGAACTTATCTTTGGCTGCCGGTTACTGTCCAACTGTTTGT 
               
               
                   
                 GCTGGTGGTCATTTCGGTGGTGGTGGTTACGGTCCATTAATGCGT 
               
               
                   
                 AACTACGGTTTGGCTGCCGATAACATCATTGATGCCCACTTAGTC 
               
               
                   
                 AACGTTCATGGTAAGGTCTTGGACCGTAAGTCTATGGGTGAGGAT 
               
               
                   
                 TTATTCTGGGCTTTGAGAGGTGGTGGTGCTGAATCTTTCGGTATT 
               
               
                   
                 ATCGTCGCTTGGAAGATTAGATTAGTTGCTGTTCCAAAGTCTACT 
               
               
                   
                 ATGTTCTCTGTTAAGAAGATCATGGAAATTCACGAGTTGGTTAAA 
               
               
                   
                 TTAGTTAACAAATGGCAAAACATTGCCTACAAGTACGATAAAGAT 
               
               
                   
                 TTGTTATTAATGACTCACTTTATCACTAGAAACATTACTGATAAC 
               
               
                   
                 CAAGGTAAGAATAAGACTGCCATTCACACTTACTTCTCTTCTGTT 
               
               
                   
                 TTCTTGGGTGGTGTTGATTCCTTGGTCGATTTGATGAACAAGTCT 
               
               
                   
                 TTTCCAGAATTAGGTATTAAGAAGACCGATTGTCGTCAATTATCT 
               
               
                   
                 TGGATTGATACCATTATTTTTTACTCCGGTGTTGTCAACTACGAC 
               
               
                   
                 ACTGATAATTTTAATAAGGAGATTTTGTTAGATAGATCTGCTGGT 
               
               
                   
                 CAAAATGGTGCCTTTAAAATCAAATTGGACTACGTTAAGAAGCCT 
               
               
                   
                 ATTCCAGAATCCGTCTTTGTTCAAATTTTGGAGAAGTTATACGAA 
               
               
                   
                 GAAGATATTGGTGCTGGTATGTACGCCTTGTATCCATATGGTGGT 
               
               
                   
                 ATTATGGATGAAATTTCTGAATCCGCCATCCCTTTCCCTCATCGT 
               
               
                   
                 GCTGGTATCTTATACGAGTTGTGGTACATCTGTTCTTGGGAAAAG 
               
               
                   
                 CAAGAAGATAATGAAAAGCATTTGAACTGGATCCGTAACATCTAT 
               
               
                   
                 AACTTCATGACTCCATACGTTTCCAAAAACCCTAGATTGGCTTAC 
               
               
                   
                 TTAAATTACAGAGACTTAGATATTGGTATTAACGACCCTAAGAAC 
               
               
                   
                 CCAAACAATTACACTCAAGCTAGAATCTGGGGTGAAAAGTACTTC 
               
               
                   
                 GGTAAGAATTTCGACAGATTAGTTAAGGTCAAGACTTTAGTTGAC 
               
               
                   
                 CCAAATAACTTCTTCAGAAACGAACAATCTATCCCACCATTGCCT 
               
               
                   
                 AGACATAGACACTAG 
               
               
                   
               
               
                 SEQ ID NO: 76 
                 MKCSTFSFWFVCKIIFFFFSFNIQTSIANPRENFLKCFSQYIPNN 
               
               
                 CBDA Synthase, Q55E 
                 ATNLKLVYTENNPLYMSVLNSTIHNLRFTSDTTPKPLVIVTPSHV 
               
               
                 variant 
                 SHIQGTILCSKKVGLQIRTRSGGHDSEGMSYISQVPFVIVDLRNM 
               
               
                 Artificial Sequence 
                 RSIKIDVHSQTAWVEAGATLGEVYYWVNEKNENLSLAAGYCPTVC 
               
               
                   
                 AGGHFGGGGYGPLMRNYGLAADNIIDAHLVNVHGKVLDRKSMGED 
               
               
                   
                 LFWALRGGGAESFGIIVAWKIRLVAVPKSTMFSVKKIMEIHELVK 
               
               
                   
                 LVNKWQNIAYKYDKDLLLMTHFITRNITDNQGKNKTAIHTYFSSW 
               
               
                   
                 LGGVDSLVDLMNKSFPELGIKKTDCRQLSWIDTIIFYSGWNYDTD 
               
               
                   
                 NFNKEILLDRSAGQNGAFKIKLDYVKKPIPESVFVQILEKLYEED 
               
               
                   
                 IGAGMYALYPYGGIMDEISESAIPFPHRAGILYELWYICSWEKQE 
               
               
                   
                 DNEKHLNWIRNIYNFMTPYVSKNPRLAYLNYRDLDIGINDPKNPN 
               
               
                   
                 NYTQARIWGEKYFGKNFDRLVKVKTLVDPNNFFRNEQSIPPLPRH 
               
               
                   
                 RH* 
               
               
                   
               
               
                 SEQ ID NO: 77 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                 CBDA Synthase, Q55P 
                 TTCTTCTTCTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 variant 
                 CGTGAGAACTTCTTGAAATGTTTTTCTCAATATATCCCAAATAAC 
               
               
                 Artificial Sequence 
                 GCTACTAACTTGAAGTTAGTCTATACTccaAACAACCCATTATAT 
               
               
                 Codon optimized 
                 ATGTCTGTCTTAAACTCTACCATTCACAACTTACGTTTCACTTCT 
               
               
                   
                 GATACTACTCCAAAACCTTTGGTCATCGTCACCCCATCCCACGTT 
               
               
                   
                 TCTCACATCCAAGGTACCATCTTGTGTTCCAAAAAGGTTGGTTTA 
               
               
                   
                 CAAATCCGTACTAGATCCGGTGGTCATGACTCCGAAGGTATGTCT 
               
               
                   
                 TACATTTCCCAAGTCCCTTTCGTCATCGTCGACTTAAGAAATATG 
               
               
                   
                 CGTTCCATCAAGATTGATGTCCATTCCCAAACTGCTTGGGTTGAA 
               
               
                   
                 GCCGGTGCCACTTTAGGTGAAGTCTATTACTGGGTTAACGAGAAG 
               
               
                   
                 AATGAGAACTTATCTTTGGCTGCCGGTTACTGTCCAACTGTTTGT 
               
               
                   
                 GCTGGTGGTCATTTCGGTGGTGGTGGTTACGGTCCATTAATGCGT 
               
               
                   
                 AACTACGGTTTGGCTGCCGATAACATCATTGATGCCCACTTAGTC 
               
               
                   
                 AACGTTCATGGTAAGGTCTTGGACCGTAAGTCTATGGGTGAGGAT 
               
               
                   
                 TTATTCTGGGCTTTGAGAGGTGGTGGTGCTGAATCTTTCGGTATT 
               
               
                   
                 ATCGTCGCTTGGAAGATTAGATTAGTTGCTGTTCCAAAGTCTACT 
               
               
                   
                 ATGTTCTCTGTTAAGAAGATCATGGAAATTCACGAGTTGGTTAAA 
               
               
                   
                 TTAGTTAACAAATGGCAAAACATTGCCTACAAGTACGATAAAGAT 
               
               
                   
                 TTGTTATTAATGACTCACTTTATCACTAGAAACATTACTGATAAC 
               
               
                   
                 CAAGGTAAGAATAAGACTGCCATTCACACTTACTTCTCTTCTGTT 
               
               
                   
                 TTCTTGGGTGGTGTTGATTCCTTGGTCGATTTGATGAACAAGTCT 
               
               
                   
                 TTTCCAGAATTAGGTATTAAGAAGACCGATTGTCGTCAATTATCT 
               
               
                   
                 TGGATTGATACCATTATTTTTTACTCCGGTGTTGTCAACTACGAC 
               
               
                   
                 ACTGATAATTTTAATAAGGAGATTTTGTTAGATAGATCTGCTGGT 
               
               
                   
                 CAAAATGGTGCCTTTAAAATCAAATTGGACTACGTTAAGAAGCCT 
               
               
                   
                 ATTCCAGAATCCGTC 
               
               
                   
                 TTTGTTCAAATTTTGGAGAAGTTATACGAAGAAGATATTGGTGCT 
               
               
                   
                 GGTATGTACGCCTTGTATCCATATGGTGGTATTATGGATGAAATT 
               
               
                   
                 TCTGAATCCGCCATCCCTTTCCCTCATCGTGCTGGTATCTTATAC 
               
               
                   
                 GAGTTGTGGTACATCTGTTCTTGGGAAAAGCAAGAAGATAATGAA 
               
               
                   
                 AAGCATTTGAACTGGATCCGTAACATCTATAACTTCATGACTCCA 
               
               
                   
                 TACGTTTCCAAAAACCCTAGATTGGCTTACTTAAATTACAGAGAC 
               
               
                   
                 TTAGATATTGGTATTAACGACCCTAAGAACCCAAACAATTACACT 
               
               
                   
                 CAAGCTAGAATCTGGGGTGAAAAGTACTTCGGTAAGAATTTCGAC 
               
               
                   
                 AGATTAGTTAAGGTCAAGACTTTAGTTGACCCAAATAACTTCTTC 
               
               
                   
                 AGAAACGAACAATCTATCCCACCATTGCCTAGACATAGACACTAG 
               
               
                   
               
               
                 SEQ ID NO: 78 
                 MKCSTFSFWFVCKIIFFFFSFNIQTSIANPRENFLKCFSQYIPNN 
               
               
                 CBDA Synthase, 
                 ATNLKLVYTPNNPLYMSVLNSTIHNLRFTSDTTPKPLVIVTPSHV 
               
               
                 Q55P 
                 SHIQGTILCSKKVGLQIRTRSGGHDSEGMSYISQVPFVIVDLRNM 
               
               
                 variant 
                 RSIKIDVHSQTAWVEAGATLGEVYYWVNEKNENLSLAAGYCPTVC 
               
               
                 Artificial Sequence 
                 AGGHFGGGGYGPLMRNYGLAADNIIDAHLVNVHGKVLDRKSMGED 
               
               
                   
                 LFWALRGGGAESFGIIVAWKIRLVAWKSTMFSVKKIMEIHELVKJ 
               
               
                   
                 LVNKWQNIAYKYDKDLLLMTHFITRNITDNQGKNKTAIHTYFSSV 
               
               
                   
                 FLGGVDSLVDLMNKSFPELGIKKTDCRQLSWIDTIIFYSGVVNYD 
               
               
                   
                 TDNFNKEILLDRSAGQNGAFKIKLDYVKKPIPESWVQILEKLYEE 
               
               
                   
                 DIGAGMYALYPYGGIMDEISESAIPFPHRAGILYELWYICSWEKQ 
               
               
                   
                 EDNEKHLNWIRNIYNFMTPYVSKNPRLAYLNYRDLDIGINDPKNP 
               
               
                   
                 NNYTQARIWGEKYFGKNFDRLVKVKTLVDPNNFFRNEQSIPPLPR 
               
               
                   
                 HRH* 
               
               
                   
               
               
                 SEQ ID NO: 79 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                 CBDA Synthase, 
                 TTCTTCTTCTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 N56E 
                 CGTGAGAACTTCTTGAAATGTTTTTCTCAATATATCCCAAATAAC 
               
               
                 variant 
                 GCTACTAACTTGAAGTTAGTCTATACTCAAgaaAACCCATTATAT 
               
               
                 Artificial Sequence 
                 ATGTCTGTCTTAAACTCTACCATTCACAACTTACGTTTCACTTCT 
               
               
                 Codon optimized 
                 GATACTACTCCAAAACCTTTGGTCATCGTCACCCCATCCCACGTT 
               
               
                   
                 TCTCACATCCAAGGTACCATCTTGTGTTCCAAAAAGGTTGGTTTA 
               
               
                   
                 CAAATCCGTACTAGATCCGGTGGTCATGACTCCGAAGGTATGTCT 
               
               
                   
                 TACATTTCCCAAGTCCCTTTCGTCATCGTCGACTTAAGAAATATG 
               
               
                   
                 CGTTCCATCAAGATTGATGTCCATTCCCAAACTGCTTGGGTTGAA 
               
               
                   
                 GCCGGTGCCACTTTAGGTGAAGTCTATTACTGGGTTAACGAGAAG 
               
               
                   
                 AATGAGAACTTATCTTTGGCTGCCGGTTACTGTCCAACTGTTTGT 
               
               
                   
                 GCTGGTGGTCATTTCGGTGGTGGTGGTTACGGTCCATTAATGCGT 
               
               
                   
                 AACTACGGTTTGGCTGCCGATAACATCATTGATGCCCACTTAGTC 
               
               
                   
                 AACGTTCATGGTAAGGTCTTGGACCGTAAGTCTATGGGTGAGGAT 
               
               
                   
                 TTATTCTGGGCTTTGAGAGGTGGTGGTGCTGAATCTTTCGGTATT 
               
               
                   
                 ATCGTCGCTTGGAAGATTAGATTAGTTGCTGTTCCAAAGTCTACT 
               
               
                   
                 ATGTTCTCTGTTAAGAAGATCATGGAAATTCACGAGTTGGTTAAA 
               
               
                   
                 TTAGTTAACAAATGGCAAAACATTGCCTACAAGTACGATAAAGAT 
               
               
                   
                 TTGTTATTAATGACTCACTTTATCACTAGAAACATTACTGATAAC 
               
               
                   
                 CAAGGTAAGAATAAGACTGCCATTCACACTTACTTCTCTTCTGTT 
               
               
                   
                 TTCTTGGGTGGTGTTGATTCCTTGGTCGATTTGATGAACAAGTCT 
               
               
                   
                 TTTCCAGAATTAGGTATTAAGAAGACCGATTGTCGTCAATTATCT 
               
               
                   
                 TGGATTGATACCATTATTTTTTACTCCGGTGTTGTCAACTACGAC 
               
               
                   
                 ACTGATAATTTTAATAAGGAGATTTTGTTAGATAGATCTGCTGGT 
               
               
                   
                 CAAAATGGTGCCTTTAAAATCAAATTGGACTACGTTAAGAAGCCT 
               
               
                   
                 ATTCCAGAATCCGTCTTTGTTCAAATTTTGGAGAAGTTATACGAA 
               
               
                   
                 GAAGATATTGGTGCTGGTATGTACGCCTTGTATCCATATGGTGGT 
               
               
                   
                 ATTATGGATGAAATTTCTGAATCCGCCATCCCTTTCCCTCATCGT 
               
               
                   
                 GCTGGTATCTTATACGAGTTGTGGTACATCTGTTCTTGGGAAAAG 
               
               
                   
                 CAAGAAGATAATGAAAAGCATTTGAACTGGATCCGTAACATCTAT 
               
               
                   
                 AACTTCATGACTCCATACGTTTCCAAAAACCCTAGATTGGCTTAC 
               
               
                   
                 TTAAATTACAGAGACTTAGATATTGGTATTAACGACCCTAAGAAC 
               
               
                   
                 CCAAACAATTACACTCAAGCTAGAATCTGGGGTGAAAAGTACTTC 
               
               
                   
                 GGTAAGAATTTCGACAGATTAGTTAAGGTCAAGACTTTAGTTGAC 
               
               
                   
                 CCAAATAACTTCTTCAGAAACGAACAATCTATCCCACCATTGCCT 
               
               
                   
                 AGACATAGACACTAG 
               
               
                   
               
               
                 SEQ ID NO: 80 
                 MKCSTFSFWFVCKIIFFFFSFNIQTSIANPRENFLKCFSQYIPNN 
               
               
                 CBDA Synthase, N56E 
                 ATNLKLVYTQENPLYMSVLNSTIHNLRFTSDTTPKPLVIVTPSHV 
               
               
                 variant 
                 SHIQGTILCSKKVGLQTRTRSGGHDSEGMSYISQVPFVIVDLRNM 
               
               
                 Artificial Sequence 
                 RSIKIDVHSQTAWVEAGATLGEVYYWVNEKNENLSLAAGYCPTVC 
               
               
                   
                 AGGHFGGGGYGPLMRNYGLAADNIIDAHLVNVHGKVLDRKSMGED 
               
               
                   
                 LFWALRGGGAESFGIIVAWKIRLVAVPKSTMFSVKKIMEIHELVK 
               
               
                   
                 LVNKWQNIAYKYDKDLLLMTHFITRNITDNQGKNKTAIHTYFSSV 
               
               
                   
                 FLGGVDSLVDLMNKSFPELGIKKTDCRQLSWIDTIIFYSGWNYDT 
               
               
                   
                 DNFNKEILLDRSAGQNGAFKKLDYVKKPIPESVFVQILEKLYEED 
               
               
                   
                 IGAGMYALYPYGGIMDEISESAIPFPHRAGILYELWYICSWEKQE 
               
               
                   
                 DNEKHLNWIRNIYNFMTPYVSKNPRLAYLNYRDLDIGINDPKNPN 
               
               
                   
                 NYTQARIWGEKYFGKNFDRLVKVKTLVDPNNFFRNEQSIPPLPRH 
               
               
                   
                 RH* 
               
               
                   
               
               
                 SEQ ID NO: 81 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                 CBDA Synthase, 
                 TTCTTCTTCTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 N57D 
                 CGTGAGAACTTCTTGAAATGTTTTTCTCAATATATCCCAAATAAC 
               
               
                 variant 
                 GCTACTAACTTGAAGTTAGTCTATACTCAAAACgatCCATTATAT 
               
               
                 Artificial Sequence 
                 ATGTCTGTCTTAAACTCTACCATTCACAACTTACGTTTCACTTCT 
               
               
                 Codon optimized 
                 GATACTACTCCAAAACCTTTGGTCATCGTCACCCCATCCCACGTT 
               
               
                   
                 TCTCACATCCAAGGTACCATCTTGTGTTCCAAAAAGGTTGGTTTA 
               
               
                   
                 CAAATCCGTACTAGATCCGGTGGTCATGACTCCGAAGGTATGTCT 
               
               
                   
                 TACATTTCCCAAGTCCCTTTCGTCATCGTCGACTTAAGAAATATG 
               
               
                   
                 CGTTCCATCAAGATTGATGTCCATTCCCAAACTGCTTGGGTTGAA 
               
               
                   
                 GCCGGTGCCACTTTAGGTGAAGTCTATTACTGGGTTAACGAGAAG 
               
               
                   
                 AATGAGAACTTATCTTTGGCTGCCGGTTACTGTCCAACTGTTTGT 
               
               
                   
                 GCTGGTGGTCATTTCGGTGGTGGTGGTTACGGTCCATTAATGCGT 
               
               
                   
                 AACTACGGTTTGGCTGCCGATAACATCATTGATGCCCACTTAGTC 
               
               
                   
                 AACGTTCATGGTAAGGTCTTGGACCGTAAGTCTATGGGTGAGGAT 
               
               
                   
                 TTATTCTGGGCTTTGAGAGGTGGTGGTGCTGAATCTTTCGGTATT 
               
               
                   
                 ATCGTCGCTTGGAAGATTAGATTAGTTGCTGTTCCAAAGTCTACT 
               
               
                   
                 ATGTTCTCTGTTAAGAAGATCATGGAAATTCACGAGTTGGTTAAA 
               
               
                   
                 TTAGTTAACAAATGGCAAAACATTGCCTACAAGTACGATAAAGAT 
               
               
                   
                 TTGTTATTAATGACTCACTTTATCACTAGAAACATTACTGATAAC 
               
               
                   
                 CAAGGTAAGAATAAGACTGCCATTCACACTTACTTCTCTTCTGTT 
               
               
                   
                 TTCTTGGGTGGTGTTGATTCCTTGGTCGATTTGATGAACAAGTCT 
               
               
                   
                 TTTCCAGAATTAGGTATTAAGAAGACCGATTGTCGTCAATTATCT 
               
               
                   
                 TGGATTGATACCATTATTTTTTACTCCGGTGTTGTCAACTACGAC 
               
               
                   
                 ACTGATAATTTTAATAAGGAGATTTTGTTAGATAGATCTGCTGGT 
               
               
                   
                 CAAAATGGTGCCTTTAAAATCAAATTGGACTACGTTAAGAAGCCT 
               
               
                   
                 ATTCCAGAATCCGTCTTTGTTCAAATTTTGGAGAAGTTATACGAA 
               
               
                   
                 GAAGATATTGGTGCTGGTATGTACGCCTTGTATCCATATGGTGGT 
               
               
                   
                 ATTATGGATGAAATTTCTGAATCCGCCATCCCTTTCCCTCATCGT 
               
               
                   
                 GCTGGTATCTTATACGAGTTGTGGTACATCTGTTCTTGGGAAAAG 
               
               
                   
                 CAAGAAGATAATGAAAAGCATTTGAACTGGATCCGTAACATCTAT 
               
               
                   
                 AACTTCATGACTCCATACGTTTCCAAAAACCCTAGATTGGCTTAC 
               
               
                   
                 TTAAATTACAGAGACTTAGATATTGGTATTAACGACCCTAAGAAC 
               
               
                   
                 CCAAACAATTACACTCAAGCTAGAATCTGGGGTGAAAAGTACTTC 
               
               
                   
                 GGTAAGAATTTCGACAGATTAGTTAAGGTCAAGACTTTAGTTGAC 
               
               
                   
                 CCAAATAACTTCTTCAGAAACGAACAATCTATCCCACCATTGCCT 
               
               
                   
                 AGACATAGACACTAG 
               
               
                   
               
               
                 SEQ ID NO: 82 
                 MKCSTFSFWFVCKIIFFFFSFNIQTSIANPRENFLKCFSQYIPNN 
               
               
                 CBDA Synthase, 
                 ATNLKLVYTQNDPLYMSVLNSTIHNLRFTSDTTPKPLVIVTPSHV 
               
               
                 N57D 
                 SHIQGTILCSKKVGLQIRTRSGGHDSEGMSYISQVPFVIVDLRNM 
               
               
                 variant 
                 RSIKIDVHSQTAWVEAGATLGEVYYWVNEKNENLSLAAGYCPTVC 
               
               
                 Artificial Sequence 
                 AGGHFGGGGYGPLMRNYGLAADNIIDAHLVNVHGKVLDRKSMGED 
               
               
                   
                 LFWALRGGGAESFGIIVAWKIRLVAVPKSTMFSVKKIMEIHELVK 
               
               
                   
                 LVNKWQNIAYKYDKDLLLMTHFITRNITDNQGKNKTAIHTYFSSV 
               
               
                   
                 FLGGVDSLVDLMNKSFPELGIKKTDCRQLSWIDTIIFYSGWNYDT 
               
               
                   
                 DNFNKEILLDRSAGQNGAFKIKLDYVKKPIPESVFVQILEKLYEE 
               
               
                   
                 DIGAGMYALYPYGGIMDEISESAIPFPHRAGILYELWYICSWEKQ 
               
               
                   
                 EDNEKHLNWIRNIYNFMTPYVSKNPRLAYLNYRDLDIGINDPKNP 
               
               
                   
                 NNYTQARIWGEKYFGKNFDRLVKVKTLVDPNNFFRNEQSIPPLPR 
               
               
                   
                 HRH* 
               
               
                   
               
               
                 SEQ ID NO: 83 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                 CBDA Synthase, 
                 TTCTTCTTCTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 N57E 
                 CGTGAGAACTTCTTGAAATGTTTTTCTCAATATATCCCAAATAAC 
               
               
                 variant 
                 GCTACTAACTTGAAGTTAGTCTATACTCAAAACgaaCCATTATAT 
               
               
                 Artificial Sequence 
                 ATGTCTGTCTTAAACTCTACCATTCACAACTTACGTTTCACTTCT 
               
               
                 Codon optimized 
                 GATACTACTCCAAAACCTTTGGTCATCGTCACCCCATCCCACGTT 
               
               
                   
                 TCTCACATCCAAGGTACCATCTTGTGTTCCAAAAAGGTTGGTTTA 
               
               
                   
                 CAAATCCGTACTAGATCCGGTGGTCATGACTCCGAAGGTATGTCT 
               
               
                   
                 TACATTTCCCAAGTCCCTTTCGTCATCGTCGACTTAAGAAATATG 
               
               
                   
                 CGTTCCATCAAGATTGATGTCCATTCCCAAACTGCTTGGGTTGAA 
               
               
                   
                 GCCGGTGCCACTTTAGGTGAAGTCTATTACTGGGTTAACGAGAAG 
               
               
                   
                 AATGAGAACTTATCTTTGGCTGCCGGTTACTGTCCAACTGTTTGT 
               
               
                   
                 GCTGGTGGTCATTTCGGTGGTGGTGGTTACGGTCCATTAATGCGT 
               
               
                   
                 AACTACGGTTTGGCTGCCGATAACATCATTGATGCCCACTTAGTC 
               
               
                   
                 AACGTTCATGGTAAGGTCTTGGACCGTAAGTCTATGGGTGAGGAT 
               
               
                   
                 TTATTCTGGGCTTTGAGAGGTGGTGGTGCTGAATCTTTCGGTATT 
               
               
                   
                 ATCGTCGCTTGGAAGATTAGATTAGTTGCTGTTCCAAAGTCTACT 
               
               
                   
                 ATGTTCTCTGTTAAGAAGATCATGGAAATTCACGAGTTGGTTAAA 
               
               
                   
                 TTAGTTAACAAATGGC 
               
               
                   
                 AAAACATTGCCTACAAGTACGATAAAGATTTGTTATTAATGACTC 
               
               
                   
                 ACTTTATCACTAGAAACATTACTGATAACCAAGGTAAGAATAAGA 
               
               
                   
                 CTGCCATTCACACTTACTTCTCTTCTGTTTTCTTGGGTGGTGTTG 
               
               
                   
                 ATTCCTTGGTCGATTTGATGAACAAGTCTTTTCCAGAATTAGGTA 
               
               
                   
                 TTAAGAAGACCGATTGTCGTCAATTATCTTGGATTGATACCATTA 
               
               
                   
                 TTTTTTACTCCGGTGTTGTCAACTACGACACTGATAATTTTAATA 
               
               
                   
                 AGGAGATTTTGTTAGATAGATCTGCTGGTCAAAATGGTGCCTTTA 
               
               
                   
                 AAATCAAATTGGACTACGTTAAGAAGCCTATTCCAGAATCCGTCT 
               
               
                   
                 TTGTTCAAATTTTGGAGAAGTTATACGAAGAAGATATTGGTGCTG 
               
               
                   
                 GTATGTACGCCTTGTATCCATATGGTGGTATTATGGATGAAATTT 
               
               
                   
                 CTGAATCCGCCATCCCTTTCCCTCATCGTGCTGGTATCTTATACG 
               
               
                   
                 AGTTGTGGTACATCTGTTCTTGGGAAAAGCAAGAAGATAATGAAA 
               
               
                   
                 AGCATTTGAACTGGATCCGTAACATCTATAACTTCATGACTCCAT 
               
               
                   
                 ACGTTTCCAAAAACCCTAGATTGGCTTACTTAAATTACAGAGACT 
               
               
                   
                 TAGATATTGGTATTAACGACCCTAAGAACCCAAACAATTACACTC 
               
               
                   
                 AAGCTAGAATCTGGGGTGAAAAGTACTTCGGTAAGAATTTCGACA 
               
               
                   
                 GATTAGTTAAGGTCAAGACTTTAGTTGACCCAAATAACTTCTTCA 
               
               
                   
                 GAAACGAACAATCTATCCCACCATTGCCTAGACATAGACACTAG 
               
               
                   
               
               
                 SEQ ID NO: 84 
                 MKCSTFSFWFVCKIIFFFFSFNIQTSIANPRENFLKCFSQYIPNN 
               
               
                 CBDA Synthase, N57E 
                 ATNLKLVYTQNEPLYMSVLNSTIHNLRFTSDTTPKPLVIVTPSHV 
               
               
                 variant 
                 SHIQGTILCSKKVGLQIRTRSGGHDSEGMSYISQVPFVIVDLRNM 
               
               
                 Artificial Sequence 
                 RSIKIDVHSQTAWVEAGATLGEVYYWVNEKNENLSLAAGYCPTVC 
               
               
                   
                 AGGHFGGGGYGPLMRNYGLAADNIIDAHLVNVHGKVLDRKSMGED 
               
               
                   
                 LFWALRGGGAESFGIIVAWKIRLVAVPKSTMFSVKKIMEIHELVK 
               
               
                   
                 LVNKWQNIAYKYDKDLLLMTHFITRNITDNQGKNKTAIHTYFSSV 
               
               
                   
                 FLGGVDSLVDLMNKSFPELGIKKTDCRQLSWIDTIIFYSGWNYDT 
               
               
                   
                 DNFNKEILLDRSAGQNGAFKIKLDYVKKPIPESVFVQILEKLYEE 
               
               
                   
                 DIGAGMYALYPYGGIMDEISESAIPFPHRAGILYELWYICSWEKQ 
               
               
                   
                 EDNEKHLNWIRNIYNFMTPYVSKNPRLAYLNYRDLDIGINDPKNP 
               
               
                   
                 NNYTQARIWGEKYFGKNFDRLVKVKTLVDPNNFFRNEQSIPPLPR 
               
               
                   
                 HRH* 
               
               
                   
               
               
                 SEQ ID NO: 85 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                 CBDA Synthase, L59E 
                 TTCTTCTTCTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 variant 
                 CGTGAGAACTTCTTGAAATGTTTTTCTCAATATATCCCAAATAAC 
               
               
                 Artificial Sequence 
                 GCTACTAACTTGAAGTTAGTCTATACTCAAAACAACCCAgaaTAT 
               
               
                 Codon optimized 
                 ATGTCTGTCTTAAACTCTACCATTCACAACTTACGTTTCACTTCT 
               
               
                   
                 GATACTACTCCAAAACCTTTGGTCATCGTCACCCCATCCCACGTT 
               
               
                   
                 TCTCACATCCAAGGTACCATCTTGTGTTCCAAAAAGGTTGGTTTA 
               
               
                   
                 CAAATCCGTACTAGATCCGGTGGTCATGACTCCGAAGGTATGTCT 
               
               
                   
                 TACATTTCCCAAGTCCCTTTCGTCATCGTCGACTTAAGAAATATG 
               
               
                   
                 CGTTCCATCAAGATTGATGTCCATTCCCAAACTGCTTGGGTTGAA 
               
               
                   
                 GCCGGTGCCACTTTAGGTGAAGTCTATTACTGGGTTAACGAGAAG 
               
               
                   
                 AATGAGAACTTATCTTTGGCTGCCGGTTACTGTCCAACTGTTTGT 
               
               
                   
                 GCTGGTGGTCATTTCGGTGGTGGTGGTTACGGTCCATTAATGCGT 
               
               
                   
                 AACTACGGTTTGGCTGCCGATAACATCATTGATGCCCACTTAGTC 
               
               
                   
                 AACGTTCATGGTAAGGTCTTGGACCGTAAGTCTATGGGTGAGGAT 
               
               
                   
                 TTATTCTGGGCTTTGAGAGGTGGTGGTGCTGAATCTTTCGGTATT 
               
               
                   
                 ATCGTCGCTTGGAAGATTAGATTAGTTGCTGTTCCAAAGTCTACT 
               
               
                   
                 ATGTTCTCTGTTAAGAAGATCATGGAAATTCACGAGTTGGTTAAA 
               
               
                   
                 TTAGTTAACAAATGGCAAAACATTGCCTACAAGTACGATAAAGAT 
               
               
                   
                 TTGTTATTAATGACTCACTTTATCACTAGAAACATTACTGATAAC 
               
               
                   
                 CAAGGTAAGAATAAGACTGCCATTCACACTTACTTCTCTTCTGTT 
               
               
                   
                 TTCTTGGGTGGTGTTGATTCCTTGGTCGATTTGATGAACAAGTCT 
               
               
                   
                 TTTCCAGAATTAGGTATTAAGAAGACCGATTGTCGTCAATTGATA 
               
               
                   
                 ATTTTAATAAGGAGATTTTGTTAGATAGATCTGCTGGTCAAAATG 
               
               
                   
                 GTGCCTTTAAAATCAAATTGGACTACGTTAAGAAGCCTATTCCAG 
               
               
                   
                 AATCCGTCTTTGTTCAAATTTTGGAGAAGTTATACGAAGAAGATA 
               
               
                   
                 TTGGTGCTGGTATGTACGCCTTGTATCCATATGGTGGTATTATGG 
               
               
                   
                 ATGAAATTTCTGAATCCGCCATCCCTTTCCCTCATCGTGCTGGTA 
               
               
                   
                 TCTTATACGAGTTGTGGTACATCTGTTCTTGGGAAAAGCAAGAAG 
               
               
                   
                 ATAATGAAAAGCATTTGAACTGGATCCGTAACATCTATAACTTCA 
               
               
                   
                 TGACTCCATACGTTTCCAAAAACCCTAGATTGGCTTACTTAAATT 
               
               
                   
                 ACAGAGACTTAGATATTGGTATTAACGACCCTAAGAACCCAAACA 
               
               
                   
                 ATTACACTCAAGCTAGAATCTGGGGTGAAAAGTACTTCGGTAAGA 
               
               
                   
                 ATTTCGACAGATTAGTTAAGGTCAAGACTTTAGTTGACCCAAATA 
               
               
                   
                 ACTTCTTCAGAAACGAACAATCTATCCCACCATTGCCTAGACATA 
               
               
                   
                 GACACTAG 
               
               
                   
               
               
                 SEQ ID NO: 86 
                 MKCSTFSFWFVCKIIFFFFSFNIQTSIANPRENFLKCFSQYIPNN 
               
               
                 CBDA Synthase, 
                 ATNLKLVYTQNNPEYMSVLNSTIHNLRFTSDTTPKPLVIVTPSHV 
               
               
                 L59E 
                 SHIQGTILCSKKVGLQIRTRSGGHDSEGMSYISQVPFVIVDLRNM 
               
               
                 variant 
                 RSIKIDVHSQTAWVEAGATLGEVYYWVNEKNENLSLAAGYCPTVC 
               
               
                 Artificial Sequence 
                 AGGHFGGGGYGPLMRNYGLAADNIIDAHLVNVHGKVLDRKSMGED 
               
               
                   
                 LFWALRGGGAESFGIIVAWKIRLVAWKSTMFSVKKIMEIHELVKL 
               
               
                   
                 VNKWQNIAYKYDKDLLLMTHFITRNITDNQGKNKTAIHTYFSSWL 
               
               
                   
                 GGVDSLVDLMNKSFPELGIKKTDCRQLSWIDTIIFYSGWNYDTDN 
               
               
                   
                 FNKEILLDRSAGQNGAFKIKLDYVKKPIPESVFVQILEKLYEEDI 
               
               
                   
                 GAGMYALYPYGGIMDEISESAIPFPHRAGILYELWYICSWEKQED 
               
               
                   
                 NEKHLNWIRNIYNFMTPYVSKNPRLAYLNYRDLDIGINDPKNPNN 
               
               
                   
                 YTQARIWGEKYFGKNFDRLVKVKTLVDPNNFFRNEQSIPPLPRHR 
               
               
                   
                 H* 
               
               
                   
               
               
                 SEQ ID NO: 87 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                 CBDA Synthase, 
                 TTCTTCTTCTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 M61H variant 
                 CGTGAGAACTTCTTGAAATGTTTTTCTCAATATATCCCAAATAAC 
               
               
                 Artificial Sequence 
                 GCTACTAACTTGAAGTTAGTCTATACTCAAAACAACCCATTATAT 
               
               
                 Codon optimized 
                 catTCTGTCTTAAACTCTACCATTCACAACTTACGTTTCACTTCT 
               
               
                   
                 GATACTACTCCAAAACCTTTGGTCATCGTCACCCCATCCCACGTT 
               
               
                   
                 TCTCACATCCAAGGTACCATCTTGTGTTCCAAAAAGGTTGGTTTA 
               
               
                   
                 CAAATCCGTACTAGATCCGGTGGTCATGACTCCGAAGGTATGTCT 
               
               
                   
                 TACATTTCCCAAGTCCCTTTCGTCATCGTCGACTTAAGAAATATG 
               
               
                   
                 CGTTCCATCAAGATTGATGTCCATTCCCAAACTGCTTGGGTTGAA 
               
               
                   
                 GCCGGTGCCACTTTAGGTGAAGTCTATTACTGGGTTAACGAGAAG 
               
               
                   
                 AATGAGAACTTATCTTTGGCTGCCGGTTACTGTCCAACTGTTTGT 
               
               
                   
                 GCTGGTGGTCATTTCGGTGGTGGTGGTTACGGTCCATTAATGCGT 
               
               
                   
                 AACTACGGTTTGGCTGCCGATAACATCATTGATGCCCACTTAGTC 
               
               
                   
                 AACGTTCATGGTAAGGTCTTGGACCGTAAGTCTATGGGTGAGGAT 
               
               
                   
                 TTATTCTGGGCTTTGAGAGGTGGTGGTGCTGAATCTTTCGGTATT 
               
               
                   
                 ATCGTCGCTTGGAAGATTAGATTAGTTGCTGTTCCAAAGTCTACT 
               
               
                   
                 ATGTTCTCTGTTAAGAAGATCATGGAAATTCACGAGTTGGTTAAA 
               
               
                   
                 TTAGTTAACAAATGGCAAAACATTGCCTACAAGTACGATAAAGAT 
               
               
                   
                 TTGTTATTAATGACTCACTTTATCACTAGAAACATTACTGATAAC 
               
               
                   
                 CAAGGTAAGAATAAGACTGCCATTCACACTTACTTCTCTTCTGTT 
               
               
                   
                 TTCTTGGGTGGTGTTGATTCCTTGGTCGATTTGATGAACAAGTCT 
               
               
                   
                 TTTCCAGAATTAGGTATTAAGAAGACCGATTGTCGTCAATTGATA 
               
               
                   
                 ATTTTAATAAGGAGATTTTGTTAGATAGATCTGCTGGTCAAAATG 
               
               
                   
                 GTGCCTTTAAAATCAAATTGGACTACGTTAAGAAGCCTATTCCAG 
               
               
                   
                 AATCCGTCTTTGTTCAAATTTTGGAGAAGTTATACGAAGAAGATA 
               
               
                   
                 TTGGTGCTGGTATGTACGCCTTGTATCCATATGGTGGTATTATGG 
               
               
                   
                 ATGAAATTTCTGAATCCGCCATCCCTTTCCCTCATCGTGCTGGTA 
               
               
                   
                 TCTTATACGAGTTGTGGTACATCTGTTCTTGGGAAAAGCAAGAAG 
               
               
                   
                 ATAATGAAAAGCATTTGAACTGGATCCGTAACATCTATAACTTCA 
               
               
                   
                 TGACTCCATACGTTTCCAAAAACCCTAGATTGGCTTACTTAAATT 
               
               
                   
                 ACAGAGACTTAGATATTGGTATTAACGACCCTAAGAACCCAAACA 
               
               
                   
                 ATTACACTCAAGCTAGAATCTGGGGTGAAAAGTACTTCGGTAAGA 
               
               
                   
                 ATTTCGACAGATTAGTTAAGGTCAAGACTTTAGTTGACCCAAATA 
               
               
                   
                 ACTTCTTCAGAAACGAACAATCTATCCCACCATTGCCTAGACATA 
               
               
                   
                 GACACTAG 
               
               
                   
               
               
                 SEQ ID NO: 88 
                 MKCSTFSFWFVCKIIFFFFSFNIQTSIANPRENFLKCFSQYIPNN 
               
               
                 CBDA Synthase, 
                 ATNLKLVYTQNNPLYHSVLNSTIHNLRFTSDTTPKPLVIVTPSHV 
               
               
                 M61H variant 
                 SHIQGTILCSKKVGLQIRTRSGGHDSEGMSYISQVPFVIVDLRNM 
               
               
                 Artificial Sequence 
                 RSIKIDVHSQTAWVEAGATLGEVYYWVNEKNENLSLAAGYCPTVC 
               
               
                   
                 AGGHFGGGGYGPLMRNYGLAADNIIDAHLVNVHGKVLDRKSMGED 
               
               
                   
                 LFWALRGGGAESFGIIVAWKIRLVAVPKSTMFSVKKIMEIHELVK 
               
               
                   
                 LVNKWQNIAYKYDKDLLLMTHFITRNITDNQGKNKTAIHTYFSSV 
               
               
                   
                 FLGGVDSLVDLMNKSFPELGIKKTDCRQLSWIDTIIFYSGVVNYD 
               
               
                   
                 TDNFNKEILLDRSAGQNGAFKIKLDYVKKPIPESVFVQILEKLYE 
               
               
                   
                 EDIGAGMYALYPYGGIMDEISESATPFPHRAGILYELWYICSWEK 
               
               
                   
                 QEDNEKHLNWIRNIYNFMTPYVSKNPRLAYLNYRDLDIGINDPKN 
               
               
                   
                 PNNYTQARIWGEKYFGKNFDRLVKVKTLVDPNNFFRNEQSIPPLP 
               
               
                   
                 RHRH* 
               
               
                   
               
               
                 SEQ ID NO: 89 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                 CBDA Synthase, M61S 
                 TTCTTCTTCTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 variant 
                 CGTGAGAACTTCTTGAAATGTTTTTCTCAATATATCCCAAATAAC 
               
               
                 Artificial Sequence 
                 GCTACTAACTTGAAGTTAGTCTATACTCAAAACAACCCATTATAT 
               
               
                 Codon optimized 
                 tctTCTGTCTTAAACTCTACCATTCACAACTTACGTTTCACTTCT 
               
               
                   
                 GATACTACTCCAAAACCTTTGGTCATCGTCACCCCATCCCACGTT 
               
               
                   
                 TCTCACATCCAAGGTACCATCTTGTGTTCCAAAAAGGTTGGTTTA 
               
               
                   
                 CAAATCCGTACTAGATCCGGTGGTCATGACTCCGAAGGTATGTCT 
               
               
                   
                 TACATTTCCCAAGTCCCTTTCGTCATCGTCGACTTAAGAAATATG 
               
               
                   
                 CGTTCCATCAAGATTGATGTCCATTCCCAAACTGCTTGGGTTGAA 
               
               
                   
                 GCCGGTGCCACTTTAGGTGAAGTCTATTACTGGGTTAACGAGAAG 
               
               
                   
                 AATGAGAACTTATCTTTGGCTGCCGGTTACTGTCCAACTGTTTGT 
               
               
                   
                 GCTGGTGGTCATTTCGGTGGTGGTGGTTACGGTCCATTAATGCGT 
               
               
                   
                 AACTACGGTTTGGCTGCCGATAACATCATTGATGCCCACTTAGTC 
               
               
                   
                 AACGTTCATGGTAAGGTCTTGGACCGTAAGTCTATGGGTGAGGAT 
               
               
                   
                 TTATTCTGGGCTTTGAGAGGTGGTGGTGCTGAATCTTTCGGTATT 
               
               
                   
                 ATCGTCGCTTGGAAGATTAGATTAGTTGCTGTTCCAAAGTCTACT 
               
               
                   
                 ATGTTCTCTGTTAAGAAGATCATGGAAATTCACGAGTTGGTTAAA 
               
               
                   
                 TTAGTTAACAAATGGCAAAACATTGCCTACAAGTACGATAAAGAT 
               
               
                   
                 TTGTTATTAATGACTCACTTTATCACTAGAAACATTACTGATAAC 
               
               
                   
                 CAAGGTAAGAATAAGACTGCCATTCACACTTACTTCTCTTCTGTT 
               
               
                   
                 TTCTTGGGTGGTGTTGATTCCTTGGTCGATTTGATGAACAAGTCT 
               
               
                   
                 TTTCCAGAATTAGGTATTAAGAAGACCGATTGTCGTCAATTATCT 
               
               
                   
                 TGGATTGATACCATTATTTTTTACTCCGGTGTTGTCAACTACGAC 
               
               
                   
                 ACTGATAATTTTAATAAGGAGATTTTGTTAGATAGATCTGCTGGT 
               
               
                   
                 CAAAATGGTGCCTTTAAAATCAAATTGGACTACGTTAAGAAGCCT 
               
               
                   
                 ATTCCAGAATCCGTCTTTGTTCAAATTTTGGAGAAGTTATACGAA 
               
               
                   
                 GAAGATATTGGTGCTGGTATGTACGCCTTGTATCCATATGGTGGT 
               
               
                   
                 ATTATGGATGAAATTTCTGAATCCGCCATCCCTTTCCCTCATCGT 
               
               
                   
                 GCTGGTATCTTATACGAGTTGTGGTACATCTGTTCTTGGGAAAAG 
               
               
                   
                 CAAGAAGATAATGAAAAGCATTTGAACTGGATCCGTAACATCTAT 
               
               
                   
                 AACTTCATGACTCCATACGTTTCCAAAAACCCTAGATTGGCTTAC 
               
               
                   
                 TTAAATTACAGAGACTTAGATATTGGTATTAACGACCCTAAGAAC 
               
               
                   
                 CCAAACAATTACACTCAAGCTAGAATCTGGGGTGAAAAGTACTTC 
               
               
                   
                 GGTAAGAATTTCGACAGATTAGTTAAGGTCAAGACTTTAGTTGAC 
               
               
                   
                 CCAAATAACTTCTTCAGAAACGAACAATCTATCCCACCATTGCCT 
               
               
                   
                 AGACATAGACACTAG 
               
               
                   
               
               
                 SEQ ID NO: 90 
                 MKCSTFSFWFVCKIIFFFFSFNIQTSIANPRENFLKCFSQYIPNN 
               
               
                 CBDA Synthase, M61S 
                 ATNLKLVYTQNNPLYSSVLNSTIHNLRFTSDTTPKPLVIVTPSHV 
               
               
                 variant 
                 SHIQGTILCSKKVGLQIRTRSGGHDSEGMSYISQVPFVIVDLRNM 
               
               
                 Artificial Sequence 
                 RSIKIDVHSQTAWVEAGATLGEVYYWVNEKNENLSLAAGYCPTVC 
               
               
                   
                 AGGHFGGGGYGPLMRNYGLAADNIIDAHLVNVHGKVLDRKSMGED 
               
               
                   
                 LFWALRGGGAESFGIIVAWKIRLVAWKSTMFSVKKIMEIHELVKL 
               
               
                   
                 VNKWQNIAYKYDKDLLLMTHFITRNITDNQGKNKTAIHTYFSSVF 
               
               
                   
                 LGGVDSLVDLMNKSFPELGIKKTDCRQLSWIDTHFYSGWNYDTDN 
               
               
                   
                 FNKEILLDRSAGQNGAFKIKLDYVKKPIPESVFVQILEKLYEEDI 
               
               
                   
                 GAGMYALYPYGGIMDEISESAIPFPHRAGILYELWYICSWEKQED 
               
               
                   
                 NEKHLNWIRNIYNFMTPYVSKNPRLAYLNYRDLDIGINDPKNPNN 
               
               
                   
                 YTQARIWGEKYFGKNFDRLVKVKTLVDPNNFFRNEQSIPPLPRHR 
               
               
                   
                 H* 
               
               
                   
               
               
                 SEQ ID NO: 91 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                 CBDA Synthase, 
                 TTCTTCTTCTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 M61W variant 
                 CGTGAGAACTTCTTGAAATGTTTTTCTCAATATATCCCAAATAAC 
               
               
                 Artificial Sequence 
                 GCTACTAACTTGAAGTTAGTCTATACTCAAAACAACCCATTATAT 
               
               
                 Codon optimized 
                 tggTCTGTCTTAAACTCTACCATTCACAACTTACGTTTCACTTCT 
               
               
                   
                 GATACTACTCCAAAACCTTTGGTCATCGTCACCCCATCCCACGTT 
               
               
                   
                 TCTCACATCCAAGGTACCATCTTGTGTTCCAAAAAGGTTGGTTTA 
               
               
                   
                 CAAATCCGTACTAGATCCGGTGGTCATGACTCCGAAGGTATGTCT 
               
               
                   
                 TACATTTCCCAAGTCCCTTTCGTCATCGTCGACTTAAGAAATATG 
               
               
                   
                 CGTTCCATCAAGATTGATGTCCATTCCCAAACTGCTTGGGTTGAA 
               
               
                   
                 GCCGGTGCCACTTTAGGTGAAGTCTATTACTGGGTTAACGAGAAG 
               
               
                   
                 AATGAGAACTTATCTTTGGCTGCCGGTTACTGTCCAACTGTTTGT 
               
               
                   
                 GCTGGTGGTCATTTCGGTGGTGGTGGTTACGGTCCATTAATGCGT 
               
               
                   
                 AACTACGGTTTGGCTGCCGATAACATCATTGATGCCCACTTAGTC 
               
               
                   
                 AACGTTCATGGTAAGGTCTTGGACCGTAAGTCTATGGGTGAGGAT 
               
               
                   
                 TTATTCTGGGCTTTGAGAGGTGGTGGTGCTGAATCTTTCGGTATT 
               
               
                   
                 ATCGTCGCTTGGAAGATTAGATTAGTTGCTGTTCCAAAGTCTACT 
               
               
                   
                 ATGTTCTCTGTTAAGAAGATCATGGAAATTCACGAGTTGGTTAAA 
               
               
                   
                 TTAGTTAACAAATGGCAAAACATTGCCTACAAGTACGATAAAGAT 
               
               
                   
                 TTGTTATTAATGACTCACTTTATCACTAGAAACATTACTGATAAC 
               
               
                   
                 CAAGGTAAGAATAAGACTGCCATTCACACTTACTTCTCTTCTGTT 
               
               
                   
                 TTCTTGGGTGGTGTTGATTCCTTGGTCGATTTGATGAACAAGTCT 
               
               
                   
                 TTTCCAGAATTAGGTATTAAGAAGACCGATTGTCGTCAATTGATA 
               
               
                   
                 ATTTTAATAAGGAGATTTTGTTAGATAGATCTGCTGGTCAAAATG 
               
               
                   
                 GTGCCTTTAAAATCAAATTGGACTACGTTAAGAAGCCTATTCCAG 
               
               
                   
                 AATCCGTCTTTGTTCAAATTTTGGAGAAGTTATACGAAGAAGATA 
               
               
                   
                 TTGGTGCTGGTATGTACGCCTTGTATCCATATGGTGGTATTATGG 
               
               
                   
                 ATGAAATTTCTGAATCCGCCATCCCTTTCCCTCATCGTGCTGGTA 
               
               
                   
                 TCTTATACGAGTTGTGGTACATCTGTTCTTGGGAAAAGCAAGAAG 
               
               
                   
                 ATAATGAAAAGCATTTGAACTGGATCCGTAACATCTATAACTTCA 
               
               
                   
                 TGACTCCATACGTTTCCAAAAACCCTAGATTGGCTTACTTAAATT 
               
               
                   
                 ACAGAGACTTAGATATTGGTATTAACGACCCTAAGAACCCAAACA 
               
               
                   
                 ATTACACTCAAGCTAGAATCTGGGGTGAAAAGTACTTCGGTAAGA 
               
               
                   
                 ATTTCGACAGATTAGTTAAGGTCAAGACTTTAGTTGACCCAAATA 
               
               
                   
                 ACTTCTTCAGAAACGAACAATCTATCCCACCATTGCCTAGACATA 
               
               
                   
                 GACACTAG 
               
               
                   
               
               
                 SEQ ID NO: 92 
                 MKCSTFSFWFVCKIIFFFFSFNIQTSIANPRENFLKCFSQYIPNN 
               
               
                 CBDA Synthase, 
                 ATNLKLVYTQNNPLYWSVLNSTIHNLRFTSDTTPKPLVIVTPSHV 
               
               
                 M61W variant 
                 SHIQGTILCSKKVGLQIRTRSGGHDSEGMSYISQVPFVIVDLRNM 
               
               
                 Artificial Sequence 
                 RSIKIDVHSQTAWVEAGATLGEVYYWVNEKNENLSLAAGYCPTVC 
               
               
                   
                 AGGHFGGGGYGPLMRNYGLAADNIIDAHLVNVHGKVLDRKSMGED 
               
               
                   
                 LFWALRGGGAESFGIIVAWKIRLVAVPKSTMFSVKKIMEIHELVK 
               
               
                   
                 LVNKWQNIAYKYDKDLLLMTHFITRNITDNQGKNKTAIHTYFSSV 
               
               
                   
                 FLGGVDSLVDLMNKSFPELGIKKTDCRQLSWIDTIIFYSGVVNYD 
               
               
                   
                 TDNFNKEILLDRSAGQNGAFKIKLDYVKKPIPESVFVQILEKLYE 
               
               
                   
                 EDIGAGMYALYPYGGIMDEISESAIPFPHRAGILYELWYICSWEK 
               
               
                   
                 QEDNEKHLNWIRNIYNFMTPYVSKNPRLAYLNYRDLDIGINDPKN 
               
               
                   
                 PNNYTQARIWGEKYFGKNFDRLVKVKTLVDPNNFFRNEQSIPPLP 
               
               
                   
                 RHRH* 
               
               
                   
               
               
                 SEQ ID NO: 93 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                 CBDA Synthase, S62N 
                 TTCTTCTTCTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 variant 
                 CGTGAGAACTTCTTGAAATGTTTTTCTCAATATATCCCAAATAAC 
               
               
                 Artificial Sequence 
                 GCTACTAACTTGAAGTTAGTCTATACTCAAAACAACCCATTATAT 
               
               
                 Codon optimized 
                 ATGaatGTCTTAAACTCTACCATTCACAACTTACGTTTCACTTCT 
               
               
                   
                 GATACTACTCCAAAACCTTTGGTCATCGTCACCCCATCCCACGTT 
               
               
                   
                 TCTCACATCCAAGGTACCATCTTGTGTTCCAAAAAGGTTGGTTTA 
               
               
                   
                 CAAATCCGTACTAGATCCGGTGGTCATGACTCCGAAGGTATGTCT 
               
               
                   
                 TACATTTCCCAAGTCCCTTTCGTCATCGTCGACTTAAGAAATATG 
               
               
                   
                 CGTTCCATCAAGATTGATGTCCATTCCCAAACTGCTTGGGTTGAA 
               
               
                   
                 GCCGGTGCCACTTTAGGTGAAGTCTATTACTGGGTTAACGAGAAG 
               
               
                   
                 AATGAGAACTTATCTTTGGCTGCCGGTTACTGTCCAACTGTTTGT 
               
               
                   
                 GCTGGTGGTCATTTCGGTGGTGGTGGTTACGGTCCATTAATGCGT 
               
               
                   
                 AACTACGGTTTGGCTGCCGATAACATCATTGATGCCCACTTAGTC 
               
               
                   
                 AACGTTCATGGTAAGGTCTTGGACCGTAAGTCTATGGGTGAGGAT 
               
               
                   
                 TTATTCTGGGCTTTGAGAGGTGGTGGTGCTGAATCTTTCGGTATT 
               
               
                   
                 ATCGTCGCTTGGAAGATTAGATTAGTTGCTGTTCCAAAGTCTACT 
               
               
                   
                 ATGTTCTCTGTTAAGAAGATCATGGAAATTCACGAGTTGGTTAAA 
               
               
                   
                 TTAGTTAACAAATGGCAAAACATTGCCTACAAGTACGATAAAGAT 
               
               
                   
                 TTGTTATTAATGACTCACTTTATCACTAGAAACATTACTGATAAC 
               
               
                   
                 CAAGGTAAGAATAAGACTGCCATTCACACTTACTTCTCTTCTGTT 
               
               
                   
                 TTCTTGGGTGGTGTTGATTCCTTGGTCGATTTGATGAACAAGTCT 
               
               
                   
                 TTTCCAGAATTAGGTATTAAGAAGACCGATTGTCGTCAATTATCT 
               
               
                   
                 TGGATTGATACCATTATTTTTTACTCCGGTGTTGTCAACTACGAC 
               
               
                   
                 ACTGATAATTTTAATAAGGAGATTTTGTTAGATAGATCTGCTGGT 
               
               
                   
                 CAAAATGGTGCCTTTAAAATCAAATTGGACTACGTTAAGAAGCCT 
               
               
                   
                 ATTCCAGAATCCGTCTTTGTTCAAATTTTGGAGAAGTTATACGAA 
               
               
                   
                 GAAGATATTGGTGCTGGTATGTACGCCTTGTATCCATATGGTGGT 
               
               
                   
                 ATTATGGATGAAATTTCTGAATCCGCCATCCCTTTCCCTCATCGT 
               
               
                   
                 GCTGGTATCTTATACGAGTTGTGGTACATCTGTTCTTGGGAAAAG 
               
               
                   
                 CAAGAAGATAATGAAAAGCATTTGAACTGGATCCGTAACATCTAT 
               
               
                   
                 AACTTCATGACTCCATACGTTTCCAAAAACCCTAGATTGGCTTAC 
               
               
                   
                 TTAAATTACAGAGACTTAGATATTGGTATTAACGACCCTAAGAAC 
               
               
                   
                 CCAAACAATTACACTCAAGCTAGAATCTGGGGTGAAAAGTACTTC 
               
               
                   
                 GGTAAGAATTTCGACAGATTAGTTAAGGTCAAGACTTTAGTTGAC 
               
               
                   
                 CCAAATAACTTCTTCAGAAACGAACAATCTATCCCACCATTGCCT 
               
               
                   
                 AGACATAGACACTAG 
               
               
                   
               
               
                 SEQ ID NO: 94 
                 MKCSTFSFWFVCKIIFFFFSFNIQTSIANPRENFLKCFSQYIPNN 
               
               
                 CBDA Synthase, S62N 
                 ATNLKLVYTQNNPLYMNVLNSTIHNLRFTSDTTPKPLVIVTPSHV 
               
               
                 variant 
                 SHIQGTILCSKKVGLQIRTRSGGHDSEGMSYISQVPFVIVDLRNM 
               
               
                 Artificial Sequence 
                 RSIKIDVHSQTAWVEAGATLGEVYYWVNEKNENLSLAAGYCPTVC 
               
               
                   
                 AGGHFGGGGYGPLMRNYGLAADNIIDAHLVNVHGKVLDRKSMGED 
               
               
                   
                 LFWALRGGGAESFGIIVAWKIRLVAVPKSTMFSVKKIMEIHELVK 
               
               
                   
                 LVNKWQNIAYKYDKDLLLMTHFITRNITDNQGKNKTAIHTYFSSV 
               
               
                   
                 FLGGVDSLVDLMNKSFPELGIKKTDCRQLSWIDTIIFYSGWNYDT 
               
               
                   
                 DNFNKEILLDRSAGQNGAFKKLDYVKKPIPESVFVQILEKLYEED 
               
               
                   
                 IGAGMYALYPYGGIMDEISESAIPFPHRAGILYELWYICSWEKQE 
               
               
                   
                 DNEKHLNWIRNIYNFMTPYVSKNPRLAYLNYRDLDIGINDPKNPN 
               
               
                   
                 NYTQARIWGEKYFGKNFDRLVKVKTLVDPNNFFRNEQSIPPLPRH 
               
               
                   
                 RH* 
               
               
                   
               
               
                 SEQ ID NO: 95 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                   
                 TTCTTCTTCTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                   
                 CGTGAGAACTTCTTG 
               
               
                 CBDA Synthase, 
                 AAATGTTTTTCTCAATATATCCCAAATAACGCTACTAACTTGAAG 
               
               
                 S62Q 
                 TTAGTCTATACTCAAAACAACCCATTATATATGcaaGTCTTAAAC 
               
               
                 variant 
                 TCTACCATTCACAACTTACGTTTCACTTCTGATACTACTCCAAAA 
               
               
                 Artificial Sequence 
                 CCTTTGGTCATCGTCACCCCATCCCACGTTTCTCACATCCAAGGT 
               
               
                 Codon optimized 
                 ACCATCTTGTGTTCCAAAAAGGTTGGTTTACAAATCCGTACTAGA 
               
               
                   
                 TCCGGTGGTCATGACTCCGAAGGTATGTCTTACATTTCCCAAGTC 
               
               
                   
                 CCTTTCGTCATCGTCGACTTAAGAAATATGCGTTCCATCAAGATT 
               
               
                   
                 GATGTCCATTCCCAAACTGCTTGGGTTGAAGCCGGTGCCACTTTA 
               
               
                   
                 GGTGAAGTCTATTACTGGGTTAACGAGAAGAATGAGAACTTATCT 
               
               
                   
                 TTGGCTGCCGGTTACTGTCCAACTGTTTGTGCTGGTGGTCATTTC 
               
               
                   
                 GGTGGTGGTGGTTACGGTCCATTAATGCGTAACTACGGTTTGGCT 
               
               
                   
                 GCCGATAACATCATTGATGCCCACTTAGTCAACGTTCATGGTAAG 
               
               
                   
                 GTCTTGGACCGTAAGTCTATGGGTGAGGATTTATTCTGGGCTTTG 
               
               
                   
                 AGAGGTGGTGGTGCTGAATCTTTCGGTATTATCGTCGCTTGGAAG 
               
               
                   
                 ATTAGATTAGTTGCTGTTCCAAAGTCTACTATGTTCTCTGTTAAG 
               
               
                   
                 AAGATCATGGAAATTCACGAGTTGGTTAAATTAGTTAACAAATGG 
               
               
                   
                 CAAAACATTGCCTACAAGTACGATAAAGATTTGTTATTAATGACT 
               
               
                   
                 CACTTTATCACTAGAAACATTACTGATAACCAAGGTAAGAATAAG 
               
               
                   
                 ACTGCCATTCACACTTACTTCTCTTCTGTTTTCTTGGGTGGTGTT 
               
               
                   
                 GATTCCTTGGTCGATTTGATGAACAAGTCTTTTCCAGAATTAGGT 
               
               
                   
                 ATTAAGAAGACCGATTGTCGTCAATTATCTTGGATTGATACCATT 
               
               
                   
                 ATTTTTTACTCCGGTGTTGTCAACTACGACACTGATAATTTTAAT 
               
               
                   
                 AAGGAGATTTTGTTAGATAGATCTGCTGGTCAAAATGGTGCCTTT 
               
               
                   
                 AAAATCAAATTGGACTACGTTAAGAAGCCTATTCCAGAATCCGTC 
               
               
                   
                 TTTGTTCAAATTTTGGAGAAGTTATACGAAGAAGATATTGGTGCT 
               
               
                   
                 GGTATGTACGCCTTGTATCCATATGGTGGTATTATGGATGAAATT 
               
               
                   
                 TCTGAATCCGCCATCCCTTTCCCTCATCGTGCTGGTATCTTATAC 
               
               
                   
                 GAGTTGTGGTACATCTGTTCTTGGGAAAAGCAAGAAGATAATGAA 
               
               
                   
                 AAGCATTTGAACTGGATCCGTAACATCTATAACTTCATGACTCCA 
               
               
                   
                 TACGTTTCCAAAAACCCTAGATTGGCTTACTTAAATTACAGAGAC 
               
               
                   
                 TTAGATATTGGTATTAACGACCCTAAGAACCCAAACAATTACACT 
               
               
                   
                 CAAGCTAGAATCTGGGGTGAAAAGTACTTCGGTAAGAATTTCGAC 
               
               
                   
                 AGATTAGTTAAGGTCAAGACTTTAGTTGACCCAAATAACTTCTTC 
               
               
                   
                 AGAAACGAACAATCTATCCCACCATTGCCTAGACATAGACACTAG 
               
               
                   
               
               
                 SEQ ID NO: 96 
                 MKCSTFSFWFVCKIIFFFFSFNIQTSIANPRENFLKCFSQYIPNN 
               
               
                 CBDA Synthase, 
                 ATNLKLVYTQNNPLYMQVLNSTIHNLRFTSDTTPKPLVIVTPSHV 
               
               
                 S62Q 
                 SHIQGTILCSKKVGLQIRTRSGGHDSEGMSYISQVPFVIVDLRNM 
               
               
                 variant 
                 RSIKIDVHSQTAWVEAGATLGEVYYWVNEKNENLSLAAGYCPTVC 
               
               
                 Artificial Sequence 
                 AGGHFGGGGYGPLMRNYGLAADNIIDAHLVNVHGKVLDRKSMGED 
               
               
                   
                 LFWALRGGGAESFGIIVAWKIRLVAVPKSTMFSVKKIMEIHELVK 
               
               
                   
                 LVNKWQNIAYKYDKDLLLMTHFITRNITDNQGKNKTAIHTYFSSV 
               
               
                   
                 FLGGVDSLVDLMNKSFPELGIKKTDCRQLSWIDTIIFYSGWNYDT 
               
               
                   
                 DNFNKEILLDRSAGQNGAFKIKLDYVKKPIPESVFVQILEKLYEE 
               
               
                   
                 DIGAGMYALYPYGGIMDEISESAIPFPHRAGILYELWYICSWEKQ 
               
               
                   
                 EDNEKHLNWIRNIYNFMTPYVSKNPRLAYLNYRDLDIGINDPKNP 
               
               
                   
                 NNYTQARIWGEKYFGKNFDRLVKVKTLVDPNNFFRNEQSIPPLPR 
               
               
                   
                 HRH* 
               
               
                   
               
               
                 SEQ ID NO: 97 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                 CBDA Synthase, 
                 TTCTTCTTCTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 V63M variant 
                 CGTGAGAACTTCTTGAAATGTTTTTCTCAATATATCCCAAATAAC 
               
               
                 Artificial Sequence 
                 GCTACTAACTTGAAGTTAGTCTATACTCAAAACAACCCATTATAT 
               
               
                 Codon optimized 
                 ATGTCTatgTTAAACTCTACCATTCACAACTTACGTTTCACTTCT 
               
               
                   
                 GATACTACTCCAAAACCTTTGGTCATCGTCACCCCATCCCACGTT 
               
               
                   
                 TCTCACATCCAAGGTACCATCTTGTGTTCCAAAAAGGTTGGTTTA 
               
               
                   
                 CAAATCCGTACTAGATCCGGTGGTCATGACTCCGAAGGTATGTCT 
               
               
                   
                 TACATTTCCCAAGTCCCTTTCGTCATCGTCGACTTAAGAAATATG 
               
               
                   
                 CGTTCCATCAAGATTGATGTCCATTCCCAAACTGCTTGGGTTGAA 
               
               
                   
                 GCCGGTGCCACTTTAGGTGAAGTCTATTACTGGGTTAACGAGAAG 
               
               
                   
                 AATGAGAACTTATCTTTGGCTGCCGGTTACTGTCCAACTGTTTGT 
               
               
                   
                 GCTGGTGGTCATTTCGGTGGTGGTGGTTACGGTCCATTAATGCGT 
               
               
                   
                 AACTACGGTTTGGCTGCCGATAACATCATTGATGCCCACTTAGTC 
               
               
                   
                 AACGTTCATGGTAAGGTCTTGGACCGTAAGTCTATGGGTGAGGAT 
               
               
                   
                 TTATTCTGGGCTTTGAGAGGTGGTGGTGCTGAATCTTTCGGTATT 
               
               
                   
                 ATCGTCGCTTGGAAGATTAGATTAGTTGCTGTTCCAAAGTCTACT 
               
               
                   
                 ATGTTCTCTGTTAAGAAGATCATGGAAATTCACGAGTTGGTTAAA 
               
               
                   
                 TTAGTTAACAAATGGCAAAACATTGCCTACAAGTACGATAAAGAT 
               
               
                   
                 TTGTTATTAATGACTCACTTTATCACTAGAAACATTACTGATAAC 
               
               
                   
                 CAAGGTAAGAATAAGACTGCCATTCACACTTACTTCTCTTCTGTT 
               
               
                   
                 TTCTTGGGTGGTGTTGATTCCTTGGTCGATTTGATGAACAAGTCT 
               
               
                   
                 TTTCCAGAATTAGGTATTAAGAAGACCGATTGTCGTCAATTGATA 
               
               
                   
                 ATTTTAATAAGGAGATTTTGTTAGATAGATCTGCTGGTCAAAATG 
               
               
                   
                 GTGCCTTTAAAATCAAATTGGACTACGTTAAGAAGCCTATTCCAG 
               
               
                   
                 AATCCGTCTTTGTTCAAATTTTGGAGAAGTTATACGAAGAAGATA 
               
               
                   
                 TTGGTGCTGGTATGTACGCCTTGTATCCATATGGTGGTATTATGG 
               
               
                   
                 ATGAAATTTCTGAATCCGCCATCCCTTTCCCTCATCGTGCTGGTA 
               
               
                   
                 TCTTATACGAGTTGTGGTACATCTGTTCTTGGGAAAAGCAAGAAG 
               
               
                   
                 ATAATGAAAAGCATTTGAACTGGATCCGTAACATCTATAACTTCA 
               
               
                   
                 TGACTCCATACGTTTCCAAAAACCCTAGATTGGCTTACTTAAATT 
               
               
                   
                 ACAGAGACTTAGATATTGGTATTAACGACCCTAAGAACCCAAACA 
               
               
                   
                 ATTACACTCAAGCTAGAATCTGGGGTGAAAAGTACTTCGGTAAGA 
               
               
                   
                 ATTTCGACAGATTAGTTAAGGTCAAGACTTTAGTTGACCCAAATA 
               
               
                   
                 ACTTCTTCAGAAACGAACAATCTATCCCACCATTGCCTAGACATA 
               
               
                   
                 GACACTAG 
               
               
                   
               
               
                 SEQ ID NO: 98 
                 MKCSTFSFWFVCKIIFFFFSFNIQTSIANPRENFLKCFSQYIPNN 
               
               
                 CBDA Synthase, 
                 ATNLKLVYTQNNPLYMSMLNSTIHNLRFTSDTTPKPLVIVTPSHV 
               
               
                 V63M variant 
                 SHIQGTILCSKKVGLQIRTRSGGHDSEGMSYISQVPFVIVDLRNM 
               
               
                 Artificial Sequence 
                 RSIKIDVHSQTAWVEAGATLGEVYYWVNEKNENLSLAAGYCPTVC 
               
               
                   
                 AGGHFGGGGYGPLMRNYGLAADNIIDAHLVNVHGKVLDRKSMGED 
               
               
                   
                 LFWALRGGGAESFGIIVAWKIRLVAVPKSTMFSVKKIMEIHELVK 
               
               
                   
                 LVNKWQNIAYKYDKDLLLMTHFITRNITDNQGKNKTAIHTYFSSW 
               
               
                   
                 LGGVDSLVDLMNKSFPELGIKKTDCRQLSWIDTIIFYSGVVNYDT 
               
               
                   
                 DNFNKEILLDRSAGQNGAFKKLDYVKKPIPESVFVQILEKLYEED 
               
               
                   
                 IGAGMYALYPYGGIMDEISESAIPFPHRAGILYELWYICSWEKQE 
               
               
                   
                 DNEKHLNWIRNIYNFMTPYVSKNPRLAYLNYRDLDIGINDPKNPN 
               
               
                   
                 NYTQARIWGEKYFGKNFDRLVKVKTLVDPNNFFRNEQSIPPLPRH 
               
               
                   
                 RH* 
               
               
                   
               
               
                 SEQ ID NO: 99 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                 CBDA Synthase, S66D 
                 TTCTTCTTCTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 variant 
                 CGTGAGAACTTCTTGAAATGTTTTTCTCAATATATCCCAAATAAC 
               
               
                 Artificial Sequence 
                 GCTACTAACTTGAAGTTAGTCTATACTCAAAACAACCCATTATAT 
               
               
                 Codon optimized 
                 ATGTCTGTCTTAAACgatACCATTCACAACTTACGTTTCACTTCT 
               
               
                   
                 GATACTACTCCAAAACCTTTGGTCATCGTCACCCCATCCCACGTT 
               
               
                   
                 TCTCACATCCAAGGTACCATCTTGTGTTCCAAAAAGGTTGGTTTA 
               
               
                   
                 CAAATCCGTACTAGATCCGGTGGTCATGACTCCGAAGGTATGTCT 
               
               
                   
                 TACATTTCCCAAGTCCCTTTCGTCATCGTCGACTTAAGAAATATG 
               
               
                   
                 CGTTCCATCAAGATTGATGTCCATTCCCAAACTGCTTGGGTTGAA 
               
               
                   
                 GCCGGTGCCACTTTAGGTGAAGTCTATTACTGGGTTAACGAGAAG 
               
               
                   
                 AATGAGAACTTATCTTTGGCTGCCGGTTACTGTCCAACTGTTTGT 
               
               
                   
                 GCTGGTGGTCATTTCGGTGGTGGTGGTTACGGTCCATTAATGCGT 
               
               
                   
                 AACTACGGTTTGGCTGCCGATAACATCATTGATGCCCACTTAGTC 
               
               
                   
                 AACGTTCATGGTAAGGTCTTGGACCGTAAGTCTATGGGTGAGGAT 
               
               
                   
                 TTATTCTGGGCTTTGAGAGGTGGTGGTGCTGAATCTTTCGGTATT 
               
               
                   
                 ATCGTCGCTTGGAAGATTAGATTAGTTGCTGTTCCAAAGTCTACT 
               
               
                   
                 ATGTTCTCTGTTAAGAAGATCATGGAAATTCACGAGTTGGTTAAA 
               
               
                   
                 TTAGTTAACAAATGGCAAAACATTGCCTACAAGTACGATAAAGAT 
               
               
                   
                 TTGTTATTAATGACTCACTTTATCACTAGAAACATTACTGATAAC 
               
               
                   
                 CAAGGTAAGAATAAGACTGCCATTCACACTTACTTCTCTTCTGTT 
               
               
                   
                 TTCTTGGGTGGTGTTGATTCCTTGGTCGATTTGATGAACAAGTCT 
               
               
                   
                 TTTCCAGAATTAGGTATTAAGAAGACCGATTGTCGTCAATTGATA 
               
               
                   
                 ATTTTAATAAGGAGATTTTGTTAGATAGATCTGCTGGTCAAAATG 
               
               
                   
                 GTGCCTTTAAAATCAAATTGGACTACGTTAAGAAGCCTATTCCAG 
               
               
                   
                 AATCCGTCTTTGTTCAAATTTTGGAGAAGTTATACGAAGAAGATA 
               
               
                   
                 TTGGTGCTGGTATGTACGCCTTGTATCCATATGGTGGTATTATGG 
               
               
                   
                 ATGAAATTTCTGAATCCGCCATCCCTTTCCCTCATCGTGCTGGTA 
               
               
                   
                 TCTTATACGAGTTGTGGTACATCTGTTCTTGGGAAAAGCAAGAAG 
               
               
                   
                 ATAATGAAAAGCATTTGAACTGGATCCGTAACATCTATAACTTCA 
               
               
                   
                 TGACTCCATACGTTTCCAAAAACCCTAGATTGGCTTACTTAAATT 
               
               
                   
                 ACAGAGACTTAGATATTGGTATTAACGACCCTAAGAACCCAAACA 
               
               
                   
                 ATTACACTCAAGCTAGAATCTGGGGTGAAAAGTACTTCGGTAAGA 
               
               
                   
                 ATTTCGACAGATTAGTTAAGGTCAAGACTTTAGTTGACCCAAATA 
               
               
                   
                 ACTTCTTCAGAAACGAACAATCTATCCCACCATTGCCTAGACATA 
               
               
                   
                 GACACTAG 
               
               
                   
               
               
                 SEQ ID NO: 100 
                 MKCSTFSFWFVCKIIFFFFSFNIQTSIANPRENFLKCFSQYIPNN 
               
               
                 CBDA Synthase, S66D 
                 ATNLKLVYTQNNPLYMSVLNDTIHNLRFTSDTTPKPLVIVTPSHV 
               
               
                 variant 
                 SHIQGTILCSKKVGLQIRTRSGGHDSEGMSYISQVPFVIVDLRNM 
               
               
                 Artificial Sequence 
                 RSIKIDVHSQTAWVEAGATLGEVYYWVNEKNENLSLAAGYCPTVC 
               
               
                   
                 AGGHFGGGGYGPLMRNYGLAADNIIDAHLVNVHGKVLDRKSMGED 
               
               
                   
                 LFWALRGGGAESFGIIVAWKIRLVAVPKSTMFSVKKIMEIHELVK 
               
               
                   
                 LVNKWQNIAYKYDKDLLLMTHFITRNITDNQGKNKTAIHTYFSSV 
               
               
                   
                 FLGG 
               
               
                   
                 VDSLVDLMNKSFPELGIKKTDCRQLSWIDTIIFYSGWNYDTDNFN 
               
               
                   
                 KEILLDRSAGQNGAFKIKLDYVKKPIPESVFVQILEKLYEEDIGA 
               
               
                   
                 GMYALYPYGGIMDEISESAIPFPHRAGILYELWYICSWEKQEDNE 
               
               
                   
                 KHLNWIRNIYNFMTPYVSKNPRLAYLNYRDLDIGINDPKNPNNYT 
               
               
                   
                 QARIWGEKYFGKNFDRLVKVKTLVDPNNFFRNEQSIPPLPRHRH* 
               
               
                   
               
               
                 SEQ ID NO: 101 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                 CBDA Synthase, L71A 
                 TTCTTCTTCTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 variant 
                 CGTGAGAACTTCTTGAAATGTTTTTCTCAATATATCCCAAATAAC 
               
               
                 Artificial Sequence 
                 GCTACTAACTTGAAGTTAGTCTATACTCAAAACAACCCATTATAT 
               
               
                 Codon optimized 
                 ATGTCTGTCTTAAACTCTACCATTCACAACgctCGTTTCACTTCT 
               
               
                   
                 GATACTACTCCAAAACCTTTGGTCATCGTCACCCCATCCCACGTT 
               
               
                   
                 TCTCACATCCAAGGTACCATCTTGTGTTCCAAAAAGGTTGGTTTA 
               
               
                   
                 CAAATCCGTACTAGATCCGGTGGTCATGACTCCGAAGGTATGTCT 
               
               
                   
                 TACATTTCCCAAGTCCCTTTCGTCATCGTCGACTTAAGAAATATG 
               
               
                   
                 CGTTCCATCAAGATTGATGTCCATTCCCAAACTGCTTGGGTTGAA 
               
               
                   
                 GCCGGTGCCACTTTAGGTGAAGTCTATTACTGGGTTAACGAGAAG 
               
               
                   
                 AATGAGAACTTATCTTTGGCTGCCGGTTACTGTCCAACTGTTTGT 
               
               
                   
                 GCTGGTGGTCATTTCGGTGGTGGTGGTTACGGTCCATTAATGCGT 
               
               
                   
                 AACTACGGTTTGGCTGCCGATAACATCATTGATGCCCACTTAGTC 
               
               
                   
                 AACGTTCATGGTAAGGTCTTGGACCGTAAGTCTATGGGTGAGGAT 
               
               
                   
                 TTATTCTGGGCTTTGAGAGGTGGTGGTGCTGAATCTTTCGGTATT 
               
               
                   
                 ATCGTCGCTTGGAAGATTAGATTAGTTGCTGTTCCAAAGTCTACT 
               
               
                   
                 ATGTTCTCTGTTAAGAAGATCATGGAAATTCACGAGTTGGTTAAA 
               
               
                   
                 TTAGTTAACAAATGGCAAAACATTGCCTACAAGTACGATAAAGAT 
               
               
                   
                 TTGTTATTAATGACTCACTTTATCACTAGAAACATTACTGATAAC 
               
               
                   
                 CAAGGTAAGAATAAGACTGCCATTCACACTTACTTCTCTTCTGTT 
               
               
                   
                 TTCTTGGGTGGTGTTGATTCCTTGGTCGATTTGATGAACAAGTCT 
               
               
                   
                 TTTCCAGAATTAGGTATTAAGAAGACCGATTGTCGTCAATTGATA 
               
               
                   
                 ATTTTAATAAGGAGATTTTGTTAGATAGATCTGCTGGTCAAAATG 
               
               
                   
                 GTGCCTTTAAAATCAAATTGGACTACGTTAAGAAGCCTATTCCAG 
               
               
                   
                 AATCCGTCTTTGTTCAAATTTTGGAGAAGTTATACGAAGAAGATA 
               
               
                   
                 TTGGTGCTGGTATGTACGCCTTGTATCCATATGGTGGTATTATGG 
               
               
                   
                 ATGAAATTTCTGAATCCGCCATCCCTTTCCCTCATCGTGCTGGTA 
               
               
                   
                 TCTTATACGAGTTGTGGTACATCTGTTCTTGGGAAAAGCAAGAAG 
               
               
                   
                 ATAATGAAAAGCATTTGAACTGGATCCGTAACATCTATAACTTCA 
               
               
                   
                 TGACTCCATACGTTTCCAAAAACCCTAGATTGGCTTACTTAAATT 
               
               
                   
                 ACAGAGACTTAGATATTGGTATTAACGACCCTAAGAACCCAAACA 
               
               
                   
                 ATTACACTCAAGCTAGAATCTGGGGTGAAAAGTACTTCGGTAAGA 
               
               
                   
                 ATTTCGACAGATTAGTTAAGGTCAAGACTTTAGTTGACCCAAATA 
               
               
                   
                 ACTTCTTCAGAAACGAACAATCTATCCCACCATTGCCTAGACATA 
               
               
                   
                 GACACTAG 
               
               
                   
               
               
                 SEQ ID NO: 102 
                 MKCSTFSFWFVCKIIFFFFSFNIQTS1ANPRENFLKCFSQYIPNN 
               
               
                 CBDA Synthase, L71A 
                 ATNLKLVYTQNNPLYMSVLNSTIHNARFTSDTTPKPLVIVTPSHV 
               
               
                 variant 
                 SHIQGTILCSKKVGLQIRTRSGGHDSEGMSYISQVPFVIVDLRNM 
               
               
                 Artificial Sequence 
                 RSIKIDVHSQTAWVEAGATLGEVYYWVNEKNENLSLAAGYCPTVC 
               
               
                   
                 AGGHFGGGGYGPLMRNYGLAADNIIDAHLVNVHGKVLDRKSMGED 
               
               
                   
                 LFWALRGGGAESFG1IVAWKIRLVAVPKSTMFSVKKIMEIHELVK 
               
               
                   
                 LVNKWQNIAYKYDKDLLLMTHFITRN1TDNQGKNKTAIHTYFSSV 
               
               
                   
                 FLGGVDSLVDLMNKSFPELGIKKTDCRQLSW1DTIIFYSGVVNYD 
               
               
                   
                 TDNFNKEILLDRSAGQNGAFKIKLDYVKKPIPESVFVQILEKLYE 
               
               
                   
                 EDIGAGMYALYPYGGIMDEISESAIPFPHRAGILYELWYICSWEK 
               
               
                   
                 QEDNEKHLNWIRNIYNFMTPYVSKNPRLAYLNYRDLDIGINDPKN 
               
               
                   
                 PNNYTQARIWGEKYFGKNFDRLVKVKTLVDPNNFFRNEQSIPPLP 
               
               
                   
                 RHRH* 
               
               
                   
               
               
                 SEQ ID NO: 103 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                 CBDA Synthase, L71H 
                 TTCTTCTTCTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 variant 
                 CGTGAGAACTTCTTGAAATGTTTTTCTCAATATATCCCAAATAAC 
               
               
                 Artificial Sequence 
                 GCTACTAACTTGAAGTTAGTCTATACTCAAAACAACCCATTATAT 
               
               
                 Codon optimized 
                 ATGTCTGTCTTAAACTCTACCATTCACAACcatCGTTTCACTTCT 
               
               
                   
                 GATACTACTCCAAAACCTTTGGTCATCGTCACCCCATCCCACGTT 
               
               
                   
                 TCTCACATCCAAGGTACCATCTTGTGTTCCAAAAAGGTTGGTTTA 
               
               
                   
                 CAAATCCGTACTAGATCCGGTGGTCATGACTCCGAAGGTATGTCT 
               
               
                   
                 TACATTTCCCAAGTCCCTTTCGTCATCGTCGACTTAAGAAATATG 
               
               
                   
                 CGTTCCATCAAGATTGATGTCCATTCCCAAACTGCTTGGGTTGAA 
               
               
                   
                 GCCGGTGCCACTTTAGGTGAAGTCTATTACTGGGTTAACGAGAAG 
               
               
                   
                 AATGAGAACTTATCTTTGGCTGCCGGTTACTGTCCAACTGTTTGT 
               
               
                   
                 GCTGGTGGTCATTTCGGTGGTGGTGGTTACGGTCCATTAATGCGT 
               
               
                   
                 AACTACGGTTTGGCTGCCGATAACATCATTGATGCCCACTTAGTC 
               
               
                   
                 AACGTTCATGGTAAGGTCTTGGACCGTAAGTCTATGGGTGAG 
               
               
                   
                 GATTTATTCTGGGCTTTGAGAGGTGGTGGTGCTGAATCTTTCGGT 
               
               
                   
                 ATTATCGTCGCTTGGAAGATTAGATTAGTTGCTGTTCCAAAGTCT 
               
               
                   
                 ACTATGTTCTCTGTTAAGAAGATCATGGAAATTCACGAGTTGGTT 
               
               
                   
                 AAATTAGTTAACAAATGGCAAAACATTGCCTACAAGTACGATAAA 
               
               
                   
                 GATTTGTTATTAATGACTCACTTTATCACTAGAAACATTACTGAT 
               
               
                   
                 AACCAAGGTAAGAATAAGACTGCCATTCACACTTACTTCTCTTCT 
               
               
                   
                 GTTTTCTTGGGTGGTGTTGATTCCTTGGTCGATTTGATGAACAAG 
               
               
                   
                 TCTTTTCCAGAATTAGGTATTAAGAAGACCGATTGTCGTCAATTA 
               
               
                   
                 TCTTGGATTGATACCATTATTTTTTACTCCGGTGTTGTCAACTAC 
               
               
                   
                 GACACTGATAATTTTAATAAGGAGATTTTGTTAGATAGATCTGCT 
               
               
                   
                 GGTCAAAATGGTGCCTTTAAAATCAAATTGGACTACGTTAAGAAG 
               
               
                   
                 CCTATTCCAGAATCCGTCTTTGTTCAAATTTTGGAGAAGTTATAC 
               
               
                   
                 GAAGAAGATATTGGTGCTGGTATGTACGCCTTGTATCCATATGGT 
               
               
                   
                 GGTATTATGGATGAAATTTCTGAATCCGCCATCCCTTTCCCTCAT 
               
               
                   
                 CGTGCTGGTATCTTATACGAGTTGTGGTACATCTGTTCTTGGGAA 
               
               
                   
                 AAGCAAGAAGATAATGAAAAGCATTTGAACTGGATCCGTAACATC 
               
               
                   
                 TATAACTTCATGACTCCATACGTTTCCAAAAACCCTAGATTGGCT 
               
               
                   
                 TACTTAAATTACAGAGACTTAGATATTGGTATTAACGACCCTAAG 
               
               
                   
                 AACCCAAACAATTACACTCAAGCTAGAATCTGGGGTGAAAAGTAC 
               
               
                   
                 TTCGGTAAGAATTTCGACAGATTAGTTAAGGTCAAGACTTTAGTT 
               
               
                   
                 GACCCAAATAACTTCTTCAGAAACGAACAATCTATCCCACCATTG 
               
               
                   
                 CCTAGACATAGACACTAG 
               
               
                   
               
               
                 SEQ ID NO: 104 
                 MKCSTFSFWFVCKIIFFFFSFNIQTSIANPRENFLKCFSQYIPNN 
               
               
                 CBDA Synthase, L71H 
                 ATNLKLVYTQNNPLYMSVLNSTIHNHRFTSDTTPKPLVIVTPSHV 
               
               
                 variant 
                 SHIQGTILCSKKVGLQIRTRSGGHDSEGMSYISQVPFVIVDLRNM 
               
               
                 Artificial Sequence 
                 RSIKIDVHSQTAWVEAGATLGEVYYWVNEKNENLSLAAGYCPTVC 
               
               
                   
                 AGGHFGGGGYGPLMRNYGLAADNIIDAHLVNVHGKVLDRKSMGED 
               
               
                   
                 LFWALRGGGAESFGIIVAWKIRLVAVPKSTMFSVKKIMEIHELVK 
               
               
                   
                 LVNKWQNIAYKYDKDLLLMTHFITRNITDNQGKNKTAIHTYFSSV 
               
               
                   
                 FLGGVDSLVDLMNKSFPELGIKKTDCRQLSWIDTIIFYSGVVNYD 
               
               
                   
                 TDNFNKEILLDRSAGQNGAFKKLDYVKKPIPESVFVQILEKLYEE 
               
               
                   
                 DIGAGMYALYPYGGIMDEISESAIPFPHRAGILYELWYICSWEKQ 
               
               
                   
                 EDNEKHLNWIRNIYNFMTPYVSKNPRLAYLNYRDLDIGINDPKNP 
               
               
                   
                 NNYTQARIWGEKYFGKNFDRLVKVKTLVDPNNFFRNEQSIPPLPR 
               
               
                   
                 HRH* 
               
               
                   
               
               
                 SEQ ID NO: 105 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                 CBDA Synthase, L71Q 
                 TTCTTCTTCTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 variant 
                 CGTGAGAACTTCTTGAAATGTTTTTCTCAATATATCCCAAATAAC 
               
               
                 Artificial Sequence 
                 GCTACTAACTTGAAGTTAGTCTATACTCAAAACAACCCATTATAT 
               
               
                 Codon optimized 
                 ATGTCTGTCTTAAACTCTACCATTCACAACcaaCGTTTCACTTCT 
               
               
                   
                 GATACTACTCCAAAACCTTTGGTCATCGTCACCCCATCCCACGTT 
               
               
                   
                 TCTCACATCCAAGGTACCATCTTGTGTTCCAAAAAGGTTGGTTTA 
               
               
                   
                 CAAATCCGTACTAGATCCGGTGGTCATGACTCCGAAGGTATGTCT 
               
               
                   
                 TACATTTCCCAAGTCCCTTTCGTCATCGTCGACTTAAGAAATATG 
               
               
                   
                 CGTTCCATCAAGATTGATGTCCATTCCCAAACTGCTTGGGTTGAA 
               
               
                   
                 GCCGGTGCCACTTTAGGTGAAGTCTATTACTGGGTTAACGAGAAG 
               
               
                   
                 AATGAGAACTTATCTTTGGCTGCCGGTTACTGTCCAACTGTTTGT 
               
               
                   
                 GCTGGTGGTCATTTCGGTGGTGGTGGTTACGGTCCATTAATGCGT 
               
               
                   
                 AACTACGGTTTGGCTGCCGATAACATCATTGATGCCCACTTAGTC 
               
               
                   
                 AACGTTCATGGTAAGGTCTTGGACCGTAAGTCTATGGGTGAGGAT 
               
               
                   
                 TTATTCTGGGCTTTGAGAGGTGGTGGTGCTGAATCTTTCGGTATT 
               
               
                   
                 ATCGTCGCTTGGAAGATTAGATTAGTTGCTGTTCCAAAGTCTACT 
               
               
                   
                 ATGTTCTCTGTTAAGAAGATCATGGAAATTCACGAGTTGGTTAAA 
               
               
                   
                 TTAGTTAACAAATGGCAAAACATTGCCTACAAGTACGATAAAGAT 
               
               
                   
                 TTGTTATTAATGACTCACTTTATCACTAGAAACATTACTGATAAC 
               
               
                   
                 CAAGGTAAGAATAAGACTGCCATTCACACTTACTTCTCTTCTGTT 
               
               
                   
                 TTCTTGGGTGGTGTTGATTCCTTGGTCGATTTGATGAACAAGTCT 
               
               
                   
                 TTTCCAGAATTAGGTATTAAGAAGACCGATTGTCGTCAATTGATA 
               
               
                   
                 ATTTTAATAAGGAGATTTTGTTAGATAGATCTGCTGGTCAAAATG 
               
               
                   
                 GTGCCTTTAAAATCAAATTGGACTACGTTAAGAAGCCTATTCCAG 
               
               
                   
                 AATCCGTCTTTGTTCAAATTTTGGAGAAGTTATACGAAGAAGATA 
               
               
                   
                 TTGGTGCTGGTATGTACGCCTTGTATCCATATGGTGGTATTATGG 
               
               
                   
                 ATGAAATTTCTGAATCCGCCATCCCTTTCCCTCATCGTGCTGGTA 
               
               
                   
                 TCTTATACGAGTTGTGGTACATCTGTTCTTGGGAAAAGCAAGAAG 
               
               
                   
                 ATAATGAAAAGCATTTGAACTGGATCCGTAACATCTATAACTTCA 
               
               
                   
                 TGACTCCATACGTTTCCAAAAACCCTAGATTGGCTTACTTAAATT 
               
               
                   
                 ACAGAGACTTAGATATTGGTATTAACGACCCTAAGAACCCAAACA 
               
               
                   
                 ATTACACTCAAGCTAGAATCTGGGGTGAAAAGTACTTCGGTAAGA 
               
               
                   
                 ATTTCGACAGATTAGTTAAGGTCAAGACTTTAGTTGACCCAAATA 
               
               
                   
                 ACTTCTTCAGAAACGAACAATCTATCCCACCATTGCCTAGACATA 
               
               
                   
                 GACACTAG 
               
               
                   
               
               
                 SEQ ID NO: 106 
                 MKCSTFSFWFVCKIIFFFFSFNIQTSIANPRENFLKCFSQYIPNN 
               
               
                 CBDA Synthase, L71Q 
                 ATNLKLVYTQNNPLYMSVLNSTIHNQRFTSDTTPKPLVIVTPSHV 
               
               
                 variant 
                 SHIQGTILCSKKVGLQIRTRSGGHDSEGMSYISQVPFVIVDLRNM 
               
               
                 Artificial Sequence 
                 RSIKIDVHSQTAWVEAGATLGEVYYWVNEKNENLSLAAGYCPTVC 
               
               
                   
                 AGGHFGGGGYGPLMRNYGLAADNIIDAHLVNVHGKVLDRKSMGED 
               
               
                   
                 LFWALRGGGAESFGIIVAWKIRLVAVPKSTMFSVKKIMEIHELVK 
               
               
                   
                 LVNKWQNIAYKYDKDLLLMTHFITRNITDNQGKNKTAIHTYFSSW 
               
               
                   
                 LGGVDSLVDLMNKSFPELGIKKTDCRQLSWIDTHFYSGWNYDTDN 
               
               
                   
                 FNKEILLDRSAGQNGAFKKLDYVKKPIPESVFVQILEKLYEEDIG 
               
               
                   
                 AGMYALYPYGGIMDEISESAIPFPHRAGILYELWYICSWEKQEDN 
               
               
                   
                 EKHLNWIRNIYNFMTPYVSKNPRLAYLNYRDLDIGINDPKNPNNY 
               
               
                   
                 TQARIWGEKYFGKNFDRLVKVKTLVDPNNFFRNEQSIPPLPRHRH 
               
               
                   
                 * 
               
               
                   
               
               
                 SEQ ID NO: 107 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                 CBDA Synthase, S75D 
                 TTCTTCTTCTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 variant 
                 CGTGAGAACTTCTTGAAATGTTTTTCTCAATATATCCCAAATAAC 
               
               
                 Artificial Sequence 
                 GCTACTAACTTGAAGTTAGTCTATACTCAAAACAACCCATTATAT 
               
               
                 Codon optimized 
                 ATGTCTGTCTTAAACTCTACCATTCACAACTTACGTTTCACTgat 
               
               
                   
                 GATACTACTCCAAAACCTTTGGTCATCGTCACCCCATCCCACGTT 
               
               
                   
                 TCTCACATCCAAGGTACCATCTTGTGTTCCAAAAAGGTTGGTTTA 
               
               
                   
                 CAAATCCGTACTAGATCCGGTGGTCATGACTCCGAAGGTATGTCT 
               
               
                   
                 TACATTTCCCAAGTCCCTTTCGTCATCGTCGACTTAAGAAATATG 
               
               
                   
                 CGTTCCATCAAGATTGATGTCCATTCCCAAACTGCTTGGGTTGAA 
               
               
                   
                 GCCGGTGCCACTTTAGGTGAAGTCTATTACTGGGTTAACGAGAAG 
               
               
                   
                 AATGAGAACTTATCTTTGGCTGCCGGTTACTGTCCAACTGTTTGT 
               
               
                   
                 GCTGGTGGTCATTTCGGTGGTGGTGGTTACGGTCCATTAATGCGT 
               
               
                   
                 AACTACGGTTTGGCTGCCGATAACATCATTGATGCCCACTTAGTC 
               
               
                   
                 AACGTTCATGGTAAGGTCTTGGACCGTAAGTCTATGGGTGAGGAT 
               
               
                   
                 TTATTCTGGGCTTTGAGAGGTGGTGGTGCTGAATCTTTCGGTATT 
               
               
                   
                 ATCGTCGCTTGGAAGATTAGATTAGTTGCTGTTCCAAAGTCTACT 
               
               
                   
                 ATGTTCTCTGTTAAGAAGATCATGGAAATTCACGAGTTGGTTAAA 
               
               
                   
                 TTAGTTAACAAATGGCAAAACATTGCCTACAAGTACGATAAAGAT 
               
               
                   
                 TTGTTATTAATGACTCACTTTATCACTAGAAACATTACTGATAAC 
               
               
                   
                 CAAGGTAAGAATAAGACTGCCATTCACACTTACTTCTCTTCTGTT 
               
               
                   
                 TTCTTGGGTGGTGTTGATTCCTTGGTCGATTTGATGAACAAGTCT 
               
               
                   
                 TTTCCAGAATTAGGTATTAAGAAGACCGATTGTCGTCAATTGATA 
               
               
                   
                 ATTTTAATAAGGAGATTTTGTTAGATAGATCTGCTGGTCAAAATG 
               
               
                   
                 GTGCCTTTAAAATCAAATTGGACTACGTTAAGAAGCCTATTCCAG 
               
               
                   
                 AATCCGTCTTTGTTCAAATTTTGGAGAAGTTATACGAAGAAGATA 
               
               
                   
                 TTGGTGCTGGTATGTACGCCTTGTATCCATATGGTGGTATTATGG 
               
               
                   
                 ATGAAATTTCTGAATCCGCCATCCCTTTCCCTCATCGTGCTGGTA 
               
               
                   
                 TCTTATACGAGTTGTGGTACATCTGTTCTTGGGAAAAGCAAGAAG 
               
               
                   
                 ATAATGAAAAGCATTTGAACTGGATCCGTAACATCTATAACTTCA 
               
               
                   
                 TGACTCCATACGTTTCCAAAAACCCTAGATTGGCTTACTTAAATT 
               
               
                   
                 ACAGAGACTTAGATATTGGTATTAACGACCCTAAGAACCCAAACA 
               
               
                   
                 ATTACACTCAAGCTAGAATCTGGGGTGAAAAGTACTTCGGTAAGA 
               
               
                   
                 ATTTCGACAGATTAGTTAAGGTCAAGACTTTAGTTGACCCAAATA 
               
               
                   
                 ACTTCTTCAGAAACGAACAATCTATCCCACCATTGCCTAGACATA 
               
               
                   
                 GACACTAG 
               
               
                   
               
               
                 SEQ ID NO: 108 
                 MKCSTFSFWFVCKIIFFFFSFNIQTSIANPRENFLKCFSQYTPNN 
               
               
                 CBDA Synthase, S75D 
                 ATNLKLVYTQNNPLYMSVLNSTIHNLRFTDDTTPKPLVIVTPSHV 
               
               
                 variant 
                 SHIQGTILCSKKVGLQIRTRSGGHDSEGMSYISQVPFVIVDLRNM 
               
               
                 Artificial Sequence 
                 RSIKIDVHSQTAWVEAGATLGEVYYWVNEKNENLSLAAGYCPTVC 
               
               
                   
                 AGGHFGGGGYGPLMRNYGLAADNIIDAHLVNVHGKVLDRKSMGED 
               
               
                   
                 LFWALRGGGAESFGIIVAWKIRLVAVPKSTMFSVKKIMEIHELVK 
               
               
                   
                 LVNKWQNIAYKYDKDLLLMTHFITRNITDNQGKNKTAIHTYFSSV 
               
               
                   
                 FLGGVDSLVDLMNKSFPELGIKKTDCRQLSWIDTIIFYSGVVNYD 
               
               
                   
                 TDNFNKEILLDRSAGQNGAFKIKLDYVKKPIPESVFVQILEKLYE 
               
               
                   
                 EDIGAGMYALYPYGGIMDEISESAIPFPHRAGILYELWYICSWEK 
               
               
                   
                 QEDNEKHLNWIRNIYNFMTPYVSKNPRLAYLNYRDLDIGINDPKN 
               
               
                   
                 PNNYTQARIWGEKYFGKNFDRLVKVKTLVDPNNFFRNEQSIPPLP 
               
               
                   
                 RHRH* 
               
               
                   
               
               
                 SEQ ID NO: 109 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                 CBDA Synthase, S75E 
                 TTCTTCTTCTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 variant 
                 CGTGAGAACTTCTTGAAATGTTTTTCTCAATATATCCCAAATAAC 
               
               
                 Artificial Sequence 
                 GCTACTAACTTGAAGTTAGTCTATACTCAAAACAACCCATTATAT 
               
               
                 Codon optimized 
                 ATGTCTGTCTTAAACTCTACCATTCACAACTTACGTTTCACTgaa 
               
               
                   
                 GATACTACTCCAAAACCTTTGGTCATCGTCACCCCATCCCACGTT 
               
               
                   
                 TCTCACATCCAAGGTACCATCTTGTGTTCCAAAAAGGTTGGTTTA 
               
               
                   
                 CAAATCCGTACTAGATCCGGTGGTCATGACTCCGAAGGTATGTCT 
               
               
                   
                 TACATTTCCCAAGTCCCTTTCGTCATCGTCGACTTAAGAAATATG 
               
               
                   
                 CGTTCCATCAAGATTGATGTCCATTCCCAAACTGCTTGGGTTGAA 
               
               
                   
                 GCCGGTGCCACTTTAGGTGAAGTCTATTACTGGGTTAACGAGAAG 
               
               
                   
                 AATGAGAACTTATCTTTGGCTGCCGGTTACTGTCCAACTGTTTGT 
               
               
                   
                 GCTGGTGGTCATTTCGGTGGTGGTGGTTACGGTCCATTAATGCGT 
               
               
                   
                 AACTACGGTTTGGCTGCCGATAACATCATTGATGCCCACTTAGTC 
               
               
                   
                 AACGTTCATGGTAAGGTCTTGGACCGTAAGTCTATGGGTGAGGAT 
               
               
                   
                 TTATTCTGGGCTTTGAGAGGTGGTGGTGCTGAATCTTTCGGTATT 
               
               
                   
                 ATCGTCGCTTGGAAGATTAGATTAGTTGCTGTTCCAAAGTCTACT 
               
               
                   
                 ATGTTCTCTGTTAAGAAGATCATGGAAATTCACGAGTTGGTTAAA 
               
               
                   
                 TTAGTTAACAAATGGCAAAACATTGCCTACAAGTACGATAAAGAT 
               
               
                   
                 TTGTTATTAATGACTCACTTTATCACTAGAAACATTACTGATAAC 
               
               
                   
                 CAAGGTAAGAATAAGACTGCCATTCACACTTACTTCTCTTCTGTT 
               
               
                   
                 TTCTTGGGTGGTGTTGATTCCTTGGTCGATTTGATGAACAAGTCT 
               
               
                   
                 TTTCCAGAATTAGGTATTAAGAAGACCGATTGTCGTCAATTATCT 
               
               
                   
                 TGGATTGATACCATTATTTTTTACTCCGGTGTTGTCAACTACGAC 
               
               
                   
                 ACTGATAATTTTAATAAGGAGATTTTGTTAGATAGATCTGCTGGT 
               
               
                   
                 CAAAATGGTGCCTTTAAAATCAAATTGGACTACGTTAAGAAGCCT 
               
               
                   
                 ATTCCAGAATCCGTCTTTGTTCAAATTTTGGAGAAGTTATACGAA 
               
               
                   
                 GAAGATATTGGTGCTGGTATGTACGCCTTGTATCCATATGGTGGT 
               
               
                   
                 ATTATGGATGAAATTTCTGAATCCGCCATCCCTTTCCCTCATCGT 
               
               
                   
                 GCTGGTATCTTATACGAGTTGTGGTACATCTGTTCTTGGGAAAAG 
               
               
                   
                 CAAGAAGATAATGAAAAGCATTTGAACTGGATCCGTAACATCTAT 
               
               
                   
                 AACTTCATGACTCCATACGTTTCCAAAAACCCTAGATTGGCTTAC 
               
               
                   
                 TTAAATTACAGAGACTTAGATATTGGTATTAACGACCCTAAGAAC 
               
               
                   
                 CCAAACAATTACACTCAAGCTAGAATCTGGGGTGAAAAGTACTTC 
               
               
                   
                 GGTAAGAATTTCGACAGATTAGTTAAGGTCAAGACTTTAGTTGAC 
               
               
                   
                 CCAAATAACTTCTTCAGAAACGAACAATCTATCCCACCATTGCCT 
               
               
                   
                 AGACATAGACACTAG 
               
               
                   
               
               
                 SEQ ID NO: 110 
                 MKCSTFSFWFVCKIIFFFFSFNIQTSIANPRENFLKCFSQYIPNN 
               
               
                 CBDA Synthase, S75E 
                 ATNLKLVYTQNNPLYMSVLNSTIHNLRFTEDTTPKPLVIVTPSHV 
               
               
                 variant 
                 SHIQGTILCSKKVGLQIRTRSGGHDSEGMSYISQVPFVIVDLRNM 
               
               
                 Artificial Sequence 
                 RSIKIDVHSQTAWVEAGATLGEVYYWVNEKNENLSLAAGYCPTVC 
               
               
                   
                 AGGHFGGGGYGPLMRNYGLAADNIIDAHLVNVHGKVLDRKSMGED 
               
               
                   
                 LFWALRGGGAESFGIIVAWKIRLVAVPKSTMFSVKKIMEIHELVK 
               
               
                   
                 LVNKWQNIAYKYDKDLLLMTHFITRNITDNQGKNKTAIHTYFSSW 
               
               
                   
                 LGGVDSLVDLMNKSFPELGIKKTDCRQLSWIDTIIFYSGWNYDTD 
               
               
                   
                 NFNKEILLDRSAGQNGAFKIKLDYVKKPIPESVFVQILEKLYEED 
               
               
                   
                 IGAGMYALYPYGGIMDEISESAIPFPHRAGILYELWYICSWEKQE 
               
               
                   
                 DNEKHLNWIRNIYNFMTPYVSKNPRLAYLNYRDLDIGINDPKNPN 
               
               
                   
                 NYTQARIWGEKYFGKNFDRLVKVKTLVDPNNFFRNEQSIPPLPRH 
               
               
                   
                 RH* 
               
               
                   
               
               
                 SEQ ID NO: 111 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                 CBDA Synthase, I97V 
                 TTCTTCTTCTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 variant 
                 CGTGAGAACTTCTTGAAATGTTTTTCTCAATATATCCCAAATAAC 
               
               
                 Artificial Sequence 
                 GCTACTAACTTGAAGTTAGTCTATACTCAAAACAACCCATTATAT 
               
               
                 Codon optimized 
                 ATGTCTGTCTTAAACTCTACCATTCACAACTTACGTTTCACTTCT 
               
               
                   
                 GATACTACTCCAAAACCTTTGGTCATCGTCACCCCATCCCACGTT 
               
               
                   
                 TCTCACATCCAAGGTACCgttTTGTGTTCCAAAAAGGTTGGTTTA 
               
               
                   
                 CAAATCCGTACTAGATCCGGTGGTCATGACTCCGAAGGTATGTCT 
               
               
                   
                 TACATTTCCCAAGTCCCTTTCGTCATCGTCGACTTAAGAAATATG 
               
               
                   
                 CGTTCCATCAAGATTGATGTCCATTCCCAAACTGCTTGGGTTGAA 
               
               
                   
                 GCCGGTGCCACTTTAGGTGAAGTCTATTACTGGGTTAACGAGAAG 
               
               
                   
                 AATGAGAACTTATCTTTGGCTGCCGGTTACTGTCCAACTGTTTGT 
               
               
                   
                 GCTGGTGGTCATTTCGGTGGTGGTGGTTACGGTCCATTAATGCGT 
               
               
                   
                 AACTACGGTTTGGCTGCCGATAACATCATTGATGCCCACTTAGTC 
               
               
                   
                 AACGTTCATGGTAAGGTCTTGGACCGTAAGTCTATGGGTGAGGAT 
               
               
                   
                 TTATTCTGGGCTTTGAGAGGTGGTGGTGCTGAATCTTTCGGTATT 
               
               
                   
                 ATCGTCGCTTGGAAGATTAGATTAGTTGCTGTTCCAAAGTCTACT 
               
               
                   
                 ATGTTCTCTGTTAAGAAGATCATGGAAATTCACGAGTTGGTTAAA 
               
               
                   
                 TTAGTTAACAAATGGCAAAACATTGCCTACAAGTACGATAAAGAT 
               
               
                   
                 TTGTTATTAATGACTCACTTTATCACTAGAAACATTACTGATAAC 
               
               
                   
                 CAAGGTAAGAATAAGACTGCCATTCACACTTACTTCTCTTCTGTT 
               
               
                   
                 TTCTTGGGTGGTGTTGATTCCTTGGTCGATTTGATGAACAAGTCT 
               
               
                   
                 TTTCCAGAATTAGGTATTAAGAAGACCGATTGTCGTCAATTATCT 
               
               
                   
                 TGGATTGATACCATTATTTTTTACTCCGGTGTTGTCAACTACGAC 
               
               
                   
                 ACTGATAATTTTAATAAGGAGATTTTGTTAGATAGATCTGCTGGT 
               
               
                   
                 CAAAATGGTGCCTTTAAAATCAAATTGGACTACGTTAAGAAGCCT 
               
               
                   
                 ATTCCAGAATCCGTC 
               
               
                   
                 TTTGTTCAAATTTTGGAGAAGTTATACGAAGAAGATATTGGTGCT 
               
               
                   
                 GGTATGTACGCCTTGTATCCATATGGTGGTATTATGGATGAAATT 
               
               
                   
                 TCTGAATCCGCCATCCCTTTCCCTCATCGTGCTGGTATCTTATAC 
               
               
                   
                 GAGTTGTGGTACATCTGTTCTTGGGAAAAGCAAGAAGATAATGAA 
               
               
                   
                 AAGCATTTGAACTGGATCCGTAACATCTATAACTTCATGACTCCA 
               
               
                   
                 TACGTTTCCAAAAACCCTAGATTGGCTTACTTAAATTACAGAGAC 
               
               
                   
                 TTAGATATTGGTATTAACGACCCTAAGAACCCAAACAATTACACT 
               
               
                   
                 CAAGCTAGAATCTGGGGTGAAAAGTACTTCGGTAAGAATTTCGAC 
               
               
                   
                 AGATTAGTTAAGGTCAAGACTTTAGTTGACCCAAATAACTTCTTC 
               
               
                   
                 AGAAACGAACAATCTATCCCACCATTGCCTAGACATAGACACTAG 
               
               
                   
               
               
                 SEQ ID NO: 112 
                 MKCSTFSFWFVCKIIFFFFSFNIQTSIANPRENFLKCFSQYIPNN 
               
               
                 CBDA Synthase, I97V 
                 ATNLKLVYTQNNPLYMSVLNSTIHNLRFTSDTTPKPLVIVTPSHV 
               
               
                 variant 
                 SHIQGTVLCSKKVGLQIRTRSGGHDSEGMSYISQVPFVIVDLRNM 
               
               
                 Artificial Sequence 
                 RSIKIDVHSQTAWVEAGATLGEVYYWVNEKNENLSLAAGYCPTVC 
               
               
                   
                 AGGHFGGGGYGPLMRNYGLAADNIIDAHLVNVHGKVLDRKSMGED 
               
               
                   
                 LFWALRGGGAESFGIIVAWKIRLVAVPKSTMFSVKKIMEIHELVK 
               
               
                   
                 LVNKWQNIAYKYDKDLLLMTHFITRNITDNQGKNKTAIHTYFSSV 
               
               
                   
                 FLGGVDSLVDLMNKSFPELGIKKTDCRQLSWIDTIIFYSGVVNYD 
               
               
                   
                 TDNFNKEILLDRSAGQNGAFKIKLDYVKKPIPESWVQILEKLYEE 
               
               
                   
                 DIGAGMYALYPYGGIMDEISESAIPFPHRAGILYELWYICSWEKQ 
               
               
                   
                 EDNEKHLNWIRNIYNFMTPYVSKNPRLAYLNYRDLDIGINDPKNP 
               
               
                   
                 NNYTQARIWGEKYFGKNFDRLVKVKTLVDPNNFFRNEOSIPPLPR 
               
               
                   
                 HRH* 
               
               
                   
               
               
                 SEQ ID NO: 113 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                 CBDA Synthase, L98V 
                 TTCTTCTTCTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 variant 
                 CGTGAGAACTTCTTGAAATGTTTTTCTCAATATATCCCAAATAAC 
               
               
                 Artificial Sequence 
                 GCTACTAACTTGAAGTTAGTCTATACTCAAAACAACCCATTATAT 
               
               
                 Codon optimized 
                 ATGTCTGTCTTAAACTCTACCATTCACAACTTACGTTTCACTTCT 
               
               
                   
                 GATACTACTCCAAAACCTTTGGTCATCGTCACCCCATCCCACGTT 
               
               
                   
                 TCTCACATCCAAGGTACCATCgttTGTTCCAAAAAGGTTGGTTTA 
               
               
                   
                 CAAATCCGTACTAGATCCGGTGGTCATGACTCCGAAGGTATGTCT 
               
               
                   
                 TACATTTCCCAAGTCCCTTTCGTCATCGTCGACTTAAGAAATATG 
               
               
                   
                 CGTTCCATCAAGATTGATGTCCATTCCCAAACTGCTTGGGTTGAA 
               
               
                   
                 GCCGGTGCCACTTTAGGTGAAGTCTATTACTGGGTTAACGAGAAG 
               
               
                   
                 AATGAGAACTTATCTTTGGCTGCCGGTTACTGTCCAACTGTTTGT 
               
               
                   
                 GCTGGTGGTCATTTCGGTGGTGGTGGTTACGGTCCATTAATGCGT 
               
               
                   
                 AACTACGGTTTGGCTGCCGATAACATCATTGATGCCCACTTAGTC 
               
               
                   
                 AACGTTCATGGTAAGGTCTTGGACCGTAAGTCTATGGGTGAGGAT 
               
               
                   
                 TTATTCTGGGCTTTGAGAGGTGGTGGTGCTGAATCTTTCGGTATT 
               
               
                   
                 ATCGTCGCTTGGAAGATTAGATTAGTTGCTGTTCCAAAGTCTACT 
               
               
                   
                 ATGTTCTCTGTTAAGAAGATCATGGAAATTCACGAGTTGGTTAAA 
               
               
                   
                 TTAGTTAACAAATGGCAAAACATTGCCTACAAGTACGATAAAGAT 
               
               
                   
                 TTGTTATTAATGACTCACTTTATCACTAGAAACATTACTGATAAC 
               
               
                   
                 CAAGGTAAGAATAAGACTGCCATTCACACTTACTTCTCTTCTGTT 
               
               
                   
                 TTCTTGGGTGGTGTTGATTCCTTGGTCGATTTGATGAACAAGTCT 
               
               
                   
                 TTTCCAGAATTAGGTATTAAGAAGACCGATTGTCGTCAATTATCT 
               
               
                   
                 TGGATTGATACCATTATTTTTTACTCCGGTGTTGTCAACTACGAC 
               
               
                   
                 ACTGATAATTTTAATAAGGAGATTTTGTTAGATAGATCTGCTGGT 
               
               
                   
                 CAAAATGGTGCCTTTAAAATCAAATTGGACTACGTTAAGAAGCCT 
               
               
                   
                 ATTCCAGAATCCGTCTTTGTTCAAATTTTGGAGAAGTTATACGAA 
               
               
                   
                 GAAGATATTGGTGCTGGTATGTACGCCTTGTATCCATATGGTGGT 
               
               
                   
                 ATTATGGATGAAATTTCTGAATCCGCCATCCCTTTCCCTCATCGT 
               
               
                   
                 GCTGGTATCTTATACGAGTTGTGGTACATCTGTTCTTGGGAAAAG 
               
               
                   
                 CAAGAAGATAATGAAAAGCATTTGAACTGGATCCGTAACATCTAT 
               
               
                   
                 AACTTCATGACTCCATACGTTTCCAAAAACCCTAGATTGGCTTAC 
               
               
                   
                 TTAAATTACAGAGACTTAGATATTGGTATTAACGACCCTAAGAAC 
               
               
                   
                 CCAAACAATTACACTCAAGCTAGAATCTGGGGTGAAAAGTACTTC 
               
               
                   
                 GGTAAGAATTTCGACAGATTAGTTAAGGTCAAGACTTTAGTTGAC 
               
               
                   
                 CCAAATAACTTCTTCAGAAACGAACAATCTATCCCACCATTGCCT 
               
               
                   
                 AGACATAGACACTAG 
               
               
                   
               
               
                 SEQ ID NO: 114 
                 MKCSTFSFWFVCKIIFFFFSFNIQTSIANPRENFLKCFSQYIPNN 
               
               
                 CBDA Synthase, L98V 
                 ATNLKLVYTQNNPLYMSVLNSTIHNLRFTSDTTPKPLVIVTPSHV 
               
               
                 variant 
                 SHIQGTIVCSKKVGLQIRTRSGGHDSEGMSYISQVPFVIVDLRNM 
               
               
                 Artificial Sequence 
                 RSIKIDVHSQTAWVEAGATLGEVYYWVNEKNENLSLAAGYCPTVC 
               
               
                   
                 AGGHFGGGGYGPLMRNYGLAADNIIDAHLVNVHGKVLDRKSMGED 
               
               
                   
                 LFWALRGGGAESFGIIVAWKIRLVAVPKSTMFSVKKIMEIHELVK 
               
               
                   
                 LVNKWQNIAYKYDKDLLLMTHFITRNITDNQGKNKTAIHTYFSSV 
               
               
                   
                 FLGGVDSLVDLMNKSFPELGIKKTDCRQLSWIDTIIFYSGWNYDT 
               
               
                   
                 DNFNKEILLDRSAGQNGAFKKLDYVKKPIPESVFVQILEKLYEED 
               
               
                   
                 IGAGMYALYPYGGIMDEISESAIPFPHRAGILYELWYICSWEKQE 
               
               
                   
                 DNEKHLNWIRNIYNFMTPYVSKNPRLAYLNYRDLDIGINDPKNPN 
               
               
                   
                 NYTQARIWGEKYFGKNFDRLVKVKTLVDPNNFFRNEQSIPPLPRH 
               
               
                   
                 RH* 
               
               
                   
               
               
                 SEQ ID NO: 115 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                 CBDA Synthase, 
                 TTCTTCTTCTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 SI00A variant 
                 CGTGAGAACTTCTTGAAATGTTTTTCTCAATATATCCCAAATAAC 
               
               
                 Artificial Sequence 
                 GCTACTAACTTGAAGTTAGTCTATACTCAAAACAACCCATTATAT 
               
               
                 Codon optimized 
                 ATGTCTGTCTTAAACTCTACCATTCACAACTTACGTTTCACTTCT 
               
               
                   
                 GATACTACTCCAAAACCTTTGGTCATCGTCACCCCATCCCACGTT 
               
               
                   
                 TCTCACATCCAAGGTACCATCTTGTGTgctAAAAAGGTTGGTTTA 
               
               
                   
                 CAAATCCGTACTAGATCCGGTGGTCATGACTCCGAAGGTATGTCT 
               
               
                   
                 TACATTTCCCAAGTCCCTTTCGTCATCGTCGACTTAAGAAATATG 
               
               
                   
                 CGTTCCATCAAGATTGATGTCCATTCCCAAACTGCTTGGGTTGAA 
               
               
                   
                 GCCGGTGCCACTTTAGGTGAAGTCTATTACTGGGTTAACGAGAAG 
               
               
                   
                 AATGAGAACTTATCTTTGGCTGCCGGTTACTGTCCAACTGTTTGT 
               
               
                   
                 GCTGGTGGTCATTTCGGTGGTGGTGGTTACGGTCCATTAATGCGT 
               
               
                   
                 AACTACGGTTTGGCTGCCGATAACATCATTGATGCCCACTTAGTC 
               
               
                   
                 AACGTTCATGGTAAGGTCTTGGACCGTAAGTCTATGGGTGAGGAT 
               
               
                   
                 TTATTCTGGGCTTTGAGAGGTGGTGGTGCTGAATCTTTCGGTATT 
               
               
                   
                 ATCGTCGCTTGGAAGATTAGATTAGTTGCTGTTCCAAAGTCTACT 
               
               
                   
                 ATGTTCTCTGTTAAGAAGATCATGGAAATTCACGAGTTGGTTAAA 
               
               
                   
                 TTAGTTAACAAATGGCAAAACATTGCCTACAAGTACGATAAAGAT 
               
               
                   
                 TTGTTATTAATGACTCACTTTATCACTAGAAACATTACTGATAAC 
               
               
                   
                 CAAGGTAAGAATAAGACTGCCATTCACACTTACTTCTCTTCTGTT 
               
               
                   
                 TTCTTGGGTGGTGTTGATTCCTTGGTCGATTTGATGAACAAGTCT 
               
               
                   
                 TTTCCAGAATTAGGTATTAAGAAGACCGATTGTCGTCAATTATCT 
               
               
                   
                 TGGATTGATACCATTATTTTTTACTCCGGTGTTGTCAACTACGAC 
               
               
                   
                 ACTGATAATTTTAATAAGGAGATTTTGTTAGATAGATCTGCTGGT 
               
               
                   
                 CAAAATGGTGCCTTTAAAATCAAATTGGACTACGTTAAGAAGCCT 
               
               
                   
                 ATTCCAGAATCCGTCTTTGTTCAAATTTTGGAGAAGTTATACGAA 
               
               
                   
                 GAAGATATTGGTGCTGGTATGTACGCCTTGTATCCATATGGTGGT 
               
               
                   
                 ATTATGGATGAAATTTCTGAATCCGCCATCCCTTTCCCTCATCGT 
               
               
                   
                 GCTGGTATCTTATACGAGTTGTGGTACATCTGTTCTTGGGAAAAG 
               
               
                   
                 CAAGAAGATAATGAAAAGCATTTGAACTGGATCCGTAACATCTAT 
               
               
                   
                 AACTTCATGACTCCATACGTTTCCAAAAACCCTAGATTGGCTTAC 
               
               
                   
                 TTAAATTACAGAGACTTAGATATTGGTATTAACGACCCTAAGAAC 
               
               
                   
                 CCAAACAATTACACTCAAGCTAGAATCTGGGGTGAAAAGTACTTC 
               
               
                   
                 GGTAAGAATTTCGACAGATTAGTTAAGGTCAAGACTTTAGTTGAC 
               
               
                   
                 CCAAATAACTTCTTCAGAAACGAACAATCTATCCCACCATTGCCT 
               
               
                   
                 AGACATAGACACTAG 
               
               
                   
               
               
                 SEQ ID NO: 116 
                 MKCSTFSFWFVCKIIFFFFSFNIQTSIANPRENFLKCFSQYIPNN 
               
               
                 CBDA Synthase, 
                 ATNLKLVYTQNNPLYMSVLNSTIHNLRFTSDTTPKPLVIVTPSHV 
               
               
                 SI00A variant 
                 SHIQGTILCAKKVGLQIRTRSGGHDSEGMSYISQVPFVIVDLRNM 
               
               
                 Artificial Sequence 
                 RSIKIDVHSQTAWVEAGATLGEVYYWVNEKNENLSLAAGYCPTVC 
               
               
                   
                 AGGHFGGGGYGPLMRNYGLAADNIIDAHLVNVHGKVLDRKSMGED 
               
               
                   
                 LFWALRGGGAESFGIIVAWKIRLVAVPKSTMFSVKKIMEIHELVK 
               
               
                   
                 LVNKWQNIAYKYDKDLLLMTHFITRNITDNQGKNKTAIHTYFSSV 
               
               
                   
                 FLGGVDSLVDLMNKSFPELGIKKTDCRQLSWIDTIIFYSGWNYDT 
               
               
                   
                 DNFNKEILLDRSAGQNGAFKIKLDYVKKPIPESVFVQILEKLYEE 
               
               
                   
                 DIGAGMYALYPYGGIMDEISESAIPFPHRAGILYELWYICSWEKQ 
               
               
                   
                 EDNEKHLNWIRNIYNFMTPYVSKNPRLAYLNYRDLDIGINDPKNP 
               
               
                   
                 NNYTQARIWGEKYFGKNFDRLVKVKTLVDPNNFFRNEQSIPPLPR 
               
               
                   
                 HRH* 
               
               
                   
               
               
                 SEQ ID NO: 117 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                 CBDA Synthase, 
                 TTCTTCTTCTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 VI03 A variant 
                 CGTGAGAACTTCTTGAAATGTTTTTCTCAATATATCCCAAATAAC 
               
               
                 Artificial Sequence 
                 GCTACTAACTTGAAGTTAGTCTATACTCAAAACAACCCATTATAT 
               
               
                 Codon optimized 
                 ATGTCTGTCTTAAACTCTACCATTCACAACTTACGTTTCACTTCT 
               
               
                   
                 GATACTACTCCAAAACCTTTGGTCATCGTCACCCCATCCCACGTT 
               
               
                   
                 TCTCACATCCAAGGTACCATCTTGTGTTCCAAAAAGgctGGTTTA 
               
               
                   
                 CAAATCCGTACTAGATCCGGTGGTCATGACTCCGAAGGTATGTCT 
               
               
                   
                 TACATTTCCCAAGTCCCTTTCGTCATCGTCGACTTAAGAAATATG 
               
               
                   
                 CGTTCCATCAAGATTGATGTCCATTCCCAAACTGCTTGGGTTGAA 
               
               
                   
                 GCCGGTGCCACTTTAGGTGAAGTCTATTACTGGGTTAACGAGAAG 
               
               
                   
                 AATGAGAACTTATCTTTGGCTGCCGGTTACTGTCCAACTGTTTGT 
               
               
                   
                 GCTGGTGGTCATTTCGGTGGTGGTGGTTACGGTCCATTAATGCGT 
               
               
                   
                 AACTACGGTTTGGCTGCCGATAACATCATTGATGCCCACTTAGTC 
               
               
                   
                 AACGTTCATGGTAAGGTCTTGGACCGTAAGTCTATGGGTGAGGAT 
               
               
                   
                 TTATTCTGGGCTTTGAGAGGTGGTGGTGCTGAATCTTTCGGTATT 
               
               
                   
                 ATCGTCGCTTGGAAGATTAGATTAGTTGCTGTTCCAAAGTCTACT 
               
               
                   
                 ATGTTCTCTGTTAAGAAGATCATGGAAATTCACGAGTTGGTTAAA 
               
               
                   
                 TTAGTTAACAAATGGCAAAACATTGCCTACAAGTACGATAAAGAT 
               
               
                   
                 TTGTTATTAATGACTCACTTTATCACTAGAAACATTACTGATAAC 
               
               
                   
                 CAAGGTAAGAATAAGACTGCCATTCACACTTACTTCTCTTCTGTT 
               
               
                   
                 TTCTTGGGTGGTGTTGATTCCTTGGTCGATTTGATGAACAAGTCT 
               
               
                   
                 TTTCCAGAATTAGGTATTAAGAAGACCGATTGTCGTCAATTATCT 
               
               
                   
                 TGGATTGATACCATTATTTTTTACTCCGGTGTTGTCAACTACGAC 
               
               
                   
                 ACTGATAATTTTAATAAGGAGATTTTGTTAGATAGATCTGCTGGT 
               
               
                   
                 CAAAATGGTGCCTTTAAAATCAAATTGGACTACGTTAAGAAGCCT 
               
               
                   
                 ATTCCAGAATCCGTCTTTGTTCAAATTTTGGAGAAGTTATACGAA 
               
               
                   
                 GAAGATATTGGTGCTGGTATGTACGCCTTGTATCCATATGGTGGT 
               
               
                   
                 ATTATGGATGAAATTTCTGAATCCGCCATCCCTTTCCCTCATCGT 
               
               
                   
                 GCTGGTATCTTATACGAGTTGTGGTACATCTGTTCTTGGGAAAAG 
               
               
                   
                 CAAGAAGATAATGAAAAGCATTTGAACTGGATCCGTAACATCTAT 
               
               
                   
                 AACTTCATGACTCCATACGTTTCCAAAAACCCTAGATTGGCTTAC 
               
               
                   
                 TTAAATTACAGAGACTTAGATATTGGTATTAACGACCCTAAGAAC 
               
               
                   
                 CCAAACAATTACACTCAAGCTAGAATCTGGGGTGAAAAGTACTTC 
               
               
                   
                 GGTAAGAATTTCGACAGATTAGTTAAGGTCAAGACTTTAGTTGAC 
               
               
                   
                 CCAAATAACTTCTTCAGAAACGAACAATCTATCCCACCATTGCCT 
               
               
                   
                 AGACATAGACACTAG 
               
               
                   
               
               
                 SEQ ID NO: 118 
                 MKCSTFSFWFVCKIIFFFFSFNIQTSIANPRENFLKCFSQYIPNN 
               
               
                 CBDA Synthase, 
                 ATNLKLVYTQNNPLYMSVLNSTIHNLRFTSDTTPKPLVIVTPSHV 
               
               
                 VI03A variant 
                 SHIQGTILCSKKAGLQIRTRSGGHDSEGMSYISQVPFVIVDLRNM 
               
               
                 Artificial Sequence 
                 RSIKIDVHSQTAWVEAGATLGEVYYWVNEKNENLSLAAGYCPTVC 
               
               
                   
                 AGGHFGGGGYGPLMRNYGLAADNIIDAHLVNVHGKVLDRKSMGED 
               
               
                   
                 LFWALRGGGAESFGIIVAWKIRLVAVPKSTMFSVKKIMEIHELVK 
               
               
                   
                 LVNKWQNIAYKYDKDLLLMTHFITRNITDNQGKNKTAIHTYFSSV 
               
               
                   
                 FLGGVDSLVDLMNKSFPELGIKKTDCRQLSWIDTIIFYSGWNYDT 
               
               
                   
                 DNFNKEILLDRSAGQNGAFKIKLDYVKKPIPESVFVQILEKLYEE 
               
               
                   
                 DIGAGMYALYPYGGIMDEISESAIPFPHRAGILYELWYICSWEKQ 
               
               
                   
                 EDNEKHLNWIRNIYNFMTPYVSKNPRLAYLNYRDLDIGINDPKNP 
               
               
                   
                 NNYTQARIWGEKYFGKNFDRLVKVKTLVDPNNFFRNEQSIPPLPR 
               
               
                   
                 HRH* 
               
               
                   
               
               
                 SEQ ID NO: 119 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                 CBDA Synthase, 
                 TTCTTCTTCTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 V103F variant 
                 CGTGAGAACTTCTTGAAATGTTTTTCTCAATATATCCCAAATAAC 
               
               
                 Artificial Sequence 
                 GCTACTAACTTGAAGTTAGTCTATACTCAAAACAACCCATTATAT 
               
               
                 Codon optimized 
                 ATGTCTGTCTTAAACTCTACCATTCACAACTTACGTTTCACTTCT 
               
               
                   
                 GATACTACTCCAAAACCTTTGGTCATCGTCACCCCATCCCACGTT 
               
               
                   
                 TCTCACATCCAAGGTACCATCTTGTGTTCCAAAAAGlttGGTTTA 
               
               
                   
                 CAAATCCGTACTAGATCCGGTGGTCATGACTCCGAAGGTATGTCT 
               
               
                   
                 TACATTTCCCAAGTCCCTTTCGTCATCGTCGACTTAAGAAATATG 
               
               
                   
                 CGTTCCATCAAGATTGATGTCCATTCCCAAACTGCTTGGGTTGAA 
               
               
                   
                 GCCGGTGCCACTTTAGGTGAAGTCTATTACTGGGTTAACGAGAAG 
               
               
                   
                 AATGAGAACTTATCTTTGGCTGCCGGTTACTGTCCAACTGTTTGT 
               
               
                   
                 GCTGGTGGTCATTTCGGTGGTGGTGGTTACGGTCCATTAATGCGT 
               
               
                   
                 AACTACGGTTTGGCTGCCGATAACATCATTGATGCCCACTTAGTC 
               
               
                   
                 AACGTTCATGGTAAGGTCTTGGACCGTAAGTCTATGGGTGAGGAT 
               
               
                   
                 TTATTCTGGGCTTTGAGAGGTGGTGGTGCTGAATCTTTCGGTATT 
               
               
                   
                 ATCGTCGCTTGGAAGATTAGATTAGTTGCTGTTCCAAAGTCTACT 
               
               
                   
                 ATGTTCTCTGTTAAGAAGATCATGGAAATTCACGAGTTGGTTAAA 
               
               
                   
                 TTAGTTAACAAATGGCAAAACATTGCCTACAAGTACGATAAAGAT 
               
               
                   
                 TTGTTATTAATGACTCACTTTATCACTAGAAACATTACTGATAAC 
               
               
                   
                 CAAGGTAAGAATAAGACTGCCATTCACACTTACTTCTCTTCTGTT 
               
               
                   
                 TTCTTGGGTGGTGTTGATTCCTTGGTCGATTTGATGAACAAGTCT 
               
               
                   
                 TTTCCAGAATTAGGTATTAAGAAGACCGATTGTCGTCAATTGATA 
               
               
                   
                 ATTTTAATAAGGAGATTTTGTTAGATAGATCTGCTGGTCAAAATG 
               
               
                   
                 GTGCCTTTAAAATCAAATTGGACTACGTTAAGAAGCCTATTCCAG 
               
               
                   
                 AATCCGTCTTTGTTCAAATTTTGGAGAAGTTATACGAAGAAGATA 
               
               
                   
                 TTGGTGCTGGTATGTACGCCTTGTATCCATATGGTGGTATTATGG 
               
               
                   
                 ATGAAATTTCTGAATCCGCCATCCCTTTCCCTCATCGTGCTGGTA 
               
               
                   
                 TCTTATACGAGTTGTGGTACATCTGTTCTTGGGAAAAGCAAGAAG 
               
               
                   
                 ATAATGAAAAGCATTTGAACTGGATCCGTAACATCTATAACTTCA 
               
               
                   
                 TGACTCCATACGTTTCCAAAAACCCTAGATTGGCTTACTTAAATT 
               
               
                   
                 ACAGAGACTTAGATATTGGTATTAACGACCCTAAGAACCCAAACA 
               
               
                   
                 ATTACACTCAAGCTAGAATCTGGGGTGAAAAGTACTTCGGTAAGA 
               
               
                   
                 ATTTCGACAGATTAGTTAAGGTCAAGACTTTAGTTGACCCAAATA 
               
               
                   
                 ACTTCTTCAGAAACGAACAATCTATCCCACCATTGCCTAGACATA 
               
               
                   
                 GACACTAG 
               
               
                   
               
               
                 SEQ ID NO: 120 
                 MKCSTFSFWFVCKIIFFFFSFNIQTSIANPRENFLKCFSQYIPNN 
               
               
                 CBDA Synthase, 
                 ATNLKLVYTQNNPLYMSVLNSTIHNLRFTSDTTPKPLVIVTPSHV 
               
               
                 V103F variant 
                 SHIQGTILCSKKFGLQIRTRSGGHDSEGMSYISQVPFVIVDLRNM 
               
               
                 Artificial Sequence 
                 RSIKIDVHSQTAWVEAGATLGEVYYWVNEKNENLSLAAGYCPTVC 
               
               
                   
                 AGGHFGGGGYGPLMRNYGLAADNIIDAHLVNVHGKVLDRKSMGED 
               
               
                   
                 LFWALRGGGAESFGIIVAWKIRLVAVPKSTMFSVKKIMEIHELVK 
               
               
                   
                 LVNKWQNIAYKYDKDLLLMTHFITRNITDNQGKNKTAIHTYFSSV 
               
               
                   
                 FLGGVDSLVDLMNKSFPELGIKKTDCRQLSWIDTIIFYSGWNYDT 
               
               
                   
                 DNFNKEILLDRSAGQNGAFKIKLDYVKKPIPESVFVQILEKLYEE 
               
               
                   
                 DIGAGMYALYPYGGIMDEISESAIPFPHRAGILYELWYICSWEKQ 
               
               
                   
                 EDNEKHLNWIRNIYNFMTPYVSKNPRLAYLNYRDLDIGINDPKNP 
               
               
                   
                 NNYTQARIWGEKYFGKNFDRLVKVKTLVDPNNFFRNEQSIPPLPR 
               
               
                   
                 HRH* 
               
               
                   
               
               
                 SEQ ID NO: 121 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                 CBDA Synthase, 
                 TTCTTCTTCTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 T109V variant 
                 CGTGAGAACTTCTTGAAATGTTTTTCTCAATATATCCCAAATAAC 
               
               
                 Artificial Sequence 
                 GCTACTAACTTGAAGTTAGTCTATACTCAAAACAACCCATTATAT 
               
               
                 Codon optimized 
                 ATGTCTGTCTTAAACTCTACCATTCACAACTTACGTTTCACTTCT 
               
               
                   
                 GATACTACTCCAAAACCTTTGGTCATCGTCACCCCATCCCACGTT 
               
               
                   
                 TCTCACATCCAAGGTACCATCTTGTGTTCCAAAAAGGTTGGTTTA 
               
               
                   
                 CAAATCCGTgttAGATCCGGTGGTCATGACTCCGAAGGTATGTCT 
               
               
                   
                 TACATTTCCCAAGTCCCTTTCGTCATCGTCGACTTAAGAAATATG 
               
               
                   
                 CGTTCCATCAAGATTGATGTCCATTCCCAAACTGCTTGGGTTGAA 
               
               
                   
                 GCCGGTGCCACTTTAGGTGAAGTCTATTACTGGGTTAACGAGAAG 
               
               
                   
                 AATGAGAACTTATCTTTGGCTGCCGGTTACTGTCCAACTGTTTGT 
               
               
                   
                 GCTGGTGGTCATTTCGGTGGTGGTGGTTACGGTCCATTAATGCGT 
               
               
                   
                 AACTACGGTTTGGCTGCCGATAACATCATTGATGCCCACTTAGTC 
               
               
                   
                 AACGTTCATGGTAAGGTCTTGGACCGTAAGTCTATGGGTGAGGAT 
               
               
                   
                 TTATTCTGGGCTTTGAGAGGTGGTGGTGCTGAATCTTTCGGTATT 
               
               
                   
                 ATCGTCGCTTGGAAGATTAGATTAGTTGCTGTTCCAAAGTCTACT 
               
               
                   
                 ATGTTCTCTGTTAAGAAGATCATGGAAATTCACGAGTTGGTTAAA 
               
               
                   
                 TTAGTTAACAAATGGCAAAACATTGCCTACAAGTACGATAAAGAT 
               
               
                   
                 TTGTTATTAATGACTCACTTTATCACTAGAAACATTACTGATAAC 
               
               
                   
                 CAAGGTAAGAATAAGACTGCCATTCACACTTACTTCTCTTCTGTT 
               
               
                   
                 TTCTTGGGTGGTGTTGATTCCTTGGTCGATTTGATGAACAAGTCT 
               
               
                   
                 TTTCCAGAATTAGGTATTAAGAAGACCGATTGTCGTCAATTGATA 
               
               
                   
                 ATTTTAATAAGGAGATTTTGTTAGATAGATCTGCTGGTCAAAATG 
               
               
                   
                 GTGCCTTTAAAATCAAATTGGACTACGTTAAGAAGCCTATTCCAG 
               
               
                   
                 AATCCGTCTTTGTTCAAATTTTGGAGAAGTTATACGAAGAAGATA 
               
               
                   
                 TTGGTGCTGGTATGTACGCCTTGTATCCATATGGTGGTATTATGG 
               
               
                   
                 ATGAAATTTCTGAATCCGCCATCCCTTTCCCTCATCGTGCTGGTA 
               
               
                   
                 TCTTATACGAGTTGTGGTACATCTGTTCTTGGGAAAAGCAAGAAG 
               
               
                   
                 ATAATGAAAAGCATTTGAACTGGATCCGTAACATCTATAACTTCA 
               
               
                   
                 TGACTCCATACGTTTCCAAAAACCCTAGATTGGCTTACTTAAATT 
               
               
                   
                 ACAGAGACTTAGATATTGGTATTAACGACCCTAAGAACCCAAACA 
               
               
                   
                 ATTACACTCAAGCTAGAATCTGGGGTGAAAAGTACTTCGGTAAGA 
               
               
                   
                 ATTTCGACAGATTAGTTAAGGTCAAGACTTTAGTTGACCCAAATA 
               
               
                   
                 ACTTCTTCAGAAACGAACAATCTATCCCACCATTGCCTAGACATA 
               
               
                   
                 GACACTAG 
               
               
                   
               
               
                 SEQ ID NO: 122 
                 MKCSTFSFWFVCKIIFFFFSFNIQTSIANPRENFLKCFSQYIPNN 
               
               
                 CBDA Synthase, 
                 ATNLKLVYTQNNPLYMSVLNSTIHNLRFTSDTTPKPLVIVTPSHV 
               
               
                 T109V variant 
                 SHIQGTILCSKKVGLQIRVRSGGHDSEGMSYISQVPFVIVDLRNM 
               
               
                 Artificial Sequence 
                 RSIKIDVHSQTAWVEAGATLGEVYYWVNEKNENLSLAAGYCPTVC 
               
               
                   
                 AGGHFGGGGYGPLMRNYGLAADNIIDAHLVNVHGKVLDRKSMGED 
               
               
                   
                 LFWALRGGGAESFGIIVAWKIRLVAVPKSTMFSVKKIMEIHELVK 
               
               
                   
                 LVNKWQNIAYKYDKDLLLMTHFITRNITDNQGKNKTAIHTYFSSV 
               
               
                   
                 FLGGVDSLVDLMNKSFPELGIKKTDCRQLSWIDTIIFYSGVVNYD 
               
               
                   
                 TDNFNKEILLDRSAGQNGAFKIKLDYVKKPIPESVFVQILEKLYE 
               
               
                   
                 EDIGAGMYALYPYGGIMDEISESAIPFPHRAGILYELWYICSWEK 
               
               
                   
                 QEDNEKHLNWIRNIYNFMTPYVSKNPRLAYLNYRDLDIGINDPKN 
               
               
                   
                 PNNYTQARIWGEKYFGKNFDRLVKVKTLVDPNNFFRNEQSIPPLP 
               
               
                   
                 RHRH* 
               
               
                   
               
               
                 SEQ ID NO: 123 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                 CBDA Synthase, 
                 TTCTTCTTCTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 Q124D variant 
                 CGTGAGAACTTCTTGAAATGTTTTTCTCAATATATCCCAAATAAC 
               
               
                 Artificial Sequence 
                 GCTACTAACTTGAAGTTAGTCTATACTCAAAACAACCCATTATAT 
               
               
                 Codon optimized 
                 ATGTCTGTCTTAAACTCTACCATTCACAACTTACGTTTCACTTCT 
               
               
                   
                 GATACTACTCCAAAACCTTTGGTCATCGTCACCCCATCCCACGTT 
               
               
                   
                 TCTCACATCCAAGGTACCATCTTGTGTTCCAAAAAGGTTGGTTTA 
               
               
                   
                 CAAATCCGTACTAGATCCGGTGGTCATGACTCCGAAGGTATGTCT 
               
               
                   
                 TACATTTCCgatGTCCCTTTCGTCATCGTCGACTTAAGAAATATG 
               
               
                   
                 CGTTCCATCAAGATTGATGTCCATTCCCAAACTGCTTGGGTTGAA 
               
               
                   
                 GCCGGTGCCACTTTAGGTGAAGTCTATTACTGGGTTAACGAGAAG 
               
               
                   
                 AATGAGAACTTATCTTTGGCTGCCGGTTACTGTCCAACTGTTTGT 
               
               
                   
                 GCTGGTGGTCATTTCGGTGGTGGTGGTTACGGTCCATTAATGCGT 
               
               
                   
                 AACTACGGTTTGGCTGCCGATAACATCATTGATGCCCACTTAGTC 
               
               
                   
                 AACGTTCATGGTAAGGTCTTGGACCGTAAGTCTATGGGTGAGGAT 
               
               
                   
                 TTATTCTGGGCTTTGAGAGGTGGTGGTGCTGAATCTTTCGGTATT 
               
               
                   
                 ATCGTCGCTTGGAAGATTAGATTAGTTGCTGTTCCAAAGTCTACT 
               
               
                   
                 ATGTTCTCTGTTAAGAAGATCATGGAAATTCACGAGTTGGTTAAA 
               
               
                   
                 TTAGTTAACAAATGGCAAAACATTGCCTACAAGTACGATAAAGAT 
               
               
                   
                 TTGTTATTAATGACTCACTTTATCACTAGAAACATTACTGATAAC 
               
               
                   
                 CAAGGTAAGAATAAGACTGCCATTCACACTTACTTCTCTTCTGTT 
               
               
                   
                 TTCTTGGGTGGTGTTGATTCCTTGGTCGATTTGATGAACAAGTCT 
               
               
                   
                 TTTCCAGAATTAGGTATTAAGAAGACCGATTGTCGTCAATTATCT 
               
               
                   
                 TGGATTGATACCATTATTTTTTACTCCGGTGTTGTCAACTACGAC 
               
               
                   
                 ACTGATAATTTTAATAAGGAGATTTTGTTAGATAGATCTGCTGGT 
               
               
                   
                 CAAAATGGTGCCTTTAAAATCAAATTGGACTACGTTAAGAAGCCT 
               
               
                   
                 ATTCCAGAATCCGTCTTTGTTCAAATTTTGGAGAAGTTATACGAA 
               
               
                   
                 GAAGATATTGGTGCTGGTATGTACGCCTTGTATCCATATGGTGGT 
               
               
                   
                 ATTATGGATGAAATTTCTGAATCCGCCATCCCTTTCCCTCATCGT 
               
               
                   
                 GCTGGTATCTTATACGAGTTGTGGTACATCTGTTCTTGGGAAAAG 
               
               
                   
                 CAAGAAGATAATGAAAAGCATTTGAACTGGATCCGTAACATCTAT 
               
               
                   
                 AACTTCATGACTCCATACGTTTCCAAAAACCCTAGATTGGCTTAC 
               
               
                   
                 TTAAATTACAGAGACTTAGATATTGGTATTAACGACCCTAAGAAC 
               
               
                   
                 CCAAACAATTACACTCAAGCTAGAATCTGGGGTGAAAAGTACTTC 
               
               
                   
                 GGTAAGAATTTCGACAGATTAGTTAAGGTCAAGACTTTAGTTGAC 
               
               
                   
                 CCAAATAACTTCTTCAGAAACGAACAATCTATCCCACCATTGCCT 
               
               
                   
                 AGACATAGACACTAG 
               
               
                   
               
               
                 SEQ ID NO: 124 
                 MKCSTFSFWFVCKIIFFFFSFNIQTSIANPRENFLKCFSQYIPNN 
               
               
                 CBDA Synthase, 
                 ATNLKLVYTQNNPLYMSVLNSTIHNLRFTSDTTPKPLVIVTPSHV 
               
               
                 Q124D variant 
                 SHIQGTILCSKKVGLQIRTRSGGHDSEGMSYISDVPFVIVDLRNM 
               
               
                 Artificial Sequence 
                 RSIKIDVHSQTAWVEAGATLGEVYYWVNEKNENLSLAAGYCPTVC 
               
               
                   
                 AGGHFGGGGYGPLMRNYGLAADNIIDAHLVNVHGKVLDRKSMGED 
               
               
                   
                 LFWALRGGGAESFGIIVAWKIRLVAVPKSTMFSVKKIMEIHELVK 
               
               
                   
                 LVNKWQNIAYKYDKDLLLMTHFITRNITDNQGKNKTAIHTYFSSV 
               
               
                   
                 FLGGVDSLVDLMNKSFPELGIKKTDCRQLSWIDTHFYSGWNYDTD 
               
               
                   
                 NFNKEILLDRSAGQNGAFKIKLDYVKKPIPESVFVQILEKLYEED 
               
               
                   
                 IGAGMYALYPYGGIMDEISESAIPFPHRAGILYELWYICSWEKQE 
               
               
                   
                 DNEKHLNWIRNIYNFMTPYVSKNPRLAYLNYRDLDIGINDPKNPN 
               
               
                   
                 NYTQARIWGEKYFGKNFDRLVKVKTLVDPNNFFRNEQSIPPLPRH 
               
               
                   
                 RH* 
               
               
                   
               
               
                 SEQ ID NO: 125 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                 CBDA Synthase, 
                 TTCTTCTTCTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 Q124E variant 
                 CGTGAGAACTTCTTGAAATGTTTTTCTCAATATATCCCAAATAAC 
               
               
                 Artificial Sequence 
                 GCTACTAACTTGAAGTTAGTCTATACTCAAAACAACCCATTATAT 
               
               
                 Codon optimized 
                 ATGTCTGTCTTAAACTCTACCATTCACAACTTACGTTTCACTTCT 
               
               
                   
                 GATACTACTCCAAAACCTTTGGTCATCGTCACCCCATCCCACGTT 
               
               
                   
                 TCTCACATCCAAGGTACCATCTTGTGTTCCAAAAAGGTTGGTTTA 
               
               
                   
                 CAAATCCGTACTAGATCCGGTGGTCATGACTCCGAAGGTATGTCT 
               
               
                   
                 TACATTTCCgaaGTCCCTTTCGTCATCGTCGACTTAAGAAATATG 
               
               
                   
                 CGTTCCATCAAGATTGATGTCCATTCCCAAACTGCTTGGGTTGAA 
               
               
                   
                 GCCGGTGCCACTTTAGGTGAAGTCTATTACTGGGTTAACGAGAAG 
               
               
                   
                 AATGAGAACTTATCTTTGGCTGCCGGTTACTGTCCAACTGTTTGT 
               
               
                   
                 GCTGGTGGTCATTTCGGTGGTGGTGGTTACGGTCCATTAATGCGT 
               
               
                   
                 AACTACGGTTTGGCTGCCGATAACATCATTGATGCCCACTTAGTC 
               
               
                   
                 AACGTTCATGGTAAGGTCTTGGACCGTAAGTCTATGGGTGAGGAT 
               
               
                   
                 TTATTCTGGGCTTTGAGAGGTGGTGGTGCTGAATCTTTCGGTATT 
               
               
                   
                 ATCGTCGCTTGGAAGATTAGATTAGTTGCTGTTCCAAAGTCTACT 
               
               
                   
                 ATGTTCTCTGTTAAGAAGATCATGGAAATTCACGAGTTGGTTAAA 
               
               
                   
                 TTAGTTAACAAATGGCAAAACATTGCCTACAAGTACGATAAAGAT 
               
               
                   
                 TTGTTATTAATGACTCACTTTATCACTAGAAACATTACTGATAAC 
               
               
                   
                 CAAGGTAAGAATAAGACTGCCATTCACACTTACTTCTCTTCTGTT 
               
               
                   
                 TTCTTGGGTGGTGTTGATTCCTTGGTCGATTTGATGAACAAGTCT 
               
               
                   
                 TTTCCAGAATTAGGTATTAAGAAGACCGATTGTCGTCAATTGATA 
               
               
                   
                 ATTTTAATAAGGAGATTTTGTTAGATAGATCTGCTGGTCAAAATG 
               
               
                   
                 GTGCCTTTAAAATCAAATTGGACTACGTTAAGAAGCCTATTCCAG 
               
               
                   
                 AATCCGTCTTTGTTCAAATTTTGGAGAAGTTATACGAAGAAGATA 
               
               
                   
                 TTGGTGCTGGTATGTACGCCTTGTATCCATATGGTGGTATTATGG 
               
               
                   
                 ATGAAATTTCTGAATCCGCCATCCCTTTCCCTCATCGTGCTGGTA 
               
               
                   
                 TCTTATACGAGTTGTGGTACATCTGTTCTTGGGAAAAGCAAGAAG 
               
               
                   
                 ATAATGAAAAGCATTTGAACTGGATCCGTAACATCTATAACTTCA 
               
               
                   
                 TGACTCCATACGTTTCCAAAAACCCTAGATTGGCTTACTTAAATT 
               
               
                   
                 ACAGAGACTTAGATATTGGTATTAACGACCCTAAGAACCCAAACA 
               
               
                   
                 ATTACACTCAAGCTAGAATCTGGGGTGAAAAGTACTTCGGTAAGA 
               
               
                   
                 ATTTCGACAGATTAGTTAAGGTCAAGACTTTAGTTGACCCAAATA 
               
               
                   
                 ACTTCTTCAGAAACGAACAATCTATCCCACCATTGCCTAGACATA 
               
               
                   
                 GACACTAG 
               
               
                   
               
               
                 SEQ ID NO: 126 
                 MKCSTFSFWFVCKIIFFFFSFNIQTSIANPRENFLKCFSQYIPNN 
               
               
                 CBDA Synthase, 
                 ATNLKLVYTQNNPLYMSVLNSTIHNLRFTSDTTPKPLVIVTPSHV 
               
               
                 Q124E variant 
                 SHIQGTILCSKKVGLQIRTRSGGHDSEGMSYISEVPFVIVDLRNM 
               
               
                 Artificial Sequence 
                 RSIKIDVHSQTAWVEAGATLGEVYYWVNEKNENLSLAAGYCPTVC 
               
               
                   
                 AGGHFGGGGYGPLMRNYGLAADNIIDAHLVNVHGKVLDRKSMGED 
               
               
                   
                 LFWALRGGGAESFGIIVAWKIRLVAVPKSTMFSVKKIMEIHELVK 
               
               
                   
                 LVNKWQNIAYKYDKDLLLMTHFITRNITDNQGKNKTAIHTYFSSV 
               
               
                   
                 FLGGVDSLVDLMNKSFPELGIKKTDCRQLSWIDTIIFYSGVVNYD 
               
               
                   
                 TDNFNKEILLDRSAGQNGAFKIKLDYVKKPIPESVFVQILEKLYE 
               
               
                   
                 EDIGAGMYALYPYGGIMDEISESAIPFPHRAGILYELWYICSWEK 
               
               
                   
                 QEDNEKHLNWIRNIYNFMTPYVSKNPRLAYLNYRDLDIGINDPKN 
               
               
                   
                 PNNYTQARIWGEKYFGKNFDRLVKVKTLVDPNNFFRNEQSIPPLP 
               
               
                   
                 RHRH* 
               
               
                   
               
               
                 SEQ ID NO: 127 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                 CBDA Synthase, 
                 TTCTTCTTCTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 Q124N variant 
                 CGTGAGAACTTCTTGAAATGTTTTTCTCAATATATCCCAAATAAC 
               
               
                 Artificial Sequence 
                 GCTACTAACTTGAAGTTAGTCTATACTCAAAACAACCCATTATAT 
               
               
                 Codon optimized 
                 ATGTCTGTCTTAAACTCTACCATTCACAACTTACGTTTCACTTCT 
               
               
                   
                 GATACTACTCCAAAACCTTTGGTCATCGTCACCCCATCCCACGTT 
               
               
                   
                 TCTCACATCCAAGGTACCATCTTGTGTTCCAAAAAGGTTGGTTTA 
               
               
                   
                 CAAATCCGTACTAGATCCGGTGGTCATGACTCCGAAGGTATGTCT 
               
               
                   
                 TACATTTCCaatGTCCCTTTCGTCATCGTCGACTTAAGAAATATG 
               
               
                   
                 CGTTCCATCAAGATTGATGTCCATTCCCAAACTGCTTGGGTTGAA 
               
               
                   
                 GCCGGTGCCACTTTAGGTGAAGTCTATTACTGGGTTAACGAGAAG 
               
               
                   
                 AATGAGAACTTATCTTTGGCTGCCGGTTACTGTCCAACTGTTTGT 
               
               
                   
                 GCTGGTGGTCATTTCGGTGGTGGTGGTTACGGTCCATTAATGCGT 
               
               
                   
                 AACTACGGTTTGGCTGCCGATAACATCATTGATGCCCACTTAGTC 
               
               
                   
                 AACGTTCATGGTAAGGTCTTGGACCGTAAGTCTATGGGTGAGGAT 
               
               
                   
                 TTATTCTGGGCTTTGAGAGGTGGTGGTGCTGAATCTTTCGGTATT 
               
               
                   
                 ATCGTCGCTTGGAAGATTAGATTAGTTGCTGTTCCAAAGTCTACT 
               
               
                   
                 ATGTTCTCTGTTAAGAAGATCATGGAAATTCACGAGTTGGTTAAA 
               
               
                   
                 TTAGTTAACAAATGGCAAAACATTGCCTACAAGTACGATAAAGAT 
               
               
                   
                 TTGTTATTAATGACTCACTTTATCACTAGAAACATTACTGATAAC 
               
               
                   
                 CAAGGTAAGAATAAGACTGCCATTCACACTTACTTCTCTTCTGTT 
               
               
                   
                 TTCTTGGGTGGTGTTGATTCCTTGGTCGATTTGATGAACAAGTCT 
               
               
                   
                 TTTCCAGAATTAGGTATTAAGAAGACCGATTGTCGTCAATTATCT 
               
               
                   
                 TGGATTGATACCATTATTTTTTACTCCGGTGTTGTCAACTACGAC 
               
               
                   
                 ACTGATAATTTTAATAAGGAGATTTTGTTAGATAGATCTGCTGGT 
               
               
                   
                 CAAAATGGTGCCTTTAAAATCAAATTGGACTACGTTAAGAAGCCT 
               
               
                   
                 ATTCCAGAATCCGTCTTTGTTCAAATTTTGGAGAAGTTATACGAA 
               
               
                   
                 GAAGATATTGGTGCTGGTATGTACGCCTTGTATCCATATGGTGGT 
               
               
                   
                 ATTATGGATGAAATTTCTGAATCCGCCATCCCTTTCCCTCATCGT 
               
               
                   
                 GCTGGTATCTTATACGAGTTGTGGTACATCTGTTCTTGGGAAAAG 
               
               
                   
                 CAAGAAGATAATGAAAAGCATTTGAACTGGATCCGTAACATCTAT 
               
               
                   
                 AACTTCATGACTCCATACGTTTCCAAAAACCCTAGATTGGCTTAC 
               
               
                   
                 TTAAATTACAGAGACTTAGATATTGGTATTAACGACCCTAAGAAC 
               
               
                   
                 CCAAACAATTACACTCAAGCTAGAATCTGGGGTGAAAAGTACTTC 
               
               
                   
                 GGTAAGAATTTCGACAGATTAGTTAAGGTCAAGACTTTAGTTGAC 
               
               
                   
                 CCAAATAACTTCTTCAGAAACGAACAATCTATCCCACCATTGCCT 
               
               
                   
                 AGACATAGACACTAG 
               
               
                   
               
               
                 SEQ ID NO: 128 
                 MKCSTFSFWFVCKIIFFFFSFNIQTSIANPRENFLKCFSQYIPNN 
               
               
                 CBDA Synthase, 
                 ATNLKLVYTQNNPLYMSVLNSTIHNLRFTSDTTPKPLVIVTPSHV 
               
               
                 Q124N variant 
                 SHIQGTILCSKKVGLQIRTRSGGHDSEGMSYISNVPFVIVDLRNM 
               
               
                 Artificial Sequence 
                 RSIKIDVHSQTAWVEAGATLGEVYYWVNEKNENLSLAAGYCPTVC 
               
               
                   
                 AGGHFGGGGYGPLMRNYGLAADNIIDAHLVNVHGKVLDRKSMGED 
               
               
                   
                 LFWALRGGGAESFGIIVAWKIRLVAVPKSTMFSVKKIMEIHELVK 
               
               
                   
                 LVNKWQNIAYKYDKDLLLMTHFITRNITDNQGKNKTAIHTYFSSV 
               
               
                   
                 FLGGVDSLVDLMNKSFPELGIKKTDCRQLSWIDTIIFYSGWNYDT 
               
               
                   
                 DNFNKEILLDRSAGQNGAFKKLDYVKKPIPESVFVQILEKLYEED 
               
               
                   
                 IGAGMYALYPYGGIMDEISESAIPFPHRAGILYELWYICSWEKQE 
               
               
                   
                 DNEKHLNWIRNIYNFMTPYVSKNPRLAYLNYRDLDIGINDPKNPN 
               
               
                   
                 NYTQARIWGEKYFGKNFDRLVKVKTLVDPNNFFRNEQSIPPLPRH 
               
               
                   
                 RH* 
               
               
                   
               
               
                 SEQ ID NO: 129 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                 CBDA Synthase, 
                 TTCTTCTTCTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 V125E variant 
                 CGTGAGAACTTCTTGAAATGTTTTTCTCAATATATCCCAAATAAC 
               
               
                 Artificial Sequence 
                 GCTACTAACTTGAAGTTAGTCTATACTCAAAACAACCCATTATAT 
               
               
                 Codon optimized 
                 ATGTCTGTCTTAAACTCTACCATTCACAACTTACGTTTCACTTCT 
               
               
                   
                 GATACTACTCCAAAACCTTTGGTCATCGTCACCCCATCCCACGTT 
               
               
                   
                 TCTCACATCCAAGGTACCATCTTGTGTTCCAAAAAGGTTGGTTTA 
               
               
                   
                 CAAATCCGTACTAGATCCGGTGGTCATGACTCCGAAGGTATGTCT 
               
               
                   
                 TACATTTCCCAAgaaCCTTTCGTCATCGTCGACTTAAGAAATATG 
               
               
                   
                 CGTTCCATCAAGATTGATGTCCATTCCCAAACTGCTTGGGTTGAA 
               
               
                   
                 GCCGGTGCCACTTTAGGTGAAGTCTATTACTGGGTTAACGAGAAG 
               
               
                   
                 AATGAGAACTTATCTTTGGCTGCCGGTTACTGTCCAACTGTTTGT 
               
               
                   
                 GCTGGTGGTCATTTCGGTGGTGGTGGTTACGGTCCATTAATGCGT 
               
               
                   
                 AACTACGGTTTGGCTGCCGATAACATCATTGATGCCCACTTAGTC 
               
               
                   
                 AACGTTCATGGTAAGGTCTTGGACCGTAAGTCTATGGGTGAGGAT 
               
               
                   
                 TTATTCTGGGCTTTGAGAGGTGGTGGTGCTGAATCTTTCGGTATT 
               
               
                   
                 ATCGTCGCTTGGAAGATTAGATTAGTTGCTGTTCCAAAGTCTACT 
               
               
                   
                 ATGTTCTCTGTTAAGAAGATCATGGAAATTCACGAGTTGGTTAAA 
               
               
                   
                 TTAGTTAACAAATGGCAAAACATTGCCTACAAGTACGATAAAGAT 
               
               
                   
                 TTGTTATTAATGACTCACTTTATCACTAGAAACATTACTGATAAC 
               
               
                   
                 CAAGGTAAGAATAAGACTGCCATTCACACTTACTTCTCTTCTGTT 
               
               
                   
                 TTCTTGGGTGGTGTTGATTCCTTGGTCGATTTGATGAACAAGTCT 
               
               
                   
                 TTTCCAGAATTAGGTATTAAGAAGACCGATTGTCGTCAATTATCT 
               
               
                   
                 TGGATTGATACCATTATTTTTTACTCCGGTGTTGTCAACTACGAC 
               
               
                   
                 ACTGATAATTTTAATAAGGAGATTTTGTTAGATAGATCTGCTGGT 
               
               
                   
                 CAAAATGGTGCCTTTAAAATCAAATTGGACTACGTTAAGAAGCCT 
               
               
                   
                 ATTCCAGAATCCGTCTTTGTTCAAATTTTGGAGAAGTTATACGAA 
               
               
                   
                 GAAGATATTGGTGCTGGTATGTACGCCTTGTATCCATATGGTGGT 
               
               
                   
                 ATTATGGATGAAATTTCTGAATCCGCCATCCCTTTCCCTCATCGT 
               
               
                   
                 GCTGGTATCTTATACGAGTTGTGGTACATCTGTTCTTGGGAAAAG 
               
               
                   
                 CAAGAAGATAATGAAAAGCATTTGAACTGGATCCGTAACATCTAT 
               
               
                   
                 AACTTCATGACTCCATACGTTTCCAAAAACCCTAGATTGGCTTAC 
               
               
                   
                 TTAAATTACAGAGACTTAGATATTGGTATTAACGACCCTAAGAAC 
               
               
                   
                 CCAAACAATTACACTCAAGCTAGAATCTGGGGTGAAAAGTACTTC 
               
               
                   
                 GGTAAGAATTTCGACAGATTAGTTAAGGTCAAGACTTTAGTTGAC 
               
               
                   
                 CCAAATAACTTCTTCAGAAACGAACAATCTATCCCACCATTGCCT 
               
               
                   
                 AGACATAGACACTAG 
               
               
                   
               
               
                 SEQ ID NO: 130 
                 MKCSTFSFWFVCKIIFFFFSFNIQTSIANPRENFLKCFSQYIPNN 
               
               
                 CBDA Synthase, 
                 ATNLKLVYTQNNPLYMSVLNSTIHNLRFTSDTTPKPLVIVTPSHV 
               
               
                 V123E variant 
                 SHIQGTILCSKKVGLQIRTRSGGHDSEGMSYISQEPFVIVDLRNM 
               
               
                 Artificial Sequence 
                 RSIKIDVHSQTAWVEAGATLGEVYYWVNEKNENLSLAAGYCPTVC 
               
               
                   
                 AGGHFGGGGYGPLMRNYGLAADNIIDAHLVNVHGKVLDRKSMGED 
               
               
                   
                 LFWALRGGGAESFGIIVAWKIRLVAVPKSTMFSVKKIMEIHELVK 
               
               
                   
                 LVNKWQNIAYKYDKDLLLMTHFITRNITDNQGKNKTAIHTYFSSV 
               
               
                   
                 FLGGVDSLVDLMNKSFPELGIKKTDCRQLSWIDTIIFYSGWNYDT 
               
               
                   
                 DNFNKEILLDRSAGQNGAFKIKLDYVKKPIPESVFVQILEKLYEE 
               
               
                   
                 DIGAGMYALYPYGGIMDEISESAIPFPHRAGILYELWYICSWEKQ 
               
               
                   
                 EDNEKHLNWIRNIYNFMTPYVSKNPRLAYLNYRDLDIGINDPKNP 
               
               
                   
                 NNYTQARIWGEKYFGKNFDRLVKVKTLVDPNNFFRNEQSIPPLPR 
               
               
                   
                 HRH* 
               
               
                   
               
               
                 SEQ ID NO: 131 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                 CBDA Synthase, 
                 TTCTTCTTCTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 V125Q variant 
                 CGTGAGAACTTCTTGAAATGTTTTTCTCAATATATCCCAAATAAC 
               
               
                 Artificial Sequence 
                 GCTACTAACTTGAAGTTAGTCTATACTCAAAACAACCCATTATAT 
               
               
                 Codon optimized 
                 ATGTCTGTCTTAAACTCTACCATTCACAACTTACGTTTCACTTCT 
               
               
                   
                 GATACTACTCCAAAACCTTTGGTCATCGTCACCCCATCCCACGTT 
               
               
                   
                 TCTCACATCCAAGGTACCATCTTGTGTTCCAAAAAGGTTGGTTTA 
               
               
                   
                 CAAATCCGTACTAGATCCGGTGGTCATGACTCCGAAGGTATGTCT 
               
               
                   
                 TACATTTCCCAAcaaCCTTTCGTCATCGTCGACTTAAGAAATATG 
               
               
                   
                 CGTTCCATCAAGATTGATGTCCATTCCCAAACTGCTTGGGTTGAA 
               
               
                   
                 GCCGGTGCCACTTTAGGTGAAGTCTATTACTGGGTTAACGAGAAG 
               
               
                   
                 AATGAGAACTTATCTTTGGCTGCCGGTTACTGTCCAACTGTTTGT 
               
               
                   
                 GCTGGTGGTCATTTCGGTGGTGGTGGTTACGGTCCATTAATGCGT 
               
               
                   
                 AACTACGGTTTGGCTGCCGATAACATCATTGATGCCCACTTAGTC 
               
               
                   
                 AACGTTCATGGTAAGGTCTTGGACCGTAAGTCTATGGGTGAGGAT 
               
               
                   
                 TTATTCTGGGCTTTGAGAGGTGGTGGTGCTGAATCTTTCGGTATT 
               
               
                   
                 ATCGTCGCTTGGAAGATTAGATTAGTTGCTGTTCCAAAGTCTACT 
               
               
                   
                 ATGTTCTCTGTTAAGAAGATCATGGAAATTCACGAGTTGGTTAAA 
               
               
                   
                 TTAGTTAACAAATGGCAAAACATTGCCTACAAGTACGATAAAGAT 
               
               
                   
                 TTGTTATTAATGACTCACTTTATCACTAGAAACATTACTGATAAC 
               
               
                   
                 CAAGGTAAGAATAAGACTGCCATTCACACTTACTTCTCTTCTGTT 
               
               
                   
                 TTCTTGGGTGGTGTTGATTCCTTGGTCGATTTGATGAACAAGTCT 
               
               
                   
                 TTTCCAGAATTAGGTATTAAGAAGACCGATTGTCGTCAATTGATA 
               
               
                   
                 ATTTTAATAAGGAGATTTTGTTAGATAGATCTGCTGGTCAAAATG 
               
               
                   
                 GTGCCTTTAAAATCAAATTGGACTACGTTAAGAAGCCTATTCCAG 
               
               
                   
                 AATCCGTCTTTGTTCAAATTTTGGAGAAGTTATACGAAGAAGATA 
               
               
                   
                 TTGGTGCTGGTATGTACGCCTTGTATCCATATGGTGGTATTATGG 
               
               
                   
                 ATGAAATTTCTGAATCCGCCATCCCTTTCCCTCATCGTGCTGGTA 
               
               
                   
                 TCTTATACGAGTTGTGGTACATCTGTTCTTGGGAAAAGCAAGAAG 
               
               
                   
                 ATAATGAAAAGCATTTGAACTGGATCCGTAACATCTATAACTTCA 
               
               
                   
                 TGACTCCATACGTTTCCAAAAACCCTAGATTGGCTTACTTAAATT 
               
               
                   
                 ACAGAGACTTAGATATTGGTATTAACGACCCTAAGAACCCAAACA 
               
               
                   
                 ATTACACTCAAGCTAGAATCTGGGGTGAAAAGTACTTCGGTAAGA 
               
               
                   
                 ATTTCGACAGATTAGTTAAGGTCAAGACTTTAGTTGACCCAAATA 
               
               
                   
                 ACTTCTTCAGAAACGAACAATCTATCCCACCATTGCCTAGACATA 
               
               
                   
                 GACACTAG 
               
               
                   
               
               
                 SEQ ID NO: 132 
                 MKCSTFSFWFVCKIIFFFFSFNIQTSIANPRENFLKCFSQYTPNN 
               
               
                 CBDA Synthase, 
                 ATNLKLVYTQNNPLYMSVLNSTIHNLRFTSDTTPKPLVIVTPSHV 
               
               
                 V125Q variant 
                 SHIQGTILCSKKVGLQIRTRSGGHDSEGMSYISQQPFVIVDLRNM 
               
               
                 Artificial Sequence 
                 RSIKIDVHSQTAWVEAGATLGEVYYWVNEKNENLSLAAGYCPTVC 
               
               
                   
                 AGGHFGGGGYGPLMRNYGLAADNIIDAHLVNVHGKVLDRKSMGED 
               
               
                   
                 LFWALRGGGAESFGIIVAWKIRLVAVPKSTMFSVKKIMEIHELVK 
               
               
                   
                 LVNKWQNIAYKYDKDLLLMTHFITRNITDNQGKNKTAIHTYFSSV 
               
               
                   
                 FLGGVDSLVDLMNKSFPELGIKKTDCRQLSWIDTIIFYSGVVNYD 
               
               
                   
                 TDNFNKEILLDRSAGQNGAFKKLDYVKKPIPESVFVQILEKLYEE 
               
               
                   
                 DIGAGMYALYPYGGIMDEISESAIPFPHRAGILYELWYICSWEKQ 
               
               
                   
                 EDNEKHLNWIRNIYNFMTPYVSKNPRLAYLNYRDLDIGINDPKNP 
               
               
                   
                 NNYTQARIWGEKYFGKNFDRLVKVKTLVDPNNFFRNEQSIPPLPR 
               
               
                   
                 HRH* 
               
               
                   
               
               
                 SEQ ID NO: 133 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                 CBDA Synthase, 1129V 
                 TTCTTCTTCTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 variant 
                 CGTGAGAACTTCTTGAAATGTTTTTCTCAATATATCCCAAATAAC 
               
               
                 Artificial Sequence 
                 GCTACTAACTTGAAGTTAGTCTATACTCAAAACAACCCATTATAT 
               
               
                 Codon optimized 
                 ATGTCTGTCTTAAACTCTACCATTCACAACTTACGTTTCACTTCT 
               
               
                   
                 GATACTACTCCAAAACCTTTGGTCATCGTCACCCCATCCCACGTT 
               
               
                   
                 TCTCACATCCAAGGTACCATCTTGTGTTCCAAAAAGGTTGGTTTA 
               
               
                   
                 CAAATCCGTACTAGATCCGGTGGTCATGACTCCGAAGGTATGTCT 
               
               
                   
                 TACATTTCCCAAGTCCCTTTCGTCgttGTCGACTTAAGAAATATG 
               
               
                   
                 CGTTCCATCAAGATTGATGTCCATTCCCAAACTGCTTGGGTTGAA 
               
               
                   
                 GCCGGTGCCACTTTAGGTGAAGTCTATTACTGGGTTAACGAGAAG 
               
               
                   
                 AATGAGAACTTATCTTTGGCTGCCGGTTACTGTCCAACTGTTTGT 
               
               
                   
                 GCTGGTGGTCATTTCGGTGGTGGTGGTTACGGTCCATTAATGCGT 
               
               
                   
                 AACTACGGTTTGGCTGCCGATAACATCATTGATGCCCACTTAGTC 
               
               
                   
                 AACGTTCATGGTAAGGTCTTGGACCGTAAGTCTATGGGTGAGGAT 
               
               
                   
                 TTATTCTGGGCTTTGAGAGGTGGTGGTGCTGAATCTTTCGGTATT 
               
               
                   
                 ATCGTCGCTTGGAAGATTAGATTAGTTGCTGTTCCAAAGTCTACT 
               
               
                   
                 ATGTTCTCTGTTAAGAAGATCATGGAAATTCACGAGTTGGTTAAA 
               
               
                   
                 TTAGTTAACAAATGGCAAAACATTGCCTACAAGTACGATAAAGAT 
               
               
                   
                 TTGTTATTAATGACTCACTTTATCACTAGAAACATTACTGATAAC 
               
               
                   
                 CAAGGTAAGAATAAGACTGCCATTCACACTTACTTCTCTTCTGTT 
               
               
                   
                 TTCTTGGGTGGTGTTGATTCCTTGGTCGATTTGATGAACAAGTCT 
               
               
                   
                 TTTCCAGAATTAGGTATTAAGAAGACCGATTGTCGTCAATTGATA 
               
               
                   
                 ATTTTAATAAGGAGATTTTGTTAGATAGATCTGCTGGTCAAAATG 
               
               
                   
                 GTGCCTTTAAAATCAAATTGGACTACGTTAAGAAGCCTATTCCAG 
               
               
                   
                 AATCCGTCTTTGTTCAAATTTTGGAGAAGTTATACGAAGAAGATA 
               
               
                   
                 TTGGTGCTGGTATGTACGCCTTGTATCCATATGGTGGTATTATGG 
               
               
                   
                 ATGAAATTTCTGAATCCGCCATCCCTTTCCCTCATCGTGCTGGTA 
               
               
                   
                 TCTTATACGAGTTGTGGTACATCTGTTCTTGGGAAAAGCAAGAAG 
               
               
                   
                 ATAATGAAAAGCATTTGAACTGGATCCGTAACATCTATAACTTCA 
               
               
                   
                 TGACTCCATACGTTTCCAAAAACCCTAGATTGGCTTACTTAAATT 
               
               
                   
                 ACAGAGACTTAGATATTGGTATTAACGACCCTAAGAACCCAAACA 
               
               
                   
                 ATTACACTCAAGCTAGAATCTGGGGTGAAAAGTACTTCGGTAAGA 
               
               
                   
                 ATTTCGACAGATTAGTTAAGGTCAAGACTTTAGTTGACCCAAATA 
               
               
                   
                 ACTTCTTCAGAAACGAACAATCTATCCCACCATTGCCTAGACATA 
               
               
                   
                 GACACTAG 
               
               
                   
               
               
                 SEQ ID NO: 134 
                 MKCSTFSFWFVCKIIFFFFSFNIQTSIANPRENFLKCFSQYIPNN 
               
               
                 CBDA Synthase, 1129V 
                 ATNLKLVYTQNNPLYMSVLNSTIHNLRFTSDTTPKPLVIVTPSHV 
               
               
                 variant 
                 SHIQGTILCSKKVGLQIRTRSGGHDSEGMSYISQVPFVVVDLRNM 
               
               
                 Artificial Sequence 
                 RSIKIDVHSQTAWVEAGATLGEVYYWVNEKNENLSLAAGYCPTVC 
               
               
                   
                 AGGHFGGGGYGPLMRNYGLAADNIIDAHLVNVHGKVLDRKSMGED 
               
               
                   
                 LFWALRGGGAESFGIIVAWKIRLVAVPKSTMFSVKKIMEIHELVK 
               
               
                   
                 LVNKWQNIAYKYDKDLLLMTHFITRNITDNQGKNKTAIHTYFSSV 
               
               
                   
                 FLGGVDSLVDLMNKSFPELGIKKTDCRQLSWIDTIIFYSGWNYDT 
               
               
                   
                 DNFNKEILLDRSAGQNGAFKIKLDYVKKPIPESVFVQILEKLYEE 
               
               
                   
                 DIGAGMYALYPYGGIMDEISESAIPFPHRAGILYELWYICSWEKQ 
               
               
                   
                 EDNEKHLNWIRNIYNFMTPYVSKNPRLAYLNYRDLDIGINDPKNP 
               
               
                   
                 NNYTQARIWGEKYFGKNFDRLVKVKTLVDPNNFFRNEQSIPPLP 
               
               
                   
                 RHRH* 
               
               
                   
               
               
                 SEQ ID NO: 135 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                 CBDA Synthase, 
                 TTCTTCTTCTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 L132M variant 
                 CGTGAGAACTTCTTGAAATGTTTTTCTCAATATATCCCAAATAAC 
               
               
                 Artificial Sequence 
                 GCTACTAACTTGAAGTTAGTCTATACTCAAAACAACCCATTATAT 
               
               
                 Codon optimized 
                 ATGTCTGTCTTAAACTCTACCATTCACAACTTACGTTTCACTTCT 
               
               
                   
                 GATACTACTCCAAAACCTTTGGTCATCGTCACCCCATCCCACGTT 
               
               
                   
                 TCTCACATCCAAGGTACCATCTTGTGTTCCAAAAAGGTTGGTTTA 
               
               
                   
                 CAAATCCGTACTAGATCCGGTGGTCATGACTCCGAAGGTATGTCT 
               
               
                   
                 TACATTTCCCAAGTCCCTTTCGTCATCGTCGACatgAGAAATATG 
               
               
                   
                 CGTTCCATCAAGATTGATGTCCATTCCCAAACTGCTTGGGTTGAA 
               
               
                   
                 GCCGGTGCCACTTTAGGTGAAGTCTATTACTGGGTTAACGAGAAG 
               
               
                   
                 AATGAGAACTTATCTTTGGCTGCCGGTTACTGTCCAACTGTTTGT 
               
               
                   
                 GCTGGTGGTCATTTCGGTGGTGGTGGTTACGGTCCATTAATGCGT 
               
               
                   
                 AACTACGGTTTGGCTGCCGATAACATCATTGATGCCCACTTAGTC 
               
               
                   
                 AACGTTCATGGTAAGGTCTTGGACCGTAAGTCTATGGGTGAGGAT 
               
               
                   
                 TTATTCTGGGCTTTGAGAGGTGGTGGTGCTGAATCTTTCGGTATT 
               
               
                   
                 ATCGTCGCTTGGAAGATTAGATTAGTTGCTGTTCCAAAGTCTACT 
               
               
                   
                 ATGTTCTCTGTTAAGAAGATCATGGAAATTCACGAGTTGGTTAAA 
               
               
                   
                 TTAGTTAACAAATGGCAAAACATTGCCTACAAGTACGATAAAGAT 
               
               
                   
                 TTGTTATTAATGACTCACTTTATCACTAGAAACATTACTGATAAC 
               
               
                   
                 CAAGGTAAGAATAAGACTGCCATTCACACTTACTTCTCTTCTGTT 
               
               
                   
                 TTCTTGGGTGGTGTTGATTCCTTGGTCGATTTGATGAACAAGTCT 
               
               
                   
                 TTTCCAGAATTAGGTATTAAGAAGACCGATTGTCGTCAATTGATA 
               
               
                   
                 ATTTTAATAAGGAGATTTTGTTAGATAGATCTGCTGGTCAAAATG 
               
               
                   
                 GTGCCTTTAAAATCAAATTGGACTACGTTAAGAAGCCTATTCCAG 
               
               
                   
                 AATCCGTCTTTGTTCAAATTTTGGAGAAGTTATACGAAGAAGATA 
               
               
                   
                 TTGGTGCTGGTATGTACGCCTTGTATCCATATGGTGGTATTATGG 
               
               
                   
                 ATGAAATTTCTGAATCCGCCATCCCTTTCCCTCATCGTGCTGGTA 
               
               
                   
                 TCTTATACGAGTTGTGGTACATCTGTTCTTGGGAAAAGCAAGAAG 
               
               
                   
                 ATAATGAAAAGCATTTGAACTGGATCCGTAACATCTATAACTTCA 
               
               
                   
                 TGACTCCATACGTTTCCAAAAACCCTAGATTGGCTTACTTAAATT 
               
               
                   
                 ACAGAGACTTAGATATTGGTATTAACGACCCTAAGAACCCAAACA 
               
               
                   
                 ATTACACTCAAGCTAGAATCTGGGGTGAAAAGTACTTCGGTAAGA 
               
               
                   
                 ATTTCGACAGATTAGTTAAGGTCAAGACTTTAGTTGACCCAAATA 
               
               
                   
                 ACTTCTTCAGAAACGAACAATCTATCCCACCATTGCCTAGACATA 
               
               
                   
                 GACACTAG 
               
               
                   
               
               
                 SEQ ID NO: 136 
                 MKCSTFSFWFVCKIIFFFFSFNIQTSIANPRENFLKCFSQYIPNN 
               
               
                 CBDA Synthase, 
                 ATNLKLVYTQNNPLYMSVLNSTIHNLRFTSDTTPKPLVIVTPSHV 
               
               
                 L132M variant 
                 SHIQGTILCSKKVGLQIRTRSGGHDSEGMSYISQVPFVIVDMRNM 
               
               
                 Artificial Sequence 
                 RSIKIDVHSQTAWVEAGATLGEVYYWVNEKNENLSLAAGYCPTVC 
               
               
                   
                 AGGHFGGGGYGPLMRNYGLAADNIIDAHLVNVHGKVLDRKSMGED 
               
               
                   
                 LFWALRGGGAESFGIIVAWKIRLVAVPKSTMFSVKKIMEIHELVK 
               
               
                   
                 LVNKWQNIAYKYDKDLLLMTHFITRNITDNQGKNKTAIHTYFSSV 
               
               
                   
                 FLGGVDSLVDLMNKSFPELGIKKTDCRQLSWIDTIIFYSGVVNYD 
               
               
                   
                 TDNFNKEILLDRSAGQNGAFKIKLDYVKKPIPESVFVQILEKLYE 
               
               
                   
                 EDIGAGMYALYPYGGIMDEISESAIPFPHRAGILYELWYICSWEK 
               
               
                   
                 QEDNEKHLNWIRNIYNFMTPYVSKNPRLAYLNYRDLDIGINDPKN 
               
               
                   
                 PNNYTQARIWGEKYFGKNFDRLVKVKTLVDPNNFFRNEQSIPPLP 
               
               
                   
                 RHRH* 
               
               
                   
               
               
                 SEQ ID NO: 137 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                 CBDA Synthase, 
                 TTCTTCTTCTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 S137G variant 
                 CGTGAGAACTTCTTGAAATGTTTTTCTCAATATATCCCAAATAAC 
               
               
                 Artificial Sequence 
                 GCTACTAACTTGAAGTTAGTCTATACTCAAAACAACCCATTATAT 
               
               
                 Codon optimized 
                 ATGTCTGTCTTAAACTCTACCATTCACAACTTACGTTTCACTTCT 
               
               
                   
                 GATACTACTCCAAAACCTTTGGTCATCGTCACCCCATCCCACGTT 
               
               
                   
                 TCTCACATCCAAGGTACCATCTTGTGTTCCAAAAAGGTTGGTTTA 
               
               
                   
                 CAAATCCGTACTAGATCCGGTGGTCATGACTCCGAAGGTATGTCT 
               
               
                   
                 TACATTTCCCAAGTCCCTTTCGTCATCGTCGACTTAAGAAATATG 
               
               
                   
                 CGTggtATCAAGATTGATGTCCATTCCCAAACTGCTTGGGTTGAA 
               
               
                   
                 GCCGGTGCCACTTTAGGTGAAGTCTATTACTGGGTTAACGAGAAG 
               
               
                   
                 AATGAGAACTTATCTTTGGCTGCCGGTTACTGTCCAACTGTTTGT 
               
               
                   
                 GCTGGTGGTCATTTCGGTGGTGGTGGTTACGGTCCATTAATGCGT 
               
               
                   
                 AACTACGGTTTGGCTGCCGATAACATCATTGATGCCCACTTAGTC 
               
               
                   
                 AACGTTCATGGTAAGGTCTTGGACCGTAAGTCTATGGGTGAGGAT 
               
               
                   
                 TTATTCTGGGCTTTGAGAGGTGGTGGTGCTGAATCTTTCGGTATT 
               
               
                   
                 ATCGTCGCTTGGAAGATTAGATTAGTTGCTGTTCCAAAGTCTACT 
               
               
                   
                 ATGTTCTCTGTTAAGAAGATCATGGAAATTCACGAGTTGGTTAAA 
               
               
                   
                 TTAGTTAACAAATGGCAAAACATTGCCTACAAGTACGATAAAGAT 
               
               
                   
                 TTGTTATTAATGACTCACTTTATCACTAGAAACATTACTGATAAC 
               
               
                   
                 CAAGGTAAGAATAAGACTGCCATTCACACTTACTTCTCTTCTGTT 
               
               
                   
                 TTCTTGGGTGGTGTTGATTCCTTGGTCGATTTGATGAACAAGTCT 
               
               
                   
                 TTTCCAGAATTAGGTATTAAGAAGACCGATTGTCGTCAATTATCT 
               
               
                   
                 TGGATTGATACCATTATTTTTTACTCCGGTGTTGTCAACTACGAC 
               
               
                   
                 ACTGATAATTTTAATAAGGAGATTTTGTTAGATAGATCTGCTGGT 
               
               
                   
                 CAAAATGGTGCCTTTAAAATCAAATTGGACTACGTTAAGAAGCCT 
               
               
                   
                 ATTCCAGAATCCGTCTTTGTTCAAATTTTGGAGAAGTTATACGAA 
               
               
                   
                 GAAGATATTGGTGCTGGTATGTACGCCTTGTATCCATATGGTGGT 
               
               
                   
                 ATTATGGATGAAATTTCTGAATCCGCCATCCCTTTCCCTCATCGT 
               
               
                   
                 GCTGGTATCTTATACGAGTTGTGGTACATCTGTTCTTGGGAAAAG 
               
               
                   
                 CAAGAAGATAATGAAAAGCATTTGAACTGGATCCGTAACATCTAT 
               
               
                   
                 AACTTCATGACTCCATACGTTTCCAAAAACCCTAGATTGGCTTAC 
               
               
                   
                 TTAAATTACAGAGACTTAGATATTGGTATTAACGACCCTAAGAAC 
               
               
                   
                 CCAAACAATTACACTCAAGCTAGAATCTGGGGTGAAAAGTACTTC 
               
               
                   
                 GGTAAGAATTTCGACAGATTAGTTAAGGTCAAGACTTTAGTTGAC 
               
               
                   
                 CCAAATAACTTCTTCAGAAACGAACAATCTATCCCACCATTGCCT 
               
               
                   
                 AGACATAGACACTAG 
               
               
                   
               
               
                 SEQ ID NO: 138 
                 MKCSTFSFWFVCKIIFFFFSFNIQTSIANPRENFLKCFSQYIPNN 
               
               
                 CBDA Synthase, 
                 ATNLKLVYTQNNPLYMSVLNSTIHNLRFTSDTTPKPLVIVTPSHV 
               
               
                 S137G variant 
                 SHIQGTILCSKKVGLQIRTRSGGHDSEGMSYISQVPFVIVDLRNM 
               
               
                 Artificial Sequence 
                 RGIKIDVHSQTAWVEAGATLGEVYYWVNEKNENLSLAAGYCPTVC 
               
               
                   
                 AGGHFGGGGYGPLMRNYGLAADNIIDAHLVNVHGKVLDRKSMGED 
               
               
                   
                 LFWALRGGGAESFGIIVAWKIRLVAVPKSTMFSVKKIMEIHELVK 
               
               
                   
                 LVNKWQNIAYKYDKDLLLMTHFITRNITDNQGKNKTAIHTYFSSV 
               
               
                   
                 FLGGVDSLVDLMNKSFPELGIKKTDCRQLSWIDTIIFYSGVVNYD 
               
               
                   
                 TDNFNKEILLDRSAGQNGAFKKLDYVKKPIPESVFVQILEKLYEE 
               
               
                   
                 DIGAGMYALYPYGGIMDEISESAIPFPHRAGILYELWYICSWEKQ 
               
               
                   
                 EDNEKHLNWIRNIYNFMTPYVSKNPRLAYLNYRDLDIGINDPKNP 
               
               
                   
                 NNYTQARIWGEKYFGKNFDRLVKVKTLVDPNNFFRNEQSIPPLPR 
               
               
                   
                 HRH* 
               
               
                   
               
               
                 SEQ ID NO: 139 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                 CBDA Synthase, 
                 TTCTTCTTCTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 H143D variant 
                 CGTGAGAACTTCTTGAAATGTTTTTCTCAATATATCCCAAATAAC 
               
               
                 Artificial Sequence 
                 GCTACTAACTTGAAGTTAGTCTATACTCAAAACAACCCATTATAT 
               
               
                 Codon optimized 
                 ATGTCTGTCTTAAACTCTACCATTCACAACTTACGTTTCACTTCT 
               
               
                   
                 GATACTACTCCAAAACCTTTGGTCATCGTCACCCCATCCCACGTT 
               
               
                   
                 TCTCACATCCAAGGTACCATCTTGTGTTCCAAAAAGGTTGGTTTA 
               
               
                   
                 CAAATCCGTACTAGATCCGGTGGTCATGACTCCGAAGGTATGTCT 
               
               
                   
                 TACATTTCCCAAGTCCCTTTCGTCATCGTCGACTTAAGAAATATG 
               
               
                   
                 CGTTCCATCAAGATTGATGTCgatTCCCAAACTGCTTGGGTTGAA 
               
               
                   
                 GCCGGTGCCACTTTAGGTGAAGTCTATTACTGGGTTAACGAGAAG 
               
               
                   
                 AATGAGAACTTATCTTTGGCTGCCGGTTACTGTCCAACTGTTTGT 
               
               
                   
                 GCTGGTGGTCATTTCGGTGGTGGTGGTTACGGTCCATTAATGCGT 
               
               
                   
                 AACTACGGTTTGGCTGCCGATAACATCATTGATGCCCACTTAGTC 
               
               
                   
                 AACGTTCATGGTAAGGTCTTGGACCGTAAGTCTATGGGTGAGGAT 
               
               
                   
                 TTATTCTGGGCTTTGAGAGGTGGTGGTGCTGAATCTTTCGGTATT 
               
               
                   
                 ATCGTCGCTTGGAAGATTAGATTAGTTGCTGTTCCAAAGTCTACT 
               
               
                   
                 ATGTTCTCTGTTAAGAAGATCATGGAAATTCACGAGTTGGTTAAA 
               
               
                   
                 TTAGTTAACAAATGGCAAAACATTGCCTACAAGTACGATAAAGAT 
               
               
                   
                 TTGTTATTAATGACTCACTTTATCACTAGAAACATTACTGATAAC 
               
               
                   
                 CAAGGTAAGAATAAGACTGCCATTCACACTTACTTCTCTTCTGTT 
               
               
                   
                 TTCTTGGGTGGTGTTGATTCCTTGGTCGATTTGATGAACAAGTCT 
               
               
                   
                 TTTCCAGAATTAGGTATTAAGAAGACCGATTGTCGTCAATTGATA 
               
               
                   
                 ATTTTAATAAGGAGATTTTGTTAGATAGATCTGCTGGTCAAAATG 
               
               
                   
                 GTGCCTTTAAAATCAAATTGGACTACGTTAAGAAGCCTATTCCAG 
               
               
                   
                 AATCCGTCTTTGTTCAAATTTTGGAGAAGTTATACGAAGAAGATA 
               
               
                   
                 TTGGTGCTGGTATGTACGCCTTGTATCCATATGGTGGTATTATGG 
               
               
                   
                 ATGAAATTTCTGAATCCGCCATCCCTTTCCCTCATCGTGCTGGTA 
               
               
                   
                 TCTTATACGAGTTGTGGTACATCTGTTCTTGGGAAAAGCAAGAAG 
               
               
                   
                 ATAATGAAAAGCATTTGAACTGGATCCGTAACATCTATAACTTCA 
               
               
                   
                 TGACTCCATACGTTTCCAAAAACCCTAGATTGGCTTACTTAAATT 
               
               
                   
                 ACAGAGACTTAGATATTGGTATTAACGACCCTAAGAACCCAAACA 
               
               
                   
                 ATTACACTCAAGCTAGAATCTGGGGTGAAAAGTACTTCGGTAAGA 
               
               
                   
                 ATTTC 
               
               
                   
                 GACAGATTAGTTAAGGTCAAGACTTTAGTTGACCCAAATAACTTC 
               
               
                   
                 TTCAGAAACGAACAATCTATCCCACCATTGCCTAGACATAGACAC 
               
               
                   
                 TAG 
               
               
                   
               
               
                 SEQ ID NO: 140 
                 MKCSTFSFWFVCKIIFFFFSFNIQTSIANPRENFLKCFSQYIPNN 
               
               
                 CBDA Synthase, 
                 ATNLKLVYTQNNPLYMSVLNSTIHNLRFTSDTTPKPLVIVTPSHV 
               
               
                 H143D variant 
                 SHIQGTILCSKKVGLQIRTRSGGHDSEGMSYISQVPFVIVDLRNM 
               
               
                 Artificial Sequence 
                 RSIKIDVDSQTAWVEAGATLGEVYYWVNEKNENLSLAAGYCPTVC 
               
               
                   
                 AGGHFGGGGYGPLMRNYGLAADNIIDAHLVNVHGKVLDRKSMGED 
               
               
                   
                 LFWALRGGGAESFGIIVAWKIRLVAVPKSTMFSVKKIMEIHELVK 
               
               
                   
                 LVNKWQNIAYKYDKDLLLMTHFITRNITDNQGKNKTAIHTYFSSV 
               
               
                   
                 FLGGVDSLVDLMNKSFPELGIKKTDCRQLSWIDTIIFYSGWNYDT 
               
               
                   
                 DNFNKEILLDRSAGQNGAFKKLDYVKKPIPESVFVQILEKLYEED 
               
               
                   
                 IGAGMYALYPYGGIMDEISESAIPFPHRAGILYELWYICSWEKQE 
               
               
                   
                 DNEKHLNWIRNIYNFMTPYVSKNPRLAYLNYRDLDIGINDPKNPN 
               
               
                   
                 NYTQARIWGEKYFGKNFDRLVKVKTLVDPNNFFRNEQSIPPLPRH 
               
               
                   
                 RH* 
               
               
                   
               
               
                 SEQ ID NO: 141 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                 CBDA Synthase, V149I 
                 TTCTTCTTCTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 variant 
                 CGTGAGAACTTCTTGAAATGTTTTTCTCAATATATCCCAAATAAC 
               
               
                 Artificial Sequence 
                 GCTACTAACTTGAAGTTAGTCTATACTCAAAACAACCCATTATAT 
               
               
                 Codon optimized 
                 ATGTCTGTCTTAAACTCTACCATTCACAACTTACGTTTCACTTCT 
               
               
                   
                 GATACTACTCCAAAACCTTTGGTCATCGTCACCCCATCCCACGTT 
               
               
                   
                 TCTCACATCCAAGGTACCATCTTGTGTTCCAAAAAGGTTGGTTTA 
               
               
                   
                 CAAATCCGTACTAGATCCGGTGGTCATGACTCCGAAGGTATGTCT 
               
               
                   
                 TACATTTCCCAAGTCCCTTTCGTCATCGTCGACTTAAGAAATATG 
               
               
                   
                 CGTTCCATCAAGATTGATGTCCATTCCCAAACTGCTTGGattGAA 
               
               
                   
                 GCCGGTGCCACTTTAGGTGAAGTCTATTACTGGGTTAACGAGAAG 
               
               
                   
                 AATGAGAACTTATCTTTGGCTGCCGGTTACTGTCCAACTGTTTGT 
               
               
                   
                 GCTGGTGGTCATTTCGGTGGTGGTGGTTACGGTCCATTAATGCGT 
               
               
                   
                 AACTACGGTTTGGCTGCCGATAACATCATTGATGCCCACTTAGTC 
               
               
                   
                 AACGTTCATGGTAAGGTCTTGGACCGTAAGTCTATGGGTGAGGAT 
               
               
                   
                 TTATTCTGGGCTTTGAGAGGTGGTGGTGCTGAATCTTTCGGTATT 
               
               
                   
                 ATCGTCGCTTGGAAGATTAGATTAGTTGCTGTTCCAAAGTCTACT 
               
               
                   
                 ATGTTCTCTGTTAAGAAGATCATGGAAATTCACGAGTTGGTTAAA 
               
               
                   
                 TTAGTTAACAAATGGCAAAACATTGCCTACAAGTACGATAAAGAT 
               
               
                   
                 TTGTTATTAATGACTCACTTTATCACTAGAAACATTACTGATAAC 
               
               
                   
                 CAAGGTAAGAATAAGACTGCCATTCACACTTACTTCTCTTCTGTT 
               
               
                   
                 TTCTTGGGTGGTGTTGATTCCTTGGTCGATTTGATGAACAAGTCT 
               
               
                   
                 TTTCCAGAATTAGGTATTAAGAAGACCGATTGTCGTCAATTGATA 
               
               
                   
                 ATTTTAATAAGGAGATTTTGTTAGATAGATCTGCTGGTCAAAATG 
               
               
                   
                 GTGCCTTTAAAATCAAATTGGACTACGTTAAGAAGCCTATTCCAG 
               
               
                   
                 AATCCGTCTTTGTTCAAATTTTGGAGAAGTTATACGAAGAAGATA 
               
               
                   
                 TTGGTGCTGGTATGTACGCCTTGTATCCATATGGTGGTATTATGG 
               
               
                   
                 ATGAAATTTCTGAATCCGCCATCCCTTTCCCTCATCGTGCTGGTA 
               
               
                   
                 TCTTATACGAGTTGTGGTACATCTGTTCTTGGGAAAAGCAAGAAG 
               
               
                   
                 ATAATGAAAAGCATTTGAACTGGATCCGTAACATCTATAACTTCA 
               
               
                   
                 TGACTCCATACGTTTCCAAAAACCCTAGATTGGCTTACTTAAATT 
               
               
                   
                 ACAGAGACTTAGATATTGGTATTAACGACCCTAAGAACCCAAACA 
               
               
                   
                 ATTACACTCAAGCTAGAATCTGGGGTGAAAAGTACTTCGGTAAGA 
               
               
                   
                 ATTTCGACAGATTAGTTAAGGTCAAGACTTTAGTTGACCCAAATA 
               
               
                   
                 ACTTCTTCAGAAACGAACAATCTATCCCACCATTGCCTAGACATA 
               
               
                   
                 GACACTAG 
               
               
                   
               
               
                 SEQ ID NO: 142 
                 MKCSTFSFWFVCKIIFFFFSFNIQTSIANPRENFLKCFSQYIPNN 
               
               
                 CBDA Synthase, VI491 
                 ATNLKLVYTQNNPLYMSVLNSTIHNLRFTSDTTPKPLVIVTPSHV 
               
               
                 variant 
                 SHIQGTILCSKKVGLQIRTRSGGHDSEGMSYISQVPFVIVDLRNM 
               
               
                 Artificial Sequence 
                 RSIKIDVHSQTAWIEAGATLGEVYYWVNEKNENLSLAAGYCPTVC 
               
               
                   
                 AGGHFGGGGYGPLMRNYGLAADNIIDAHLVNVHGKVLDRKSMGED 
               
               
                   
                 LFWALRGGGAESFGIIVAWKIRLVAVPKSTMFSVKKIMEIHELVK 
               
               
                   
                 LVNKWQNIAYKYDKDLLLMTHFITRNITDNQGKNKTAIHTYFSSV 
               
               
                   
                 FLGGVDSLVDLMNKSFPELGIKKTDCRQLSWIDTIIFYSGVVNYD 
               
               
                   
                 TDNFNKEILLDRSAGQNGAFKIKLDYVKKPIPESVFVQILEKLYE 
               
               
                   
                 EDIGAGMYALYPYGGIMDEISESAIPFPHRAGILYELWYICSWEK 
               
               
                   
                 QEDNEKHLNWIRNIYNFMTPYVSKNPRLAYLNYRDLDIGINDPKN 
               
               
                   
                 PNNYTQARIWGEKYFGKNFDRLVKVKTLVDPNNFFRNEQSIPPLP 
               
               
                   
                 RHRH* 
               
               
                   
               
               
                 SEQ ID NO: 143 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                 CBDA Synthase, 
                 TTCTTCTTCTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 W161K variant 
                 CGTGAGAACTTCTTGAAATGTTTTTCTCAATATATCCCAAATAAC 
               
               
                 Artificial Sequence 
                 GCTACTAACTTGAAGTTAGTCTATACTCAAAACAACCCATTATAT 
               
               
                 Codon optimized 
                 ATGTCTGTCTTAAACTCTACCATTCACAACTTACGTTTCACTTCT 
               
               
                   
                 GATACTACTCCAAAACCTTTGGTCATCGTCACCCC 
               
               
                   
                 ATCCCACGTTTCTCACATCCAAGGTACCATCTTGTGTTCCAAAAA 
               
               
                   
                 GGTTGGTTTACAAATCCGTACTAGATCCGGTGGTCATGACTCCGA 
               
               
                   
                 AGGTATGTCTTACATTTCCCAAGTCCCTTTCGTCATCGTCGACTT 
               
               
                   
                 AAGAAATATGCGTTCCATCAAGATTGATGTCCATTCCCAAACTGC 
               
               
                   
                 TTGGGTTGAAGCCGGTGCCACTTTAGGTGAAGTCTATTACaaaGT 
               
               
                   
                 TAACGAGAAGAATGAGAACTTATCTTTGGCTGCCGGTTACTGTCC 
               
               
                   
                 AACTGTTTGTGCTGGTGGTCATTTCGGTGGTGGTGGTTACGGTCC 
               
               
                   
                 ATTAATGCGTAACTACGGTTTGGCTGCCGATAACATCATTGATGC 
               
               
                   
                 CCACTTAGTCAACGTTCATGGTAAGGTCTTGGACCGTAAGTCTAT 
               
               
                   
                 GGGTGAGGATTTATTCTGGGCTTTGAGAGGTGGTGGTGCTGAATC 
               
               
                   
                 TTTCGGTATTATCGTCGCTTGGAAGATTAGATTAGTTGCTGTTCC 
               
               
                   
                 AAAGTCTACTATGTTCTCTGTTAAGAAGATCATGGAAATTCACGA 
               
               
                   
                 GTTGGTTAAATTAGTTAACAAATGGCAAAACATTGCCTACAAGTA 
               
               
                   
                 CGATAAAGATTTGTTATTAATGACTCACTTTATCACTAGAAACAT 
               
               
                   
                 TACTGATAACCAAGGTAAGAATAAGACTGCCATTCACACTTACTT 
               
               
                   
                 CTCTTCTGTTTTCTTGGGTGGTGTTGATTCCTTGGTCGATTTGAT 
               
               
                   
                 GAACAAGTCTTTTCCAGAATTAGGTATTAAGAAGACCGATTGTCG 
               
               
                   
                 TCAATTATCTTGGATTGATACCATTATTTTTTACTCCGGTGTTGT 
               
               
                   
                 CAACTACGACACTGATAATTTTAATAAGGAGATTTTGTTAGATAG 
               
               
                   
                 ATCTGCTGGTCAAAATGGTGCCTTTAAAATCAAATTGGACTACGT 
               
               
                   
                 TAAGAAGCCTATTCCAGAATCCGTCTTTGTTCAAATTTTGGAGAA 
               
               
                   
                 GTTATACGAAGAAGATATTGGTGCTGGTATGTACGCCTTGTATCC 
               
               
                   
                 ATATGGTGGTATTATGGATGAAATTTCTGAATCCGCCATCCCTTT 
               
               
                   
                 CCCTCATCGTGCTGGTATCTTATACGAGTTGTGGTACATCTGTTC 
               
               
                   
                 TTGGGAAAAGCAAGAAGATAATGAAAAGCATTTGAACTGGATCCG 
               
               
                   
                 TAACATCTATAACTTCATGACTCCATACGTTTCCAAAAACCCTAG 
               
               
                   
                 ATTGGCTTACTTAAATTACAGAGACTTAGATATTGGTATTAACGA 
               
               
                   
                 CCCTAAGAACCCAAACAATTACACTCAAGCTAGAATCTGGGGTGA 
               
               
                   
                 AAAGTACTTCGGTAAGAATTTCGACAGATTAGTTAAGGTCAAGAC 
               
               
                   
                 TTTAGTTGACCCAAATAACTTCTTCAGAAACGAACAATCTATCCC 
               
               
                   
                 ACCATTGCCTAGACATAGACACTAG 
               
               
                   
               
               
                 SEQ ID NO: 144 
                 MKCSTFSFWFVCKIIFFFFSFNIQTSIANPRENFLKCFSQYIPNN 
               
               
                 CBDA Synthase, 
                 ATNLKLVYTQNNPLYMSVLNSTIHNLRFTSDTTPKPLVIVTPSHV 
               
               
                 W161K variant 
                 SHIQGTILCSKKVGLQIRTRSGGHDSEGMSYISQVPFVIVDLRNM 
               
               
                 Artificial 
                 RSIKIDVHSQTAWVEAGATLGEVYYKVNEKNENLSLAAGYCPTVC 
               
               
                 Sequence 
                 AGGHFGGGGYGPLMRNYGLAADNIIDAHLVNVHGKVLDRKSMGED 
               
               
                   
                 LFWALRGGGAESFGIIVAWKIRLVAVPKSTMFSVKKIMEIHELVK 
               
               
                   
                 LVNKWQNIAYKYDKDLLLMTHFITRNITDNQGKNKTAIHTYFSSV 
               
               
                   
                 FLGGVDSLVDLMNKSFPELGIKKTDCRQLSWIDTIIFYSGWNYDT 
               
               
                   
                 DNFNKEILLDRSAGQNGAFKIKLDYVKKPIPESVFVQILEKLYEE 
               
               
                   
                 DIGAGMYALYPYGGIMDEISESAIPFPHRAGILYELWYICSWEKQ 
               
               
                   
                 EDNEKHLNWIRNTYNFMTPYVSKNPRLAYLNYRDLDIGINDPKNP 
               
               
                   
                 NNYTQARIWGEKYFGKNFDRLVKVKTLVDPNNFFRNEQSIPPLPR 
               
               
                   
                 HRH* 
               
               
                   
               
               
                 SEQ ID NO: 145 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                 CBDA Synthase, 
                 TTCTTCTTCTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 W161R variant 
                 CGTGAGAACTTCTTGAAATGTTTTTCTCAATATATCCCAAATAAC 
               
               
                 Artificial 
                 GCTACTAACTTGAAGTTAGTCTATACTCAAAACAACCCATTATAT 
               
               
                 Sequence 
                 ATGTCTGTCTTAAACTCTACCATTCACAACTTACGTTTCACTTCT 
               
               
                 Codon optimized 
                 GATACTACTCCAAAACCTTTGGTCATCGTCACCCCATCCCACGTT 
               
               
                   
                 TCTCACATCCAAGGTACCATCTTGTGTTCCAAAAAGGTTGGTTTA 
               
               
                   
                 CAAATCCGTACTAGATCCGGTGGTCATGACTCCGAAGGTATGTCT 
               
               
                   
                 TACATTTCCCAAGTCCCTTTCGTCATCGTCGACTTAAGAAATATG 
               
               
                   
                 CGTTCCATCAAGATTGATGTCCATTCCCAAACTGCTTGGGTTGAA 
               
               
                   
                 GCCGGTGCCACTTTAGGTGAAGTCTATTACagaGTTAACGAGAAG 
               
               
                   
                 AATGAGAACTTATCTTTGGCTGCCGGTTACTGTCCAACTGTTTGT 
               
               
                   
                 GCTGGTGGTCATTTCGGTGGTGGTGGTTACGGTCCATTAATGCGT 
               
               
                   
                 AACTACGGTTTGGCTGCCGATAACATCATTGATGCCCACTTAGTC 
               
               
                   
                 AACGTTCATGGTAAGGTCTTGGACCGTAAGTCTATGGGTGAGGAT 
               
               
                   
                 TTATTCTGGGCTTTGAGAGGTGGTGGTGCTGAATCTTTCGGTATT 
               
               
                   
                 ATCGTCGCTTGGAAGATTAGATTAGTTGCTGTTCCAAAGTCTACT 
               
               
                   
                 ATGTTCTCTGTTAAGAAGATCATGGAAATTCACGAGTTGGTTAAA 
               
               
                   
                 TTAGTTAACAAATGGCAAAACATTGCCTACAAGTACGATAAAGAT 
               
               
                   
                 TTGTTATTAATGACTCACTTTATCACTAGAAACATTACTGATAAC 
               
               
                   
                 CAAGGTAAGAATAAGACTGCCATTCACACTTACTTCTCTTCTGTT 
               
               
                   
                 TTCTTGGGTGGTGTTGATTCCTTGGTCGATTTGATGAACAAGTCT 
               
               
                   
                 TTTCCAGAATTAGGTATTAAGAAGACCGATTGTCGTCAATTATCT 
               
               
                   
                 TGGATTGATACCATTATTTTTTACTCCGGTGTTGTCAACTACGAC 
               
               
                   
                 ACTGATAATTTTAATAAGGAGATTTTGTTAGATAGATCTGCTGGT 
               
               
                   
                 CAAAATGGTGCCTTTAAAATCAAATTGGACTACGTTAAGAAGCCT 
               
               
                   
                 ATTCCAGAATCCGTCTTTGTTCAAATTTTGGAGAAGTTATACGAA 
               
               
                   
                 GAAGATATTGGTGCTGGTATGTACGCCTTGTATCCATATGGTGGT 
               
               
                   
                 ATTATGGATGAAATTTCTGAATCCGCCATCCCTTTCCCTCATCGT 
               
               
                   
                 GCTGGTATCTTATACGAGTTGTGGTACATCTGTTCTTGGGAAAAG 
               
               
                   
                 CAAGAAGATAATGAAAAGCATTTGAACTGGATCCGTAACATCTAT 
               
               
                   
                 AACTTCATGACTCCATACGTTTCCAAAAACCCTAGATTGGCTTAC 
               
               
                   
                 TTAAATTACAGAGACTTAGATATTGGTATTAACGACCCTAAGAAC 
               
               
                   
                 CCAAACAATTACACTCAAGCTAGAATCTGGGGTGAAAAGTACTTC 
               
               
                   
                 GGTAAGAATTTCGACAGATTAGTTAAGGTCAAGACTTTAGTTGAC 
               
               
                   
                 CCAAATAACTTCTTCAGAAACGAACAATCTATCCCACCATTGCCT 
               
               
                   
                 AGACATAGACACTAG 
               
               
                   
               
               
                 SEQ ID NO: 146 
                 MKCSTFSFWFVCKIIFFFFSFNIQTSIANPRENFLKCFSQYIPNN 
               
               
                 CBDA Synthase, 
                 ATNLKLVYTQNNPLYMSVLNSTIHNLRFTSDTTPKPLVIVTPSHV 
               
               
                 W161R variant 
                 SHIQGTILCSKKVGLQIRTRSGGHDSEGMSYISQVPFVIVDLRNM 
               
               
                 Artificial  
                 RSIKIDVHSQTAWVEAGATLGEVYYRVNEKNENLSLAAGYCPTVC 
               
               
                 Sequence 
                 AGGHFGGGGYGPLMRNYGLAADNIIDAHLVNVHGKVLDRKSMGED 
               
               
                   
                 LFWALRGGGAESFGIIVAWKIRLVAVPKSTMFSVKKIMEIHELVK 
               
               
                   
                 LVNKWQNIAYKYDKDLLLMTHFITRNITDNQGKNKTAIHTYFSSV 
               
               
                   
                 FLGGVDSLVDLMNKSFPELGIKKTDCRQLSWIDTIIFYSGVVNYD 
               
               
                   
                 TDNFNKEILLDRSAGQNGAFKIKLDYVKKPIPESVFVQILEKLYE 
               
               
                   
                 EDIGAGMYALYPYGGIMDEISESAIPFPHRAGILYELWYICSWEK 
               
               
                   
                 QEDNEKHLNWIRNIYNFMTPYVSKNPRLAYLNYRDLDIGINDPKN 
               
               
                   
                 PNNYTQARIWGEKYFGKNFDRLVKVKTLVDPNNFFRNEQSIPPLP 
               
               
                   
                 RHRH* 
               
               
                   
               
               
                 SEQ ID NO: 147 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                 CBDA Synthase, 
                 TTCTTCTTCTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 W161Y variant 
                 CGTGAGAACTTCTTGAAATGTTTTTCTCAATATATCCCAAATAAC 
               
               
                 Artificial 
                 GCTACTAACTTGAAGTTAGTCTATACTCAAAACAACCCATTATAT 
               
               
                 Sequence 
                 ATGTCTGTCTTAAACTCTACCATTCACAACTTACGTTTCACTTCT 
               
               
                 Codon optimized 
                 GATACTACTCCAAAACCTTTGGTCATCGTCACCCCATCCCACGTT 
               
               
                   
                 TCTCACATCCAAGGTACCATCTTGTGTTCCAAAAAGGTTGGTTTA 
               
               
                   
                 CAAATCCGTACTAGATCCGGTGGTCATGACTCCGAAGGTATGTCT 
               
               
                   
                 TACATTTCCCAAGTCCCTTTCGTCATCGTCGACTTAAGAAATATG 
               
               
                   
                 CGTTCCATCAAGATTGATGTCCATTCCCAAACTGCTTGGGTTGAA 
               
               
                   
                 GCCGGTGCCACTTTAGGTGAAGTCTATTAClatGTTAACGAGAAG 
               
               
                   
                 AATGAGAACTTATCTTTGGCTGCCGGTTACTGTCCAACTGTTTGT 
               
               
                   
                 GCTGGTGGTCATTTCGGTGGTGGTGGTTACGGTCCATTAATGCGT 
               
               
                   
                 AACTACGGTTTGGCTGCCGATAACATCATTGATGCCCACTTAGTC 
               
               
                   
                 AACGTTCATGGTAAGGTCTTGGACCGTAAGTCTATGGGTGAGGAT 
               
               
                   
                 TTATTCTGGGCTTTGAGAGGTGGTGGTGCTGAATCTTTCGGTATT 
               
               
                   
                 ATCGTCGCTTGGAAGATTAGATTAGTTGCTGTTCCAAAGTCTACT 
               
               
                   
                 ATGTTCTCTGTTAAGAAGATCATGGAAATTCACGAGTTGGTTAAA 
               
               
                   
                 TTAGTTAACAAATGGCAAAACATTGCCTACAAGTACGATAAAGAT 
               
               
                   
                 TTGTTATTAATGACTCACTTTATCACTAGAAACATTACTGATAAC 
               
               
                   
                 CAAGGTAAGAATAAGACTGCCATTCACACTTACTTCTCTTCTGTT 
               
               
                   
                 TTCTTGGGTGGTGTTGATTCCTTGGTCGATTTGATGAACAAGTCT 
               
               
                   
                 TTTCCAGAATTAGGTATTAAGAAGACCGATTGTCGTCAATTATCT 
               
               
                   
                 TGGATTGATACCATTATTTTTTACTCCGGTGTTGTCAACTACGAC 
               
               
                   
                 ACTGATAATTTTAATAAGGAGATTTTGTTAGATAGATCTGCTGGT 
               
               
                   
                 CAAAATGGTGCCTTTAAAATCAAATTGGACTACGTTAAGAAGCCT 
               
               
                   
                 ATTCCAGAATCCGTCTTTGTTCAAATTTTGGAGAAGTTATACGAA 
               
               
                   
                 GAAGATATTGGTGCTGGTATGTACGCCTTGTATCCATATGGTGGT 
               
               
                   
                 ATTATGGATGAAATTTCTGAATCCGCCATCCCTTTCCCTCATCGT 
               
               
                   
                 GCTGGTATCTTATACGAGTTGTGGTACATCTGTTCTTGGGAAAAG 
               
               
                   
                 CAAGAAGATAATGAAAAGCATTTGAACTGGATCCGTAACATCTAT 
               
               
                   
                 AACTTCATGACTCCATACGTTTCCAAAAACCCTAGATTGGCTTAC 
               
               
                   
                 TTAAATTACAGAGACTTAGATATTGGTATTAACGACCCTAAGAAC 
               
               
                   
                 CCAAACAATTACACTCAAGCTAGAATCTGGGGTGAAAAGTACTTC 
               
               
                   
                 GGTAAGAATTTCGACAGATTAGTTAAGGTCAAGACTTTAGTTGAC 
               
               
                   
                 CCAAATAACTTCTTCAGAAACGAACAATCTATCCCACCATTGCCT 
               
               
                   
                 AGACATAGACACTAG 
               
               
                   
               
               
                 SEQ ID NO: 148 
                 MKCSTFSFWFVCKIIFFFFSFNIQTSIANPRENFLKCFSQYIPNN 
               
               
                 CBDA Synthase, 
                 ATNLKLVYTQNNPLYMSVLNSTIHNLRFTSDTTPKPLVIVTPSHV 
               
               
                 W161Y variant 
                 SHIQGTILCSKKVGLQIRTRSGGHDSEGMSYISQVPFVIVDLRNM 
               
               
                 Artificial 
                 RSIKIDVHSQTAWVEAGATLGEVYYYVNEKNENLSLAAGYCPTVC 
               
               
                 Sequence 
                 AGGHFGGGGYGPLMRNYGLAADNIIDAHLVNVHGKVLDRKSMGED 
               
               
                   
                 LFWALRGGGAESFGIIVAWKIRLVAVPKSTMFSVKKIMEIHELVK 
               
               
                   
                 LVNKWQNIAYKYDKDLLLMTHFITRNITDNQGKNKTAIHTYFSSV 
               
               
                   
                 FLGGVDSLVDLMNKSFPELGIKKTDCRQLSWIDTIIFYSGWNYDT 
               
               
                   
                 DNFNKEILLDRSAGQNGAFKKLDYVKKPIPESVFVQILEKLYEED 
               
               
                   
                 IGAGMYALYPYGGIMDEISESAIPFPHRAGILYELWYICSWEKQE 
               
               
                   
                 DNEKHLNWIRNIYNFMTPYVSKNPRLAYLNYRDLDIGINDPKNPN 
               
               
                   
                 NYTQARIVVGEKYFGKNFDRLVKVKTLVDPNNFFRNEQSIPPLPR 
               
               
                   
                 HRH* 
               
               
                   
               
               
                 SEQ ID NO: 149 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                 CBDA Synthase, 
                 TTCTTCTTCTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 K165A variant 
                 CGTGAGAACTTCTTGAAATGTTTTTCTCAATATATCCCAAATAAC 
               
               
                 Artificial 
                 GCTACTAACTTGAAGTTAGTCTATACTCAAAACAACCCATTATAT 
               
               
                 Sequence 
                 ATGTCTGTCTTAAACTCTACCATTCACAACTTACGTTTCACTTCT 
               
               
                 Codon optimized 
                 GATACTACTCCAAAACCTTTGGTCATCGTCACCCCATCCCACGTT 
               
               
                   
                 TCTCACATCCAAGGTACCATCTTGTGTTCCAAAAAGGTTGGTTTA 
               
               
                   
                 CAAATCCGTACTAGATCCGGTGGTCATGACTCCGAAGGTATGTCT 
               
               
                   
                 TACATTTCCCAAGTCCCTTTCGTCATCGTCGACTTAAGAAATATG 
               
               
                   
                 CGTTCCATCAAGATTGATGTCCATTCCCAAACTGCTTGGGTTGAA 
               
               
                   
                 GCCGGTGCCACTTTAGGTGAAGTCTATTACTGGGTTAACGAGgct 
               
               
                   
                 AATGAGAACTTATCTTTGGCTGCCGGTTACTGTCCAACTGTTTGT 
               
               
                   
                 GCTGGTGGTCATTTCGGTGGTGGTGGTTACGGTCCATTAATGCGT 
               
               
                   
                 AACTACGGTTTGGCTGCCGATAACATCATTGATGCCCACTTAGTC 
               
               
                   
                 AACGTTCATGGTAAGGTCTTGGACCGTAAGTCTATGGGTGAGGAT 
               
               
                   
                 TTATTCTGGGCTTTGAGAGGTGGTGGTGCTGAATCTTTCGGTATT 
               
               
                   
                 ATCGTCGCTTGGAAGATTAGATTAGTTGCTGTTCCAAAGTCTACT 
               
               
                   
                 ATGTTCTCTGTTAAGAAGATCATGGAAATTCACGAGTTGGTTAAA 
               
               
                   
                 TTAGTTAACAAATGGCAAAACATTGCCTACAAGTACGATAAAGAT 
               
               
                   
                 TTGTTATTAATGACTCACTTTATCACTAGAAACATTACTGATAAC 
               
               
                   
                 CAAGGTAAGAATAAGACTGCCATTCACACTTACTTCTCTTCTGTT 
               
               
                   
                 TTCTTGGGTGGTGTTGATTCCTTGGTCGATTTGATGAACAAGTCT 
               
               
                   
                 TTTCCAGAATTAGGTATTAAGAAGACCGATTGTCGTCAATTATCT 
               
               
                   
                 TGGATTGATACCATTATTTTTTACTCCGGTGTTGTCAACTACGAC 
               
               
                   
                 ACTGATAATTTTAATAAGGAGATTTTGTTAGATAGATCTGCTGGT 
               
               
                   
                 CAAAATGGTGCCTTTAAAATCAAATTGGACTACGTTAAGAAGCCT 
               
               
                   
                 ATTCCAGAATCCGTCTTTGTTCAAATTTTGGAGAAGTTATACGAA 
               
               
                   
                 GAAGATATTGGTGCTGGTATGTACGCCTTGTATCCATATGGTGGT 
               
               
                   
                 ATTATGGATGAAATTTCTGAATCCGCCATCCCTTTCCCTCATCGT 
               
               
                   
                 GCTGGTATCTTATACGAGTTGTGGTACATCTGTTCTTGGGAAAAG 
               
               
                   
                 CAAGAAGATAATGAAAAGCATTTGAACTGGATCCGTAACATCTAT 
               
               
                   
                 AACTTCATGACTCCATACGTTTCCAAAAACCCTAGATTGGCTTAC 
               
               
                   
                 TTAAATTACAGAGACTTAGATATTGGTATTAACGACCCTAAGAAC 
               
               
                   
                 CCAAACAATTACACTCAAGCTAGAATCTGGGGTGAAAAGTACTTC 
               
               
                   
                 GGTAAGAATTTCGACAGATTAGTTAAGGTCAAGACTTTAGTTGAC 
               
               
                   
                 CCAAATAACTTCTTCAGAAACGAACAATCTATCCCACCATTGCCT 
               
               
                   
                 AGACATAGACACTAG 
               
               
                   
               
               
                 SEQ ID NO: 150 
                 MKCSTFSFWFVCKIIFFFFSFNIQTSIANPRENFLKCFSQYIPNN 
               
               
                 CBDA Synthase, 
                 ATNLKLVYTQNNPLYMSVLNSTIHNLRFTSDTTPKPLVIVTPSHV 
               
               
                 K165A variant 
                 SHIQGTILCSKKVGLQIRTRSGGHDSEGMSYISQVPFVIVDLRNM 
               
               
                 Artificial 
                 RSIKIDVHSQTAWVEAGATLGEVYYWVNEANENLSLAAGYCPTVC 
               
               
                 Sequence 
                 AGGHFGGGGYGPLMRNYGLAADNIIDAHLVNVHGKVLDRKSMGED 
               
               
                   
                 LFWALRGGGAESFGIIVAWKIRLVAVPKSTMFSVKKIMEIHELVK 
               
               
                   
                 LVNKWQNIAYKYDKDLLLMTHFITRNITDNQGKNKTAIHTYFSSV 
               
               
                   
                 FLGGVDSLVDLMNKSFPELGIKKTDCRQLSWIDTIIFYSGWNYDT 
               
               
                   
                 DNFNKEILLDRSAGQNGAFKKLDYVKKPIPESVFVQILEKLYEED 
               
               
                   
                 IGAGMYALYPYGGIMDEISESAIPFPHRAGILYELWYICSWEKQE 
               
               
                   
                 DNEKHLNWIRNIYNFMTPYVSKNPRLAYLNYRDLDIGINDPKNPN 
               
               
                   
                 NYTQARIWGEKYFGKNFDRLVKVKTLVDPNNFFRNEQSIPPLPRH 
               
               
                   
                 RH* 
               
               
                   
               
               
                 SEQ ID NO: 151 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                 CBDA Synthase, 
                 TTCTTCTTCTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 E167P variant 
                 CGTGAGAACTTCTTGAAATGTTTTTCTCAATATATCCCAAATAAC 
               
               
                 Artificial 
                 GCTACTAACTTGAAGTTAGTCTATACTCAAAACAACCCATTATAT 
               
               
                 Sequence 
                 ATGTCTGTCTTAAACTCTACCATTCACAACTTACGTTTCACTTCT 
               
               
                 Codon optimized 
                 GATACTACTCCAAAACCTTTGGTCATCGTCACCCCATCCCACGTT 
               
               
                   
                 TCTCACATCCAAGGTACCATCTTGTGTTCCAAAAAGGTTGGTTTA 
               
               
                   
                 CAAATCCGTACTAGATCCGGTGGTCATGACTCCGAAGGTATGTCT 
               
               
                   
                 TACATTTCCCAAGTCCCTTTCGTCATCGTCGACTTAAGAAATATG 
               
               
                   
                 CGTTCCATCAAGATTGATGTCCATTCCCAAACTGCTTGGGTTGAA 
               
               
                   
                 GCCGGTGCCACTTTAGGTGAAGTCTATTACTGGGTTAACGAGAAG 
               
               
                   
                 AATccaAACTTATCTTTGGCTGCCGGTTACTGTCCAACTGTTTGT 
               
               
                   
                 GCTGGTGGTCATTTCGGTGGTGGTGGTTACGGTCCATTAATGCGT 
               
               
                   
                 AACTACGGTTTGGCTGCCGATAACATCATTGATGCCCACTTAGTC 
               
               
                   
                 AACGTTCATGGTAAGGTCTTGGACCGTAAGTCTATGGGTGAGGAT 
               
               
                   
                 TTATTCTGGGCTTTGAGAGGTGGTGGTGCTGAATCTTTCGGTATT 
               
               
                   
                 ATCGTCGCTTGGAAGATTAGATTAGTTGCTGTTCCAAAGTCTACT 
               
               
                   
                 ATGTTCTCTGTTAAGAAGATCATGGAAATTCACGAGTTGGTTAAA 
               
               
                   
                 TTAGTTAACAAATGGCAAAACATTGCCTACAAGTACGATAAAGAT 
               
               
                   
                 TTGTTATTAATGACTCACTTTATCACTAGAAACATTACTGATAAC 
               
               
                   
                 CAAGGTAAGAATAAGACTGCCATTCACACTTACTTCTCTTCTGTT 
               
               
                   
                 TTCTTGGGTGGTGTTGATTCCTTGGTCGATTTGATGAACAAGTCT 
               
               
                   
                 TTTCCAGAATTAGGTATTAAGAAGACCGATTGTCGTCAATTATCT 
               
               
                   
                 TGGATTGATACCATTATTTTTTACTCCGGTGTTGTCAACTACGAC 
               
               
                   
                 ACTGATAATTTTAATAAGGAGATTTTGTTAGATAGATCTGCTGGT 
               
               
                   
                 CAAAATGGTGCCTTTAAAATCAAATTGGACTACGTTAAGAAGCCT 
               
               
                   
                 ATTCCAGAATCCGTCTTTGTTCAAATTTTGGAGAAGTTATACGAA 
               
               
                   
                 GAAGATATTGGTGCTGGTATGTACGCCTTGTATCCATATGGTGGT 
               
               
                   
                 ATTATGGATGAAATTTCTGAATCCGCCATCCCTTTCCCTCATCGT 
               
               
                   
                 GCTGGTATCTTATACGAGTTGTGGTACATCTGTTCTTGGGAAAAG 
               
               
                   
                 CAAGAAGATAATGAAAAGCATTTGAACTGGATCCGTAACATCTAT 
               
               
                   
                 AACTTCATGACTCCATACGTTTCCAAAAACCCTAGATTGGCTTAC 
               
               
                   
                 TTAAATTACAGAGACTTAGATATTGGTATTAACGACCCTAAGAAC 
               
               
                   
                 CCAAACAATTACACTCAAGCTAGAATCTGGGGTGAAAAGTACTTC 
               
               
                   
                 GGTAAGAATTTCGACAGATTAGTTAAGGTCAAGACTTTAGTTGAC 
               
               
                   
                 CCAAATAACTTCTTCAGAAACGAACAATCTATCCCACCATTGCCT 
               
               
                   
                 AGACATAGACACTAG 
               
               
                   
               
               
                 SEQ ID NO: 152 
                 MKCSTFSFWFVCKIIFFFFSFNIQTSIANPRENFLKCFSQYIPNN 
               
               
                 CBDA Synthase, 
                 ATNLKLVYTQNNPLYMSVLNSTIHNLRFTSDTTPKPLVIVTPSHV 
               
               
                 E167P variant 
                 SHIQGTILCSKKVGLQIRTRSGGHDSEGMSYISQVPFVIVDLRNM 
               
               
                 Artificial 
                 RSIKIDVHSQTAWVEAGATLGEVYYWVNEKNPNLSLAAGYCPTVC 
               
               
                 Sequence 
                 AGGHFGGGGYGPLMRNYGLAADNIIDAHLVNVHGKVLDRKSMGED 
               
               
                   
                 LFWALRGGGAESFGIIVAWKIRLVAVPKSTMFSVKKIMEIHELVK 
               
               
                   
                 LVNKWQNIAYKYDKDLLLMTHFITRNITDNQGKNKTAIHTYFSSV 
               
               
                   
                 FLGGVDSLVDLMNKSFPELGIKKTDCRQLSWIDTIIFYSGWNYDT 
               
               
                   
                 DNFNKEILLDRSAGQNGAFKIKLDYVKKPIPESVFVQILEKLYEE 
               
               
                   
                 DIGAGMYALYPYGGIMDEISESAIPFPHRAGILYELWYICSWEKQ 
               
               
                   
                 EDNEKHLNWIRNIYNFMTPYVSKNPRLAYLNYRDLDIGINDPKNP 
               
               
                   
                 NNYTQARIWGEKYFGKNFDRLVKVKTLVDPNNFFRNEQSIPPLPR 
               
               
                   
                 HRH* 
               
               
                   
               
               
                 SEQ ID NO: 153 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                 CBDA Synthase, 
                 TTCTTCTTCTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 N168S variant 
                 CGTGAGAACTTCTTGAAATGTTTTTCTCAATATATCCCAAATAAC 
               
               
                 Artificial 
                 GCTACTAACTTGAAGTTAGTCTATACTCAAAACAACCCATTATAT 
               
               
                 Sequence 
                 ATGTCTGTCTTAAACTCTACCATTCACAACTTACGTTTCACTTCT 
               
               
                 Codon optimized 
                 GATACTACTCCAAAACCTTTGGTCATCGTCACCCCATCCCACGTT 
               
               
                   
                 TCTCACATCCAAGGTACCATCTTGTGTTCCAAAAAGGTTGGTTTA 
               
               
                   
                 CAAATCCGTACTAGATCCGGTGGTCATGACTCCGAAGGTATGTCT 
               
               
                   
                 TACATTTCCCAAGTCCCTTTCGTCATCGTCGACTTAAGAAATATG 
               
               
                   
                 CGTTCCATCAAGATTGATGTCCATTCCCAAACTGCTTGGGTTGAA 
               
               
                   
                 GCCGGTGCCACTTTAGGTGAAGTCTATTACTGGGTTAACGAGAAG 
               
               
                   
                 AATGAGtctTTATCTTTGGCTGCCGGTTACTGTCCAACTGTTTGT 
               
               
                   
                 GCTGGTGGTCATTTCGGTGGTGGTGGTTACGGTCCATTAATGCGT 
               
               
                   
                 AACTACGGTTTGGCTGCCGATAACATCATTGATGCCCACTTAGTC 
               
               
                   
                 AACGTTCATGGTAAGGTCTTGGACCGTAAGTCTATGGGTGAGGAT 
               
               
                   
                 TTATTCTGGGCTTTGAGAGGTGGTGGTGCTGAATCTTTCGGTATT 
               
               
                   
                 ATCGTCGCTTGGAAGATTAGATTAGTTGCTGTTCCAAAGTCTACT 
               
               
                   
                 ATGTTCTCTGTTAAGAAGATCATGGAAATTCACGAGTTGGTTAAA 
               
               
                   
                 TTAGTTAACAAATGGCAAAACATTGCCTACAAGTACGATAAAGAT 
               
               
                   
                 TTGTTATTAATGACTCACTTTATCACTAGAAACATTACTGATAAC 
               
               
                   
                 CAAGGTAAGAATAAGACTGCCATTCACACTTACTTCTCTTCTGTT 
               
               
                   
                 TTCTTGGGTGGTGTTGATTCCTTGGTCGATTTGATGAACAAGTCT 
               
               
                   
                 TTTCCAGAATTAGGTATTAAGAAGACCGATTGTCGTCAATTATCT 
               
               
                   
                 TGGATTGATACCATTATTTTTTACTCCGGTGTTGTCAACTACGAC 
               
               
                   
                 ACTGATAATTTTAATAAGGAGATTTTGTTAGATAGATCTGCTGGT 
               
               
                   
                 CAAAATGGTGCCTTTAAAATCAAATTGGACTACGTTAAGAAGCCT 
               
               
                   
                 ATTCCAGAATCCGTCTTTGTTCAAATTTTGGAGAAGTTATACGAA 
               
               
                   
                 GAAGATATTGGTGCTGGTATGTACGCCTTGTATCCATATGGTGGT 
               
               
                   
                 ATTATGGATGAAATTTCTGAATCCGCCATCCCTTTCCCTCATCGT 
               
               
                   
                 GCTGGTATCTTATACGAGTTGTGGTACATCTGTTCTTGGGAAAAG 
               
               
                   
                 CAAGAAGATAATGAAAAGCATTTGAACTGGATCCGTAACATCTAT 
               
               
                   
                 AACTTCATGACTCCATACGTTTCCAAAAACCCTAGATTGGCTTAC 
               
               
                   
                 TTAAATTACAGAGACTTAGATATTGGTATTAACGACCCTAAGAAC 
               
               
                   
                 CCAAACAATTACACTCAAGCTAGAATCTGGGGTGAAAAGTACTTC 
               
               
                   
                 GGTAAGAATTTCGACAGATTAGTTAAGGTCAAGACTTTAGTTGAC 
               
               
                   
                 CCAAATAACTTCTTCAGAAACGAACAATCTATCCCACCATTGCCT 
               
               
                   
                 AGACATAGACACTAG 
               
               
                   
               
               
                 SEQ ID NO: 154 
                 MKCSTFSFWFVCKIIFFFFSFNIQTSIANPRENFLKCFSQYIPNN 
               
               
                 CBDA Synthase, 
                 ATNLKLVYTQNNPLYMSVLNSTIHNLRFTSDTTPKPLVIVTPSHV 
               
               
                 N168S variant 
                 SHIQGTILCSKKVGLQIRTRSGGHDSEGMSYISQVPFVIVDLRNM 
               
               
                 Artificial 
                 RSIKIDVHSQTAWVEAGATLGEVYYWVNEKNESLSLAAGYCPTVC 
               
               
                 Sequence 
                 AGGHFGGGGYGPLMRNYGLAADNIIDAHLVNVHGKVLDRKSMGED 
               
               
                   
                 LFWALRGGGAESFGIIVAWKIRLVAVPKSTMFSVKKIMEIHELVK 
               
               
                   
                 LVNKWQNIAYKYDKDLLLMTHFITRNITDNQGKNKTAIHTYFSSV 
               
               
                   
                 FLGGVDSLVDLMNKSFPELGIKKTDCRQLSWIDTIIFYSGWNYDT 
               
               
                   
                 DNFNKEILLDRSAGQNGAFKIKLDYVKKPIPESVFVQILEKLYEE 
               
               
                   
                 DIGAGMYALYPYGGIMDEISESAIPFPHRAGILYELWYICSWEKQ 
               
               
                   
                 EDNEKHLNWIRNIYNFMTPYVSKNPRLAYLNYRDLDIGINDPKNP 
               
               
                   
                 NNYTQARIWGEKYFGKNFDRLVKVKTLVDPNNFFRNEQSIPPLPR 
               
               
                   
                 HRH* 
               
               
                   
               
               
                 SEQ ID NO: 155 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                 CBDA Synthase, 
                 TTCTTCTTCTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 S170T variant 
                 CGTGAGAACTTCTTGAAATGTTTTTCTCAATATATCCCAAATAAC 
               
               
                 Artificial 
                 GCTACTAACTTGAAGTTAGTCTATACTCAAAACAACCCATTATAT 
               
               
                 Sequence 
                 ATGTCTGTCTTAAACTCTACCATTCACAACTTACGTTTCACTTCT 
               
               
                 Codon optimized 
                 GATACTACTCCAAAACCTTTGGTCATCGTCACCCCATCCCACGTT 
               
               
                   
                 TCTCACATCCAAGGTACCATCTTGTGTTCCAAAAAGGTTGGTTTA 
               
               
                   
                 CAAATCCGTACTAGATCCGGTGGTCATGACTCCGAAGGTATGTCT 
               
               
                   
                 TACATTTCCCAAGTCCCTTTCGTCATCGTCGACTTAAGAAATATG 
               
               
                   
                 CGTTCCATCAAGATTGATGTCCATTCCCAAACTGCTTGGGTTGAA 
               
               
                   
                 GCCGGTGCCACTTTAGGTGAAGTCTATTACTGGGTTAACGAGAAG 
               
               
                   
                 AATGAGAACTTAactTTGGCTGCCGGTTACTGTCCAACTGTTTGT 
               
               
                   
                 GCTGGTGGTCATTTCGGTGGTGGTGGTTACGGTCCATTAATGCGT 
               
               
                   
                 AACTACGGTTTGGCTGCCGATAACATCATTGATGCCCACTTAGTC 
               
               
                   
                 AACGTTCATGGTAAGGTCTTGGACCGTAAGTCTATGGGTGAGGAT 
               
               
                   
                 TTATTCTGGGCTTTGAGAGGTGGTGGTGCTGAATCTTTCGGTATT 
               
               
                   
                 ATCGTCGCTTGGAAGATTAGATTAGTTGCTGTTCCAAAGTCTACT 
               
               
                   
                 ATGTTCTCTGTTAAGAAGATCATGGAAATTCACGAGTTGGTTAAA 
               
               
                   
                 TTAGTTAACAAATGGCAAAACATTGCCTACAAGTACGATAAAGAT 
               
               
                   
                 TTGTTATTAATGACTCACTTTATCACTAGAAACATTACTGATAAC 
               
               
                   
                 CAAGGTAAGAATAAGACTGCCATTCACACTTACTTCTCTTCTGTT 
               
               
                   
                 TTCTTGGGTGGTGTTGATTCCTTGGTCGATTTGATGAACAAGTCT 
               
               
                   
                 TTTCCAGAATTAGGTATTAAGAAGACCGATTGTCGTCAATTATCT 
               
               
                   
                 TGGATTGATACCATTATTTTTTACTCCGGTGTTGTCAACTACGAC 
               
               
                   
                 ACTGATAATTTTAATAAGGAGATTTTGTTAGATAGATCTGCTGGT 
               
               
                   
                 CAAAATGGTGCCTTTAAAATCAAATTGGACTACGTTAAGAAGCCT 
               
               
                   
                 ATTCCAGAATCCGTCTTTGTTCAAATTTTGGAGAAGTTATACGAA 
               
               
                   
                 GAAGATATTGGTGCTGGTATGTACGCCTTGTATCCATATGGTGGT 
               
               
                   
                 ATTATGGATGAAATTTCTGAATCCGCCATCCCTTTCCCTCATCGT 
               
               
                   
                 GCTGGTATCTTATACGAGTTGTGGTACATCTGTTCTTGGGAAAAG 
               
               
                   
                 CAAGAAGATAATGAAAAGCATTTGAACTGGATCCGTAACATCTAT 
               
               
                   
                 AACTTCATGACTCCATACGTTTCCAAAAACCCTAGATTGGCTTAC 
               
               
                   
                 TTAAATTACAGAGACTTAGATATTGGTATTAACGACCCTAAGAAC 
               
               
                   
                 CCAAACAATTACACTCAAGCTAGAATCTGGGGTGAAAAGTACTTC 
               
               
                   
                 GGTAAGAATTTCGACAGATTAGTTAAGGTCAAGACTTTAGTTGAC 
               
               
                   
                 CCAAATAACTTCTTCAGAAACGAACAATCTATCCCACCATTGCCT 
               
               
                   
                 AGACATAGACACTAG 
               
               
                   
               
               
                 SEQ ID NO: 156 
                 MKCSTFSFWFVCKIIFFFFSFNIQTSIANPRENFLKCFSQYIPNN 
               
               
                 CBDA Synthase, 
                 ATNLKLVYTQNNPLYMSVLNSTIHNLRFTSDTTPKPLVIVTPSHV 
               
               
                 S170T variant 
                 SHIQGTILCSKKVGLQIRTRSGGHDSEGMSYISQVPFVIVDLRNM 
               
               
                 Artificial 
                 RSIKIDVHSQTAWVEAGATLGEVYYWVNEKNENLTLAAGYCPTVC 
               
               
                 Sequence 
                 AGGHFGGGGYGPLMRNYGLAADNIIDAHLVNVHGKVLDRKSMGED 
               
               
                   
                 LFWALRGGGAESFGIIVAWKIRLVAVPKSTMFSVKKIMEIHELVK 
               
               
                   
                 LVNKWQNIAYKYDKDLLLMTHFITRNITDNQGKNKTAIHTYFSSV 
               
               
                   
                 FLGGVDSLVDLMNKSFPELGIKKTDCRQLSWIDTIIFYSGVVNYD 
               
               
                   
                 TDNFNKEILLDRSAGQNGAFKIKLDYVKKPIPESVFVQILEKLYE 
               
               
                   
                 EDIGAGMYALYPYGGIMDEISESAIPFPHRAGILYELWYICSWEK 
               
               
                   
                 QEDNEKHLNWIRNIYNFMTPYVSKNPRLAYLNYRDLDIGINDPKN 
               
               
                   
                 PNNYTQARIWGEKYFGKNFDRLVKVKTLVDPNNFFRNEQSIPPLP 
               
               
                   
                 RHRH* 
               
               
                   
               
               
                 SEQ ID NO: 157 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                 CBDA Synthase, LI711 
                 TTCTTCTTCTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 variant 
                 CGTGAGAACTTCTTGAAATGTTTTTCTCAATATATCCCAAATAAC 
               
               
                 Artificial 
                 GCTACTAACTTGAAGTTAGTCTATACTCAAAACAACCCATTATAT 
               
               
                 Sequence 
                 ATGTCTGTCTTAAACTCTACCATTCACAACTTACGTTTCACTTCT 
               
               
                 Codon optimized 
                 GATACTACTCCAAAACCTTTGGTCATCGTCACCCCATCCCACGTT 
               
               
                   
                 TCTCACATCCAAGGTACCATCTTGTGTTCCAAAAAGGTTGGTTTA 
               
               
                   
                 CAAATCCGTACTAGATCCGGTGGTCATGACTCCGAAGGTATGTCT 
               
               
                   
                 TACATTTCCCAAGTCCCTTTCGTCATCGTCGACTTAAGAAATATG 
               
               
                   
                 CGTTCCATCAAGATTGATGTCCATTCCCAAACTGCTTGGGTTGAA 
               
               
                   
                 GCCGGTGCCACTTTAGGTGAAGTCTATTACTGGGTTAACGAGAAG 
               
               
                   
                 AATGAGAACTTATCTattGCTGCCGGTTACTGTCCAACTGTTTGT 
               
               
                   
                 GCTGGTGGTCATTTCGGTGGTGGTGGTTACGGTCCATTAATGCGT 
               
               
                   
                 AACTACGGTTTGGCTGCCGATAACATCATTGATGCCCACTTAGTC 
               
               
                   
                 AACGTTCATGGTAAGGTCTTGGACCGTAAGTCTATGGGTGAGGAT 
               
               
                   
                 TTATTCTGGGCTTTGAGAGGTGGTGGTGCTGAATCTTTCGGTATT 
               
               
                   
                 ATCGTCGCTTGGAAGATTAGATTAGTTGCTGTTCCAAAGTCTACT 
               
               
                   
                 ATGTTCTCTGTTAAGAAGATCATGGAAATTCACGAGTTGGTTAAA 
               
               
                   
                 TTAGTTAACAAATGGCAAAACATTGCCTACAAGTACGATAAAGAT 
               
               
                   
                 TTGTTATTAATGACTCACTTTATCACTAGAAACATTACTGATAAC 
               
               
                   
                 CAAGGTAAGAATAAGACTGCCATTCACACTTACTTCTCTTCTGTT 
               
               
                   
                 TTCTTGGGTGGTGTTGATTCCTTGGTCGATTTGATGAACAAGTCT 
               
               
                   
                 TTTCCAGAATTAGGTATTAAGAAGACCGATTGTCGTCAATTATCT 
               
               
                   
                 TGGATTGATACCATTATTTTTTACTCCGGTGTTGTCAACTACGAC 
               
               
                   
                 ACTGATAATTTTAATAAGGAGATTTTGTTAGATAGATCTGCTGGT 
               
               
                   
                 CAAAATGGTGCCTTTAAAATCAAATTGGACTACGTTAAGAAGCCT 
               
               
                   
                 ATTCCAGAATCCGTCTTTGTTCAAATTTTGGAGAAGTTATACGAA 
               
               
                   
                 GAAGATATTGGTGCTGGTATGTACGCCTTGTATCCATATGGTGGT 
               
               
                   
                 ATTATGGATGAAATTTCTGAATCCGCCATCCCTTTCCCTCATCGT 
               
               
                   
                 GCTGGTATCTTATACGAGTTGTGGTACATCTGTTCTTGGGAAAAG 
               
               
                   
                 CAAGAAGATAATGAAAAGCATTTGAACTGGATCCGTAACATCTAT 
               
               
                   
                 AACTTCATGACTCCATACGTTTCCAAAAACCCTAGATTGGCTTAC 
               
               
                   
                 TTAAATTACAGAGACTTAGATATTGGTATTAACGACCCTAAGAAC 
               
               
                   
                 CCAAACAATTACACTCAAGCTAGAATCTGGGGTGAAAAGTACTTC 
               
               
                   
                 GGTAAGAATTTCGACAGATTAGTTAAGGTCAAGACTTTAGTTGAC 
               
               
                   
                 CCAAATAACTTCTTCAGAAACGAACAATCTATCCCACCATTGCCT 
               
               
                   
                 AGACATAGACACTAG 
               
               
                   
               
               
                 SEQ ID NO: 158 
                 MKCSTFSFWFVCKIIFFFFSFNIQTSIANPRENFLKCFSQYIPNN 
               
               
                 CBDA Synthase, L171I 
                 ATNLKLVYTQNNPLYMSVLNSTIHNLRFTSDTTPKPLVIVTPSHV 
               
               
                 variant 
                 SHIQGTILCSKKVGLQIRTRSGGHDSEGMSYISQVPFVIVDLRNM 
               
               
                 Artificial Sequence 
                 RSIKIDVHSQTAWVEAGATLGEVYYWVNEKNENLSIAAGYCPTVC 
               
               
                   
                 AGGHFGGGGYGPLMRNYGLAADNIIDAHLVNVHGKVLDRKSMGED 
               
               
                   
                 LFWALRGGGAESFGIIVAWKIRLVAVPKSTMFSVKKIME1HELVK 
               
               
                   
                 LVNKWQNIAYKYDKDLLLMTHFITRNITDNQGKNKTAIHTYFSSV 
               
               
                   
                 FLGGVDSLVDLMNKSFPELGIKKTDCRQLSWIDTIIFYSGVVNYD 
               
               
                   
                 TDNFNKEILLDRSAGQNGAFKIKLDYVKKP1PESVFVQ1LEKLYE 
               
               
                   
                 EDIGAGMYALYPYGGIMDEISESAIPFPHRAGILYELWYICSWEK 
               
               
                   
                 QEDNEKHLNWIRNIYNFMTPYVSKNPRLAYLNYRDLDIGINDPKN 
               
               
                   
                 PNNYTQARIWGEKYFGKNFDRLVKVKTLVDPNNFFRNEQSIPPLP 
               
               
                   
                 RHRH* 
               
               
                   
               
               
                 SEQ ID NO: 159 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                 CBDA Synthase, 
                 TTCTTCTTCTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 A172V variant 
                 CGTGAGAACTTCTTGAAATGTTTTTCTCAATATATCCCAAATAAC 
               
               
                 Artificial Sequence 
                 GCTACTAACTTGAAGTTAGTCTATACTCAAAACAACCCATTATAT 
               
               
                 Codon optimized 
                 ATGTCTGTCTTAAACTCTACCATTCACAACTTACGTTTCACTTCT 
               
               
                   
                 GATACTACTCCAAAACCTTTGGTCATCGTCACCCCATCCCACGTT 
               
               
                   
                 TCTCACATCCAAGGTACCATCTTGTGTTCCAAAAAGGTTGGTTTA 
               
               
                   
                 CAAATCCGTACTAGATCCGGTGGTCATGACTCCGAAGGTATGTCT 
               
               
                   
                 TACATTTCCCAAGTCCCTTTCGTCATCGTCGACTTAAGAAATATG 
               
               
                   
                 CGTTCCATCAAGATTGATGTCCATTCCCAAACTGCTTGGGTTGAA 
               
               
                   
                 GCCGGTGCCACTTTAGGTGAAGTCTATTACTGGGTTAACGAGAAG 
               
               
                   
                 AATGAGAACTTATCTTTGgttGCCGGTTACTGTCCAACTGTTTGT 
               
               
                   
                 GCTGGTGGTCATTTCGGTGGTGGTGGTTACGGTCCATTAATGCGT 
               
               
                   
                 AACTACGGTTTGGCTGCCGATAACATCATTGATGCCCACTTAGTC 
               
               
                   
                 AACGTTCATGGTAAGGTCTTGGACCGTAAGTCTATGGGTGAGGAT 
               
               
                   
                 TTATTCTGGGCTTTGAGAGGTGGTGGTGCTGAATCTTTCGGTATT 
               
               
                   
                 ATCGTCGCTTGGAAGATTAGATTAGTTGCTGTTCCAAAGTCTACT 
               
               
                   
                 ATGTTCTCTGTTAAGAAGATCATGGAAATTCACGAGTTGGTTAAA 
               
               
                   
                 TTAGTTAACAAATGGCAAAACATTGCCTACAAGTACGATAAAGAT 
               
               
                   
                 TTGTTATTAATGACTCACTTTATCACTAGAAACATTACTGATAAC 
               
               
                   
                 CAAGGTAAGAATAAGACTGCCATTCACACTTACTTCTCTTCTGTT 
               
               
                   
                 TTCTTGGGTGGTGTTGATTCCTTGGTCGATTTGATGAACAAGTCT 
               
               
                   
                 TTTCCAGAATTAGGTATTAAGAAGACCGATTGTCGTCAATTATCT 
               
               
                   
                 TGGATTGATACCATTATTTTTTACTCCGGTGTTGTCAACTACGAC 
               
               
                   
                 ACTGATAATTTTAATAAGGAGATTTTGTTAGATAGATCTGCTGGT 
               
               
                   
                 CAAAATGGTGCCTTTAAAATCAAATTGGACTACGTTAAGAAGCCT 
               
               
                   
                 ATTCCAGAATCCGTCTTTGTTCAAATTTTGGAGAAGTTATACGAA 
               
               
                   
                 GAAGATATTGGTGCTGGTATGTACGCCTTGTATCCATATGGTGGT 
               
               
                   
                 ATTATGGATGAAATTTCTGAATCCGCCATCCCTTTCCCTCATCGT 
               
               
                   
                 GCTGGTATCTTATACGAGTTGTGGTACATCTGTTCTTGGGAAAAG 
               
               
                   
                 CAAGAAGATAATGAAAAGCATTTGAACTGGATCCGTAAC 
               
               
                   
                 ATCTATAACTTCATGACTCCATACGTTTCCAAAAACCCTAGATTG 
               
               
                   
                 GCTTACTTAAATTACAGAGACTTAGATATTGGTATTAACGACCCT 
               
               
                   
                 AAGAACCCAAACAATTACACTCAAGCTAGAATCTGGGGTGAAAAG 
               
               
                   
                 TACTTCGGTAAGAATTTCGACAGATTAGTTAAGGTCAAGACTTTA 
               
               
                   
                 GTTGACCCAAATAACTTCTTCAGAAACGAACAATCTATCCCACCA 
               
               
                   
                 TTGCCTAGACATAGACACTAG 
               
               
                   
               
               
                 SEQ ID NO: 160 
                 MKCSTFSFWFVCKIIFFFFSFNIQTSIANPRENFLKCFSQYIPNN 
               
               
                 CBDA Synthase, 
                 ATNLKLVYTQNNPLYMSVLNSTIHNLRFTSDTTPKPLVIVTPSHV 
               
               
                 A172V variant 
                 SHIQGTILCSKKVGLQIRTRSGGHDSEGMSYISQVPFVIVDLRNM 
               
               
                 Artificial Sequence 
                 RSIKIDVHSQTAWVEAGATLGEVYYVVVNEKNENLSLVAGYCPTV 
               
               
                   
                 CAGGHFGGGGYGPLMRNYGLAADNIIDAHLVNVHGKVLDRKSMGE 
               
               
                   
                 DLFWALRGGGAESFGIIVAWKIRLVAVPKSTMFSVKKIMEIHELV 
               
               
                   
                 KLVNKWQNIAYKYDKDLLLMTHFITRNITDNQGKNKTAIHTYFSS 
               
               
                   
                 VFLGGVDSLVDLMNKSFPELGIKKTDCRQLSWIDTIIFYSGWNYD 
               
               
                   
                 TDNFNKEILLDRSAGQNGAFKIKLDYVKKPIPESVFVQILEKLYE 
               
               
                   
                 EDIGAGMYALYPYGGIMDEISESAIPFPHRAGILYELWYICSWEK 
               
               
                   
                 QEDNEKHLNWIRNIYNFMTPYVSKNPRLAYLNYRDLDIGINDPKN 
               
               
                   
                 PNNYTQARIWGEKYFGKNFDRLVKVKTLVDPNNFFRNEQSIPPLP 
               
               
                   
                 RHRH* 
               
               
                   
               
               
                 SEQ ID NO: 161 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                 CBDA Synthase, 
                 TTCTTCTTCTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 Y175F variant 
                 CGTGAGAACTTCTTGAAATGTTTTTCTCAATATATCCCAAATAAC 
               
               
                 Artificial Sequence 
                 GCTACTAACTTGAAGTTAGTCTATACTCAAAACAACCCATTATAT 
               
               
                 Codon optimized 
                 ATGTCTGTCTTAAACTCTACCATTCACAACTTACGTTTCACTTCT 
               
               
                   
                 GATACTACTCCAAAACCTTTGGTCATCGTCACCCCATCCCACGTT 
               
               
                   
                 TCTCACATCCAAGGTACCATCTTGTGTTCCAAAAAGGTTGGTTTA 
               
               
                   
                 CAAATCCGTACTAGATCCGGTGGTCATGACTCCGAAGGTATGTCT 
               
               
                   
                 TACATTTCCCAAGTCCCTTTCGTCATCGTCGACTTAAGAAATATG 
               
               
                   
                 CGTTCCATCAAGATTGATGTCCATTCCCAAACTGCTTGGGTTGAA 
               
               
                   
                 GCCGGTGCCACTTTAGGTGAAGTCTATTACTGGGTTAACGAGAAG 
               
               
                   
                 AATGAGAACTTATCTTTGGCTGCCGGTtttTGTCCAACTGTTTGT 
               
               
                   
                 GCTGGTGGTCATTTCGGTGGTGGTGGTTACGGTCCATTAATGCGT 
               
               
                   
                 AACTACGGTTTGGCTGCCGATAACATCATTGATGCCCACTTAGTC 
               
               
                   
                 AACGTTCATGGTAAGGTCTTGGACCGTAAGTCTATGGGTGAGGAT 
               
               
                   
                 TTATTCTGGGCTTTGAGAGGTGGTGGTGCTGAATCTTTCGGTATT 
               
               
                   
                 ATCGTCGCTTGGAAGATTAGATTAGTTGCTGTTCCAAAGTCTACT 
               
               
                   
                 ATGTTCTCTGTTAAGAAGATCATGGAAATTCACGAGTTGGTTAAA 
               
               
                   
                 TTAGTTAACAAATGGCAAAACATTGCCTACAAGTACGATAAAGAT 
               
               
                   
                 TTGTTATTAATGACTCACTTTATCACTAGAAACATTACTGATAAC 
               
               
                   
                 CAAGGTAAGAATAAGACTGCCATTCACACTTACTTCTCTTCTGTT 
               
               
                   
                 TTCTTGGGTGGTGTTGATTCCTTGGTCGATTTGATGAACAAGTCT 
               
               
                   
                 TTTCCAGAATTAGGTATTAAGAAGACCGATTGTCGTCAATTATCT 
               
               
                   
                 TGGATTGATACCATTATTTTTTACTCCGGTGTTGTCAACTACGAC 
               
               
                   
                 ACTGATAATTTTAATAAGGAGATTTTGTTAGATAGATCTGCTGGT 
               
               
                   
                 CAAAATGGTGCCTTTAAAATCAAATTGGACTACGTTAAGAAGCCT 
               
               
                   
                 ATTCCAGAATCCGTCTTTGTTCAAATTTTGGAGAAGTTATACGAA 
               
               
                   
                 GAAGATATTGGTGCTGGTATGTACGCCTTGTATCCATATGGTGGT 
               
               
                   
                 ATTATGGATGAAATTTCTGAATCCGCCATCCCTTTCCCTCATCGT 
               
               
                   
                 GCTGGTATCTTATACGAGTTGTGGTACATCTGTTCTTGGGAAAAG 
               
               
                   
                 CAAGAAGATAATGAAAAGCATTTGAACTGGATCCGTAACATCTAT 
               
               
                   
                 AACTTCATGACTCCATACGTTTCCAAAAACCCTAGATTGGCTTAC 
               
               
                   
                 TTAAATTACAGAGACTTAGATATTGGTATTAACGACCCTAAGAAC 
               
               
                   
                 CCAAACAATTACACTCAAGCTAGAATCTGGGGTGAAAAGTACTTC 
               
               
                   
                 GGTAAGAATTTCGACAGATTAGTTAAGGTCAAGACTTTAGTTGAC 
               
               
                   
                 CCAAATAACTTCTTCAGAAACGAACAATCTATCCCACCATTGCCT 
               
               
                   
                 AGACATAGACACTAG 
               
               
                   
               
               
                 SEQ ID NO: 162 
                 MKCSTFSFWFVCKIIFFFFSFNIQTSIANPRENFLKCFSQYIPNN 
               
               
                 CBDA Synthase, 
                 ATNLKLVYTQNNPLYMSVLNSTIHNLRFTSDTTPKPLVIVTPSHV 
               
               
                 Y175F variant 
                 SHIQGTILCSKKVGLQIRTRSGGHDSEGMSYISQVPFVIVDLRNM 
               
               
                 Artificial Sequence 
                 RSIKIDVHSQTAWVEAGATLGEVYYVVVNEKNENLSLAAGFCPTV 
               
               
                   
                 CAGGHFGGGGYGPLMRNYGLAADNIIDAHLVNVHGKVLDRKSMGE 
               
               
                   
                 DLFWALRGGGAESFGIIVAWKIRLVAVPKSTMFSVKKIMEIHELV 
               
               
                   
                 KLVNKWQNIAYKYDKDLLLMTHFITRNITDNQGKNKTAIHTYFSS 
               
               
                   
                 VFLGGVDSLVDLMNKSFPELGIKKTDCRQLSWIDTIIFYSGWNYD 
               
               
                   
                 TDNFNKEILLDRSAGQNGAFKIKLDYVKKPIPESVFVQILEKLYE 
               
               
                   
                 EDIGAGMYALYPYGGIMDEISESAIPFPHRAGILYELWYICSWEK 
               
               
                   
                 QEDNEKHLNWIRNIYNFMTPYVSKNPRLAYLNYRDLDIGINDPKN 
               
               
                   
                 PNNYTQARIWGEKYFGKNFDRLVKVKTLVDPNNFFRNEQSIPPLP 
               
               
                   
                 RHRH* 
               
               
                   
               
               
                 SEQ ID NO: 163 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                 CBDA Synthase, 
                 TTCTTCTTCTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 Cl80A variant 
                 CGTGAGAACTTCTTGAAATGTTTTTCTCAATATATCCCAAATAAC 
               
               
                 Artificial Sequence 
                 GCTACTAACTTGAAGTTAGTCTATACTCAAAACAACCCATTATAT 
               
               
                 Codon optimized 
                 ATGTCTGTCTTAAACTCTACCATTCACAACTTACGTTTCACTTCT 
               
               
                   
                 GATACTACTCCAAAACCTTTGGTCATCGTCACCCCATCCCACGTT 
               
               
                   
                 TCTCACATCCAAGGTACCATCTTGTGTTCCAAAAAGGTTGGTTTA 
               
               
                   
                 CAAATCCGTACTAGATCCGGTGGTCATGACTCCGAAGGTATGTCT 
               
               
                   
                 TACATTTCCCAAGTCCCTTTCGTCATCGTCGACTTAAGAAATATG 
               
               
                   
                 CGTTCCATCAAGATTGATGTCCATTCCCAAACTGCTTGGGTTGAA 
               
               
                   
                 GCCGGTGCCACTTTAGGTGAAGTCTATTACTGGGTTAACGAGAAG 
               
               
                   
                 AATGAGAACTTATCTTTGGCTGCCGGTTACTGTCCAACTGTTgct 
               
               
                   
                 GCTGGTGGTCATTTCGGTGGTGGTGGTTACGGTCCATTAATGCGT 
               
               
                   
                 AACTACGGTTTGGCTGCCGATAACATCATTGATGCCCACTTAGTC 
               
               
                   
                 AACGTTCATGGTAAGGTCTTGGACCGTAAGTCTATGGGTGAGGAT 
               
               
                   
                 TTATTCTGGGCTTTGAGAGGTGGTGGTGCTGAATCTTTCGGTATT 
               
               
                   
                 ATCGTCGCTTGGAAGATTAGATTAGTTGCTGTTCCAAAGTCTACT 
               
               
                   
                 ATGTTCTCTGTTAAGAAGATCATGGAAATTCACGAGTTGGTTAAA 
               
               
                   
                 TTAGTTAACAAATGGCAAAACATTGCCTACAAGTACGATAAAGAT 
               
               
                   
                 TTGTTATTAATGACTCACTTTATCACTAGAAACATTACTGATAAC 
               
               
                   
                 CAAGGTAAGAATAAGACTGCCATTCACACTTACTTCTCTTCTGTn 
               
               
                   
                 TCTTGGGTGGTGTTGATrCCTTGGTCGATTTGATGAACAAGTCTT 
               
               
                   
                 TTCCAGAATTAGGTATTAAGAAGACCGATTGTCGTCAATTGATAA 
               
               
                   
                 TTTTAATAAGGAGATTTTGTTAGATAGATCTGCTGGTCAAAATGG 
               
               
                   
                 TGCCTTTAAAATCAAATTGGACTACGTTAAGAAGCCTATTCCAGA 
               
               
                   
                 ATCCGTCTTTGTTCAAATTTTGGAGAAGTTATACGAAGAAGATAT 
               
               
                   
                 TGGTGCTGGTATGTACGCCTTGTATCCATATGGTGGTATTATGGA 
               
               
                   
                 TGAAATTTCTGAATCCGCCATCCCTTTCCCTCATCGTGCTGGTAT 
               
               
                   
                 CTTATACGAGTTGTGGTACATCTGTTCTTGGGAAAAGCAAGAAGA 
               
               
                   
                 TAATGAAAAGCATTTGAACTGGATCCGTAACATCTATAACTTCAT 
               
               
                   
                 GACTCCATACGTTTCCAAAAACCCTAGATTGGCTTACTTAAATTA 
               
               
                   
                 CAGAGACTTAGATATTGGTATTAACGACCCTAAGAACCCAAACAA 
               
               
                   
                 TTACACTCAAGCTAGAATCTGGGGTGAAAAGTACTTCGGTAAGAA 
               
               
                   
                 TTTCGACAGATTAGTTAAGGTCAAGACTTTAGTTGACCCAAATAA 
               
               
                   
                 CTTCTTCAGAAACGAACAATCTATCCCACCATTGCCTAGACATAG 
               
               
                   
                 ACACTAG 
               
               
                   
               
               
                 SEQ ID NO: 164 
                 MKCSTFSFWFVCKIIFFFFSFNIQTSIANPRENFLKCFSQYIPNN 
               
               
                 CBDA Synthase, 
                 ATNLKLVYTQNNPLYMSVLNSTIHNLRFTSDTTPKPLVIVTPSHV 
               
               
                 Cl80A variant 
                 SHIQGTILCSKKVGLQIRTRSGGHDSEGMSYISQVPFVIVDLRNM 
               
               
                 Artificial Sequence 
                 RSIKIDVHSQTAWVEAGATLGEVYYWVNEKNENLSLAAGYCPTVA 
               
               
                   
                 AGGHFGGGGYGPLMRNYGLAADNIIDAHLVNVHGKVLDRKSMGED 
               
               
                   
                 LFWALRGGGAESFGIIVAWKIRLVAVPKSTMFSVKKIMEIHELVK 
               
               
                   
                 LVNKWQNIAYKYDKDLLLMTHFITRNITDNQGKNKTAIHTYFSSV 
               
               
                   
                 FLGGVDSLVDLMNKSFPELGIKKTDCRQLSWIDTIIFYSGWNYDT 
               
               
                   
                 DNFNKEILLDRSAGQNGAFKIKLDYVKKPIPESVFVQILEKLYEE 
               
               
                   
                 DIGAGMYALYPYGGIMDEISESAIPFPHRAGILYELWYICSWEKQ 
               
               
                   
                 EDNEKHLNWIRNIYNFMTPYVSKNPRLAYLNYRDLDIGINDPKNP 
               
               
                   
                 NNYTQARIWGEKYFGKNFDRLVKVKTLVDPNNFFRNEQSIPPLPR 
               
               
                   
                 HRH* 
               
               
                   
               
               
                 SEQ ID NO: 165 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                 CBDA Synthase, 
                 TTCTTCTTCTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 A181V variant 
                 CGTGAGAACTTCTTGAAATGTTTTTCTCAATATATCCCAAATAAC 
               
               
                 Artificial Sequence 
                 GCTACTAACTTGAAGTTAGTCTATACTCAAAACAACCCATTATAT 
               
               
                 Codon optimized 
                 ATGTCTGTCTTAAACTCTACCATTCACAACTTACGTTTCACTTCT 
               
               
                   
                 GATACTACTCCAAAACCTTTGGTCATCGTCACCCCATCCCACGTT 
               
               
                   
                 TCTCACATCCAAGGTACCATCTTGTGTTCCAAAAAGGTTGGTTTA 
               
               
                   
                 CAAATCCGTACTAGATCCGGTGGTCATGACTCCGAAGGTATGTCT 
               
               
                   
                 TACATTTCCCAAGTCCCTTTCGTCATCGTCGACTTAAGAAATATG 
               
               
                   
                 CGTTCCATCAAGATTGATGTCCATTCCCAAACTGCTTGGGTTGAA 
               
               
                   
                 GCCGGTGCCACTTTAGGTGAAGTCTATTACTGGGTTAACGAGAAG 
               
               
                   
                 AATGAGAACTTATCTTTGGCTGCCGGTTACTGTCCAACTGTTTGT 
               
               
                   
                 gttGGTGGTCATTTCGGTGGTGGTGGTTACGGTCCATTAATGCGT 
               
               
                   
                 AACTACGGTTTGGCTGCCGATAACATCATTGATGCCCACTTAGTC 
               
               
                   
                 AACGTTCATGGTAAGGTCTTGGACCGTAAGTCTATGGGTGAGGAT 
               
               
                   
                 TTATTCTGGGCTTTGAGAGGTGGTGGTGCTGAATCTTTCGGTATT 
               
               
                   
                 ATCGTCGCTTGGAAGATTAGATTAGTTGCTGTTCCAAAGTCTACT 
               
               
                   
                 ATGTTCTCTGTTAAGAAGATCATGGAAATTCACGAGTTGGTTAAA 
               
               
                   
                 TTAGTTAACAAATGGCAAAACATTGCCTACAAGTACGATAAAGAT 
               
               
                   
                 TTGTTATTAATGACTCACTTTATCACTAGAAACATTACTGATAAC 
               
               
                   
                 CAAGGTAAGAATAAGACTGCCATTCACACTTACTTCTCTTCTGTT 
               
               
                   
                 TTCTTGGGTGGTGTTGATTCCTTGGTCGATTTGATGAACAAGTCT 
               
               
                   
                 TTTCCAGAATTAGGTATTAAGAAGACCGATTGTCGTCAATT 
               
               
                   
                 GATAATTTTAATAAGGAGATTTTGTTAGATAGATCTGCTGGTCAA 
               
               
                   
                 AATGGTGCCTTTAAAATCAAATTGGACTACGTTAAGAAGCCTATT 
               
               
                   
                 CCAGAATCCGTCTTTGTTCAAATTTTGGAGAAGTTATACGAAGAA 
               
               
                   
                 GATATTGGTGCTGGTATGTACGCCTTGTATCCATATGGTGGTATT 
               
               
                   
                 ATGGATGAAATTTCTGAATCCGCCATCCCTTTCCCTCATCGTGCT 
               
               
                   
                 GGTATCTTATACGAGTTGTGGTACATCTGTTCTTGGGAAAAGCAA 
               
               
                   
                 GAAGATAATGAAAAGCATTTGAACTGGATCCGTAACATCTATAAC 
               
               
                   
                 TTCATGACTCCATACGTTTCCAAAAACCCTAGATTGGCTTACTTA 
               
               
                   
                 AATTACAGAGACTTAGATATTGGTATTAACGACCCTAAGAACCCA 
               
               
                   
                 AACAATTACACTCAAGCTAGAATCTGGGGTGAAAAGTACTTCGGT 
               
               
                   
                 AAGAATTTCGACAGATTAGTTAAGGTCAAGACTTTAGTTGACCCA 
               
               
                   
                 AATAACTTCTTCAGAAACGAACAATCTATCCCACCATTGCCTAGA 
               
               
                   
                 CATAGACACTAG 
               
               
                   
               
               
                 SEQ ID NO: 166 
                 MKCSTFSFWFVCKIIFFFFSFNIQTSIANPRENFLKCFSQYIPNN 
               
               
                 CBDA Synthase, 
                 ATNLKLVYTQNNPLYMSVLNSTIHNLRFTSDTTPKPLVIVTPSHV 
               
               
                 A181V variant 
                 SHIQGTILCSKKVGLQIRTRSGGHDSEGMSYISQVPFVIVDLRNM 
               
               
                 Artificial Sequence 
                 RSIKIDVHSQTAWVEAGATLGEVYYWVNEKNENLSLAAGYCPTVC 
               
               
                   
                 VGGHFGGGGYGPLMRNYGLAADNIIDAHLVNVHGKVLDRKSMGED 
               
               
                   
                 LFWALRGGGAESFGIIVAWKIRLVAVPKSTMFSVKKIMEIHELVK 
               
               
                   
                 LVNKWQNIAYKYDKDLLLMTHFITRNITDNQGKNKTAIHTYFSSV 
               
               
                   
                 FLGGVDSLVDLMNKSFPELGIKKTDCRQLSWIDTIIFYSGVVNYD 
               
               
                   
                 TDNFNKEILLDRSAGQNGAFKIKLDYVKKPIPESVFVQILEKLYE 
               
               
                   
                 EDIGAGMYALYPYGGIMDEISESAIPFPHRAGILYELWYICSWEK 
               
               
                   
                 QEDNEKHLNVVIRNIYNFMTPYVSKNPRLAYLNYRDLDIGINDPK 
               
               
                   
                 NPNNYTQARIWGEKYFGKNFDRLVKVKTLVDPNNFFRNEQSIPPL 
               
               
                   
                 PRHRH* 
               
               
                   
               
               
                 SEQ ID NO: 167 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                 CBDA Synthase, 
                 TTCTTCTTCTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 N196Q variant 
                 CGTGAGAACTTCTTGAAATGTTTTTCTCAATATATCCCAAATAAC 
               
               
                 Artificial Sequence 
                 GCTACTAACTTGAAGTTAGTCTATACTCAAAACAACCCATTATAT 
               
               
                 Codon optimized 
                 ATGTCTGTCTTAAACTCTACCATTCACAACTTACGTTTCACTTCT 
               
               
                   
                 GATACTACTCCAAAACCTTTGGTCATCGTCACCCCATCCCACGTT 
               
               
                   
                 TCTCACATCCAAGGTACCATCTTGTGTTCCAAAAAGGTTGGTTTA 
               
               
                   
                 CAAATCCGTACTAGATCCGGTGGTCATGACTCCGAAGGTATGTCT 
               
               
                   
                 TACATTTCCCAAGTCCCTTTCGTCATCGTCGACTTAAGAAATATG 
               
               
                   
                 CGTTCCATCAAGATTGATGTCCATTCCCAAACTGCTTGGGTTGAA 
               
               
                   
                 GCCGGTGCCACTTTAGGTGAAGTCTATTACTGGGTTAACGAGAAG 
               
               
                   
                 AATGAGAACTTATCTTTGGCTGCCGGTTACTGTCCAACTGTTTGT 
               
               
                   
                 GCTGGTGGTCATTTCGGTGGTGGTGGTTACGGTCCATTAATGCGT 
               
               
                   
                 caaTACGGTTTGGCTGCCGATAACATCATTGATGCCCACTTAGTC 
               
               
                   
                 AACGTTCATGGTAAGGTCTTGGACCGTAAGTCTATGGGTGAGGAT 
               
               
                   
                 TTATTCTGGGCTTTGAGAGGTGGTGGTGCTGAATCTTTCGGTATT 
               
               
                   
                 ATCGTCGCTTGGAAGATTAGATTAGTTGCTGTTCCAAAGTCTACT 
               
               
                   
                 ATGTTCTCTGTTAAGAAGATCATGGAAATTCACGAGTTGGTTAAA 
               
               
                   
                 TTAGTTAACAAATGGCAAAACATTGCCTACAAGTACGATAAAGAT 
               
               
                   
                 TTGTTATTAATGACTCACTTTATCACTAGAAACATTACTGATAAC 
               
               
                   
                 CAAGGTAAGAATAAGACTGCCATTCACACTTACTTCTCTTCTGTT 
               
               
                   
                 TTCTTGGGTGGTGTTGATTCCTTGGTCGATTTGATGAACAAGTCT 
               
               
                   
                 TTTCCAGAATTAGGTATTAAGAAGACCGATTGTCGTCAATTGATA 
               
               
                   
                 ATTTTAATAAGGAGATTTTGTTAGATAGATCTGCTGGTCAAAATG 
               
               
                   
                 GTGCCTTTAAAATCAAATTGGACTACGTTAAGAAGCCTATTCCAG 
               
               
                   
                 AATCCGTCTTTGTTCAAATTTTGGAGAAGTTATACGAAGAAGATA 
               
               
                   
                 TTGGTGCTGGTATGTACGCCTTGTATCCATATGGTGGTATTATGG 
               
               
                   
                 ATGAAATTTCTGAATCCGCCATCCCTTTCCCTCATCGTGCTGGTA 
               
               
                   
                 TCTTATACGAGTTGTGGTACATCTGTTCTTGGGAAAAGCAAGAAG 
               
               
                   
                 ATAATGAAAAGCATTTGAACTGGATCCGTAACATCTATAACTTCA 
               
               
                   
                 TGACTCCATACGTTTCCAAAAACCCTAGATTGGCTTACTTAAATT 
               
               
                   
                 ACAGAGACTTAGATATTGGTATTAACGACCCTAAGAACCCAAACA 
               
               
                   
                 ATTACACTCAAGCTAGAATCTGGGGTGAAAAGTACTTCGGTAAGA 
               
               
                   
                 ATTTCGACAGATTAGTTAAGGTCAAGACTTTAGTTGACCCAAATA 
               
               
                   
                 ACTTCTTCAGAAACGAACAATCTATCCCACCATTGCCTAGACATA 
               
               
                   
                 GACACTAG 
               
               
                   
               
               
                 SEQ ID NO: 168 
                 MKCSTFSFWFVCKIIFFFFSFNIQTSIANPRENFLKCFSQYIPNN 
               
               
                 CBDA Synthase, 
                 ATNLKLVYTQNNPLYMSVLNSTIHNLRFTSDTTPKPLVIVTPSHV 
               
               
                 N196Q variant 
                 SHIQGTILCSKKVGLQIRTRSGGHDSEGMSYISQVPFVIVDLRNM 
               
               
                 Artificial Sequence 
                 RSIKIDVHSQTAWVEAGATLGEVYYWVNEKNENLSLAAGYCPTVC 
               
               
                   
                 AGGHFGGGGYGPLMRQYGLAADNIIDAHLVNVHGKVLDRKSMGED 
               
               
                   
                 LFWALRGGGAESFGIIVAWKIRLVAVPKSTMFSVKKIMEIHELVK 
               
               
                   
                 LVNKWQNIAYKYDKDLLLMTHFITRNITDNQGKNKTAIHTYFSSV 
               
               
                   
                 FLGGVDSLVDLMNKSFPELGIKKTDCRQLSWIDTIIFYSGVVNYD 
               
               
                   
                 TDNFNKEILLDRSAGQNGAFKIKLDYVKKPIPESVFVQILEKLYE 
               
               
                   
                 EDIGAGMYALYPYGGIMDEISESAIPFPHRAGILYELWYICSWEK 
               
               
                   
                 QEDNEKHLNWIRNIYNFMTPYVSKNPRLAYLNYRDLDIGINDPKN 
               
               
                   
                 PNNYTQARIWGEKYFGKNFDRLVKVKTLVDPNNFFRNEQSIPPLP 
               
               
                   
                 RHRH* 
               
               
                   
               
               
                 SEQ ID NO: 169 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                 CBDA Synthase, 
                 TTCTTCTTCTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 NI96T variant 
                 CGTGAGAACTTCTTGAAATGTTTTTCTCAATATATCCCAAATAAC 
               
               
                 Artificial Sequence 
                 GCTACTAACTTGAAGTTAGTCTATACTCAAAACAACCCATTATAT 
               
               
                 Codon optimized 
                 ATGTCTGTCTTAAACTCTACCATTCACAACTTACGTTTCACTTCT 
               
               
                   
                 GATACTACTCCAAAACCTTTGGTCATCGTCACCCCATCCCACGTT 
               
               
                   
                 TCTCACATCCAAGGTACCATCTTGTGTTCCAAAAAGGTTGGTTTA 
               
               
                   
                 CAAATCCGTACTAGATCCGGTGGTCATGACTCCGAAGGTATGTCT 
               
               
                   
                 TACATTTCCCAAGTCCCTTTCGTCATCGTCGACTTAAGAAATATG 
               
               
                   
                 CGTTCCATCAAGATTGATGTCCATTCCCAAACTGCTTGGGTTGAA 
               
               
                   
                 GCCGGTGCCACTTTAGGTGAAGTCTATTACTGGGTTAACGAGAAG 
               
               
                   
                 AATGAGAACTTATCTTTGGCTGCCGGTTACTGTCCAACTGTTTGT 
               
               
                   
                 GCTGGTGGTCATTTCGGTGGTGGTGGTTACGGTCCATTAATGCGT 
               
               
                   
                 actTACGGTTTGGCTGCCGATAACATCATTGATGCCCACTTAGTC 
               
               
                   
                 AACGTTCATGGTAAGGTCTTGGACCGTAAGTCTATGGGTGAGGAT 
               
               
                   
                 TTATTCTGGGCTTTGAGAGGTGGTGGTGCTGAATCTTTCGGTATT 
               
               
                   
                 ATCGTCGCTTGGAAGATTAGATTAGTTGCTGTTCCAAAGTCTACT 
               
               
                   
                 ATGTTCTCTGTTAAGAAGATCATGGAAATTCACGAGTTGGTTAAA 
               
               
                   
                 TTAGTTAACAAATGGCAAAACATTGCCTACAAGTACGATAAAGAT 
               
               
                   
                 TTGTTATTAATGACTCACTTTATCACTAGAAACATTACTGATAAC 
               
               
                   
                 CAAGGTAAGAATAAGACTGCCATTCACACTTACTTCTCTTCTGTT 
               
               
                   
                 TTCTTGGGTGGTGTTGATTCCTTGGTCGATTTGATGAACAAGTCT 
               
               
                   
                 TTTCCAGAATTAGGTATTAAGAAGACCGATTGTCGTCAATTGATA 
               
               
                   
                 ATTTTAATAAGGAGATTTTGTTAGATAGATCTGCTGGTCAAAATG 
               
               
                   
                 GTGCCTTTAAAATCAAATTGGACTACGTTAAGAAGCCTATTCCAG 
               
               
                   
                 AATCCGTCTTTGTTCAAATTTTGGAGAAGTTATACGAAGAAGATA 
               
               
                   
                 TTGGTGCTGGTATGTACGCCTTGTATCCATATGGTGGTATTATGG 
               
               
                   
                 ATGAAATTTCTGAATCCGCCATCCCTTTCCCTCATCGTGCTGGTA 
               
               
                   
                 TCTTATACGAGTTGTGGTACATCTGTTCTTGGGAAAAGCAAGAAG 
               
               
                   
                 ATAATGAAAAGCATTTGAACTGGATCCGTAACATCTATAACTTCA 
               
               
                   
                 TGACTCCATACGTTTCCAAAAACCCTAGATTGGCTTACTTAAATT 
               
               
                   
                 ACAGAGACTTAGATATTGGTATTAACGACCCTAAGAACCCAAACA 
               
               
                   
                 ATTACACTCAAGCTAGAATCTGGGGTGAAAAGTACTTCGGTAAGA 
               
               
                   
                 ATTTCGACAGATTAGTTAAGGTCAAGACTTTAGTTGACCCAAATA 
               
               
                   
                 ACTTCTTCAGAAACGAACAATCTATCCCACCATTGCCTAGACATA 
               
               
                   
                 GACACTAG 
               
               
                   
               
               
                 SEQ ID NO: 170 
                 MKCSTFSFWFVCKIIFFFFSFNIQTSIANPRENFLKCFSQYIPNN 
               
               
                 CBDA Synthase, 
                 ATNLKLVYTQNNPLYMSVLNSTIHNLRFTSDTTPKPLVIVTPSHV 
               
               
                 N196T variant 
                 SHIQGTILCSKKVGLQIRTRSGGHDSEGMSYISQVPFVIVDLRNM 
               
               
                 Artificial Sequence 
                 RSIKIDVHSQTAWVEAGATLGEVYYWVNEKNENLSLAAGYCPTVC 
               
               
                   
                 AGGHFGGGGYGPLMRTYGLAADNIIDAHLVNVHGKVLDRKSMGED 
               
               
                   
                 LFWALRGGGAESFGIIVAWKIRLVAVPKSTMFSVKKIMEIHELVK 
               
               
                   
                 LVNKWQNIAYKYDKDLLLMTHFITRNITDNQGKNKTAIHTYFSSV 
               
               
                   
                 FLGGVDSLVDLMNKSFPELGIKKTDCRQLSWIDTIIFYSGVVNYD 
               
               
                   
                 TDNFNKEILLDRSAGQNGAFKIKLDYVKKPIPESVFVQILEKLYE 
               
               
                   
                 EDIGAGMYALYPYGGIMDEISESAIPFPHRAGILYELWYICSWEK 
               
               
                   
                 QEDNEKHLNWIRNIYNFMTPYVSKNPRLAYLNYRDLDIGINDPKN 
               
               
                   
                 PNNYTQARIWGEKYFGKNFDRLVKVKTLVDPNNFFRNEQSIPPLP 
               
               
                   
                 RHRH* 
               
               
                   
               
               
                 SEQ ID NO: 171 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                 CBDA Synthase, 
                 TTCTTCTTCTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 N196V variant 
                 CGTGAGAACTTCTTGAAATGTTTTTCTCAATATATCCCAAATAAC 
               
               
                 Artificial Sequence 
                 GCTACTAACTTGAAGTTAGTCTATACTCAAAACAACCCATTATAT 
               
               
                 Codon optimized 
                 ATGTCTGTCTTAAACTCTACCATTCACAACTTACGTTTCACTTCT 
               
               
                   
                 GATACTACTCCAAAACCTTTGGTCATCGTCACCCCATCCCACGTT 
               
               
                   
                 TCTCACATCCAAGGTACCATCTTGTGTTCCAAAAAGGTTGGTTTA 
               
               
                   
                 CAAATCCGTACTAGATCCGGTGGTCATGACTCCGAAGGTATGTCT 
               
               
                   
                 TACATTTCCCAAGTCCCTTTCGTCATCGTCGACTTAAGAAATATG 
               
               
                   
                 CGTTCCATCAAGATTGATGTCCATTCCCAAACTGCTTGGGTTGAA 
               
               
                   
                 GCCGGTGCCACTTTAGGTGAAGTCTATTACTGGGTTAACGAGAAG 
               
               
                   
                 AATGAGAACTTATCTTTGGCTGCCGGTTACTGTCCAACTGTTTGT 
               
               
                   
                 GCTGGTGGTCATTTCGGTGGTGGTGGTTACGGTCCATTAATGCGT 
               
               
                   
                 gttTACGGTTTGGCTGCCGATAACATCATTGATGCCCACTTAGTC 
               
               
                   
                 AACGTTCATGGTAAGGTCTTGGACCGTAAGTCTATGGGTGAG 
               
               
                   
                 GATTTATTCTGGGCTTTGAGAGGTGGTGGTGCTGAATCTTTCGGT 
               
               
                   
                 ATTATCGTCGCTTGGAAGATTAGATTAGTTGCTGTTCCAAAGTCT 
               
               
                   
                 ACTATGTTCTCTGTTAAGAAGATCATGGAAATTCACGAGTTGGTT 
               
               
                   
                 AAATTAGTTAACAAATGGCAAAACATTGCCTACAAGTACGATAAA 
               
               
                   
                 GATTTGTTATTAATGACTCACTTTATCACTAGAAACATTACTGAT 
               
               
                   
                 AACCAAGGTAAGAATAAGACTGCCATTCACACTTACTTCTCTTCT 
               
               
                   
                 GTTTTCTTGGGTGGTGTTGATTCCTTGGTCGATTTGATGAACAAG 
               
               
                   
                 TCTTTTCCAGAATTAGGTATTAAGAAGACCGATTGTCGTCAATTG 
               
               
                   
                 ATAATTTTAATAAGGAGATTTTGTTAGATAGATCTGCTGGTCAAA 
               
               
                   
                 ATGGTGCCTTTAAAATCAAATTGGACTACGTTAAGAAGCCTATTC 
               
               
                   
                 CAGAATCCGTCTTTGTTCAAATTTTGGAGAAGTTATACGAAGAAG 
               
               
                   
                 ATATTGGTGCTGGTATGTACGCCTTGTATCCATATGGTGGTATTA 
               
               
                   
                 TGGATGAAATTTCTGAATCCGCCATCCCTTTCCCTCATCGTGCTG 
               
               
                   
                 GTATCTTATACGAGTTGTGGTACATCTGTTCTTGGGAAAAGCAAG 
               
               
                   
                 AAGATAATGAAAAGCATTTGAACTGGATCCGTAACATCTATAA 
               
               
                   
                 CTTCATGACTCCATACGTTTCCAAAAACCCTAGATT 
               
               
                   
                 GGCTTACTTAAATTACAGAGACTTAGATATTGGTATTAACGACC 
               
               
                   
                 CTAAGAACCCAAACAATTACACTCAAGCTAGAATCTGGGGTGAAA 
               
               
                   
                 AGTACTTCGGTAAGAATTTCGACAGATTAGTTAAGGTCAAGACTT 
               
               
                   
                 TAGTTGACCCAAATAACTTCTTCAGAAACGAACAATCTATCCCAC 
               
               
                   
                 CATTGCCTAGACATAGACACTAG 
               
               
                   
               
               
                 SEQ ID NO: 172 
                 MKCSTFSFWFVCKIIFFFFSFNIQTSIANPRENFLKCFSQYIPNN 
               
               
                 CBDA Synthase, 
                 ATNLKLVYTQNNPLYMSVLNSTIHNLRFTSDTTPKPLVIVTPSHV 
               
               
                 N196V variant 
                 SHIQGTILCSKKVGLQIRTRSGGHDSEGMSYISQVPFVIVDLRNM 
               
               
                 Artificial Sequence 
                 RSIKIDVHSQTAWVEAGATLGEVYYYVVNEKNENLSLAAGYCP 
               
               
                   
                 TVCAGGHFGGGGYGPLMRVYGLAADNIIDAHLVNVHGK 
               
               
                   
                 VLDRKSMGEDLFWALRGGGAESFGIIVAYVKIRLVAVPKSTMFSV 
               
               
                   
                 KKIMEIHELVKLVNKVVQNIAYKYDKDLLLMTHFITRNITDNQGK 
               
               
                   
                 NKTAIHTYFSSVFLGGVDSLVDLMNKSFPELGIKKTDCRQLSWID 
               
               
                   
                 TIIFYSGVVNYDTDNFNKEILLDRSAGQNGAFKIKLDYVKXPIPE 
               
               
                   
                 SVFVQILEKLYEEDIGAGMYALYPYGGIMDEISESAIPFPHRAGI 
               
               
                   
                 LYELWYICSWEKQEDNEKHLNVVIRNIYNFMTPYVSKNPRLAYLN 
               
               
                   
                 YRDLDIGINDPKNPNNYTQARIWGEKYFGKNFDRLVKVKTLVDPN 
               
               
                   
                 NFFRNEQSIPPLPRHRH* 
               
               
                   
               
               
                 SEQ ID NO: 173 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                 CBDA Synthase, 
                 TTCTTCTTCTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 H208T variant 
                 CGTGAGAACTTCTTGAAATGTTTTTCTCAATATATCCCA 
               
               
                 Artificial Sequence 
                 AATAACGCTACTAACTTGAAGTTAGTCTATACTCAAAAC 
               
               
                 Codon optimized 
                 AACCCATTATATATGTCTGTCTTAAACTCTACCATTCACAACTTA 
               
               
                   
                 CGTTTCACTTCTGATACTACTCCAAAACCTTTGGTCATCGTCACC 
               
               
                   
                 CCATCCCACGTTTCTCACATCCAAGGTACCATCTTGTGTTCCAAA 
               
               
                   
                 AAGGTTGGTTTACAAATCCGTACTAGATCCGGTGGTCATGACTCC 
               
               
                   
                 GAAGGTATGTCTTACATTTCCCAAGTCCCTTTCGTCATCGTC 
               
               
                   
                 GACTTAAGAAATATGCGTTCCATCAAGATTGATGTCCATT 
               
               
                   
                 CCCAAACTGCTTGGGTTGAAGCCGGTGCCACTTTAGGTGAAGTCT 
               
               
                   
                 ATTACTGGGTTAACGAGAAGAATGAGAACTTATCTTTGGCTGCCG 
               
               
                   
                 GTTACTGTCCAACTGTTTGTGCTGGTGGTCATTTCGGTGGTGGTG 
               
               
                   
                 GTTACGGTCCATTAATGCGTAACTACGGTTTGGCTGCCGATAACA 
               
               
                   
                 TCATTGATGCCactTTAGTCAACGTTCATGGTAAGGTCTT 
               
               
                   
                 GGACCGTAAGTCTATGGGTGAGGATTTATTCTGGGCTTTGAG 
               
               
                   
                 AGGTGGTGGTGCTGAATCTTTCGGTATTATCGTCGCTTGGAAGAT 
               
               
                   
                 TAGATTAGTTGCTGTTCCAAAGTCTACTATGTTCTCTGTTAAGAA 
               
               
                   
                 GATCATGGAAATTCACGAGTTGGTTAAATTAGTTAACAAATGGCA 
               
               
                   
                 AAACATTGCCTACAAGTACGATAAAGATTTGTTATTAATGACTCA 
               
               
                   
                 CTTTATCACTAGAAACATTACTGATAACCAAGGT 
               
               
                   
                 AAGAATAAGACTGCCATTCACACTTACTTCTCTTCTGT 
               
               
                   
                 TTTCTTGGGTGGTGTTGATTCCTTGGTCGATTTGATGAACAAGTC 
               
               
                   
                 TTTTCCAGAATTAGGTATTAAGAAGACCGATTGTCGTCAATTGAT 
               
               
                   
                 AATTTTAATAAGGAGATTTTGTTAGATAGATCTGCTGGTCAAAAT 
               
               
                   
                 GGTGCCTTTAAAATCAAATTGGACTACGTTAAGAAGCCTATTCCA 
               
               
                   
                 GAATCCGTCTTTGTTCAAATTTTGGAGAAGTTATACGAAGAAGAT 
               
               
                   
                 ATTGGTGCTGGTATGTACGCCTTGTATCCATATGGTGGTATTATG 
               
               
                   
                 GATGAAATTTCTGAATCCGCCATCCCTTTCCCTCATCGTGCTGGT 
               
               
                   
                 ATCTTATACGAGTTGTGGTACATCTGTTCTTGGGAAAAGCAAGAA 
               
               
                   
                 GATAATGAAAAGCATTTGAACTGGATCCGTAACATCTATAACTTC 
               
               
                   
                 ATGACTCCATACGTTTCCAAAAACCCTAGATTGGCTTACTTAA 
               
               
                   
                 ATTACAGAGACTTAGATATTGGTATTAACGACCCT 
               
               
                   
                 AAGAACCCAAACAATTACACTCAAGCTAGAATCTGGGGT 
               
               
                   
                 GAAAAGTACTTCGGTAAGAATTTC 
               
               
                   
                 GACAGATTAGTTAAGGTCAAGACTTTAGTTGACCCAAATAACTTC 
               
               
                   
                 TTCAGAAACGAACAATCTATCCCACCATTGCCTAGA 
               
               
                   
                 CATAGACACTAG 
               
               
                   
               
               
                 SEQ ID NO: 174 
                 MKCSTFSFWFVCKIIFFFFSFNIQTSIANPRENFLKCFSQYIPNN 
               
               
                 CBDA Synthase, 
                 ATNLKLVYTQNNPLYMSVLNSTIHNLRFTSDTTPKPLVIVTPSH 
               
               
                 H208T variant 
                 VSHIQGTILCSKKVGLQIRTRSGGHDSEGMSYISQVPFVIVDLRN 
               
               
                 Artificial Sequence 
                 MRSIKIDVHSQTAWVEAGATLGEVYYWVNEKNENLSLAAGYCPTV 
               
               
                   
                 CAGGHFGGGGYGPLMRNYGLAADNIIDATLVNVHGKVLDRKSMGE 
               
               
                   
                 DLFWALRGGGAESFGIIVAWKIRLVAVPKSTMFSVKKIMEIHELV 
               
               
                   
                 KLVNKWQNIAYKYDKDLLLMTHFITRNITDNQGKNKTAIHTYFSS 
               
               
                   
                 VFLGGVDSLVDLMNKSFPELGIKKTDCRQLSWIDTIIFYSGWNYD 
               
               
                   
                 TDNFNKEILLDRSAGQNGAFKIKLDYVKKPIPESVFVQILEKLYE 
               
               
                   
                 EDIGAGMYALYPYGGIMDEISESAIPFPHRAGILYELWYICSWEK 
               
               
                   
                 QEDNEKHLNWIRNIYNFMTPYVSKNPRLAYLNYRDLDIGINDPKN 
               
               
                   
                 PNNYTQARIWGEKYFGKNFDRLVKVKTLVDPNNFFRNEQSIPPLP 
               
               
                   
                 RHRH* 
               
               
                   
               
               
                 SEQ ID NO: 175 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                 CBDA Synthase, 
                 TTCTTCTTCTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 A235P variant 
                 CGTGAGAACTTCTTGAAATGTTTTTCTCAATATATCCCAAATAAC 
               
               
                 Artificial Sequence 
                 GCTACTAACTTGAAGTTAGTCTATACTCAAAACAACCC 
               
               
                 Codon optimized 
                 ATTATATATGTCTGTCTTAAACTCTACCATTCACAA 
               
               
                   
                 CTTACGTTTCACTTCTGATACTACTCCAAAACCTTT 
               
               
                   
                 GGTCATCGTCACCCCATCCCACGTTTCTCACATCCAAGGTACC 
               
               
                   
                 ATCTTGTGTTCCAAAAAGGTTGGTTTACAAATCCGTACTA 
               
               
                   
                 GATCCGGTGGTCATGACTCCGAAGGTATGTCTTACATTTC 
               
               
                   
                 CCAAGTCCCTTTCGTCATCGTCGACTTAAGAAATATGCGTTCCAT 
               
               
                   
                 CAAGATTGATGTCCATTCCCAAACTGCTTGGGTTGAAGCCGGTGC 
               
               
                   
                 CACTTTAGGTGAAGTCTATTACTGGGTTAACGAGAAGAATGAGAA 
               
               
                   
                 CTTATCTTTGGCTGCCGGTTACTGTCCAACTGTTTGTGCTGGTGG 
               
               
                   
                 TCATTTCGGTGGTGGTGGTTACGGTCCATTAATGCGTAACTACGG 
               
               
                   
                 TTTGGCTGCCGATAACATCATTGATGCCCACTTAGTCAACGTTCA 
               
               
                   
                 TGGTAAGGTCTTGGACCGTAAGTCTATGGGTGAGGATTTATTCTG 
               
               
                   
                 GGCTTTGAGAGGTGGTGGTccaGAATCTTTCGGTATTATCGTCGC 
               
               
                   
                 TTGGAAGATTAGATTAGTTGCTGTTCCAAAGTCTACTATGTTCTC 
               
               
                   
                 TGTTAAGAAGATCATGGAAATTCACGAGTTGGTTAAATTAGTTAA 
               
               
                   
                 CAAATGGCAAAACATTGCCTACAAGTACGATA 
               
               
                   
                 AAGATTTGTTATTAATGACTCACTTTATCACTAGA 
               
               
                   
                 AACATTACTGATAACCAAGGTAAGAATAAGACTGCCATTCA 
               
               
                   
                 CACTTACTTCTCTTCTGTTTTCTTGGGTGGTGTTGATTCCTTGGT 
               
               
                   
                 CGATTTGATGAACAAGTCTTTTCCAGAATTAGGTATT 
               
               
                   
                 AAGAAGACCGATTGTCGTCAACTGATAATTTTAATAAGG 
               
               
                   
                 AGATTTTGTTAGATAGATCTGCTGGTCAAAATGGTGCCTTTAA 
               
               
                   
                 AATCAAATTGGACTACGTTAAGAAGCCTATTCCAG 
               
               
                   
                 AATCCGTCTTTGTTCAAATTTTGGAGAAGTTATACGAAGAAGAT 
               
               
                   
                 ATTGGTGCTGGTATGTACGCCTTGTATCCATATGGTGGTATTATG 
               
               
                   
                 GATGAAATTTCTGAATCCGCCATCCCTTTCCCTCATCGTGCTGG 
               
               
                   
                 TATCTTATACGAGTTGTGGTACATCTGTTCTTGGGAAAAGCAAGA 
               
               
                   
                 AGATAATGAAAAGCATTTGAACTGGATCCGTAACATCTATAACTT 
               
               
                   
                 CATGACTCCATACGTTTCCAAAAACCCTAGATTGGCTTACTTAAA 
               
               
                   
                 TTACAGAGACTTAGATATTGGTATTAACGACCCTAAGAACCCAAA 
               
               
                   
                 CAATTACACTCAAGCTAGAATCTGGGGTGAAAAGTACTTCGGTAA 
               
               
                   
                 GAATTTCGACAGATTAGTTAAGGTCAAGACTTTAGTTGACCCAAA 
               
               
                   
                 TAACTTCTTCAGAAACGAACAATCTATCCCACCATTGCCTAGACA 
               
               
                   
                 TAGACACTAG 
               
               
                   
               
               
                 SEQ ID NO: 176 
                 MKCSTFSFWFVCKIIFFFFSFNIQTSIANPRENFLKCFSQYIPNN 
               
               
                 CBDA Synthase, 
                 ATNLKLVYTQNNPLYMSVLNSTIHNLRFTSDTTPKPLVIVTPSH 
               
               
                 A235P variant 
                 VSHIQGTILCSKKVGLQIRTRSGGHDSEGMSYISQVPFVIVDLRN 
               
               
                 Artificial Sequence 
                 MRSIKIDVHSQTAWVEAGATLGEVYYWVNEKNENLSLAAGYCPTV 
               
               
                   
                 CAGGHFGGGGYGPLMRNYGLAADNIIDAHLVNVHGKVLDRKSMGE 
               
               
                   
                 DLFWALRGGGPESFGIIVAWKIRLVAVPKSTMFSVKKIMEIHELV 
               
               
                   
                 KLVNKWQNIAYKYDKDLLLMTHFITRNITDNQGKNKTAIHTYFSS 
               
               
                   
                 VFLGGVDSLVDLMNKSFPELGIKKTDCRQLSWIDTIIFYSGVVNY 
               
               
                   
                 DTDNFNKEILLDRSAGQNGAFKIKLDYVKKPIPESVFVQILEKLY 
               
               
                   
                 EEDIGAGMYALYPYGGIMDEISESAIPFPHRAGILYELWYICSWE 
               
               
                   
                 KQEDNEKHLNVVIRNIYNFMTPYVSKNPRLAYLNYRDLDIGINDP 
               
               
                   
                 KNPNNYTQARIWGEKYFGKNFDRLVKVKTLVDPNNFFRNEQSIPP 
               
               
                   
                 LPRHRH* 
               
               
                   
               
               
                 SEQ ID NO: 177 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                 CBDA Synthase, 
                 TTCTTCTTCTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 A250T variant 
                 CGTGAGAACTTCTTGAAATGTTTTTCTCAATATATCCCA 
               
               
                 Artificial Sequence 
                 AATAACGCTACTAACTTGAAGTTAGTCTATACTCAAAA 
               
               
                 Codon optimized 
                 CAACCCATTATATATGTCTGTCTTAAACTCTACCATTCACAACTT 
               
               
                   
                 ACGTTTCACTTCTGATACTACTCCAAAACCTTTGGTCATC 
               
               
                   
                 GTCACCCCATCCCACGTTTCTCACATCCAAGGTACCATCTTGTGT 
               
               
                   
                 TCCAAAAAGGTTGGTTTACAAATCCGTACTAGATCCGGTGGTCA 
               
               
                   
                 TGACTCCGAAGGTATGTCTTACATTTCCCAAGTCCCTTTCGTCA 
               
               
                   
                 TCGTCGACTTAAGAAATATGCGTTCCATCAAGATTGATGTCCATT 
               
               
                   
                 CCCAAACTGCTTGGGTTGAAGCCGGTGCCACTTTAGGTGAAGTCT 
               
               
                   
                 ATTACTGGGTTAACGAGAAGAATGAGAACTTATCTTTGGCTGCCG 
               
               
                   
                 GTTACTGTCCAACTGTTTGTGCTGGTGGTCATTTCGGTGGTGGTG 
               
               
                   
                 GTTACGGTCCATTAATGCGTAACTACGGTTTGGCTGCCGATAACA 
               
               
                   
                 TCATTGATGCCCACTTAGTCAACGTTCATGGTAAGGTCTTGGACC 
               
               
                   
                 GTAAGTCTATGGGTGAGGATTTATTCTGGGCTTTGAGAGGTG 
               
               
                   
                 GTGGTGCTGAATCTTTCGGTATTATCGTCGCTTGGAAGATT 
               
               
                   
                 AGATTAGTTactGTTCCAAAGTCTACTATGTTCTCTGTTAAGAAG 
               
               
                   
                 ATCATGGAAATTCACGAGTTGGTTAAATTAGTTAACAAATGGCAA 
               
               
                   
                 AACATTGCCTACAAGTACGATAAAGATTTGTTATTAATGACTCAC 
               
               
                   
                 TTTATCACTAGAAACATTACTGATAACCAAGGTAAGAATAAGACT 
               
               
                   
                 GCCATTCACACTTACTTCTCTTCTGTTTTCTTGGGTGGTGTTGAT 
               
               
                   
                 TCCTTGGTCGATTTGATGAACAAGTCTTTTCCAGAATTAGGTATT 
               
               
                   
                 AAGAAGACCGATTGTCGTCAACTGATAATTTTAATAAGGAGATTT 
               
               
                   
                 TGTTAGATAGATCTGCTGGTCAAAATGGTGCCTTTAAAATCAAAT 
               
               
                   
                 TGGACTACGTTAAGAAGCCTATTCCAGAATCCGTCTTTGTTC 
               
               
                   
                 AAATTTTGGAGAAGTTATACGAAGAAGATATTGGTGCT 
               
               
                   
                 GGTATGTACGCCTTGTATCCATATGGTGGTATTATGGATGAAATT 
               
               
                   
                 TCTGAATCCGCCATCCCTTTCCCTCATCGTGCTGGTATCTTATA 
               
               
                   
                 CGAGTTGTGGTACATCTGTTCTTGGGAAAAGCAAGAAGATAATGA 
               
               
                   
                 AAAGCATTTGAACTGGATCCGTAACATCTATAACTTCATGAC 
               
               
                   
                 TCCATACGTTTCCAAAAACCCTAGATTGGCTTACTTAAA 
               
               
                   
                 TTACAGAGACTTAGATATTGGTATTAACGACCCTAAGAACCCAAA 
               
               
                   
                 CAATTACACTCAAGCTAGAATCTGGGGTGAAAAGTACTTCGGTAA 
               
               
                   
                 GAATTTCGACAGATTAGTTAAGGTCAAGACTTTAGTTGACCCAAA 
               
               
                   
                 TAACTTCTTCAGAAACGAACAATCTATCCCACCATT 
               
               
                   
                 GCCTAGACATAGACACTAG 
               
               
                   
               
               
                 SEQ ID NO: 178 
                 MKCSTFSFWFVCKIIFFFFSFNIQTSIANPRENFLKCFSQYIPNN 
               
               
                 CBDA Synthase, 
                 ATNLKLVYTQNNPLYMSVLNSTIHNLRFTSDTTPKPLVIVTPSH 
               
               
                 A250T variant 
                 VSHIQGTILCSKKVGLQIRTRSGGHDSEGMSYISQVPFVIVDLRN 
               
               
                 Artificial Sequence 
                 MRSIKIDVHSQTAWVEAGATLGEVYYWVNEKNENLSLAAGYCPTV 
               
               
                   
                 CAGGHFGGGGYGPLMRNYGLAADNIIDAHLVNVHGKVLDRKSMGE 
               
               
                   
                 DLFWALRGGGAESFGIIVAWKIRLVTVPKSTMFSVKKIMEIHELV 
               
               
                   
                 KLVNKWQNIAYKYDKDLLLMTHFITRNITDNQGKNKTAIHTYFSS 
               
               
                   
                 VFLGGVDSLVDLMNKSFPELGIKKTDCRQLSWIDTIIFYSGWNYD 
               
               
                   
                 TDNFNKEILLDRSAGQNGAFKKLDYVKKPIPESVFVQILEK 
               
               
                   
                 LYEEDIGAGMYALYPYGGIMDEISESAIPFPHRAGILYELWY 
               
               
                   
                 ICSWEKQEDNEKHLNWIRNIYNFMTPYVSKNPRLAYLNYRDLDIG 
               
               
                   
                 INDPKNPNNYTQARIVVGEKYFGKNFDRLVKVKTLVDPNNFFRN 
               
               
                   
                 EQSIPPLPRHRH* 
               
               
                   
               
               
                 SEQ ID NO: 179 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                 CBDA Synthase, 
                 TTCTTCTTCTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 M256V variant 
                 CGTGAGAACTTCTTGAAATGTTTTTCTCAATATATCCCAAATAAC 
               
               
                 Artificial Sequence 
                 GCTACTAACTTGAAGTTAGTCTATACTCAAAACAACCCATTATAT 
               
               
                 Codon optimized 
                 ATGTCTGTCTTAAACTCTACCATTCACAACTTACGTTTCACTTC 
               
               
                   
                 TGATACTACTCCAAAACCTTTGGTCATCGTCACCCCATCC 
               
               
                   
                 CACGTTTCTCACATCCAAGGTACCATCTTGTGTTCCAAAAAGGTT 
               
               
                   
                 GGTTTACAAATCCGTACTAGATCCGGTGGTCATGACTCCGAAGG 
               
               
                   
                 TATGTCTTACATTTCCCAAGTCCCTTTCGTCATCGTCGACTTA 
               
               
                   
                 AGAAATATGCGTTCCATCAAGATTGATGTCCATTCCCAAACTGCT 
               
               
                   
                 TGGGTTGAAGCCGGTGCCACTTTAGGTGAAGTCTATTACTGGGTT 
               
               
                   
                 AACGAGAAGAATGAGAACTTATCTTTGGCTGCCGGTTACTGTCCA 
               
               
                   
                 ACTGTTTGTGCTGGTGGTCATTTCGGTGGTGGTGGTTACGGTCCA 
               
               
                   
                 TTAATGCGTAACTACGGTTTGGCTGCCGATAACATCATTGATGCC 
               
               
                   
                 CACTTAGTCAACGTTCATGGTAAGGTCTTGGACCGTAAGTCTATG 
               
               
                   
                 GGTGAGGATTTATTCTGGGCTTTGAGAGGTGGTGGTGCTGAATCT 
               
               
                   
                 TTCGGTATTATCGTCGCTTGGAAGATTAGATTAGTTGCTGTTCCA 
               
               
                   
                 AAGTCTACTgUTTCTCTGTTAAGAAGATCATGGAAATTCACGAGT 
               
               
                   
                 TGGTTAAATTAGTTAACAAATGGCAAAACATTGCCTAC 
               
               
                   
                 AAGTACGATAAAGATTTGTTATTAATGACTCACT 
               
               
                   
                 TTATCACTAGAAACATTACTGATAACCAAGGTAAGAATAAGACTG 
               
               
                   
                 CCATTCACACTTACTTCTCTTCTGTTTTCTTGGGTGGTGTTGATT 
               
               
                   
                 CCTTGGTCGATTTGATGAACAAGTCTTTTCCAGAATTAGGTATTA 
               
               
                   
                 AGAAGACCGATTGTCGTCAACTGATAATTTTAATAAGGAGATTTT 
               
               
                   
                 GTTAGATAGATCTGCTGGTCAAAATGGTGCCTTTAAAATCAAATT 
               
               
                   
                 GGACTACGTTAAGAAGCCTATTCCAGAATCCG 
               
               
                   
                 TCTTTGTTCAAATTTTGGAGAAGTTATACGAAGAAGATATTGGTG 
               
               
                   
                 CTGGTATGTACGCCTTGTATCCATATGGTGGTATTATGG 
               
               
                   
                 ATGAAATTTCTGAATCCGCCATCCCTTTCCCTCATCGTGC 
               
               
                   
                 TGGTATCTTATACGAGTTGTGGTACATCTGTTCTTGGGAAAAGCA 
               
               
                   
                 AGAAGATAATGAAAAGCATTTGAACTGGATCCGTAACATCTATAA 
               
               
                   
                 CTTCATGACTCCATACGTTTCCAAAAACCCTAGATTGGCTTACTT 
               
               
                   
                 AAATTACAGAGACTTAGATATTGGTATTAACGA 
               
               
                   
                 CCCTAAGAACCCAAACAATTACACTCAAGCTAGAATCTGGG 
               
               
                   
                 GTGAAAAGTACTTCGGTAAGAATTTCGACAGATTAGTTAAGGTCA 
               
               
                   
                 AGACTTTAGTTGACCCAAATAACTTCTTCAGAAACGAACAATCTA 
               
               
                   
                 TCCCACCATTGCCTAGACATAGACACTAG 
               
               
                   
               
               
                 SEQ ID NO: 180 
                 MKCSTFSFWFVCKIIFFFFSFNIQTSIANPRENFLKCFSQYIPNN 
               
               
                 CBDA Synthase, 
                 ATNLKLVYTQNNPLYMSVLNSTIHNLRFTSDTTPKPLVIVTPSH 
               
               
                 M256V variant 
                 VSHIQGTILCSKKVGLQIRTRSGGHDSEGMSYISQVPFVIVDLRN 
               
               
                 Artificial Sequence 
                 MRSIKIDVHSQTAWVEAGATLGEVYYWVNEKNENLSLAAGYCPTV 
               
               
                   
                 CAGGHFGGGGYGPLMRNYGLAADNIIDAHLVNVHGKVLDRKSMGE 
               
               
                   
                 DLFWALRGGGAESFGIIVAWKIRLVAVPKSTVFSVKKIMEIHELV 
               
               
                   
                 KLVNKWQNIAYKYDKDLLLMTHFITRNITDNQGKNKTAIHTYFSS 
               
               
                   
                 VFLGGVDSLVDLMNKSFPELGIKKTDCRQLSWIDTIIFYSGWNYD 
               
               
                   
                 TDNFNKEILLDRSAGQNGAFKIKLDYVKKPIPESVFVQILEKLYE 
               
               
                   
                 EDIGAGMYALYPYGGIMDEISESAIPFPHRAGILYELWYICSWEK 
               
               
                   
                 QEDNEKHLNWIRNIYNFMTPYVSKNPRLAYLNYRDLDIGINDPKN 
               
               
                   
                 PNNYTQARIWGEKYFGKNFDRLVKVKTLVDPNNFFRNEQSIPPLP 
               
               
                   
                 RHRH* 
               
               
                   
               
               
                 SEQ ID NO: 181 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                 CBDA Synthase, 
                 TTCTTCTTCTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 K260C variant 
                 CGTGAGAACTTCTTGAAATGTTTTTCTCAATATATCCCAAATAAC 
               
               
                 Artificial Sequence 
                 GCTACTAACTTGAAGTTAGTCTATACTCAAAACAACCCATTATAT 
               
               
                 Codon optimized 
                 ATGTCTGTCTTAAACTCTACCATTCACAACTTACGTTTCACTTCT 
               
               
                   
                 GATACTACTCCAAAACCTTTGGTCATCGTCACCCCATCCCACGTT 
               
               
                   
                 TCTCACATCCAAGGTACCATCTTGTGTTCCAAAAAGGTTGGTTTA 
               
               
                   
                 CAAATCCGTACTAGATCCGGTGGTCATGACTCCGAAGGTATGTCT 
               
               
                   
                 TACATTTCCCAAGTCCCTTTCGTCATCGTCGACTTAAGAAATATG 
               
               
                   
                 CGTTCCATCAAGATTGATGTCCATTCCCAAACTGCTTGGGTTGAA 
               
               
                   
                 GCCGGTGCCACTTTAGGTGAAGTCTATTACTGGGTTAACGAGAAG 
               
               
                   
                 AATGAGAACTTATCTTTGGCTGCCGGTTACTGTCCAACTGTTTGT 
               
               
                   
                 GCTGGTGGTCATTTCGGTGGTGGTGGTTACGGTCCATTAATGCGT 
               
               
                   
                 AACTACGGTTTGGCTGCCGATAACATCATTGATGCCCACTTAG 
               
               
                   
                 TCAACGTTCATGGTAAGGTCTTGGACCGTAAGTCTATG 
               
               
                   
                 GGTGAGGATTTATTCTGGGCTTTGAGAGGTGGTGGTGCTGAATCT 
               
               
                   
                 TTCGGTATTATCGTCGCTTGGAAGATTAGATTAGTTGCTGTTCCA 
               
               
                   
                 AAGTCTACTATGTTCTCTGTTtgtAAGATCATGGAAATTCACGAG 
               
               
                   
                 TTGGTTAAATTAGTTAACAAATGGCAAAACATTGCCTACAAGTAC 
               
               
                   
                 GATAAAGATTTGTTATTAATGACTCACTTTATCACTAGAAACATT 
               
               
                   
                 ACTGATAACCAAGGTAAGAATAAGACTGCCATTCACACTTACTTC 
               
               
                   
                 TCTTCTGTTTTCTTGGGTGGTGTTGATTCCTTGGTCGATTTGATG 
               
               
                   
                 AACAAGTCTTTTCCAGAATTAGGTATTAAGAAGACCGATTGTCGT 
               
               
                   
                 CAATTGATAATTTTAATAAGGAGATTTTGTTAGATAGATCTGCTG 
               
               
                   
                 GTCAAAATGGTGCCTTTAAAATCAAATTGGACTACGTTAAGAAGC 
               
               
                   
                 CTATTCCAGAATCCGTCTTTGTTCAAATTTTGGAGAAGTTATAC 
               
               
                   
                 GAAGAAGATATTGGTGCTGGTATGTACGCCTTGTATCCATAT 
               
               
                   
                 GGTGGTATTATGGATGAAATTTCTGAATCCGCCATCCCTTTCCCT 
               
               
                   
                 CATCGTGCTGGTATCTTATACGAGTTGTGGTACATCTGTTCTTGG 
               
               
                   
                 GAAAAGCAAGAAGATAATGAAAAGCATTTGAACTGGATCCGTAAC 
               
               
                   
                 ATCTATAACTTCATGACTCCATACGTTTCCAAAAACCCTAGATTG 
               
               
                   
                 GCTTACTTAAATTACAGAGACTTAGATATTGGTATTAACGACCCT 
               
               
                   
                 AAGAACCCAAACAATTACACTCAAGCTAGAATCTGGGGTGAAAAG 
               
               
                   
                 TACTTCGGTAAGAATTTCGACAGATTAGTTAAGGTCA 
               
               
                   
                 AGACTTTAGTTGACCCAAATAACTTCTTCAGAAACG 
               
               
                   
                 AACAATCTATCCCACCATTGCCTAGACATAGACA 
               
               
                   
                 CTAG 
               
               
                   
               
               
                 SEQ ID NO: 182 
                 MKCSTFSFWFVCKIIFFFFSFNIQTSIANPRENFLKCFSQYIPNN 
               
               
                 CBDA Synthase, 
                 ATNLKLVYTQNNPLYMSVLNSTIHNLRFTSDTTPKPLVIVTPSH 
               
               
                 K260C variant 
                 VSHIQGTILCSKKVGLQIRTRSGGHDSEGMSYISQVPFVIVDLRN 
               
               
                 Artificial Sequence 
                 MRSIKIDVHSQTAWVEAGATLGEVYYWVNEKNENLSLAAGYCPTV 
               
               
                   
                 CAGGHFGGGGYGPLMRNYGLAADNIIDAHLVNVHGKVLDRKSMG 
               
               
                   
                 EDLFWALRGGGAESFGIIVAWKIRLVAVPKSTMFSVCKIMEIHEL 
               
               
                   
                 VKLVNKWQNIAYKYDKDLLLMTHFITRNITDNQGKNKTAIHTYFS 
               
               
                   
                 SVFLGGVDSLVDLMNKSFPELGIKKTDCRQLSWIDTIIFYSG 
               
               
                   
                 VVNYDTDNFNKEILLDRSAGQNGAFKKLDYVKKPIPESVFV 
               
               
                   
                 QILEKLYEEDIGAGMYALYPYGGIMDEISESAIPFPHRAGIL 
               
               
                   
                 YELWYICSWEKQEDNEKHLNWIRNIYNFMTPYVSKNPRLAYLNYR 
               
               
                   
                 DLDIGINDPKNPNNYTQARIWGEKYFGKNFDRLVKVKTLVDPNNF 
               
               
                   
                 FRNEQSIPPLPRHRH* 
               
               
                   
               
               
                 SEQ ID NO: 183 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                 CBDA Synthase, 
                 TTCTTCTTCTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 K260W variant 
                 CGTGAGAACTTCTTGAAATGTTTTTCTCAATATATCCCAAATAAC 
               
               
                 Artificial Sequence 
                 GCTACTAACTTGAAGTTAGTCTATACTCAAAACAACCCATTATAT 
               
               
                 Codon optimized 
                 ATGTCTGTCTTAAACTCTACCATTCACAACTTACGTTTCACTTCT 
               
               
                   
                 GATACTACTCCAAAACCTTTGGTCATCGTCACCCCATCCCACGTT 
               
               
                   
                 TCTCACATCCAAGGTACCATCTTGTGTTCCAAAAAGGTTGGTTTA 
               
               
                   
                 CAAATCCGTACTAGATCCGGTGGTCATGACTCCGAAGGTATGTCT 
               
               
                   
                 TACATTTCCCAAGTCCCTTTCGTCATCGTCGACTTAAGAAATATG 
               
               
                   
                 CGTTCCATCAAGATTGATGTCCATTCCCAAACTGCTTGGGTTGAA 
               
               
                   
                 GCCGGTGCCACTTTAGGTGAAGTCTATTACTGGGTTAACGAGAAG 
               
               
                   
                 AATGAGAACTTATCTTTGGCTGCCGGTTACTGTCCAACTGTTTGT 
               
               
                   
                 GCTGGTGGTCATTTCGGTGGTGGTGGTTACGGTCCATTAATGCGT 
               
               
                   
                 AACTACGGTTTGGCTGCCGATAACATCATTGATGCCCACTTAGTC 
               
               
                   
                 AACGTTCATGGTAAGGTCTTGGACCGTAAGTCTATGGGTGAGGAT 
               
               
                   
                 TTATTCTGGGCTTTGAGAGGTGGTGGTGCTGAATCTTTCGGTATT 
               
               
                   
                 ATCGTCGCTTGGAAGATTAGATTAGTTGCTGTTCCAAAG 
               
               
                   
                 TCTACTATGTTCTCTGTTtggAAGATCATGGAAATTCACGAGT 
               
               
                   
                 TGGTTAAATTAGTTAACAAATGGCAAAACATTGCCTACAAGTACG 
               
               
                   
                 ATAAAGATTTGTTATTAATGACTCACTTTATCACTAGAAACA 
               
               
                   
                 TTACTGATAACCAAGGTAAGAATAAGACTGCCA 
               
               
                   
                 TTCACACTTACTTCTCTTCTGTTTTCTTGGGTGGTGTTGATTCC 
               
               
                   
                 TTGGTCGATTTGATGAACAAGTCTTTTCCAGAATTAG 
               
               
                   
                 GTATTAAGAAGACCGATTGTCGTCAATTGATAATTT 
               
               
                   
                 TAATAAGGAGATTTTGTTAGATAGATCTGCTGGTCAAAATGGTGC 
               
               
                   
                 CTTTAAAATCAAATTGGACTACGTTAAGAAGCCTATTCCAGAA 
               
               
                   
                 TCCGTCTTTGTTCAAATTTTGGAGAAGTTATACGAAGAAGATATT 
               
               
                   
                 GGTGCTGGTATGTACGCCTTGTATCCATATGGTGGTATTATG 
               
               
                   
                 GATGAAATTTCTGAATCCGCCATCCCTTTCCCTCATCGTGCTGGT 
               
               
                   
                 ATCTTATACGAGTTGTGGTACATCTGTTCTTGGGAAAAGCAAGAA 
               
               
                   
                 GATAATGAAAAGCATTTGAACTGGATCCGTAACATCTATAA 
               
               
                   
                 CTTCATGACTCCATACGTTTCCAAAAACCCTAG 
               
               
                   
                 ATTGGCTTACTTAAATTACAGAGACTTAGATATTGGTATTAACG 
               
               
                   
                 ACCCTAAGAACCCAAACAATTACACTCAAGCTAGAATCTGGGGTG 
               
               
                   
                 AAAAGTACTTCGGTAAGAATTTCGACAGATTAGTTAAGGTCAAGA 
               
               
                   
                 CTTTAGTTGACCCAAATAACTTCTTCAGAAACGAACAATCT 
               
               
                   
                 ATCCCACCATTGCCTAGACATAGACACTAG 
               
               
                   
               
               
                 SEQ ID NO: 184 
                 MKCSTFSFWFVCKIIFFFFSFNIQTSIANPRENFLKCFSQYIPNN 
               
               
                 CBDA Synthase, 
                 ATNLKLVYTQNNPLYMSVLNSTIHNLRFTSDTTPKPLVIVTPSH 
               
               
                 K260W variant 
                 VSHIQGTILCSKKVGLQIRTRSGGHDSEGMSYISQVPFVIVDLRN 
               
               
                 Artificial Sequence 
                 MRSIKIDVHSQTAWVEAGATLGEVYYWVNEKNENLSLAAGYCPTV 
               
               
                   
                 CAGGHFGGGGYGPLMRNYGLAADNIIDAHLVNVHGKVLDRKSMGE 
               
               
                   
                 DLFWALRGGGAESFGIIVAWKIRLVAVPKSTMFSVWKIMEIHEL 
               
               
                   
                 VKLVNKWQNIAYKYDKDLLLMTHFITRNITDNQGKNKTAIHTY 
               
               
                   
                 FSSVFLGGVDSLVDLMNKSFPELGIKKTDCRQLSWIDTIIFYSG 
               
               
                   
                 WNYDTDNFNKEILLDRSAGQNGAFKIKLDYVKKPIPESVFVQILE 
               
               
                   
                 KLYEEDIGAGMYALYPYGGIMDEISESAIPFPHRAGILYELWYIC 
               
               
                   
                 SWEKQEDNEKHLNWIRNIYNFMTPYVSKNPRLAYLNYRDLDIGIN 
               
               
                   
                 DPKNPNNYTQARIWGEKYFGKNFDRLVKVKTLVDPNNFFRNEQSI 
               
               
                   
                 PPLPRHRH* 
               
               
                   
               
               
                 SEQ ID NO: 185 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                 CBDA Synthase, L268I 
                 TTCTTCTTCTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 variant 
                 CGTGAGAACTTCTTGAAATGTTTTTCTCAATATATCCCAAATAAC 
               
               
                 Artificial Sequence 
                 GCTACTAACTTGAAGTTAGTCTATACTCAAAACAACCCATTATAT 
               
               
                 Codon optimized 
                 ATGTCTGTCTTAAACTCTACCATTCACAACTTACGTTTCACTTCT 
               
               
                   
                 GATACTACTCCAAAACCTTTGGTCATCGTCACCCCATCCCACGTT 
               
               
                   
                 TCTCACATCCAAGGTACCATCTTGTGTTCCAAAAAGGTTGGTTT 
               
               
                   
                 ACAAATCCGTACTAGATCCGGTGGTCATGACTCCGAAG 
               
               
                   
                 GTATGTCTTACATTTCCCAAGTCCCTTTCGTCATCGTCGACTT 
               
               
                   
                 AAGAAATATGCGTTCCATCAAGATTGATGTCCATTCCCAAACTGC 
               
               
                   
                 TTGGGTTGAAGCCGGTGCCACTTTAGGTGAAGTCTATTACTGGGT 
               
               
                   
                 TAACGAGAAGAATGAGAACTTATCTTTGGCTGCCGGTTACTGTCC 
               
               
                   
                 AACTGTTTGTGCTGGTGGTCATTTCGGTGGTGGTGGTTACGGTCC 
               
               
                   
                 ATTAATGCGTAACTACGGTTTGGCTGCCGATAACATCATTGATGC 
               
               
                   
                 CCACTTAGTCAACGTTCATGGTAAGGTCTTGGACCGTAAGTCT 
               
               
                   
                 ATGGGTGAGGATTTATTCTGGGCTTTGAGAGGTGGTGGTGCTGAA 
               
               
                   
                 TCTTTCGGTATTATCGTCGCTTGGAAGATTAGATTAGTTGCTGTT 
               
               
                   
                 CCAAAGTCTACTATGTTCTCTGTTAAGAAGATCATGGAAATTCAC 
               
               
                   
                 GAGattGTTAAATTAGTTAACAAATGGCAAAACATTGCCTACAAG 
               
               
                   
                 TACGATAAAGATTTGTTATTAATGACTCACTTTATCACTAGA 
               
               
                   
                 AACATTACTGATAACCAAGGTAAGAATAAGAC 
               
               
                   
                 TGCCATTCACACTTACTTCTCTTCTGTTTTCTTGGGTGGTGTT 
               
               
                   
                 GATTCCTTGGTCGATTTGATGAACAAGTCTTTTCCAGAATTAGGT 
               
               
                   
                 ATTAAGAAGACCGATTGTCGTCAATTGATAATTTTAATAAGGAGA 
               
               
                   
                 TTTTGTTAGATAGATCTGCTGGTCAAAATGGTGCCTTTAAAATCA 
               
               
                   
                 AATTGGACTACGTTAAGAAGCCTATTCCAGAATCCGTCTTTGTTC 
               
               
                   
                 AAATTTTGGAGAAGTTATACGAAGAAGATATTG 
               
               
                   
                 GTGCTGGTATGTACGCCTTGTATCCATATGGTGGTATT 
               
               
                   
                 ATGGATGAAATTTCTGAATCCGCCATCCCTTTCCCTCATC 
               
               
                   
                 GTGCTGGTATCTTATACGAGTTGTGGTACATCTGTTCTTGGGAAA 
               
               
                   
                 AGCAAGAAGATAATGAAAAGCATTTGAACTGGATCCGTAAC 
               
               
                   
                 ATCTATAACTTCATGACTCCATACGTTTCCAAAA 
               
               
                   
                 ACCCTAGATTGGCTTACTTAAATTACAGAGACTTAGAT 
               
               
                   
                 ATTGGTATTAACGACCCTAAGAACCCAAACAATTACACTC 
               
               
                   
                 AAGCTAGAATCTGGGGTGAAAAGTACTTCGGTAAGAATTTCGACA 
               
               
                   
                 GATTAGTTAAGGTCAAGACTTTAGTTGACCCAAAT 
               
               
                   
                 AACTTCTTCAGAAACGAACAATCTATCCCACCATTGCCTAGACA 
               
               
                   
                 TAGACACTAG 
               
               
                   
               
               
                 SEQ ID NO: 186 
                 MKCSTFSFWFVCKIIFFFFSFNIQTSIANPRENFLKCFSQYIPNN 
               
               
                 CBDA Synthase, 
                 ATNLKLVYTQNNPLYMSVLNSTIHNLRFTSDTTPKPLVIVTPSH 
               
               
                 L268I 
                 VSHIQGTILCSKKVGLQIRTRSGGHDSEGMSYISQVPFVIVDLR 
               
               
                 variant 
                 NMRSIKIDVHSQTAWVEAGATLGEVYYWVNEKNENLSLAAGYCPT 
               
               
                 Artificial Sequence 
                 VCAGGHFGGGGYGPLMRNYGLAADNIIDAHLVNVHGKVLDRKSMG 
               
               
                   
                 EDLFWALRGGGAESFGIIVAWKIRLVAVPKSTMFSVKKIMEIHEI 
               
               
                   
                 VKLVNKWQNIAYKYDKDLLLMTHFITRNITDNQGKNKTAIHTYFS 
               
               
                   
                 SVFLGGVDSLVDLMNKSFPELGIKKTDCRQLSWIDTIIFYSGWNY 
               
               
                   
                 DTDNFNKEILLDRSAGQNGAFKIKLDYVKKPIPESVFVQILEK 
               
               
                   
                 LYEEDIGAGMYALYPYGGIMDEISESAIPFPHRAGILYELWY 
               
               
                   
                 ICSWEKQEDNEKHLNWIRNIYNFMTPYVSKNPRLAYLNYRDLDIG 
               
               
                   
                 INDPKNPNNYTQARIWGEKYFGKNFDRLVKVKTLVDPNNFFRNEQ 
               
               
                   
                 SIPPLPRHRH* 
               
               
                   
               
               
                 SEQ ID NO: 187 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                 CBDA Synthase, 
                 TTCTTCTTCTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 H309V variant 
                 CGTGAGAACTTCTTGAAATGTTTTTCTCAATATATCCCAAATAAC 
               
               
                 Artificial Sequence 
                 GCTACTAACTTGAAGTTAGTCTATACTCAAAACAACCCATTATAT 
               
               
                 Codon optimized 
                 ATGTCTGTCTTAAACTCTACCATTCACAACTTACGTTTCACTTC 
               
               
                   
                 TGATACTACTCCAAAACCTTTGGTCATCGTCACCCCATCCC 
               
               
                   
                 ACGTTTCTCACATCCAAGGTACCATCTTGTGTTCCAAAAAGGTTG 
               
               
                   
                 GTTTACAAATCCGTACTAGATCCGGTGGTCATGACTCCGAAGGT 
               
               
                   
                 ATGTCTTACATTTCCCAAGTCCCTTTCGTCATCGTCGACTTAA 
               
               
                   
                 GAAATATGCGTTCCATCAAGATTGATGTCCATTCCCAAACTGCTT 
               
               
                   
                 GGGTTGAAGCCGGTGCCACTTTAGGTGAAGTCTATTACTGGGTTA 
               
               
                   
                 ACGAGAAGAATGAGAACTTATCTTTGGCTGCCGGTTACTGTCCAA 
               
               
                   
                 CTGTTTGTGCTGGTGGTCATTTCGGTGGTGGTGGTTACGGTCCAT 
               
               
                   
                 TAATGCGTAACTACGGTTTGGCTGCCGATAACATCATTGATGCCC 
               
               
                   
                 ACTTAGTCAACGTTCATGGTAAGGTCTTGGACCGTAAGTCTATGG 
               
               
                   
                 GTGAGGATTTATTCTGGGCTTTGAGAGGTGGTGGTGCTGAATCTT 
               
               
                   
                 TCGGTATTATCGTCGCTTGGAAGATTAGATTAGTTGCTGTTC 
               
               
                   
                 CAAAGTCTACTATGTTCTCTGTTAAGAAGATCATG 
               
               
                   
                 GAAATTCACGAGTTGGTTAAATTAGTTAACAA 
               
               
                   
                 ATGGCAAAACATTGCCTACAAGTACGATAAAGATTTGTTATTAAT 
               
               
                   
                 GACTCACTTTATCACTAGAAACATTACTGATAACCAAGGT 
               
               
                   
                 AAGAATAAGACTGCCATTgttACTTACTTCTCTTCTGTTTTCTT 
               
               
                   
                 GGGTGGTGTTGATTCCTTGGTCGATTTGATGAACAAGTCTTTTC 
               
               
                   
                 CAGAATTAGGTATTAAGAAGACCGATTGTCGTCAATTGATAA 
               
               
                   
                 TTTTAATAAGGAGATTTTGTTAGATAGATCTGCTGGTCAAAATGG 
               
               
                   
                 TGCCTTTAAAATCAAATTGGACTACGTTAAGAAGCCTATTCCAGA 
               
               
                   
                 ATCCGTCTTTGTTCAAATTTTGGAGAAGTTATACGAAGAAGATAT 
               
               
                   
                 TGGTGCTGGTATGTACGCCTTGTATCCATATGGTGGTATT 
               
               
                   
                 ATGGATGAAATTTCTGAATCCGCCATCCCTTTCCCTCA 
               
               
                   
                 TCGTGCTGGTATCTTATACGAGTTGTGGTACATCTGTTCTTGGG 
               
               
                   
                 AAAAGCAAGAAGATAATGAAAAGCATTTGAACT 
               
               
                   
                 GGATCCGTAACATCTATAACTTCATGACTCCATACGTTTCCAAA 
               
               
                   
                 AACCCTAGATTGGCTTACTTAAATTACAGAGACTTAGATATTGGT 
               
               
                   
                 ATTAACGACCCTAAGAACCCAAACAATTACACTCAAGCTAGAATC 
               
               
                   
                 TGGGGTGAAAAGTACTTCGGTAAGAATTTCGACAGATTAGTTAAG 
               
               
                   
                 GTCAAGACTTTAGTTGACCCAAATAACTTCTTCAGAAACGAACAA 
               
               
                   
                 TCTATCCCACCATTGCCTAGACATAGACACTAG 
               
               
                   
               
               
                 SEQ ID NO: 188 
                 MKCSTFSFWFVCKIIFFFFSFNIQTSIANPRENFLKCFSQYIPNN 
               
               
                 CBDA Synthase, 
                 ATNLKLVYTQNNPLYMSVLNSTIHNLRFTSDTTPKPLVIVTPSH 
               
               
                 H309V variant 
                 VSHIQGTILCSKKVGLQIRTRSGGHDSEGMSYISQVPFVIV 
               
               
                 Artificial Sequence 
                 DLRNMRSIKIDVHSQTAWVEAGATLGEVYYWVNEKNENLSLAA 
               
               
                   
                 GYCPTVCAGGHFGGGGYGPLMRNYGLAADNIIDAHL 
               
               
                   
                 VNVHGKVLDRKSMGEDLFWALRGGGAESFGIIVAWKIRLVAVPKS 
               
               
                   
                 TMFSVKKIMEIHELVKLVNKWQNIAYKYDKDLLLMTHFITRNITD 
               
               
                   
                 NQGKNKTAIVTYFSSVFLGGVDSLVDLMNKSFPELGIKKTDCRQL 
               
               
                   
                 SWIDTIIFYSGVVNYDTDNFNKEILLDRSAGQNGAFKIKLDYVKK 
               
               
                   
                 PIPESVFVQILEKLYEEDIGAGMYALYPYGGIMDEISESAIPFPH 
               
               
                   
                 RAGILYELWYICSWEKQEDNEKHLNWIRNIYNFMTPYVSKNPRLA 
               
               
                   
                 YLNYRDLDIGINDPKNPNNYTQARIWGEKYFGKNFDRLVKVKTLV 
               
               
                   
                 DPNNFFRNEQSIPPLPRHRH* 
               
               
                   
               
               
                 SEQ ID NO: 189 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                 CBDA Synthase, 
                 TTCTTCTTCTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 T310A variant 
                 CGTGAGAACTTCTTGAAATGTTTTTCTCAATATATCCCAAATAAC 
               
               
                 Artificial Sequence 
                 GCTACTAACTTGAAGTTAGTCTATACTCAAAACAACCC 
               
               
                 Codon optimi/ed 
                 ATTATATATGTCTGTCTTAAACTCTACCATTCACAA 
               
               
                   
                 CTTACGTTTCACTTCTGATACTACTCCAAAACCTTTGGTCATCGT 
               
               
                   
                 CACCCCATCCCACGTTTCTCACATCCAAGGTACCATCTTGTGTTC 
               
               
                   
                 CAAAAAGGTTGGTTTACAAATCCGTACTAGATCCGGTGGTCATGA 
               
               
                   
                 CTCCGAAGGTATGTCTTACATTTCCCAAGTCCCTTTCGTCATCGT 
               
               
                   
                 CGACTTAAGAAATATGCGTTCCATCAAGATTGATGTCCATTCCCA 
               
               
                   
                 AACTGCTTGGGTTGAAGCCGGTGCCACTTTAGGTGAAGTCTATTA 
               
               
                   
                 CTGGGTTAACGAGAAGAATGAGAACTTATCTTTGGCTGCCGGTTA 
               
               
                   
                 CTGTCCAACTGTTTGTGCTGGTGGTCATTTCGGTGGTGGTGGTTA 
               
               
                   
                 CGGTCCATTAATGCGTAACTACGGTTTGGCTGCCGATAACATCAT 
               
               
                   
                 TGATGCCCACTTAGTCAACGTTCATGGTAAGGTCTTGGACCGTAA 
               
               
                   
                 GTCTATGGGTGAGGATTTATTCTGGGCTTTGAGAGGTGGTGGTGC 
               
               
                   
                 TGAATCTTTCGGTATTATCGTCGCTTGGAAGATTAGATTAGTT 
               
               
                   
                 GCTGTTCCAAAGTCTACTATGTTCTCTGTTAAGAAGATC 
               
               
                   
                 ATGGAAATTCACGAGTTGGTTAAATTAGTTAACA 
               
               
                   
                 AATGGCAAAACATTGCCTACAAGTACGATAAAGATTTGTTATTA 
               
               
                   
                 ATGACTCACTTTATCACTAGAAACATTACTGATAACCA 
               
               
                   
                 AGGTAAGAATAAGACTGCCATTCACgctTACTTCTCTTCTG 
               
               
                   
                 TTTTCTTGGGTGGTGTTGATTCCTTGGTCGATTTGATGAAC 
               
               
                   
                 AAGTCTTTTCCAGAATTAGGTATTAAGAAGACCGATTGTCGTCAA 
               
               
                   
                 TTGATAATTTTAATAAGGAGATTTTGTTAGATAGATCTGCTGGTC 
               
               
                   
                 AAAATGGTGCCTTTAAAATCAAATTGGACTACGTTAAGAAGCCTA 
               
               
                   
                 TTCCAGAATCCGTCTTTGTTCAAATTTTGGAGAAGTTATACGA 
               
               
                   
                 AGAAGATATTGGTGCTGGTATGTACGCCTTGTATCCATATGGTG 
               
               
                   
                 GTATTATGGATGAAATTTCTGAATCCGCCATCCCTTTCCCTC 
               
               
                   
                 ATCGTGCTGGTATCTTATACGAGTTGTGGTACATCTGTTCTTGGG 
               
               
                   
                 AAAAGCAAGAAGATAATGAAAAGCATTTGAACTGGATCCGTA 
               
               
                   
                 ACATCTATAACTTCATGACTCCATACGTTTCCAA 
               
               
                   
                 AAACCCTAGATTGGCTTACTTAAATTACAGAGACTT 
               
               
                   
                 AGATATTGGTATTAACGACCCTAAGAACCCAAAC 
               
               
                   
                 AATTACACTCAAGCTAGAATCTGGGGTGAAAAGTACTTCGGTAAG 
               
               
                   
                 AATTTCGACAGATTAGTTAAGGTCAAGACTTTAGTTGA 
               
               
                   
                 CCCAAATAACTTCTTCAGAAACGAACAATCTATCCC 
               
               
                   
                 ACCATTGCCTAGACATAGACACTAG 
               
               
                   
               
               
                 SEQ ID NO: 190 
                 MKCSTFSFWFVCKIIFFFFSFNIQTSIANPRENFLKCFSQYIPNN 
               
               
                 CBDA Synthase, 
                 ATNLKLVYTQNNPLYMSVLNSTIHNLRFTSDTTPKPLVIVTPSHV 
               
               
                 T310A variant 
                 SHIQGTILCSKKVGLQIRTRSGGHDSEGMSYISQVPFVIVDLRNM 
               
               
                 Artificial Sequence 
                 RSIKIDVHSQTAWVEAGATLGEVYYWVNEKNENLSLAAGYCPT 
               
               
                   
                 VCAGGHFGGGGYGPLMRNYGLAADNIIDAHLVNVHGKVLDRKSM 
               
               
                   
                 GEDLFWALRGGGAESFGIIVAWKIRLVAVPKSTMFSVKKIMEIHE 
               
               
                   
                 LVKLVNKVVQNIAYKYDKDLLLMTHFITRNITDNQGKNKTAIHAY 
               
               
                   
                 FSSVFLGGVDSLVDLMNKSFPELGIKKTDCRQLSWIDTIIFYSGW 
               
               
                   
                 NYDTDNFNKEILLDRSAGQNGAFKIKLDYVKKPIPESVFVQILEK 
               
               
                   
                 LYEEDIGAGMYALYPYGGIMDEISESAIPFPHRAGILYELWYICS 
               
               
                   
                 WEKQEDNEKHLNWIRNIYNFMTPYVSKNPRLAYLNYRDLDIGIND 
               
               
                   
                 PKNPNNYTQARIWGEKYFGKNFDRLVKVKTLVDPNNFFRNEQSIP 
               
               
                   
                 PLPRHRH* 
               
               
                   
               
               
                 SEQ ID NO: 191 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                 CBDA Synthase, 
                 TTCTTCTTCTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 T310C variant 
                 CGTGAGAACTTCTTGAAATGTTTTTCTCAATATATCCCAAATAAC 
               
               
                 Artificial Sequence 
                 GCTACTAACTTGAAGTTAGTCTATACTCAAAACAACCCATTATAT 
               
               
                 Codon optimized 
                 ATGTCTGTCTTAAACTCTACCATTCACAACTTACGTTTCACTT 
               
               
                   
                 CTGATACTACTCCAAAACCTTTGGTCATCGTCACCCCA 
               
               
                   
                 TCCCACGTTTCTCACATCCAAGGTACCATCTTGTGTTCCAAAAAG 
               
               
                   
                 GTTGGTTTACAAATCCGTACTAGATCCGGTGGTCATGA 
               
               
                   
                 CTCCGAAGGTATGTCTTACATTTCCCAAGTCCCTTTCGTCAT 
               
               
                   
                 CGTCGACTTAAGAAATATGCGTTCCATCAAGATTGATGTCCATTC 
               
               
                   
                 CCAAACTGCTTGGGTTGAAGCCGGTGCCACTTTAGGTGAAGTCTA 
               
               
                   
                 TTACTGGGTTAACGAGAAGAATGAGAACTTATCTTTGGCTGCCGG 
               
               
                   
                 TTACTGTCCAACTGTTTGTGCTGGTGGTCATTTCGGTGGTGGTGG 
               
               
                   
                 TTACGGTCCATTAATGCGTAACTACGGTTTGGCTGCCGATAACAT 
               
               
                   
                 CATTGATGCCCACTTAGTCAACGTTCATGGTAAGGTCTTGGACCG 
               
               
                   
                 TAAGTCTATGGGTGAGGATTTATTCTGGGCTTTGAGAGGTGGTGG 
               
               
                   
                 TGCTGAATCTTTCGGTATTATCGTCGCTTGGAAGATTAGAT 
               
               
                   
                 TAGTTGCTGTTCCAAAGTCTACTATGTTCTCTGTTAAGAA 
               
               
                   
                 GATCATGGAAATTCACGAGTTGGTTAAATTAGTTAACAAATGGCA 
               
               
                   
                 AAACATTGCCTACAAGTACGATAAAGATTTGTTATTAATGACTCA 
               
               
                   
                 CTTTATCACTAGAAACATTACTGATAACCAAGGTAAGAATAAGAC 
               
               
                   
                 TGCCATTCACtgtTACTTCTCTTCTGTTTTCTTGGGTGGTGTTGA 
               
               
                   
                 TTCCTTGGTCGATTTGATGAACAAGTCTTTTCCAGAATTAGGTAT 
               
               
                   
                 TAAGAAGACCGATTGTCGTCAATTATCTTGGATTGATACCATTAT 
               
               
                   
                 TTTTTACTCCGGTGTTGTCAACTACGACACTGATAATTTTAATAA 
               
               
                   
                 GGAGATTTTGTTAGATAGATCTGCTGGTCAAAATGGTGCCTTTAA 
               
               
                   
                 AATCAAATTGGACTACGTTAAGAAGCCTATTCCAGAATCCGTCTT 
               
               
                   
                 TGTTCAAATTTTGGAGAAGTTATACGAAGAAGATA 
               
               
                   
                 TTGGTGCTGGTATGTACGCCTTGTATCCATATGGTGGTAT 
               
               
                   
                 TATGGATGAAATTTCTGAATCCGCCATCCCTTTCCCTC 
               
               
                   
                 ATCGTGCTGGTATCTTATACGAGTTGTGGTACATCTGTTCTTGGG 
               
               
                   
                 AAAAGCAAGAAGATAATGAAAAGCATTTGAACTGGATCCGTA 
               
               
                   
                 ACATCTATAACTTCATGACTCCATACGTTTCCAAAAACCCTAGAT 
               
               
                   
                 TGGCTTACTTAAATTACAGAGACTTAGATATTGGTATTAACGACC 
               
               
                   
                 CTAAGAACCCAAACAATTACACTCAAGCTAGAATCTGGGGTGAAA 
               
               
                   
                 AGTACTTCGGTAAGAATTTCGACAGATTAGTTAAGGTCAAGACTT 
               
               
                   
                 TAGTTGACCCAAATAACTTCTTCAGAAACGAACAATCT 
               
               
                   
                 ATCCCACCATTGCCTAGACATAGACACTAG 
               
               
                   
               
               
                 SEQ ID NO: 192 
                 MKCSTFSFWFVCKIIFFFFSFNIQTSIANPRENFLKCFSQYIPNN 
               
               
                 CBDA Synthase, 
                 ATNLKLVYTQNNPLYMSVLNSTIHNLRFTSDTTPKPLVIVTPSH 
               
               
                 T310C variant 
                 VSHIQGTILCSKKVGLQIRTRSGGHDSEGMSYISQVPFVIVDLRN 
               
               
                 Artificial Sequence 
                 MRSIKIDVHSQTAWVEAGATLGEVYYWVNEKNENLSLAAGYCP 
               
               
                   
                 TVCAGGHFGGGGYGPLMRNYGLAADNIIDAHLVNVHGKVLDRKS 
               
               
                   
                 MGEDLFWALRGGGAESFGIIVAWKIRLVAVPKSTMFSVKKIMEIH 
               
               
                   
                 ELVKLVNKVVQNIAYKYDKDLLLMTHFITRNITDNQGKNKTAIHC 
               
               
                   
                 YFSSVFLGGVDSLVDLMNKSFPELGIKKTDCRQLSWIDTIIFYSG 
               
               
                   
                 WNYDTDNFNKEILLDRSAGQNGAFKIKLDYVKKPIPESVFVQI 
               
               
                   
                 LEKLYEEDIGAGMYALYPYGGIMDEISESAIPFPHRAGILYELWY 
               
               
                   
                 ICSWEKQEDNEKHLNWIRNIYNFMTPYVSKNPRLAYLNYRDLDIG 
               
               
                   
                 INDPKNPNNYTQARIWGEKYFGKNFDRLVKVKTLVDPNNFFRNEQ 
               
               
                   
                 SIPPLPRHRH* 
               
               
                   
               
               
                 SEQ ID NO: 193 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                 CBDA Synthase, 
                 TTCTTCTTCTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 F316Y variant 
                 CGTGAGAACTTCTTGAAATGTTTTTCTCAATATATCCCAAATAAC 
               
               
                 Artificial Sequence 
                 GCTACTAACTTGAAGTTAGTCTATACTCAAAACAACCC 
               
               
                 Codon optimized 
                 ATTATATATGTCTGTCTTAAACTCTACCATTCACAA 
               
               
                   
                 CTTACGTTTCACTTCTGATACTACTCCAAAACCTTTGGTCATCGT 
               
               
                   
                 CACCCCATCCCACGTTTCTCACATCCAAGGTACCATCTTGTGTTC 
               
               
                   
                 CAAAAAGGTTGGTTTACAAATCCGTACTAGATCCGGTGGTCATGA 
               
               
                   
                 CTCCGAAGGTATGTCTTACATTTCCCAAGTCCCTTTCGTCATCGT 
               
               
                   
                 CGACTTAAGAAATATGCGTTCCATCAAGATTGATGTCCATTCCCA 
               
               
                   
                 AACTGCTTGGGTTGAAGCCGGTGCCACTTTAGGTGAAGTCTATTA 
               
               
                   
                 CTGGGTTAACGAGAAGAATGAGAACTTATCTTTGGCTGCCGGTTA 
               
               
                   
                 CTGTCCAACTGTTTGTGCTGGTGGTCATTTCGGTGGTGGTGGTTA 
               
               
                   
                 CGGTCCATTAATGCGTAACTACGGTTTGGCTGCCGATAACATCAT 
               
               
                   
                 TGATGCCCACTTAGTCAACGTTCATGGTAAGGTCTTGGACCGTAA 
               
               
                   
                 GTCTATGGGTGAGGATTTATTCTGGGCTTTGAGAGGTGGTGGTGC 
               
               
                   
                 TGAATCTTTCGGTATTATCGTCGCTTGGAAGATTAGATTAGTTGC 
               
               
                   
                 TGTTCCAAAGTCTACTATGTTCTCTGTTAAGAAGATCATGGAAAT 
               
               
                   
                 TCACGAGTTGGTTAAATTAGTTAACAAATGGCAAAACATTGCCTA 
               
               
                   
                 CAAGTACGATAAAGATTTGTTATTAATGACTCACTTTATCACT 
               
               
                   
                 AGAAACATTACTGATAACCAAGGTAAGAATAAGACTG 
               
               
                   
                 CCATTCACACTTACTTCTCTTCTGTTtatTTGGGTGGTGTTGATT 
               
               
                   
                 CCTTGGTCGATTTGATGAACAAGTCTTTTCCAGAATT 
               
               
                   
                 AGGTATTAAGAAGACCGATTGTCGTCAATTGATAAT 
               
               
                   
                 TTTAATAAGGAGATTTTGTTAGATAGATCTGCTGGTCAAAATGGT 
               
               
                   
                 GCCTTTAAAATCAAATTGGACTACGTTAAGAAGCCTATTCCAGA 
               
               
                   
                 ATCCGTCTTTGTTCAAATTTTGGAGAAGTTATACGAAGAAGAT 
               
               
                   
                 ATTGGTGCTGGTATGTACGCCTTGTATCCATATGGTGGTA 
               
               
                   
                 TTATGGATGAAATTTCTGAATCCGCCATCCCTTTCCCTCA 
               
               
                   
                 TCGTGCTGGTATCTTATACGAGTTGTGGTACATCTGTTCTTGGGA 
               
               
                   
                 AAAGCAAGAAGATAATGAAAAGCATTTGAACTGGATCCGTAA 
               
               
                   
                 GGTGAAGTCTATTACTGGGTTAACGAGAAGAATGAGAACTTATCT 
               
               
                   
                 TTGGCTGCCGGTTACTGTCCAACTGTTTGTGCTGGTGGTCATTTC 
               
               
                   
                 GGTGGTGGTGGTTACGGTCCATTAATGCGTAACTACGGTTTGGCT 
               
               
                   
                 GCCGATAACATCATTGATGCCCACTTAGTCAACGTTCATGGTAAG 
               
               
                   
                 GTCTTGGACCGTAAGTCTATGGGTGAGGATTTATTCTGGGCTTTG 
               
               
                   
                 AGAGGTGGTGGTGCTGAATCTTTCGGTATTATCGTCGCTTGGA 
               
               
                   
                 AGATTAGATTAGTTGCTGTTCCAAAGTCTACTATGTTC 
               
               
                   
                 TCTGTTAAGAAGATCATGGAAATTCACGAGTTGGTTAAATTAGTT 
               
               
                   
                 AACAAATGGCAAAACATTGCCTACAAGTACGATAAAGATTTGTTA 
               
               
                   
                 TTAATGACTCACTTTATCACTAGAAACATTACTGATAACCAAGGT 
               
               
                   
                 AAGAATAAGACTGCCATTCACtgtTACTTCTCTTCTGTTTTCTTG 
               
               
                   
                 GGTGGTGTTGATTCCTTGGTCGATTTGATGAACAAGTCTTTTCCA 
               
               
                   
                 GAATTAGGTATTAAGAAGACCGATTGTCGTCAATTATCTTGGATT 
               
               
                   
                 GATACCATTATTTTTTACTCCGGTGTTGTCAACTACGACACTGAT 
               
               
                   
                 AATTTTAATAAGGAGATTTTGTTAGATAGATCTGCTGGTCAAAAT 
               
               
                   
                 GGTGCCTTTAAAATCAAATTGGACTACGTTAAGAAGCCTATTCCA 
               
               
                   
                 GAATCCGTCTTTGTTCAAATTTTGGAGAAGTTATACGA 
               
               
                   
                 AGAAGATATTGGTGCTGGTATGTACGCCTTGTATCCAT 
               
               
                   
                 ATGGTGGTATTATGGATGAAATTTCTGAATCCGCCAT 
               
               
                   
                 CCCTTTCCCTCATCGTGCTGGTATCTTATACGAGTTGTGGTACAT 
               
               
                   
                 CTGTTCTTGGGAAAAGCAAGAAGATAATGAAAAGCATTTGAAC 
               
               
                   
                 TGGATCCGTAACATCTATAACTTCATGACTCCATACGTTTCCAA 
               
               
                   
                 AAACCCTAGATTGGCTTACTTAAATTACAGAGACTTAGATATTGG 
               
               
                   
                 TATTAACGACCCTAAGAACCCAAACAATTACACTCAAGCTAGAAT 
               
               
                   
                 CTGGGGTGAAAAGTACTTCGGTAAGAATTTCGACAGATTAGTTAA 
               
               
                   
                 GGTCAAGACTTTAGTTGACCCAAATAACTTCTTCAGAAACGA 
               
               
                   
                 ACAATCTATCCCACCATTGCCTAGACATAGACAC 
               
               
                   
                 TAG 
               
               
                   
               
               
                 SEQ ID NO: 192 
                 MKCSTFSFWFVCKIIFFFFSFNIQTSIANPRENFLKCFSQYIPNN 
               
               
                 CBDA Synthase, 
                 ATNLKLVYTQNNPLYMSVLNSTIHNLRFTSDTTPKPLVIVTPSH 
               
               
                 T310C variant 
                 VSHIQGTILCSKKVGLQIRTRSGGHDSEGMSYISQVPFVIVDLRN 
               
               
                 Artificial Sequence 
                 MRSIKIDVHSQTAWVEAGATLGEVYYWVNEKNENLSLAAGYCP 
               
               
                   
                 TVCAGGHFGGGGYGPLMRNYGLAADNIIDAHLVNVHGKVLDRKS 
               
               
                   
                 MGEDLFWALRGGGAESFGIIVAWKIRLVAVPKSTMFSVKKIMEIH 
               
               
                   
                 ELVKLVNKVVQNIAYKYDKDLLLMTHFITRNITDNQGKNKTAIHC 
               
               
                   
                 YFSSVFLGGVDSLVDLMNKSFPELGIKKTDCRQLSWIDTIIFYSG 
               
               
                   
                 WNYDTDNFNKEILLDRSAGQNGAFKIKLDYVKKPIPESVFVQI 
               
               
                   
                 LEKLYEEDIGAGMYALYPYGGIMDEISESAIPFPHRAGILYELWY 
               
               
                   
                 ICSWEKQEDNEKHLNWIRNIYNFMTPYVSKNPRLAYLNYRDLDIG 
               
               
                   
                 INDPKNPNNYTQARIWGEKYFGKNFDRLVKVKTLVDPNNFFRNEQ 
               
               
                   
                 SIPPLPRHRH* 
               
               
                   
               
               
                 SEQ ID NO: 193 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                 CBDA Synthase, 
                 TTCTTCTTCTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 F316Y variant 
                 CGTGAGAACTTCTTGAAATGTTTTTCTCAATATATCCCAAATAAC 
               
               
                 Artificial Sequence 
                 GCTACTAACTTGAAGTTAGTCTATACTCAAAACAACCC 
               
               
                 Codon optimized 
                 ATTATATATGTCTGTCTTAAACTCTACCATTCACAA 
               
               
                   
                 CTTACGTTTCACTTCTGATACTACTCCAAAACCTTTGGTCATCGT 
               
               
                   
                 CACCCCATCCCACGTTTCTCACATCCAAGGTACCATCTTGTGTTC 
               
               
                   
                 CAAAAAGGTTGGTTTACAAATCCGTACTAGATCCGGTGGTCATGA 
               
               
                   
                 CTCCGAAGGTATGTCTTACATTTCCCAAGTCCCTTTCGTCATCGT 
               
               
                   
                 CGACTTAAGAAATATGCGTTCCATCAAGATTGATGTCCATTCCCA 
               
               
                   
                 AACTGCTTGGGTTGAAGCCGGTGCCACTTTAGGTGAAGTCTATTA 
               
               
                   
                 CTGGGTTAACGAGAAGAATGAGAACTTATCTTTGGCTGCCGGTTA 
               
               
                   
                 CTGTCCAACTGTTTGTGCTGGTGGTCATTTCGGTGGTGGTGGTTA 
               
               
                   
                 CGGTCCATTAATGCGTAACTACGGTTTGGCTGCCGATAACATCAT 
               
               
                   
                 TGATGCCCACTTAGTCAACGTTCATGGTAAGGTCTTGGACCGTAA 
               
               
                   
                 GTCTATGGGTGAGGATTTATTCTGGGCTTTGAGAGGTGGTGGTGC 
               
               
                   
                 TGAATCTTTCGGTATTATCGTCGCTTGGAAGATTAGATTAGTTGC 
               
               
                   
                 TGTTCCAAAGTCTACTATGTTCTCTGTTAAGAAGATCATGGAAAT 
               
               
                   
                 TCACGAGTTGGTTAAATTAGTTAACAAATGGCAAAACATTGCCTA 
               
               
                   
                 CAAGTACGATAAAGATTTGTTATTAATGACTCACTTTATCACT 
               
               
                   
                 AGAAACATTACTGATAACCAAGGTAAGAATAAGACTG 
               
               
                   
                 CCATTCACACTTACTTCTCTTCTGTTtatTTGGGTGGTGTTGATT 
               
               
                   
                 CCTTGGTCGATTTGATGAACAAGTCTTTTCCAGAATT 
               
               
                   
                 AGGTATTAAGAAGACCGATTGTCGTCAATTGATAAT 
               
               
                   
                 TTTAATAAGGAGATTTTGTTAGATAGATCTGCTGGTCAAAATGGT 
               
               
                   
                 GCCTTTAAAATCAAATTGGACTACGTTAAGAAGCCTATTCCAGA 
               
               
                   
                 ATCCGTCTTTGTTCAAATTTTGGAGAAGTTATACGAAGAAGAT 
               
               
                   
                 ATTGGTGCTGGTATGTACGCCTTGTATCCATATGGTGGTA 
               
               
                   
                 TTATGGATGAAATTTCTGAATCCGCCATCCCTTTCCCTCA 
               
               
                   
                 TCGTGCTGGTATCTTATACGAGTTGTGGTACATCTGTTCTTGGGA 
               
               
                   
                 AAAGCAAGAAGATAATGAAAAGCATTTGAACTGGATCCGTAA 
               
               
                   
                 CATCTATAACTTCATGACTCCATACGTTTCCAAAAACCCTAGATT 
               
               
                   
                 GGCTTACTTAAATTACAGAGACTTAGATATTGGTATTAACGACCC 
               
               
                   
                 TAAGAACCCAAACAATTACACTCAAGCTAGAATCTGGGGTGAAAA 
               
               
                   
                 GTACTTCGGTAAGAATTTCGACAGATTAGTTAAGGTCAAGACTTT 
               
               
                   
                 AGTTGACCCAAATAACTTCTTCAGAAACGAACAATCTATCCCACC 
               
               
                   
                 ATTGCCTAGACATAGACACTAG 
               
               
                   
               
               
                 SEQ ID NO: 194 
                 MKCSTFSFWFVCKIIFFFFSFNIQTSIANPRENFLKCFSQYIPNN 
               
               
                 CBDA Synthase, 
                 ATNLKLVYTQNNPLYMSVLNSTIHNLRFTSDTTPKPLVIVTPSHV 
               
               
                 F316Y variant 
                 SHIQGTILCSKKVGLQIRTRSGGHDSEGMSYISQVPFVIVDLRNM 
               
               
                 Artificial Sequence 
                 RSIKIDVHSQTAWVEAGATLGEVYYWVNEKNENLSLAAGYCPTVC 
               
               
                   
                 AGGHFGGGGYGPLMRNYGLAADNIIDAHLVNVHGKVLDRKSMGED 
               
               
                   
                 LFWALRGGGAESFGIIVAWKIRLVAVPKSTMFSVKKIMEIHELVK 
               
               
                   
                 LVNKWQNIAYKYDKDLLLMTHFITRNITDNQGKNKTAIHTYFSSV 
               
               
                   
                 YLGGVDSLVDLMNKSFPELGIKKTDCRQLSWIDTIIFYSGWNYDT 
               
               
                   
                 DNFNKEILLDRSAGQNGAFKIKLDYVKKPIPESVFVQILEKLYEE 
               
               
                   
                 DIGAGMYALYPYGGIMDEISESAIPFPHRAGILYELWYICSWEKQ 
               
               
                   
                 EDNEKHLNWIRNIYNFMTPYVSKNPRLAYLNYRDLDIGINDPKNP 
               
               
                   
                 NNYTQARIWGEKYFGKNFDRLVKVKTLVDPNNFFRNEQSIPPLPR 
               
               
                   
                 HRH* 
               
               
                   
               
               
                 SEQ ID NO: 195 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                 CBDA Synthase, L326I 
                 TTCTTCTTCTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 variant 
                 CGTGAGAACTTCTTGAAATGTTTTTCTCAATATATCCCAAATAAC 
               
               
                 Artificial Sequence 
                 GCTACTAACTTGAAGTTAGTCTATACTCAAAACAACCCATTATAT 
               
               
                 Codon optimized 
                 ATGTCTGTCTTAAACTCTACCATTCACAACTTACGTTTCACTTCT 
               
               
                   
                 GATACTACTCCAAAACCTTTGGTCATCGTCACCCCATCCCACGTT 
               
               
                   
                 TCTCACATCCAAGGTACCATCTTGTGTTCCAAAAAGGTTGGTTTA 
               
               
                   
                 CAAATCCGTACTAGATCCGGTGGTCATGACTCCGAAGGTATGTCT 
               
               
                   
                 TACATTTCCCAAGTCCCTTTCGTCATCGTCGACTTAAGAAATATG 
               
               
                   
                 CGTTCCATCAAGATTGATGTCCATTCCCAAACTGCTTGGGTTGAA 
               
               
                   
                 GCCGGTGCCACTTTAGGTGAAGTCTATTACTGGGTTAACGAGAAG 
               
               
                   
                 AATGAGAACTTATCTTTGGCTGCCGGTTACTGTCCAACTGTTTGT 
               
               
                   
                 GCTGGTGGTCATTTCGGTGGTGGTGGTTACGGTCCATTAATGCGT 
               
               
                   
                 AACTACGGTTTGGCTGCCGATAACATCATTGATGCCCACTTAGTC 
               
               
                   
                 AACGTTCATGGTAAGGTCTTGGACCGTAAGTCTATGGGTGAGGAT 
               
               
                   
                 TTATTCTGGGCTTTGAGAGGTGGTGGTGCTGAATCTTTCGGTATT 
               
               
                   
                 ATCGTCGCTTGGAAGATTAGATTAGTTGCTGTTCCAAAGTCTACT 
               
               
                   
                 ATGTTCTCTGTTAAGAAGATCATGGAAATTCACGAGTTGGTTAAA 
               
               
                   
                 TTAGTTAACAAATGGCAAAACATTGCCTACAAGTACGATAAAGAT 
               
               
                   
                 TTGTTATTAATGACTCACTTTATCACTAGAAACATTACTGATAAC 
               
               
                   
                 CAAGGTAAGAATAAGACTGCCATTCACACTTACTTCTCTTCTGTT 
               
               
                   
                 TTCTTGGGTGGTGTTGATTCCTTGGTCGATattATGAACAAGTCT 
               
               
                   
                 TTTCCAGAATTAGGTATTAAGAAGACCGATTGTCGTCAATTATCT 
               
               
                   
                 TGGATTGATACCATTATTTTTTACTCCGGTGTTGTCAACTACGAC 
               
               
                   
                 ACTGATAATTTTAATAAGGAGATTTTGTTAGATAGATCTGCTGGT 
               
               
                   
                 CAAAATGGTGCCTTTAAAATCAAATTGGACTACGTTAAGAAGCCT 
               
               
                   
                 ATTCCAGAATCCGTCTTTGTTCAAATTTTGGAGAAGTTATACGAA 
               
               
                   
                 GAAGATATTGGTGCTGGTATGTACGCCTTGTATCCATATGGTGGT 
               
               
                   
                 ATTATGGATGAAATTTCTGAATCCGCCATCCCTTTCCCTCATCGT 
               
               
                   
                 GCTGGTATCTTATACGAGTTGTGGTACATCTGTTCTTGGGAAAAG 
               
               
                   
                 CAAGAAGATAATGAAAAGCATTTGAACTGGATCCGTAACATCTAT 
               
               
                   
                 AACTTCATGACTCCATACGTTTCCAAAAACCCTAGATTGGCTTAC 
               
               
                   
                 TTAAATTACAGAGACTTAGATATTGGTATTAACGACCCTAAGAAC 
               
               
                   
                 CCAAACAATTACACTCAAGCTAGAATCTGGGGTGAAAAGTACTTC 
               
               
                   
                 GGTAAGAATTTCGACAGATTAGTTAAGGTCAAGACTTTAGTTGAC 
               
               
                   
                 CCAAATAACTTCTTCAGAAACGAACAATCTATCCCACCATTGCCT 
               
               
                   
                 AGACATAGACACTAG 
               
               
                   
               
               
                 SEQ ID NO: 196 
                 MKCSTFSFWFVCKIIFFFFSFNIQTSIANPRENFLKCFSQYIPNN 
               
               
                 CBDA Synthase, L326I 
                 ATNLKLVYTQNNPLYMSVLNSTIHNLRFTSDTTPKPLVIVTPSHV 
               
               
                 variant 
                 SHIQGTILCSKKVGLQIRTRSGGHDSEGMSYISQVPFVIVDLRNM 
               
               
                 Artificial Sequence 
                 RSIKIDVHSQTAVVVEAGATLGEVYYVVVNEKNENLSLAAGYCPT 
               
               
                   
                 VCAGGHFGGGGYGPLMRNYGLAADNIIDAHLVNVHGKVLDRKSMG 
               
               
                   
                 EDLFWALRGGGAESFGIIVAWKIRLVAVPKSTMFSVKKIMEIHEL 
               
               
                   
                 VKLVNKWQNIAYKYDKDLLLMTHFITRNITDNQGKNKTAIHTYFS 
               
               
                   
                 SVFLGGVDSLVDIMNKSFPELGIKKTDCRQLSWIDTIIFYSGVVN 
               
               
                   
                 YDTDNFNKEILLDRSAGQNGAFKIKLDYVKKPIPESVFVQILEKL 
               
               
                   
                 YEEDIGAGMYALYPYGGIMDEISESAIPFPHRAGILYELWYICSV 
               
               
                   
                 VEKQEDNEKHLNWIRNIYNFMTPYVSKNPRLAYLNYRDLDIGIND 
               
               
                   
                 PKNPNNYTQARIWGEKYFGKNFDRLVKVKTLVDPNNFFRNEQSIP 
               
               
                   
                 PLPRHRH* 
               
               
                   
               
               
                 SEQ ID NO: 197 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                 CBDA Synthase, 
                 TTCTTCTTCTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 G378T variant 
                 CGTGAGAACTTCTTG 
               
               
                 Artificial Sequence 
                 AAATGTTTTTCTCAATATATCCCAAATAACGCTACTAACTTGAAG 
               
               
                 Codon optimized 
                 TTAGTCTATACTCAAAACAACCCATTATATATGTCTGTCTTAAAC 
               
               
                   
                 TCTACCATTCACAACTTACGTTTCACTTCTGATACTACTCCAAAA 
               
               
                   
                 CCTTTGGTCATCGTCACCCCATCCCACGTTTCTCACATCCAAGGT 
               
               
                   
                 ACCATCTTGTGTTCCAAAAAGGTTGGTTTACAAATCCGTACTAGA 
               
               
                   
                 TCCGGTGGTCATGACTCCGAAGGTATGTCTTACATTTCCCAAGTC 
               
               
                   
                 CCTTTCGTCATCGTCGACTTAAGAAATATGCGTTCCATCAAGATT 
               
               
                   
                 GATGTCCATTCCCAAACTGCTTGGGTTGAAGCCGGTGCCACTTTA 
               
               
                   
                 GGTGAAGTCTATTACTGGGTTAACGAGAAGAATGAGAACTTATCT 
               
               
                   
                 TTGGCTGCCGGTTACTGTCCAACTGTTTGTGCTGGTGGTCATTTC 
               
               
                   
                 GGTGGTGGTGGTTACGGTCCATTAATGCGTAACTACGGTTTGGCT 
               
               
                   
                 GCCGATAACATCATTGATGCCCACTTAGTCAACGTTCATGGTAAG 
               
               
                   
                 GTCTTGGACCGTAAGTCTATGGGTGAGGATTTATTCTGGGCTTTG 
               
               
                   
                 AGAGGTGGTGGTGCTGAATCTTTCGGTATTATCGTCGCTTGGAAG 
               
               
                   
                 ATTAGATTAGTTGCTGTTCCAAAGTCTACTATGTTCTCTGTTAA 
               
               
                   
                 GAAGATCATGGAAATTCACGAGTTGGTTAAATTAGTTAACAAATG 
               
               
                   
                 GCAAAACATTGCCTACAAGTACGATAAAGATTTGTTATTAATGAC 
               
               
                   
                 TCACTTTATCACTAGAAACATTACTGATAACCAAGGTAAGAATAA 
               
               
                   
                 GACTGCCATTCACACTTACTTCTCTTCTGTTTTCTTGGGTGGTGT 
               
               
                   
                 TGATTCCTTGGTCGATTTGATGAACAAGTCTTTTCCAGA 
               
               
                   
                 ATTAGGTATTAAGAAGACCGATTGTCGTCAACTGAT 
               
               
                   
                 AATTTTAATAAGGAGATTTTGTTAGATAGATCTGCTGG 
               
               
                   
                 TCAAAATactGCCTTTAAAATCAAATTGGACTACGTTAAGA 
               
               
                   
                 AGCCTATTCCAGAATCCGTCTTTGTTCAAATTTTGGAGAAGTTAT 
               
               
                   
                 ACGAAGAAGATATTGGTGCTGGTATGTACGCCTTGTATCCAT 
               
               
                   
                 ATGGTGGTATTATGGATGAAATTTCTGAATCCGCCATC 
               
               
                   
                 CCTTTCCCTCATCGTGCTGGTATCTTATACGAGTTGTGGTACATC 
               
               
                   
                 TGTTCTTGGGAAAAGCAAGAAGATAATGAAAAGCATTTGAACTGG 
               
               
                   
                 ATCCGTAACATCTATAACTTCATGACTCCATACGTTTCCAAAAAC 
               
               
                   
                 CCTAGATTGGCTTACTTAAATTACAGAGACTTAGATATTGGTATT 
               
               
                   
                 AACGACCCTAAGAACCCAAACAATTACACTCAAGCTAGAATCTGG 
               
               
                   
                 GGTGAAAAGTACTTCGGTAAGAATTTCGACAGATTAGTTAAGGTC 
               
               
                   
                 AAGACTTTAGTTGACCCAAATAACTTCTTCAGAAACGAACAATCT 
               
               
                   
                 ATCCCACCATTGCCTAGACATAGACACTAG 
               
               
                   
               
               
                 SEQ ID NO: 198 
                 MKCSTFSFWFVCKIIFFFFSFNIQTSIANPRENFLKCFSQYIPNN 
               
               
                 CBDA Synthase, 
                 ATNLKLVYTQNNPLYMSVLNSTIHNLRFTSDTTPKPLVIVTPSH 
               
               
                 G378T variant 
                 VSHIQGTILCSKKVGLQIRTRSGGHDSEGMSYISQVPFVIVDLRN 
               
               
                 Artificial Sequence 
                 MRSIKIDVHSQTAWVEAGATLGEVYYWVNEKNENLSLAAGYCPTV 
               
               
                   
                 CAGGHFGGGGYGPLMRNYGLAADNIIDAHLVNVHGKVLDRKSMGE 
               
               
                   
                 DLFWALRGGGAESFGIIVAWKIRLVAVPKSTMFSVKKIMEIHELV 
               
               
                   
                 KLVNKWQNIAYKYDKDLLLMTHFITRNITDNQGKNKTAIHTYFSS 
               
               
                   
                 VFLGGVDSLVDLMNKSFPELGIKKTDCRQLSWIDTIIFYSGWNYD 
               
               
                   
                 TDNFNKEILLDRSAGQNTAFKIKLDYVKKPIPESVFVQILEKLYE 
               
               
                   
                 EDIGAGMYALYPYGGIMDEISESAIPFPHRAGILYELWYICSWEK 
               
               
                   
                 QEDNEKHLNWIRNIYNFMTPYVSKNPRLAYLNYRDLDIGINDPKN 
               
               
                   
                 PNNYTQARIWGEKYFGKNFDRLVKVKTLVDPNNFFRNEQSIPPLP 
               
               
                   
                 RHRH* 
               
               
                   
               
               
                 SEQ ID NO: 199 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                 CBDA Synthase, 
                 TTCTTCTTCTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 G378S variant 
                 CGTGAGAACTTCTTGAAATGTTTTTCTCAATATATCCCAAATAAC 
               
               
                 Artificial Sequence 
                 GCTACTAACTTGAAGTTAGTCTATACTCAAAACAACCCATTATAT 
               
               
                 Codon optimized 
                 ATGTCTGTCTTAAACTCTACCATTCACAACTTACGTTTCACTTCT 
               
               
                   
                 GATACTACTCCAAAACCTTTGGTCATCGTCACCCCATCCCACGTT 
               
               
                   
                 TCTCACATCCAAGGTACCATCTTGTGTTCCAAAAAGGTTGGTTT 
               
               
                   
                 ACAAATCCGTACTAGATCCGGTGGTCATGACTCCGA 
               
               
                   
                 AGGTATGTCTTACATTTCCCAAGTCCCTTTCGTCATCGTCGAC 
               
               
                   
                 TTAAGAAATATGCGTTCCATCAAGATTGATGTCCATTCCCAAACT 
               
               
                   
                 GCTTGGGTTGAAGCCGGTGCCACTTTAGGTGAAGTCTATTACTGG 
               
               
                   
                 GTTAACGAGAAGAATGAGAACTTATCTTTGGCTGCCGGTTACTGT 
               
               
                   
                 CCAACTGTTTGTGCTGGTGGTCATTTCGGTGGTGGTGGTTACGGT 
               
               
                   
                 CCATTAATGCGTAACTACGGTTTGGCTGCCGATAACATCATTGAT 
               
               
                   
                 GCCCACTTAGTCAACGTTCATGGTAAGGTCTTGGACCGTAAGTCT 
               
               
                   
                 ATGGGTGAGGATTTATTCTGGGCTTTGAGAGGTGGTGGTGCTGAA 
               
               
                   
                 TCTTTCGGTATTATCGTCGCTTGGAAGATTAGATTAGTTGCTG 
               
               
                   
                 TTCCAAAGTCTACTATGTTCTCTGTTAAGAAGATC 
               
               
                   
                 ATGGAAATTCACGAGTTGGTTAAATTAGTTAACA 
               
               
                   
                 AATGGCAAAACATTGCCTACAAGTACGATAAAGATTTGTTATT 
               
               
                   
                 AATGACTCACTTTATCACTAGAAACATTACTGATAACCA 
               
               
                   
                 AGGTAAGAATAAGACTGCCATTCACACTTACTTCTCTTCT 
               
               
                   
                 GTTTTCTTGGGTGGTGTTGATTCCTTGGTCGATTTGATGAACAAG 
               
               
                   
                 TCTTTTCCAGAATTAGGTATTAAGAAGACCGATTGTCGTCAA 
               
               
                   
                 CTGATAATTTTAATAAGGAGATTTTGTTAGATAG 
               
               
                   
                 ATCTGCTGGTCAAAATtctGCCTTTAAAATCAAATTGGAC 
               
               
                   
                 TACGTTAAGAAGCCTATTCCAGAATCCGTCTTTGTTCAAATT 
               
               
                   
                 TTGGAGAAGTTATACGAAGAAGATATTGGTGCTGGT 
               
               
                   
                 ATGTACGCCTTGTATCCATATGGTGGTATTATGGATGAAATTTC 
               
               
                   
                 TGAATCCGCCATCCCTTTCCCTCATCGTGCTGGTATCTTATACGA 
               
               
                   
                 GTTGTGGTACATCTGTTCTTGGGAAAAGCAAGAAGATAATGAAAA 
               
               
                   
                 GCATTTGAACTGGATCCGTAACATCTATAACTTCATGACTCCATA 
               
               
                   
                 CGTTTCCAAAAACCCTAGATTGGCTTACTTAAATTACAGAGACTT 
               
               
                   
                 AGATATTGGTATTAACGACCCTAAGAACCCAAACAATTACACTCA 
               
               
                   
                 AGCTAGAATCTGGGGTGAAAAGTACTTCGGTAAGAATTTCGACAG 
               
               
                   
                 ATTAGTTAAGGTCAAGACTTTAGTTGACCCAAATAACTTCTTCAG 
               
               
                   
                 AAACGAACAATCTATCCCACCATTGCCTAGACATAGACACTAG 
               
               
                   
               
               
                 SEQ ID NO: 200 
                 MKCSTFSFWFVCKIIFFFFSFNIQTSIANPRENFLKCFSQYIPNN 
               
               
                 CBDA Synthase, 
                 ATNLKLVYTQNNPLYMSVLNSTIHNLRFTSDTTPKPLVIVTPSH 
               
               
                 G378S variant 
                 VSHIQGTILCSKKVGLQIRTRSGGHDSEGMSYISQVPFVIVDLRN 
               
               
                 Artificial Sequence 
                 MRSIKIDVHSQTAWVEAGATLGEVYYWVNEKNENLSLAAGYCPT 
               
               
                   
                 VCAGGHFGGGGYGPLMRNYGLAADNIIDAHLVNVHGKVLDRKSM 
               
               
                   
                 GEDLFWALRGGGAESFGIIVAWKIRLVAVPKSTMFSVKKIMEIHE 
               
               
                   
                 LVKLVNKWQNIAYKYDKDLLLMTHFITRNITDNQGKNKTAIHTYF 
               
               
                   
                 SSVFLGGVDSLVDLMNKSFPELGIKKTDCRQLSWIDTIIFYSGVV 
               
               
                   
                 NYDTDNFNKEILLDRSAGQNSAFKIKLDYVKKPIPESVFVQIL 
               
               
                   
                 EKLYEEDIGAGMYALYPYGGIMDEISESAIPFPHRAGILYELWYI 
               
               
                   
                 CSWEKQEDNEKHLNVVIRNIYNFMTPYVSKNPRLAYLNYRDLDIG 
               
               
                   
                 INDPKNPNNYTQARIWGEKYFGKNFDRLVKVKTLVDPNNFFRNEQ 
               
               
                   
                 SIPPLPRHRH* 
               
               
                   
               
               
                 SEQ ID NO: 201 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                 CBDA Synthase, 
                 TTCTTCTTCTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 K389E variant 
                 CGTGAGAACTTCTTGAAATGTTTTTCTCAATATATCCC 
               
               
                 Artificial Sequence 
                 AAATAACGCTACTAACTTGAAGTTAGTCTATACTC 
               
               
                 Codon optimized 
                 AAAACAACCCATTATATATGTCTGTCTTAAACTCTACCATTCACA 
               
               
                   
                 ACTTACGTTTCACTTCTGATACTACTCCAAAACCTTTGGTCATCG 
               
               
                   
                 TCACCCCATCCCACGTTTCTCACATCCAAGGTACCATCTTGTGTT 
               
               
                   
                 CCAAAAAGGTTGGTTTACAAATCCGTACTAGATCCGGTGGTCATG 
               
               
                   
                 ACTCCGAAGGTATGTCTTACATTTCCCAAGTCCCTTTCGTCATCG 
               
               
                   
                 TCGACTTAAGAAATATGCGTTCCATCAAGATTGATGTCCATTCCC 
               
               
                   
                 AAACTGCTTGGGTTGAAGCCGGTGCCACTTTAGGTGAAGTCTA 
               
               
                   
                 TTACTGGGTTAACGAGAAGAATGAGAACTTATCTTTGGC 
               
               
                   
                 TGCCGGTTACTGTCCAACTGTTTGTGCTGGTGGTCATTTCGGTGG 
               
               
                   
                 TGGTGGTTACGGTCCATTAATGCGTAACTACGGTTTGGCTGCCGA 
               
               
                   
                 TAACATCATTGATGCCCACTTAGTCAACGTTCATGGTAAGGTCTT 
               
               
                   
                 GGACCGTAAGTCTATGGGTGAGGATTTATTCTGGGCTTTGAGAGG 
               
               
                   
                 TGGTGGTGCTGAATCTTTCGGTATTATCGTCGCTTGGAAGATTAG 
               
               
                   
                 ATTAGTTGCTGTTCCAAAGTCTACTATGTTCTCTGTTAAGAAGA 
               
               
                   
                 TCATGGAAATTCACGAGTTGGTTAAATTAGTTAACAAATGGCAAA 
               
               
                   
                 ACATTGCCTACAAGTACGATAAAGATTTGTTATTAATGACTCACT 
               
               
                   
                 TTATCACTAGAAACATTACTGATAACCAAGGTAAGAATAAGACTG 
               
               
                   
                 CCATTCACACTTACTTCTCTTCTGTTTTCTTGGGTGGTGTTGATT 
               
               
                   
                 CCTTGGTCGATTTGATGAACAAGTCTTTTCCAGAATTAG 
               
               
                   
                 GTATTAAGAAGACCGATTGTCGTCAACTGATAAT 
               
               
                   
                 TTTAATAAGGAGATTTTGTTAGATAGATCTGCTGGTCA 
               
               
                   
                 AAATGGTGCCTTTAAAATCAAATTGGACTACGTTAAGgaaCC 
               
               
                   
                 TATTCCAGAATCCGTCTTTGTTCAAATTTTGGAGAAGTT 
               
               
                   
                 ATACGAAGAAGATATTGGTGCTGGTATGTACGCCTTG 
               
               
                   
                 TATCCATATGGTGGTATTATGGATGAAATTTCTGAATCCGCCATC 
               
               
                   
                 CCTTTCCCTCATCGTGCTGGTATCTTATACGAGTTGTGGTACATC 
               
               
                   
                 TGTTCTTGGGAAAAGCAAGAAGATAATGAAAAGCATTTGAACT 
               
               
                   
                 GGATCCGTAACATCTATAACTTCATGACTCCATACGTTTCCAAA 
               
               
                   
                 AACCCTAGATTGGCTTACTTAAATTACAGAGACTTAGAT 
               
               
                   
                 ATTGGTATTAACGACCCTAAGAACCCAAACAATTACA 
               
               
                   
                 CTCAAGCTAGAATCTGGGGTGAAAAGTACTTCGGTAAGAATTTCG 
               
               
                   
                 ACAGATTAGTTAAGGTCAAGACTTTAGTTGACCCAAATAACTTCT 
               
               
                   
                 TCAGAAACGAACAATCTATCCCACCATTGCCTAGACATAGACACT 
               
               
                   
                 AG 
               
               
                   
               
               
                 SEQ ID NO: 202 
                 MKCSTFSFWFVCKIIFFFFSFNIQTSIANPRENFLKCFSQYIPNN 
               
               
                 CBDA Synthase, 
                 ATNLKLVYTQNNPLYMSVLNSTIHNLRFTSDTTPKPLVIVTPSH 
               
               
                 K389E variant 
                 VSHIQGTILCSKKVGLQIRTRSGGHDSEGMSYISQVPFVIVD 
               
               
                 Artificial Sequence 
                 LRNMRSIKIDVHSQTAWVEAGATLGEVYYWVNEKNENLSLAAG 
               
               
                   
                 YCPTVCAGGHFGGGGYGPLMRNYGLAADNIIDAHLVNVHGKVLD 
               
               
                   
                 RKSMGEDLFWALRGGGAESFGIIVAWKIRLVAVPKSTMFSVKKIM 
               
               
                   
                 EIHELVKLVNKWQNIAYKYDKDLLLMTHFITRNITDNQGKNKTAI 
               
               
                   
                 HTYFSSVFLGGVDSLVDLMNKSFPELGIKKTDCRQLSWIDTIIFY 
               
               
                   
                 SGVVNYDTDNFNKEILLDRSAGQNGAFKIKLDYVKEPIPESVFVQ 
               
               
                   
                 ILEKLYEEDIGAGMYALYPYGGIMDEISESAIPFPHRAGILYELW 
               
               
                   
                 YICSWEKQEDNEKHLNWIRNIYNFMTPYVSKNPRLAYLNYRDLDI 
               
               
                   
                 GINDPKNPNNYTQARIWGEKYFGKNFDRLVKVKTLVDPNNFFRNE 
               
               
                   
                 QSIPPLPRHRH* 
               
               
                   
               
               
                 SEQ ID NO: 203 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                 CBDA Synthase, 
                 TTCTTCTTCTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 E406K variant 
                 CGTGAGAACTTCTTGAAATGTTTTTCTCAATATATCCCAAATAAC 
               
               
                 Artificial Sequence 
                 GCTACTAACTTGAAGTTAGTCTATACTCAAAACAACCCATTATAT 
               
               
                 Codon optimized 
                 ATGTCTGTCTTAAACTCTACCATTCACAACTTACGTTTCACTTCT 
               
               
                   
                 GATACTACTCCAAAACCTTTGGTCATCGTCACCCCATCCCACGTT 
               
               
                   
                 TCTCACATCCAAGGTACCATCTTGTGTTCCAAAAAGGTTGGTTTA 
               
               
                   
                 CAAATCCGTACTAGATCCGGTGGTCATGACTCCGAAGGTATGTCT 
               
               
                   
                 TACATTTCCCAAGTCCCTTTCGTCATCGTCGACTTAAGA 
               
               
                   
                 AATATGCGTTCCATCAAGATTGATGTCCATTCCCAAACTGCTT 
               
               
                   
                 GGGTTGAAGCCGGTGCCACTTTAGGTGAAGTCTATTACTGGGTTA 
               
               
                   
                 ACGAGAAGAATGAGAACTTATCTTTGGCTGCCGGTTACTGTCCAA 
               
               
                   
                 CTGTTTGTGCTGGTGGTCATTTCGGTGGTGGTGGTTACGGTCCAT 
               
               
                   
                 TAATGCGTAACTACGGTTTGGCTGCCGATAACATCATTGATGCCC 
               
               
                   
                 ACTTAGTCAACGTTCATGGTAAGGTCTTGGACCGTAAGTCTATGG 
               
               
                   
                 GTGAGGATTTATTCTGGGCTTTGAGAGGTGGTGGTGCTGAATCTT 
               
               
                   
                 TCGGTATTATCGTCGCTTGGAAGATTAGATTAGTTGCTGTT 
               
               
                   
                 CCAAAGTCTACTATGTTCTCTGTTAAGAAGATCATGGAAA 
               
               
                   
                 TTCACGAGTTGGTTAAATTAGTTAACAAATGGCAAAACATTGCCT 
               
               
                   
                 ACAAGTACGATAAAGATTTGTTATTAATGACTCACTTTATCACT 
               
               
                   
                 AGAAACATTACTGATAACCAAGGTAAGAATAAGA 
               
               
                   
                 CTGCCATTCACACTTACTTCTCTTCTGTTTTCTTGGGTGGTGTTG 
               
               
                   
                 ATTCCTTGGTCGATTTGATGAACAAGTCTTTTCCAGAATTAGGTA 
               
               
                   
                 TTAAGAAGACCGATTGTCGTCAACTGATAATTrTAATAAGGAGAT 
               
               
                   
                 TTTGTTAGATAGATCTGCTGGTCAAAATGGTGCCTTTAAAATCAA 
               
               
                   
                 ATTGGACTACGTTAAGAAGCCTATTCCAGAATCCGTCTTTGTTC 
               
               
                   
                 AAATTTTGGAGAAGTTATACGAAaaaGATATTGGTGC 
               
               
                   
                 TGGTATGTACGCCTTGTATCCATATGGTGGTATTATGGATGAA 
               
               
                   
                 ATTTCTGAATCCGCCATCCCTTTCCCTCATCGTGCTGGTATCTTA 
               
               
                   
                 TACGAGTTGTGGTACATCTGTTCTTGGGAAAAGCAAGAAGATAAT 
               
               
                   
                 GAAAAGCATTTGAACTGGATCCGTAACATCTATAACTTCATGACT 
               
               
                   
                 CCATACGTTTCCAAAAACCCTAGATTGGCTTACTTAAATTAC 
               
               
                   
                 AGAGACTTAGATATTGGTATTAACGACCCTAAGAACC 
               
               
                   
                 CAAACAATTACACTCAAGCTAGAATCTGGGGTGAAAAGTACTT 
               
               
                   
                 CGGTAAGAATTTCGACAGATTAGTTAAGGTCAAGACTTT 
               
               
                   
                 AGTTGACCCAAATAACTTCTTCAGAAACGAACAATCT 
               
               
                   
                 ATCCCACCATTGCCTAGACATAGACACTAG 
               
               
                   
               
               
                 SEQ ID NO: 204 
                 MKCSTFSFWFVCKIIFFFFSFNIQTSIANPRENFLKCFSQYIPNN 
               
               
                 CBDA Synthase, 
                 ATNLKLVYTQNNPLYMSVLNSTIHNLRFTSDTTPKPLVIVTPSH 
               
               
                 E406K variant 
                 VSHIQGTILCSKKVGLQIRTRSGGHDSEGMSYISQVPFVIVDLRN 
               
               
                 Artificial Sequence 
                 MRSIKIDVHSQTAWVEAGATLGEVYYWVNEKNENLSLAAGYCP 
               
               
                   
                 TVCAGGHFGGGGYGPLMRNYGLAADNIIDAHLVNVHGKVLDRKS 
               
               
                   
                 MGEDLFWALRGGGAESFGIIVAWKIRLVAVPKSTMFSVKKIMEIH 
               
               
                   
                 ELVKLVNKWQNIAYKYDKDLLLMTHFITRNITDNQGKNKTAIHTY 
               
               
                   
                 FSSVFLGGVDSLVDLMNKSFPELGIKKTDCRQLSWIDTIIFYSGV 
               
               
                   
                 VNYDTDNFNKEILLDRSAGQNGAFKIKLDYVKKPIPESVFVQILE 
               
               
                   
                 KLYEKDIGAGMYALYPYGGIMDEISESAIPFPHRAGILYELWYIC 
               
               
                   
                 SWEKQEDNEKHLNWIRNIYNFMTPYVSKNPRLAYLNYRDLDIGIN 
               
               
                   
                 DPKNPNNYTQARIWGEKYFGKNFDRLVKVKTLVDPNNFFRNEQSI 
               
               
                   
                 PPLPRHRH* 
               
               
                   
               
               
                 SEQ ID NO: 205 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                 CBDA Synthase, 
                 TTCTTCTTCTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 S428L variant 
                 CGTGAGAACTTCTTGAAATGTTTTTCTCAATATATCCCAAATAAC 
               
               
                 Artificial Sequence 
                 GCTACTAACTTGAAGTTAGTCTATACTCAAAACAACCCA 
               
               
                 Codon optimized 
                 TTATATATGTCTGTCTTAAACTCTACCATTCACAACT 
               
               
                   
                 TACGTTTCACTTCTGATACTACTCCAAAACCTTTGGTCATCGTCA 
               
               
                   
                 CCCCATCCCACGTTTCTCACATCCAAGGTACCATCTTGTGTTCCA 
               
               
                   
                 AAAAGGTTGGTTTACAAATCCGTACTAGATCCGGTGGTC 
               
               
                   
                 ATGACTCCGAAGGTATGTCTTACATTTCCCAAGTCCCTTTC 
               
               
                   
                 GTCATCGTCGACTTAAGAAATATGCGTTCCATCAAGATTGATGTC 
               
               
                   
                 CATTCCCAAACTGCTTGGGTTGAAGCCGGTGCCACTTTAGGTGA 
               
               
                   
                 AGTCTATTACTGGGTTAACGAGAAGAATGAGAACTTATCTTTGG 
               
               
                   
                 CTGCCGGTTACTGTCCAACTGTTTGTGCTGGTGGTCATTTCGGTG 
               
               
                   
                 GTGGTGGTTACGGTCCATTAATGCGTAACTACGGTTTGGCTGCC 
               
               
                   
                 GATAACATCATTGATGCCCACTTAGTCAACGTTCATGGTAAGGT 
               
               
                   
                 CTTGGACCGTAAGTCTATGGGTG 
               
               
                   
                 AGGATTTATTCTGGGCTTTGAGAGGTGGTGGTGCTGAATCTTTCG 
               
               
                   
                 GTATTATCGTCGCTTGGAAGATTAGATTAGTTGCTGTTCCAAAGT 
               
               
                   
                 CTACTATGTTCTCTGTTAAGAAGATCATGGAAATTCACGAGTTGG 
               
               
                   
                 TTAAATTAGTTAACAAATGGCAAAACATTGCCTACAA 
               
               
                   
                 GTACGATAAAGATTTGTTATTAATGACTCACTTTATC 
               
               
                   
                 ACTAGAAACATTACTGATAACCAAGGTAAGAATAAGACTGCCATT 
               
               
                   
                 CACACTTACTTCTCTTCTGTTTTCTTGGGTGGTGTTGATTCCTTG 
               
               
                   
                 GTCGATTTGATGAACAAGTCTTTTCCAGAATTAGGTATTAAGAAG 
               
               
                   
                 ACCGATTGTCGTCAACTGATAATTTTAATAAGGAGATTTTGTTAG 
               
               
                   
                 ATAGATCTGCTGGTCAAAATGGTGCCTTTAAAATCAAATTGGACT 
               
               
                   
                 ACGTTAAGAAGCCTATTCCAGAATCCGTCTTTGTTCAAATTTTGG 
               
               
                   
                 AGAAGTTATACGAAGAAGATATTGGTGCTGGTATGTACGCCTTGT 
               
               
                   
                 ATCCATATGGTGGTATTATGGATGAAATTTCTGAAttgGCCATCC 
               
               
                   
                 CTTTCCCTCATCGTGCTGGTATCTTATACGAGTTGTGGTACATCT 
               
               
                   
                 GTTCTTGGGAAAAGCAAGAAGATAATGAAAAGCATTTGAACTGGA 
               
               
                   
                 TCCGTAACATCTATAACTTCATGACTCCATACGTTTCCA 
               
               
                   
                 AAAACCCTAGATTGGCTTACTTAAATTACAGAGACTTAG 
               
               
                   
                 ATATTGGTATTAACGACCCTAAGAACCCAAACAATTACACTCAAG 
               
               
                   
                 CTAGAATCTGGGGTGAAAAGTACTTCGGTAAGAATTTCGACAGAT 
               
               
                   
                 TAGTTAAGGTCAAGACTTTAGTTGACCCAAATAACTTCTTCAGAA 
               
               
                   
                 ACGAACAATCTATCCCACCATTGCCTAGACATAGACACTAG 
               
               
                   
               
               
                 SEQ ID NO: 206 
                 MKCSTFSFWFVCKIIFFFFSFNIQTSIANPRENFLKCFSQYIPNN 
               
               
                 CBDA Synthase, 
                 ATNLKLVYTQNNPLYMSVLNSTIHNLRFTSDTTPKPLVIVTPSH 
               
               
                 S428L variant 
                 VSHIQGTILCSKKVGLQIRTRSGGHDSEGMSYISQVPFVIVDLRN 
               
               
                 Artificial Sequence 
                 MRSIKIDVHSQTAWVEAGATLGEVYYVVVNEKNENLSLAAGYC 
               
               
                   
                 PTVCAGGHFGGGGYGPLMRNYGLAADNIIDAHLVNVHGK 
               
               
                   
                 VLDRKSMGEDLFVVALRGGGAESFGIIVAVVKIRLVAVPKSTMFS 
               
               
                   
                 VKKIMEIHELVKLVNKVVQNIAYKYDKDLLLMTHFITRNITDNQG 
               
               
                   
                 KNKTAIHTYFSSVFLGGVDSLVDLMNKSFPELGIKKTDCRQLSWI 
               
               
                   
                 DTIIFYSGVVNYDTDNFNKEILLDRSAGQNGAFKIKLDYVKKPIP 
               
               
                   
                 ESVFVQILEKLYEEDIGAGMYALYPYGGIMDEISELAIPFPHRAG 
               
               
                   
                 ILYELWYICSWEKQEDNEKHLNWIRNIYNFMTPYVSKNPRLAYLN 
               
               
                   
                 YRDLDIGINDPKNPNNYTQARIWGEKYFGKNFDRLVKVKTLVDPN 
               
               
                   
                 NFFRNEQSIPPLPRHRH* 
               
               
                   
               
               
                 SEQ ID NO: 207 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                 CBDA Synthase, 
                 TTCTTCTTCTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 L439M variant 
                 CGTGAGAACTTCTTGAAATGTTTTTCTCAATATATCCCA 
               
               
                 Artificial Sequence 
                 AATAACGCTACTAACTTGAAGTTAGTCTATACTCAAAAC 
               
               
                 Codon optimized 
                 AACCCATTATATATGTCTGTCTTAAACTCTACCATTCACAACTTA 
               
               
                   
                 CGTTTCACTTCTGATACTACTCCAAAACCTTTGGTCATCGTCACC 
               
               
                   
                 CCATCCCACGTTTCTCACATCCAAGGTACCATCTTGTGTTCCAAA 
               
               
                   
                 AAGGTTGGTTTACAAATCCGTACTAGATCCGGTGGTCATGACTCC 
               
               
                   
                 GAAGGTATGTCTTACATTTCCCAAGTCCCTTTCGTCATCGTC 
               
               
                   
                 GACTTAAGAAATATGCGTTCCATCAAGATTGATGTCCATT 
               
               
                   
                 CCCAAACTGCTTGGGTTGAAGCCGGTGCCACTTTAGGTGAAGTCT 
               
               
                   
                 ATTACTGGGTTAACGAGAAGAATGAGAACTTATCTTTGGCTGCCG 
               
               
                   
                 GTTACTGTCCAACTGTTTGTGCTGGTGGTCATTTCGGTGGTGGTG 
               
               
                   
                 GTTACGGTCCATTAATGCGTAACTACGGTTTGGCTGCCGATAACA 
               
               
                   
                 TCATTGATGCCCACTTAGTCAACGTTCATGGTAAGGTCTTGGACC 
               
               
                   
                 GTAAGTCTATGGGTGAGGATTTATTCTGGGCTTTGAGAGGTGGTG 
               
               
                   
                 GTGCTGAATCTTTCGGTATTATCGTCGCTTGGAAGATTAGA 
               
               
                   
                 TTAGTTGCTGTTCCAAAGTCTACTATGTTCTCTGTTAAG 
               
               
                   
                 AAGATCATGGAAATTCACGAGTTGGTTAAATTAGTT 
               
               
                   
                 AACAAATGGCAAAACATTGCCTACAAGTACGAT 
               
               
                   
                 AAAGATTTGTTATTAATGACTCACTTTATCACTAG 
               
               
                   
                 AAACATTACTGATAACCAAGGTAAGAATAAG 
               
               
                   
                 ACTGCCATTCACACTTACTTCTCTTCTGTTTTCTTGGGTGGTGT 
               
               
                   
                 TGATTCCTTGGTCGATTTGATGAACAAGTCTTTTCCAGAATTAGG 
               
               
                   
                 TATTAAGAAGACCGATTGTCGTCAACTGATAATTTTAATA 
               
               
                   
                 AGGAGATTTTGTTAGATAGATCTGCTGGTCAAAATGGTG 
               
               
                   
                 CCTTTAAAATCAAATTGGACTACGTTAAGAAGCCTATTCCAGAAT 
               
               
                   
                 CCGTCTTTGTTCAAATTTTGGAGAAGTTATACGAAGAAGATATTG 
               
               
                   
                 GTGCTGGTATGTACGCCTTGTATCCATATGGTGGTATTATGGATG 
               
               
                   
                 AAATTTCTGAATCCGCCATCCCTTTCCCTCATCGTGCTGGTA 
               
               
                   
                 TCalgTACGAGTTGTGGTACATCTGTTCTTGGGAAAAGCAA 
               
               
                   
                 GAAGATAATGAAAAGCATTTGAACTGGATCCGTAACA 
               
               
                   
                 TCTATAACTTCATGACTCCATACGTTTCCAAAAACCCTAGATTGG 
               
               
                   
                 CTTACTTAAATTACAGAGACTTAGATATTGGTATT 
               
               
                   
                 AACGACCCTAAGAACCCAAACAATTACACTCAAGCTAGA 
               
               
                   
                 ATCTGGGGTGAAAAGTACTTCGGTAAGAATTT 
               
               
                   
                 CGACAGATTAGTTAAGGTCAAGACTTTAGTTGACCCAAATAACTT 
               
               
                   
                 CTTCAGAAACGAACAATCTATCCCACCATTGCCTAGACATAG 
               
               
                   
                 ACACTAG 
               
               
                   
               
               
                 SEQ ID NO: 208 
                 MKCSTFSFWFVCKIIFFFFSFNIQTSIANPRENFLKCFSQYIPNN 
               
               
                 CBDA Synthase, 
                 ATNLKLVYTQNNPLYMSVLNSTIHNLRFTSDTTPKPLVIVTPSH 
               
               
                 L439M variant 
                 VSHIQGTILCSKKVGLQIRTRSGGHDSEGMSYISQVPFVIVDLRN 
               
               
                 Artificial Sequence 
                 MRSIKIDVHSQTAWVEAGATLGEVYYWVNEKNENLSLAAGYCP 
               
               
                   
                 TVCAGGHFGGGGYGPLMRNYGLAADNIIDAHLVNVHGKVLDRKSM 
               
               
                   
                 GEDLFWALRGGGAESFGIIVAWKIRLVAVPKSTMFSVKKIMEIHE 
               
               
                   
                 LVKLVNKVVQNIAYKYDKDLLLMTHFITRNITDNQGKNKTAIHTY 
               
               
                   
                 FSSVFLGGVDSLVDLMNKSFPELGIKKTDCRQLSWIDTIIFYSGW 
               
               
                   
                 NYDTDNFNKEILLDRSAGQNGAFKIKLDYVKKPIPESVFVQILEK 
               
               
                   
                 LYEEDIGAGMYALYPYGGIMDEISESAIPFPHRAGIMYELWYICS 
               
               
                   
                 WEKQEDNEKHLNWIRNIYNFMTPYVSKNPRLAYLNYRDLDIGIND 
               
               
                   
                 PKNPNNYTQARIWGEKYFGKNFDRLVKVKTLVDPNNFFRNEQSIP 
               
               
                   
                 PLPRHRH* 
               
               
                   
               
               
                 SEQ ID NO: 209 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                 CBDA Synthase, 
                 TTCTTCTTCTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 N466D variant 
                 CGTGAGAACTTCTTGAAATGTTTTTCTCAATATATCCCAAATAAC 
               
               
                 Artificial Sequence 
                 GCTACTAACTTGAAGTTAGTCTATACTCAAAACAACCC 
               
               
                 Codon optimized 
                 ATTATATATGTCTGTCTTAAACTCTACCATTCACAA 
               
               
                   
                 CTTACGTTTCACTTCTGATACTACTCCAAAACCTTTGG 
               
               
                   
                 TCATCGTCACCCCATCCCACGTTTCTCACATCCAAGGTACCAT 
               
               
                   
                 CTTGTGTTCCAAAAAGGTTGGTTTACAAATCCGTACTAGA 
               
               
                   
                 TCCGGTGGTCATGACTCCGAAGGTATGTCTTACATTTCCC 
               
               
                   
                 AAGTCCCTTTCGTCATCGTCGACTTAAGAAATATGCGTTCCATCA 
               
               
                   
                 AGATTGATGTCCATTCCCAAACTGCTTGGGTTGAAGCCGGTGCCA 
               
               
                   
                 CTTTAGGTGAAGTCTATTACTGGGTTAACGAGAAGAATGAGAACT 
               
               
                   
                 TATCTTTGGCTGCCGGTTACTGTCCAACTGTTTGTGCTGGTGGTC 
               
               
                   
                 ATTTCGGTGGTGGTGGTTACGGTCCATTAATGCGTAACTACGGTT 
               
               
                   
                 TGGCTGCCGATAACATCATTGATGCCCACTTAGTCAACGTTCATG 
               
               
                   
                 GTAAGGTCTTGGACCGTAAGTCTATGGGTGAGGATTTATTCTGGG 
               
               
                   
                 CTTTGAGAGGTGGTGGTGCTGAATCTTTCGGTATTATCGTCGCTT 
               
               
                   
                 GGAAGATTAGATTAGTTGCTGTTCCAAAGTCTACTATGTTCTCTG 
               
               
                   
                 TTAAGAAGATCATGGAAATTCACGAGTTGGTTAAATTAGTTAACA 
               
               
                   
                 AATGGCAAAACATTGCCTACAAGTACGATAA 
               
               
                   
                 AGATTTGTTATTAATGACTCACTTTATCACTAGAAA 
               
               
                   
                 CATTACTGATAACCAAGGTAAGAATAAGACTGCCATTCACA 
               
               
                   
                 CTTACTTCTCTTCTGTTTTCTTGGGTGGTGTTGATTCCTTGGTCG 
               
               
                   
                 ATTTGATGAACAAGTCTTTTCCAGAATTAGGTATTA 
               
               
                   
                 AGAAGACCGATTGTCGTCAACTGATAATTTTAATAAGGAG 
               
               
                   
                 ATTTTGTTAGATAGATCTGCTGGTCAAAATGGTGCCTTTAAA 
               
               
                   
                 ATCAAATTGGACTACGTTAAGAAGCCTATTCCAGA 
               
               
                   
                 ATCCGTCTTTGTTCAAATTTTGGAGAAGTTATACGAAGAAGATAT 
               
               
                   
                 TGGTGCTGGTATGTACGCCTTGTATCCATATGGTGGTATTATGGA 
               
               
                   
                 TGAAATTTCTGAATCCGCCATCCCTTTCCCTCATCGTGCTGGTA 
               
               
                   
                 TCTTATACGAGTTGTGGTACATCTGTTCTTGGGAAAAGCAAGAAG 
               
               
                   
                 ATAATGAAAAGCATTTGAACTGGATCCGTAACATCTATgatTTCA 
               
               
                   
                 TGACTCCATACGTTTCCAAAAACCCTAGATTGGCTTACTTAAATT 
               
               
                   
                 ACAGAGACTTAGATATTGGTATTAACGACCCTAAGAACCCAAACA 
               
               
                   
                 ATTACACTCAAGCTAGAATCTGGGGTGAAAAGTACTTCGGTAAGA 
               
               
                   
                 ATTTCGACAGATTAGTTAAGGTCAAGACTTTAGTTGACCCAAATA 
               
               
                   
                 ACTTCTTCAGAAACGAACAATCTATCCCACCATTGCCTAGACATA 
               
               
                   
                 GACACTAG 
               
               
                   
               
               
                 SEQ ID NO: 210 
                 MKCSTFSFWFVCKIIFFFFSFNIQTSIANPRENFLKCFSQYIPNN 
               
               
                 CBDA Synthase, 
                 ATNLKLVYTQNNPLYMSVLNSTIHNLRFTSDTTPKPLVIVTPSH 
               
               
                 N466D variant 
                 VSHIQGTILCSKKVGLQIRTRSGGHDSEGMSYISQVPFVIVDLRN 
               
               
                 Artificial Sequence 
                 MRSIKIDVHSQTAWVEAGATLGEVYYWVNEKNENLSLAAGYCPT 
               
               
                   
                 VCAGGHFGGGGYGPLMRNYGLAADNIIDAHLVNVHGKVLDRKSM 
               
               
                   
                 GEDLFVVALRGGGAESFGIIVAVVKIRLVAVPKSTMFSVKKIMEI 
               
               
                   
                 HELVKLVNKWQNIAYKYDKDLLLMTHFITRNITDNQGKNKTAIHT 
               
               
                   
                 YFSSVFLGGVDSLVDLMNKSFPELGIKKTDCRQLSWIDTIIFYSG 
               
               
                   
                 VVNYDTDNFNKEILLDRSAGQNGAFKIKLDYVKKPIPESVFVQIL 
               
               
                   
                 EKLYEEDIGAGMYALYPYGGIMDEISESAIPFPHRAGILYELWYI 
               
               
                   
                 CSWEKQEDNEKHLNVVIRNIYDFMTPYVSKNPRLAYLNYRDLDIG 
               
               
                   
                 INDPKNPNNYTQARIWGEKYFGKNFDRLVKVKTLVDPNNFFRNEQ 
               
               
                   
                 SIPPLPRHRH* 
               
               
                   
               
               
                 SEQ ID NO: 211 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                 CBDA Synthase, 
                 TTCTTCTTCTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 K474S variant 
                 CGTGAGAACTTCTTGAAATGTTTTTCTCAATATATCCCA 
               
               
                   
                 AATAACGCTACTAACTTGAAGTTAGTCTATACTCAAAA 
               
               
                   
                 CAACCCATTATATATGTCTGTCTTAAACTCTACCATTCACAACTT 
               
               
                   
                 ACGTTTCACTTCTGATACTACTCCAAAACCTTTGGTCATC 
               
               
                   
                 GTCACCCC 
               
               
                 Artificial Sequence 
                 ATCCCACGTTTCTCACATCCAAGGTACCATCTTGTGTTCCAAAAA 
               
               
                 Codon optimized 
                 GGTTGGTTTACAAATCCGTACTAGATCCGGTGGTCATGACTCCGA 
               
               
                   
                 AGGTATGTCTTACATTTCCCAAGTCCCTTTCGTCATCGTCGACTT 
               
               
                   
                 AAGAAATATGCGTTCCATCAAGATTGATGTCCATTCCCAAACTGC 
               
               
                   
                 TTGGGTTGAAGCCGGTGCCACTTTAGGTGAAGTCTATTACTGGGT 
               
               
                   
                 TAACGAGAAGAATGAGAACTTATCTTTGGCTGCCGGTTACTGTCC 
               
               
                   
                 AACTGTTTGTGCTGGTGGTCATTTCGGTGGTGGTGGTTACGGTCC 
               
               
                   
                 ATTAATGCGTAACTACGGTTTGGCTGCCGATAACATCATTGATGC 
               
               
                   
                 CCACTTAGTCAACGTTCATGGTAAGGTCTTGGACCGTAAGTCTAT 
               
               
                   
                 GGGTGAGGATTTATTCTGGGCTTTGAGAGGTGGTGGTGCTGAATC 
               
               
                   
                 TTTCGGTATTATCGTCGCTTGGAAGATTAGATTAGTTGCTGTTCC 
               
               
                   
                 AAAGTCTACTATGTTCTCTGTTAAGAAGATCATGGAAATTCACGA 
               
               
                   
                 GTTGGTTAAATTAGTTAACAAATGGCAAAACATTGCCTACAAGTA 
               
               
                   
                 CGATAAAGATTTGTTATTAATGACTCACTTTATCACTAGAAACAT 
               
               
                   
                 TACTGATAACCAAGGTAAGAATAAGACTGCCATTCACACTTACTT 
               
               
                   
                 CTCTTCTGTTTTCTTGGGTGGTGTTGATTCCTTGGTCGATTTGAT 
               
               
                   
                 GAACAAGTCTTTTCCAGAATTAGGTATTAAGAAGACCGATTGTCG 
               
               
                   
                 TCAACTGATAATTTTAATAAGGAGATTTTGTTAGATAGATCTGCT 
               
               
                   
                 GGTCAAAATGGTGCCTTTAAAATCAAATTGGACTACGTTAAGAAG 
               
               
                   
                 CCTATTCCAGAATCCGTCTTTGTTCAAATTTTGGAGAAGTTATAC 
               
               
                   
                 GAAGAAGATATTGGTGCTGGTATGTACGCCTTGTATCCATATGGT 
               
               
                   
                 GGTATTATGGATGAAATTTCTGAATCCGCCATCCCTTTCCCTCAT 
               
               
                   
                 CGTGCTGGTATCTTATACGAGTTGTGGTACATCTGTTCTTGGGAA 
               
               
                   
                 AAGCAAGAAGATAATGAAAAGCATTTGAACTGGATCCGTAACATC 
               
               
                   
                 TATAACTTCATGACTCCATACGTTTCCtctAACCCTAGATTGGCT 
               
               
                   
                 TACTTAAATTACAGAGACTTAGATATTGGTATTAACGACCCTAAG 
               
               
                   
                 AACCCAAACAATTACACTCAAGCTAGAATCTGGGGTGAAAAGTAC 
               
               
                   
                 TTCGGTAAGAATTTCGACAGATTAGTTAAGGTCAAGACTTTAGTT 
               
               
                   
                 GACCCAAATAACTTCTTCAGAAACGAACAATCTATCCCACCATTG 
               
               
                   
                 CCTAGACATAGACACTAG 
               
               
                   
               
               
                 SEQ ID NO: 212 
                 MKCSTFSFWFVCKIIFFFFSFNIQTSIANPRENFLKCFSQYIPNN 
               
               
                 CBDA Synthase, 
                 ATNLKLVYTQNNPLYMSVLNSTIHNLRFTSDTTPKPLVIVTPSHV 
               
               
                 K474S variant 
                 SHIQGTILCSKKVGLQIRTRSGGHDSEGMSYISQVPFVIVDLRNM 
               
               
                 Artificial Sequence 
                 RSIKIDVHSQTAWVEAGATLGEVYYWVNEKNENLSLAAGYCPTVC 
               
               
                   
                 AGGHFGGGGYGPLMRNYGLAADNIIDAHLVNVHGKVLDRKSMGED 
               
               
                   
                 LFWALRGGGAESFGIIVAWKIRLVAVPKSTMFSVKKIMEIHELVK 
               
               
                   
                 LVNKWQNIAYKYDKDLLLMTHFITRNITDNQGKNKTAIHTYFSSV 
               
               
                   
                 FLGGVDSLVDLMNKSFPELGIKKTDCRQLSWIDTIIFYSGWNYDT 
               
               
                   
                 DNFNKEILLDRSAGQNGAFKKLDYVKKPIPESVFVQILEKLYEED 
               
               
                   
                 IGAGMYALYPYGGIMDEISESAIPFPHRAGILYELWYICSWEKQE 
               
               
                   
                 DNEKHLNWIRNIYNFMTPYVSSNPRLAYLNYRDLDIGINDPKNPN 
               
               
                   
                 NYTQARIWGEKYFGKNFDRLVKVKTLVDPNNFFRNEQSIPPLPRH 
               
               
                   
                 RH* 
               
               
                   
               
               
                 SEQ ID NO: 213 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                 CBDA Synthase, 
                 TTCTTCTTCTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 Y499M variant 
                 CGTGAGAACTTCTTGAAATGTTTTTCTCAATATATCCCAAATAAC 
               
               
                 Artificial Sequence 
                 GCTACTAACTTGAAGTTAGTCTATACTCAAAACAACCCATTATAT 
               
               
                 Codon optimized 
                 ATGTCTGTCTTAAACTCTACCATTCACAACTTACGTTTCACTTCT 
               
               
                   
                 GATACTACTCCAAAACCTTTGGTCATCGTCACCCCATCCCACGTT 
               
               
                   
                 TCTCACATCCAAGGTACCATCTTGTGTTCCAAAAAGGTTGGTTTA 
               
               
                   
                 CAAATCCGTACTAGATCCGGTGGTCATGACTCCGAAGGTATGTCT 
               
               
                   
                 TACATTTCCCAAGTCCCTTTCGTCATCGTCGACTTAAGAAATATG 
               
               
                   
                 CGTTCCATCAAGATTGATGTCCATTCCCAAACTGCTTGGGTTGAA 
               
               
                   
                 GCCGGTGCCACTTTAGGTGAAGTCTATTACTGGGTTAACGAGAAG 
               
               
                   
                 AATGAGAACTTATCTTTGGCTGCCGGTTACTGTCCAACTGTTTGT 
               
               
                   
                 GCTGGTGGTCATTTCGGTGGTGGTGGTTACGGTCCATTAATGCGT 
               
               
                   
                 AACTACGGTTTGGCTGCCGATAACATCATTGATGCCCACTTAGTC 
               
               
                   
                 AACGTTCATGGTAAGGTCTTGGACCGTAAGTCTATGGGTGAGGAT 
               
               
                   
                 TTATTCTGGGCTTTGAGAGGTGGTGGTGCTGAATCTTTCGGTATT 
               
               
                   
                 ATCGTCGCTTGGAAGATTAGATTAGTTGCTGTTCCAAAGTCTACT 
               
               
                   
                 ATGTTCTCTGTTAAGAAGATCATGGAAATTCACGAGTTGGTTAAA 
               
               
                   
                 TTAGTTAACAAATGGCAAAACATTGCCTACAAGTACGATAAAGAT 
               
               
                   
                 TTGTTATTAATGACTCACTTTATCACTAGAAACATTACTGATAAC 
               
               
                   
                 CAAGGTAAGAATAAGACTGCCATTCACACTTACTTCTCTTCTGTT 
               
               
                   
                 TTCTTGGGTGGTGTTGATTCCTTGGTCGATTTGATGAACAAGTCT 
               
               
                   
                 TTTCCAGAATTAGGTATTAAGAAGACCGATTGTCGTCAACTGATA 
               
               
                   
                 ATTTTAATAAGGAGATTTTGTTAGATAGATCTGCTGGTCAAAATG 
               
               
                   
                 GTGCCTTTAAAATCAAATTGGACTACGTTAAGAAGCCTATTCCAG 
               
               
                   
                 AATCCGTCTTTGTTCAAATTTTGGAGAAGTTATACGAAGAAGATA 
               
               
                   
                 TTGGTGCTGGTATGTACGCCTTGTATCCATATGGTGGTATTATGG 
               
               
                   
                 ATGAAATTTCTGAATCCGCCATCCCTTTCCCTCATCGTGCTGGTA 
               
               
                   
                 TCTTATACGAGTTGTGGTACATCTGTTCTTGGGAAAAGCAAGAAG 
               
               
                   
                 ATAATGAAAAGCATTTGAACTGGATCCGTAACATCTATAACTTCA 
               
               
                   
                 TGACTCCATACGTTTCCAAAAACCCTAGATTGGCTTACTTAAATT 
               
               
                   
                 ACAGAGACTTAGATATTGGTATTAACGACCCTAAGAACCCAAACA 
               
               
                   
                 ATatgACTCAAGCTAGAATCTGGGGTGAAAAGTACTTCGGTAAGA 
               
               
                   
                 ATTTCGACAGATTAGTTAAGGTCAAGACTTTAGTTGACCCAAATA 
               
               
                   
                 ACTTCTTCAGAAACGAACAATCTATCCCACCATTGCCTAGACATA 
               
               
                   
                 GACACTAG 
               
               
                   
               
               
                 SEQ ID NO: 214 
                 MKCSTFSFWFVCKIIFFFFSFNIQTSIANPRENFLKCFSQYIPNN 
               
               
                 CBDA Synthase, 
                 ATNLKLVYTQNNPLYMSVLNSTIHNLRFTSDTTPKPLVIVTPSHV 
               
               
                 Y499M variant 
                 SHIQGTILCSKKVGLQIRTRSGGHDSEGMSYISQVPFVIVDLRNM 
               
               
                 Artificial Sequence 
                 RSIKIDVHSQTAWVEAGATLGEVYYWVNEKNENLSLAAGYCPTVC 
               
               
                   
                 AGGHFGGGGYGPLMRNYGLAADNIIDAHLVNVHGKVLDRKSMGED 
               
               
                   
                 LFWALRGGGAESFGIIVAWKIRLVAVPKSTMFSVKKIMEIHELVK 
               
               
                   
                 LVNKWQNIAYKYDKDLLLMTHFITRNITDNQGKNKTAIHTYFSSV 
               
               
                   
                 FLGGVDSLVDLMNKSFPELGIKKTDCRQLSWIDTIIFYSGWNYDT 
               
               
                   
                 DNFNKEILLDRSAGQNGAFKIKLDYVKKPIPESVFVQILEKLYEE 
               
               
                   
                 DIGAGMYALYPYGGIMDEISESAIPFPHRAGILYELWYICSWEKQ 
               
               
                   
                 EDNEKHLNWIRNIYNFMTPYVSKNPRLAYLNYRDLDIGINDPKNP 
               
               
                   
                 NNMTQARIWGEKYFGKNFDRLVKVKTLVDPNNFFRNEQSIPPLPR 
               
               
                   
                 HRH* 
               
               
                   
               
               
                 SEQ ID NO: 215 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                 CBDA Synthase, 
                 TTCTTCTTCTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 Y499V variant 
                 CGTGAGAACTTCTTGAAATGTTTTTCTCAATATATCCCAAATAAC 
               
               
                 Artificial Sequence 
                 GCTACTAACTTGAAGTTAGTCTATACTCAAAACAACCCATTATAT 
               
               
                 Codon optimized 
                 ATGTCTGTCTTAAACTCTACCATTCACAACTTACGTTTCACTTCT 
               
               
                   
                 GATACTACTCCAAAACCTTTGGTCATCGTCACCCCATCCCACGTT 
               
               
                   
                 TCTCACATCCAAGGTACCATCTTGTGTTCCAAAAAGGTTGGTTTA 
               
               
                   
                 CAAATCCGTACTAGATCCGGTGGTCATGACTCCGAAGGTATGTCT 
               
               
                   
                 TACATTTCCCAAGTCCCTTTCGTCATCGTCGACTTAAGAAATATG 
               
               
                   
                 CGTTCCATCAAGATTGATGTCCATTCCCAAACTGCTTGGGTTGAA 
               
               
                   
                 GCCGGTGCCACTTTAGGTGAAGTCTATTACTGGGTTAACGAGAAG 
               
               
                   
                 AATGAGAACTTATCTTTGGCTGCCGGTTACTGTCCAACTGTTTGT 
               
               
                   
                 GCTGGTGGTCATTTCGGTGGTGGTGGTTACGGTCCATTAATGCGT 
               
               
                   
                 AACTACGGTTTGGCTGCCGATAACATCATTGATGCCCACTTAGTC 
               
               
                   
                 AACGTTCATGGTAAGGTCTTGGACCGTAAGTCTATGGGTGAGGAT 
               
               
                   
                 TTATTCTGGGCTTTGAGAGGTGGTGGTGCTGAATCTTTCGGTATT 
               
               
                   
                 ATCGTCGCTTGGAAGATTAGATTAGTTGCTGTTCCAAAGTCTACT 
               
               
                   
                 ATGTTCTCTGTTAAGAAGATCATGGAAATTCACGAGTTGGTTAAA 
               
               
                   
                 TTAGTTAACAAATGGCAAAACATTGCCTACAAGTACGATAAAGAT 
               
               
                   
                 TTGTTATTAATGACTCACTTTATCACTAGAAACATTACTGATAAC 
               
               
                   
                 CAAGGTAAGAATAAGACTGCCATTCACACTTACTTCTCTTCTGTT 
               
               
                   
                 TTCTTGGGTGGTGTTGATTCCTTGGTCGATTTGATGAACAAGTCT 
               
               
                   
                 TTTCCAGAATTAGGTATTAAGAAGACCGATTGTCGTCAACTGATA 
               
               
                   
                 ATTTTAATAAGGAGATTTTGTTAGATAGATCTGCTGGTCAAAATG 
               
               
                   
                 GTGCCTTTAAAATCAAATTGGACTACGTTAAGAAGCCTATTCCAG 
               
               
                   
                 AATCCGTCTTTGTTCAAATTTTGGAGAAGTTATACGAAGAAGATA 
               
               
                   
                 TTGGTGCTGGTATGTACGCCTTGTATCCATATGGTGGTATTATGG 
               
               
                   
                 ATGAAATTTCTGAATCCGCCATCCCTTTCCCTCATCGTGCTGGTA 
               
               
                   
                 TCTTATACGAGTTGTGGTACATCTGTTCTTGGGAAAAGCAAGAAG 
               
               
                   
                 ATAATGAAAAGCATTTGAACTGGATCCGTAACATCTATAACTTCA 
               
               
                   
                 TGACTCCATACGTTTCCAAAAACCCTAGATTGGCTTACTTAAATT 
               
               
                   
                 ACAGAGACTTAGATATTGGTATTAACGACCCTAAGAACCCAAACA 
               
               
                   
                 ATgttACTCAAGCTAGAATCTGGGGTGAAAAGTACTTCGGTAAGA 
               
               
                   
                 ATTTCGACAGATTAGTTAAGGTCAAGACTTTAGTTGACCCAAATA 
               
               
                   
                 ACTTCTTCAGAAACGAACAATCTATCCCACCATTGCCTAGACATA 
               
               
                   
                 GACACTAG 
               
               
                   
               
               
                 SEQ ID NO: 216 
                 MKCSTFSFWFVCKIIFFFFSFNIQTSIANPRENFLKCFSQYIPNN 
               
               
                 CBDA Synthase, 
                 ATNLKLVYTQNNPLYMSVLNSTIHNLRFTSDTTPKPLVIVTPSHV 
               
               
                 Y499V variant 
                 SHIQGTILCSKKVGLQIRTRSGGHDSEGMSYISQVPFVIVDLRNM 
               
               
                 Artificial Sequence 
                 RSIKIDVHSQTAWVEAGATLGEVYYWVNEKNENLSLAAGYCPTVC 
               
               
                   
                 AGGHFGGGGYGPLMRNYGLAADNIIDAHLVNVHGKVLDRKSMGED 
               
               
                   
                 LFWALRGGGAESFGIIVAWKIRLVAVPKSTMFSVKKIMEIHELVK 
               
               
                   
                 LVNKWQNIAYKYDKDLLLMTHFITRNITDNQGKNKTAIHTYFSSV 
               
               
                   
                 FLGGVDSLVDLMNKSFPELGIKKTDCRQLSWIDTIIFYSGVVNYD 
               
               
                   
                 TDNFNKEILLDRSAGQNGAFKKLDYVKKPIPESVFVQILEKLYEE 
               
               
                   
                 DIGAGMYALYPYGGIMDEISESAIPFPHRAGILYELWYICSWEKQ 
               
               
                   
                 EDNEKHLNWIRNIYNFMTPYVSKNPRLAYLNYRDLDIGINDPKNP 
               
               
                   
                 NNVTQARIWGEKYFGKNFDRLVKVKTLVDPNNFFRNEQSIPPLPR 
               
               
                   
                 HRH* 
               
               
                   
               
               
                 SEQ ID NO: 217 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                 CBDA Synthase, 
                 TTCTTCTTCTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 N527E variant 
                 CGTGAGAACTTCTTGAAATGTTTTTCTCAATATATCCCAAATAAC 
               
               
                 Artificial Sequence 
                 GCTACTAACTTGAAGTTAGTCTATACTCAAAACAACCCATTATAT 
               
               
                 Codon optimized 
                 ATGTCTGTCTTAAACTCTACCATTCACAACTTACGTTTCACTTCT 
               
               
                   
                 GATACTACTCCAAAACCTTTGGTCATCGTCACCCCATCCCACGTT 
               
               
                   
                 TCTCACATCCAAGGTACCATCTTGTGTTCCAAAAAGGTTGGTTTA 
               
               
                   
                 CAAATCCGTACTAGATCCGGTGGTCATGACTCCGAAGGTATGTCT 
               
               
                   
                 TACATTTCCCAAGTCCCTTTCGTCATCGTCGACTTAAGAAATATG 
               
               
                   
                 CGTTCCATCAAGATTGATGTCCATTCCCAAACTGCTTGGGTTGAA 
               
               
                   
                 GCCGGTGCCACTTTAGGTGAAGTCTATTACTGGGTTAACGAGAAG 
               
               
                   
                 AATGAGAACTTATCTTTGGCTGCCGGTTACTGTCCAACTGTTTGT 
               
               
                   
                 GCTGGTGGTCATTTCGGTGGTGGTGGTTACGGTCCATTAATGCGT 
               
               
                   
                 AACTACGGTTTGGCTGCCGATAACATCATTGATGCCCACTTAGTC 
               
               
                   
                 AACGTTCATGGTAAGGTCTTGGACCGTAAGTCTATGGGTGAGGAT 
               
               
                   
                 TTATTCTGGGCTTTGAGAGGTGGTGGTGCTGAATCTTTCGGTATT 
               
               
                   
                 ATCGTCGCTTGGAAGATTAGATTAGTTGCTGTTCCAAAGTCTACT 
               
               
                   
                 ATGTTCTCTGTTAAGAAGATCATGGAAATTCACGAGTTGGTTAAA 
               
               
                   
                 TTAGTTAACAAATGGCAAAACATTGCCTACAAGTACGATAAAGAT 
               
               
                   
                 TTGTTATTAATGACTCACTTTATCACTAGAAACATTACTGATAAC 
               
               
                   
                 CAAGGTAAGAATAAGACTGCCATTCACACTTACTTCTCTTCTGTT 
               
               
                   
                 TTCTTGGGTGGTGTTGATTCCTTGGTCGATTTGATGAACAAGTCT 
               
               
                   
                 TTTCCAGAATTAGGTATTAAGAAGACCGATTGTCGTCAACTGATA 
               
               
                   
                 ATTTTAATAAGGAGATTTTGTTAGATAGATCTGCTGGTCAAAATG 
               
               
                   
                 GTGCCTTTAAAATCAAATTGGACTACGTTAAGAAGCCTATTCCAG 
               
               
                   
                 AATCCGTCTTTGTTCAAATTTTGGAGAAGTTATACGAAGAAGATA 
               
               
                   
                 TTGGTGCTGGTATGTACGCCTTGTATCCATATGGTGGTATTATGG 
               
               
                   
                 ATGAAATTTCTGAATCCGCCATCCCTTTCCCTCATCGTGCTGGTA 
               
               
                   
                 TCTTATACGAGTTGTGGTACATCTGTTCTTGGGAAAAGCAAGAAG 
               
               
                   
                 ATAATGAAAAGCATTTGAACTGGATCCGTAACATCTATAACTTCA 
               
               
                   
                 TGACTCCATACGTTTCCAAAAACCCTAGATTGGCTTACTTAAATT 
               
               
                   
                 ACAGAGACTTAGATATTGGTATTAACGACCCTAAGAACCCAAACA 
               
               
                   
                 ATTACACTCAAGCTAGAATCTGGGGTGAAAAGTACTTCGGTAAGA 
               
               
                   
                 ATTTCGACAGATTAGTTAAGGTCAAGACTTTAGTTGACCCAgaaA 
               
               
                   
                 ACTTCTTCAGAAACGAACAATCTATCCCACCATTGCCTAGACATA 
               
               
                   
                 GACACTAG 
               
               
                   
               
               
                 SEQ ID NO: 218 
                 MKCSTFSFWFVCKIIFFFFSFNIQTSIANPRENFLKCFSQYIPNN 
               
               
                 CBDA Synthase, 
                 ATNLKLVYTQNNPLYMSVLNSTIHNLRFTSDTTPKPLVIVTPSHV 
               
               
                 N527E variant 
                 SHIQGTILCSKKVGLQIRTRSGGHDSEGMSYISQVPFVIVDLRNM 
               
               
                 Artificial Sequence 
                 RSIKIDVHSQTAWVEAGATLGEVYYWVNEKNENLSLAAGYCPTVC 
               
               
                   
                 AGGHFGGGGYGPLMRNYGLAADNIIDAHLVNVHGKVLDRKSMGED 
               
               
                   
                 LFWALRGGGAESFGIIVAWKIRLVAVPKSTMFSVKKIMEIHELVK 
               
               
                   
                 LVNKWQNIAYKYDKDLLLMTHFITRNITDNQGKNKTAIHTYFSSV 
               
               
                   
                 FLGGVDSLVDLMNKSFPELGIKKTDCRQLSWIDTIIFYSGWNYDT 
               
               
                   
                 DNFNKEILLDRSAGQNGAFKIKLDYVKKPIPESVFVQILEKLYEE 
               
               
                   
                 DIGAGMYALYPYGGIMDEISESAIPFPHRAGILYELWYICSWEKQ 
               
               
                   
                 EDNEKHLNWIRNIYNFMTPYVSKNPRLAYLNYRDLDIGINDPKNP 
               
               
                   
                 NNYTQARIWGEKYFGKNFDRLVKVKTLVDPENFFRNEQSIPPLPR 
               
               
                   
                 HRH* 
               
               
                   
               
               
                 SEQ ID NO: 219 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                 CBDA Synthase, 
                 TTCTTCTTCTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 P538T variant 
                 CGTGAGAACTTCTTGAAATGTTTTTCTCAATATATCCCAAATAAC 
               
               
                 Artificial Sequence 
                 GCTACTAACTTGAAGTTAGTCTATACTCAAAACAACCCATTATAT 
               
               
                 Codon optimized 
                 ATGTCTGTCTTAAACTCTACCATTCACAACTTACGTTTCACTTCT 
               
               
                   
                 GATACTACTCCAAAACCTTTGGTCATCGTCACCCCATCCCACGTT 
               
               
                   
                 TCTCACATCCAAGGTACCATCTTGTGTTCCAAAAAGGTTGGTTTA 
               
               
                   
                 CAAATCCGTACTAGATCCGGTGGTCATGACTCCGAAGGTATGTCT 
               
               
                   
                 TACATTTCCCAAGTCCCTTTCGTCATCGTCGACTTAAGAAATATG 
               
               
                   
                 CGTTCCATCAAGATTGATGTCCATTCCCAAACTGCTTGGGTTGAA 
               
               
                   
                 GCCGGTGCCACTTTAGGTGAAGTCTATTACTGGGTTAACGAGAAG 
               
               
                   
                 AATGAGAACTTATCTTTGGCTGCCGGTTACTGTCCAACTGTTTGT 
               
               
                   
                 GCTGGTGGTCATTTCGGTGGTGGTGGTTACGGTCCATTAATGCGT 
               
               
                   
                 AACTACGGTTTGGCTGCCGATAACATCATTGATGCCCACTTAGTC 
               
               
                   
                 AACGTTCATGGTAAGGTCTTGGACCGTAAGTCTATGGGTGAGGAT 
               
               
                   
                 TTATTCTGGGCTTTGAGAGGTGGTGGTGCTGAATCTTTCGGTATT 
               
               
                   
                 ATCGTCGCTTGGAAGATTAGATTAGTTGCTGTTCCAAAGTCTACT 
               
               
                   
                 ATGTTCTCTGTTAAGAAGATCATGGAAATTCACGAGTTGGTTAAA 
               
               
                   
                 TTAGTTAACAAATG 
               
               
                   
                 GCAAAACATTGCCTACAAGTACGATAAAGATTTGTTATTAATGAC 
               
               
                   
                 TCACTTTATCACTAGAAACATTACTGATAACCAAGGTAAGAATAA 
               
               
                   
                 GACTGCCATTCACACTTACTTCTCTTCTGTTTTCTTGGGTGGTGT 
               
               
                   
                 TGATTCCTTGGTCGATTTGATGAACAAGTCTTTTCCAGAATTAGG 
               
               
                   
                 TATTAAGAAGACCGATTGTCGTCAACTGATAATTTTAATAAGGAG 
               
               
                   
                 ATTTTGTTAGATAGATCTGCTGGTCAAAATGGTGCCTTTAAAATC 
               
               
                   
                 AAATTGGACTACGTTAAGAAGCCTATTCCAGAATCCGTCTTTGTT 
               
               
                   
                 CAAATTTTGGAGAAGTTATACGAAGAAGATATTGGTGCTGGTATG 
               
               
                   
                 TACGCCTTGTATCCATATGGTGGTATTATGGATGAAATTTCTGAA 
               
               
                   
                 TCCGCCATCCCTTTCCCTCATCGTGCTGGTATCTTATACGAGTTG 
               
               
                   
                 TGGTACATCTGTTCTTGGGAAAAGCAAGAAGATAATGAAAAGCAT 
               
               
                   
                 TTGAACTGGATCCGTAACATCTATAACTTCATGACTCCATACGTT 
               
               
                   
                 TCCAAAAACCCTAGATTGGCTTACTTAAATTACAGAGACTTAGAT 
               
               
                   
                 ATTGGTATTAACGACCCTAAGAACCCAAACAATTACACTCAAGCT 
               
               
                   
                 AGAATCTGGGGTGAAAAGTACTTCGGTAAGAATTTCGACAGATTA 
               
               
                   
                 GTTAAGGTCAAGACTTTAGTTGACCCAAATAACTTCTTCAGAAAC 
               
               
                   
                 GAACAATCTATCCCAactTTGCCTAGACATAGACACTAG 
               
               
                   
               
               
                 SEQ ID NO: 220 
                 MKCSTFSFWFVCKIIFFFFSFNIQTSIANPRENFLKCFSQYIPNN 
               
               
                 CBDA Synthase, 
                 ATNLKLVYTQNNPLYMSVLNSTIHNLRFTSDTTPKPLVIVTPSHV 
               
               
                 P538T variant 
                 SHIQGTILCSKKVGLQIRTRSGGHDSEGMSYISQVPFVIVDLRNM 
               
               
                 Artificial Sequence 
                 RSIKIDVHSQTAWVEAGATLGEVYYWVNEKNENLSLAAGYCPTVC 
               
               
                   
                 AGGHFGGGGYGPLMRNYGLAADNIIDAHLVNVHGKVLDRKSMGED 
               
               
                   
                 LFWALRGGGAESFGIIVAWKIRLVAVPKSTMFSVKKIMEIHELVK 
               
               
                   
                 LVNKVVQNIAYKYDKDLLLMTHFITRNITDNQGKNKTAIHTYFSS 
               
               
                   
                 VFLGGVDSLVDLMNKSFPELGIKKTDCRQLSWIDTIIFYSGWNYD 
               
               
                   
                 TDNFNKEILLDRSAGQNGAFKIKLDYVKKPIPESVFVQILEKLYE 
               
               
                   
                 EDIGAGMYALYPYGGIMDEISESAIPFPHRAGILYELWYICSWEK 
               
               
                   
                 QEDNEKHLNWIRNIYNFMTPYVSKNPRLAYLNYRDLDIGINDPKN 
               
               
                   
                 PNNYTQARIWGEKYFGKNFDRLVKVKTLVDPNNFFRNEQSIPTLP 
               
               
                   
                 RHRH* 
               
               
                   
               
               
                 SEQ ID NO: 221 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                 CBDA Synthase, 
                 TTCTTCTTCTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 R541E variant 
                 CGTGAGAACTTCTTGAAATGTTTTTCTCAATATATCCCAAATAAC 
               
               
                 Artificial Sequence 
                 GCTACTAACTTGAAGTTAGTCTATACTCAAAACAACCCATTATAT 
               
               
                 Codon optimized 
                 ATGTCTGTCTTAAACTCTACCATTCACAACTTACGTTTCACTTCT 
               
               
                   
                 GATACTACTCCAAAACCTTTGGTCATCGTCACCCCATCCCACGTT 
               
               
                   
                 TCTCACATCCAAGGTACCATCTTGTGTTCCAAAAAGGTTGGTTTA 
               
               
                   
                 CAAATCCGTACTAGATCCGGTGGTCATGACTCCGAAGGTATGTCT 
               
               
                   
                 TACATTTCCCAAGTCCCTTTCGTCATCGTCGACTTAAGAAATATG 
               
               
                   
                 CGTTCCATCAAGATTGATGTCCATTCCCAAACTGCTTGGGTTGAA 
               
               
                   
                 GCCGGTGCCACTTTAGGTGAAGTCTATTACTGGGTTAACGAGAAG 
               
               
                   
                 AATGAGAACTTATCTTTGGCTGCCGGTTACTGTCCAACTGTTTGT 
               
               
                   
                 GCTGGTGGTCATTTCGGTGGTGGTGGTTACGGTCCATTAATGCGT 
               
               
                   
                 AACTACGGTTTGGCTGCCGATAACATCATTGATGCCCACTTAGTC 
               
               
                   
                 AACGTTCATGGTAAGGTCTTGGACCGTAAGTCTATGGGTGAGGAT 
               
               
                   
                 TTATTCTGGGCTTTGAGAGGTGGTGGTGCTGAATCTTTCGGTATT 
               
               
                   
                 ATCGTCGCTTGGAAGATTAGATTAGTTGCTGTTCCAAAGTCTACT 
               
               
                   
                 ATGTTCTCTGTTAAGAAGATCATGGAAATTCACGAGTTGGTTAAA 
               
               
                   
                 TTAGTTAACAAATGGCAAAACATTGCCTACAAGTACGATAAAGAT 
               
               
                   
                 TTGTTATTAATGACTCACTTTATCACTAGAAACATTACTGATAAC 
               
               
                   
                 CAAGGTAAGAATAAGACTGCCATTCACACTTACTTCTCTTCTGTT 
               
               
                   
                 TTCTTGGGTGGTGTTGATTCCTTGGTCGATTTGATGAACAAGTCT 
               
               
                   
                 TTTCCAGAATTAGGTATTAAGAAGACCGATTGTCGTCAACTGATA 
               
               
                   
                 ATTTTAATAAGGAGATTTTGTTAGATAGATCTGCTGGTCAAAATG 
               
               
                   
                 GTGCCTTTAAAATCAAATTGGACTACGTTAAGAAGCCTATTCCAG 
               
               
                   
                 AATCCGTCTTTGTTCAAATTTTGGAGAAGTTATACGAAGAAGATA 
               
               
                   
                 TTGGTGCTGGTATGTACGCCTTGTATCCATATGGTGGTATTATGG 
               
               
                   
                 ATGAAATTTCTGAATCCGCCATCCCTTTCCCTCATCGTGCTGGTA 
               
               
                   
                 TCTTATACGAGTTGTGGTACATCTGTTCTTGGGAAAAGCAAGAAG 
               
               
                   
                 ATAATGAAAAGCATTTGAACTGGATCCGTAACATCTATAACTTCA 
               
               
                   
                 TGACTCCATACGTTTCCAAAAACCCTAGATTGGCTTACTTAAATT 
               
               
                   
                 ACAGAGACTTAGATATTGGTATTAACGACCCTAAGAACCCAAACA 
               
               
                   
                 ATTACACTCAAGCTAGAATCTGGGGTGAAAAGTACTTCGGTAAGA 
               
               
                   
                 ATTTCGACAGATTAGTTAAGGTCAAGACTTTAGTTGACCCAAATA 
               
               
                   
                 ACTTCTTCAGAAACGAACAATCTATCCCACCATTGCCTgaaCATA 
               
               
                   
                 GACACTAG 
               
               
                   
               
               
                 SEQ ID NO: 222 
                 MKCSTFSFWFVCKIIFFFFSFNIQTSIANPRENFLKCFSQYIPNN 
               
               
                 CBDA Synthase, 
                 ATNLKLVYTQNNPLYMSVLNSTIHNLRFTSDTTPKPLVIVTPSHV 
               
               
                 R541E variant 
                 SHIQGTILCSKKVGLQIRTRSGGHDSEGMSYISQVPFVIVDLRNM 
               
               
                 Artificial Sequence 
                 RSIKIDVHSQTAWVEAGATLGEVYYWVNEKNENLSLAAGYCPTVC 
               
               
                   
                 AGGHFGGGGYGPLMRNYGLAADNIIDAHLVNVHGKVLDRKSMGED 
               
               
                   
                 LFWALRGGGAESFGIIVAWKIRLVAVPKSTMFSVKKIMEIHELVK 
               
               
                   
                 LVNKWQNIAYKYDKDLLLMTHFITRNITDNQGKNKTAIHTYFSSV 
               
               
                   
                 FLGGVDSLVDLMNKSFPELGIKKTDCRQLSWIDTIIFYSGVVNYD 
               
               
                   
                 TDNFNKEILLDRSAGQNGAFKIKLDYVKKPIPESVFVQILEKLYE 
               
               
                   
                 EDIGAGMYALYPYGGIMDEISESAIPFPHRAGILYELWYICSWEK 
               
               
                   
                 QEDNEKHLNWIRNIYNFMTPYVSKNPRLAYLNYRDLDIGINDPKN 
               
               
                   
                 PNNYTQARIWGEKYFGKNFDRLVKVKTLVDPNNFFRNEQSIPPLP 
               
               
                   
                 EHRH* 
               
               
                   
               
               
                 SEQ ID NO: 223 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                 CBDA Synthase, 
                 TTCTTCTTCTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 R541V variant 
                 CGTGAGAACTTCTTGAAATGTTTTTCTCAATATATCCCAAATAAC 
               
               
                 Artificial Sequence 
                 GCTACTAACTTGAAGTTAGTCTATACTCAAAACAACCCATTATAT 
               
               
                 Codon optimized 
                 ATGTCTGTCTTAAACTCTACCATTCACAACTTACGTTTCACTTCT 
               
               
                   
                 GATACTACTCCAAAACCTTTGGTCATCGTCACCCCATCCCACGTT 
               
               
                   
                 TCTCACATCCAAGGTACCATCTTGTGTTCCAAAAAGGTTGGTTTA 
               
               
                   
                 CAAATCCGTACTAGATCCGGTGGTCATGACTCCGAAGGTATGTCT 
               
               
                   
                 TACATTTCCCAAGTCCCTTTCGTCATCGTCGACTTAAGAAATATG 
               
               
                   
                 CGTTCCATCAAGATTGATGTCCATTCCCAAACTGCTTGGGTTGAA 
               
               
                   
                 GCCGGTGCCACTTTAGGTGAAGTCTATTACTGGGTTAACGAGAAG 
               
               
                   
                 AATGAGAACTTATCTTTGGCTGCCGGTTACTGTCCAACTGTTTGT 
               
               
                   
                 GCTGGTGGTCATTTCGGTGGTGGTGGTTACGGTCCATTAATGCGT 
               
               
                   
                 AACTACGGTTTGGCTGCCGATAACATCATTGATGCCCACTTAGTC 
               
               
                   
                 AACGTTCATGGTAAGGTCTTGGACCGTAAGTCTATGGGTGAGGAT 
               
               
                   
                 TTATTCTGGGCTTTGAGAGGTGGTGGTGCTGAATCTTTCGGTATT 
               
               
                   
                 ATCGTCGCTTGGAAGATTAGATTAGTTGCTGTTCCAAAGTCTACT 
               
               
                   
                 ATGTTCTCTGTTAAGAAGATCATGGAAATTCACGAGTTGGTTAAA 
               
               
                   
                 TTAGTTAACAAATGGCAAAACATTGCCTACAAGTACGATAAAGAT 
               
               
                   
                 TTGTTATTAATGACTCACTTTATCACTAGAAACATTACTGATAAC 
               
               
                   
                 CAAGGTAAGAATAAGACTGCCATTCACACTTACTTCTCTTCTGTT 
               
               
                   
                 TTCTTGGGTGGTGTTGATTCCTTGGTCGATTTGATGAACAAGTCT 
               
               
                   
                 TTTCCAGAATTAGGTATTAAGAAGACCGATTGTCGTCAACTGATA 
               
               
                   
                 ATTTTAATAAGGAGATTTTGTTAGATAGATCTGCTGGTCAAAATG 
               
               
                   
                 GTGCCTTTAAAATCAAATTGGACTACGTTAAGAAGCCTATTCCAG 
               
               
                   
                 AATCCGTCTTTGTTCAAATTTTGGAGAAGTTATACGAAGAAGATA 
               
               
                   
                 TTGGTGCTGGTATGTACGCCTTGTATCCATATGGTGGTATTATGG 
               
               
                   
                 ATGAAATTTCTGAATCCGCCATCCCTTTCCCTCATCGTGCTGGTA 
               
               
                   
                 TCTTATACGAGTTGTGGTACATCTGTTCTTGGGAAAAGCAAGAAG 
               
               
                   
                 ATAATGAAAAGCATTTGAACTGGATCCGTAACATCTATAACTTCA 
               
               
                   
                 TGACTCCATACGTTTCCAAAAACCCTAGATTGGCTTACTTAAATT 
               
               
                   
                 ACAGAGACTTAGATATTGGTATTAACGACCCTAAGAACCCAAACA 
               
               
                   
                 ATTACACTCAAGCTAGAATCTGGGGTGAAAAGTACTTCGGTAAGA 
               
               
                   
                 ATTTCGACAGATTAGTTAAGGTCAAGACTTTAGTTGACCCAAATA 
               
               
                   
                 ACTTCTTCAGAAACGAACAATCTATCCCACCATTGCCTgttCATA 
               
               
                   
                 GACACTAG 
               
               
                   
               
               
                 SEQ ID NO: 224 
                 MKCSTFSFWFVCKIIFFFFSFNIQTSIANPRENFLKCFSQYIPNN 
               
               
                 CBDA Synthase, 
                 ATNLKLVYTQNNPLYMSVLNSTIHNLRFTSDTTPKPLVIVTPSHV 
               
               
                 R541V variant 
                 SHIQGTILCSKKVGLQIRTRSGGHDSEGMSYISQVPFVIVDLRNM 
               
               
                 Artificial Sequence 
                 RSIKIDVHSQTAWVEAGATLGEVYYWVNEKNENLSLAAGYCPTVC 
               
               
                   
                 AGGHFGGGGYGPLMRNYGLAADNIIDAHLVNVHGKVLDRKSMGED 
               
               
                   
                 LFWALRGGGAESFGIIVAWKIRLVAVPKSTMFSVKKIMEIHELVK 
               
               
                   
                 LVNKVVQNIAYKYDKDLLLMTHFITRNITDNQGKNKTAIHTYFSS 
               
               
                   
                 VFLGGVDSLVDLMNKSFPELGIKKTDCRQLSWIDTIIFYSGWNYD 
               
               
                   
                 TDNFNKEILLDRSAGQNGAFKIKLDYVKKPIPESVFVQILEKLYE 
               
               
                   
                 EDIGAGMYALYPYGGIMDEISESAIPFPHRAGILYELWYICSWEK 
               
               
                   
                 QEDNEKHLNWIRNIYNFMTPYVSKNPRLAYLNYRDLDIGINDPKN 
               
               
                   
                 PNNYTQARIWGEKYFGKNFDRLVKVKTLVDPNNFFRNEQSIPPLP 
               
               
                   
                 VHRH* 
               
               
                   
               
               
                 SEQ ID NO: 225 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                 CBDA Synthase 
                 TTCTTCTTCTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 H542V variant 
                 CGTGAGAACTTCTTGAAATGTTTTTCTCAATATATCCCAAATAAC 
               
               
                 Artificial Sequence 
                 GCTACTAACTTGAAGTTAGTCTATACTCAAAACAACCCATTATAT 
               
               
                 Codon optimized 
                 ATGTCTGTCTTAAACTCTACCATTCACAACTTACGTTTCACTTCT 
               
               
                   
                 GATACTACTCCAAAACCTTTGGTCATCGTCACCCCATCCCACGTT 
               
               
                   
                 TCTCACATCCAAGGTACCATCTTGTGTTCCAAAAAGGTTGGTTTA 
               
               
                   
                 CAAATCCGTACTAGATCCGGTGGTCATGACTCCGAAGGTATGTCT 
               
               
                   
                 TACATTTCCCAAGTCCCTTTCGTCATCGTCGACTTAAGAAATATG 
               
               
                   
                 CGTTCCATCAAGATTGATGTCCATTCCCAAACTGCTTGGGTTGAA 
               
               
                   
                 GCCGGTGCCACTTTAGGTGAAGTCTATTACTGGGTTAACGAGAAG 
               
               
                   
                 AATGAGAACTTATCTTTGGCTGCCGGTTACTGTCCAACTGTTTGT 
               
               
                   
                 GCTGGTGGTCATTTCGGTGGTGGTGGTTACGGTCCATTAATGCGT 
               
               
                   
                 AACTACGGTTTGGCTGCCGATAACATCATTGATGCCCACTTAGTC 
               
               
                   
                 AACGTTCATGGTAAGGTCTTGGACCGTAAGTCTATGGGTGAGGAT 
               
               
                   
                 TTATTCTGGGCTTTGAGAGGTGGTGGTGCTGAATCTTTCGGTATT 
               
               
                   
                 ATCGTCGCTTGGAAGATTAGATTAGTTGCTGTTCCAAAGTCTACT 
               
               
                   
                 ATGTTCTCTGTTAAGAAGATCATGGAAATTCACGAGTTGGTTAAA 
               
               
                   
                 TTAGTTAACAAATGGCAAAACATTGCCTACAAGTACGATAAAGAT 
               
               
                   
                 TTGTTATTAATGACTCACTTTATCACTAGAAACATTACTGATAAC 
               
               
                   
                 CAAGGTAAGAATAAGACTGCCATTCACACTTACTTCTCTTCTGTT 
               
               
                   
                 TTCTTGGGTGGTGTTGATTCCTTGGTCGATTTGATGAACAAGTCT 
               
               
                   
                 TTTCCAGAATTAGGTATTAAGAAGACCGATTGTCGTCAATTATCT 
               
               
                   
                 TGGATTGATACCATTATTTTTTACTCCGGTGTTGTCAACTACGAC 
               
               
                   
                 ACTGATAATTTTAATAAGGAGATTTTGTTAGATAGATCTGCTGGT 
               
               
                   
                 CAAAATGGTGCCTTTAAAATCAAATTGGACTACGTTAAGAAGCCT 
               
               
                   
                 ATTCCAGAATCCGTCTTTGTTCAAATTTTGGAGAAGTTATACGAA 
               
               
                   
                 GAAGATATTGGTGCTGGTATGTACGCCTTGTATCCATATGGTGGT 
               
               
                   
                 ATTATGGATGAAATTTCTGAATCCGCCATCCCTTTCCCTCATCGT 
               
               
                   
                 GCTGGTATCTTATACGAGTTGTGGTACATCTGTTCTTGGGAAAAG 
               
               
                   
                 CAAGAAGATAATGAAAAGCATTTGAACTGGATCCGTAACATCTAT 
               
               
                   
                 AACTTCATGACTCCATACGTTTCCAAAAACCCTAGATTGGCTTAC 
               
               
                   
                 TTAAATTACAGAGACTTAGATATTGGTATTAACGACCCTAAGAAC 
               
               
                   
                 CCAAACAATTACACTCAAGCTAGAATCTGGGGTGAAAAGTACTTC 
               
               
                   
                 GGTAAGAATTTCGACAGATTAGTTAAGGTCAAGACTTTAGTTGAC 
               
               
                   
                 CCAAATAACTTCTTCAGAAACGAACAATCTATCCCACCATTGCCT 
               
               
                   
                 AGAgttAGACACTAG 
               
               
                   
               
               
                 SEQ ID NO: 226 
                 MKCSTFSFWFVCKIIFFFFSFNIQTSIANPRENFLKCFSQYIPNN 
               
               
                 CBDA Synthase, 
                 ATNLKLVYTQNNPLYMSVLNSTIHNLRFTSDTTPKPLVIVTPSHV 
               
               
                 H542V variant 
                 SHIQGTILCSKKVGLQIRTRSGGHDSEGMSYISQVPFVIVDLRNM 
               
               
                 Artificial Sequence 
                 RSIKIDVHSQTAWVEAGATLGEVYYWVNEKNENLSLAAGYCPTVC 
               
               
                   
                 AGGHFGGGGYGPLMRNYGLAADNIIDAHLVNVHGKVLDRKSMGED 
               
               
                   
                 LFWALRGGGAESFGIIVAWKIRLVAVPKSTMFSVKKIMEIHELVK 
               
               
                   
                 LVNKVVQNIAYKYDKDLLLMTHFITRNITDNQGKNKTAIHTYFSS 
               
               
                   
                 VFLGGVDSLVDLMNKSFPELGIKKTDCRQLSWIDTIIFYSGWNYD 
               
               
                   
                 TDNFNKEILLDRSAGQNGAFKIKLDYVKKPIPESVFVQILEKLYE 
               
               
                   
                 EDIGAGMYALYPYGGIMDEISESAIPFPHRAGILYELWYICSWEK 
               
               
                   
                 QEDNEKHLNWIRNIYNFMTPYVSKNPRLAYLNYRDLDIGINDPKN 
               
               
                   
                 PNNYTQARIWGEKYFGKNFDRLVKVKTLVDPNNFFRNEQSIPPLP 
               
               
                   
                 RVRH* 
               
               
                   
               
               
                 SEQ ID NO: 227 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                 CBDA Synthase, 
                 TTCTTCTTCTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 R543A variant 
                 CGTGAGAACTTCTTGAAATGTTTTTCTCAATATATCCCAAATAAC 
               
               
                 Artificial Sequence 
                 GCTACTAACTTGAAGTTAGTCTATACTCAAAACAACCCATTATAT 
               
               
                 Codon optimized 
                 ATGTCTGTCTTAAACTCTACCATTCACAACTTACGTTTCACTTCT 
               
               
                   
                 GATACTACTCCAAAACCTTTGGTCATCGTCACCCCATCCCACGTT 
               
               
                   
                 TCTCACATCCAAGGTACCATCTTGTGTTCCAAAAAGGTTGGTTTA 
               
               
                   
                 CAAATCCGTACTAGATCCGGTGGTCATGACTCCGAAGGTATGTCT 
               
               
                   
                 TACATTTCCCAAGTCCCTTTCGTCATCGTCGACTTAAGAAATATG 
               
               
                   
                 CGTTCCATCAAGATTGATGTCCATTCCCAAACTGCTTGGGTTGAA 
               
               
                   
                 GCCGGTGCCACTTTAGGTGAAGTCTATTACTGGGTTAACGAGAAG 
               
               
                   
                 AATGAGAACTTATCTTTGGCTGCCGGTTACTGTCCAACTGTTTGT 
               
               
                   
                 GCTGGTGGTCATTTCGGTGGTGGTGGTTACGGTCCATTAATGCGT 
               
               
                   
                 AACTACGGTTTGGCTGCCGATAACATCATTGATGCCCACTTAGTC 
               
               
                   
                 AACGTTCATGGTAAGGTCTTGGACCGTAAGTCTATGGGTGAGGAT 
               
               
                   
                 TTATTCTGGGCTTTGAGAGGTGGTGGTGCTGAATCTTTCGGTATT 
               
               
                   
                 ATCGTCGCTTGGAAGATTAGATTAGTTGCTGTTCCAAAGTCTACT 
               
               
                   
                 ATGTTCTCTGTTAAGAAGATCATGGAAATTCACGAGTTGGTTAAA 
               
               
                   
                 TTAGTTAACAAATGGCAAAACATTGCCTACAAGTACGATAAAGAT 
               
               
                   
                 TTGTTATTAATGACTCACTTTATCACTAGAAACATTACTGATAAC 
               
               
                   
                 CAAGGTAAGAATAAGACTGCCATTCACACTTACTTCTCTTCTGTT 
               
               
                   
                 TTCTTGGGTGGTGTTGATTCCTTGGTCGATTTGATGAACAAGTCT 
               
               
                   
                 TTTCCAGAATTAGGTATTAAGAAGACCGATTGTCGTCAATTATCT 
               
               
                   
                 TGGATTGATACCATTATTTTTTACTCCGGTGTTGTCAACTACGAC 
               
               
                   
                 ACTGATAATTTTAATAAGGAGATTTTGTTAGATAGATCTGCTGGT 
               
               
                   
                 CAAAATGGTGCCTTTAAAATCAAATTGGACTACGTTAAGAAGCCT 
               
               
                   
                 ATTCCAGAATCCGTCTTTGTTCAAATTTTGGAGAAGTTATACGAA 
               
               
                   
                 GAAGATATTGGTGCTGGTATGTACGCCTTGTATCCATATGGTGGT 
               
               
                   
                 ATTATGGATGAAATTTCTGAATCCGCCATCCCTTTCCCTCATCGT 
               
               
                   
                 GCTGGTATCTTATACGAGTTGTGGTACATCTGTTCTTGGGAAAAG 
               
               
                   
                 CAAGAAGATAATGAAAAGCATTTGAACTGGATCCGTAACATCTAT 
               
               
                   
                 AACTTCATGACTCCATACGTTTCCAAAAACCCTAGATTGGCTTAC 
               
               
                   
                 TTAAATTACAGAGACTTAGATATTGGTATTAACGACCCTAAGAAC 
               
               
                   
                 CCAAACAATTACACTCAAGCTAGAATCTGGGGTGAAAAGTACTTC 
               
               
                   
                 GGTAAGAATTTCGACAGATTAGTTAAGGTCAAGACTTTAGTTGAC 
               
               
                   
                 CCAAATAACTTCTTCAGAAACGAACAATCTATCCCACCATTGCCT 
               
               
                   
                 AGACATgctCACTAG 
               
               
                   
               
               
                 SEQ ID NO: 228 
                 MKCSTFSFWFVCKIIFFFFSFNIQTSIANPRENFLKCFSQYIPNN 
               
               
                 CBDA Synthase, 
                 ATNLKLVYTQNNPLYMSVLNSTIHNLRFTSDTTPKPLVIVTPSHV 
               
               
                 R543A variant 
                 SHIQGTILCSKKVGLQIRTRSGGHDSEGMSYISQVPFVIVDLRNM 
               
               
                 Artificial Sequence 
                 RSIKIDVHSQTAWVEAGATLGEVYYVVVNEKNENLSLAAGYCPTV 
               
               
                   
                 CAGGHFGGGGYGPLMRNYGLAADNIIDAHLVNVHGKVLDRKSMGE 
               
               
                   
                 DLFWALRGGGAESFGIIVAWKIRLVAVPKSTMFSVKKIMEIHELV 
               
               
                   
                 KLVNKWQNIAYKYDKDLLLMTHFITRNITDNQGKNKTAIHTYFSS 
               
               
                   
                 VFLGGVDSLVDLMNKSFPELGIKKTDCRQLSWIDTIIFYSGWNYD 
               
               
                   
                 TDNFNKEILLDRSAGQNGAFKIKLDYVKKPIPESVFVQILEKLYE 
               
               
                   
                 EDIGAGMYALYPYGGIMDEISESAIPFPHRAGILYELWYICSWEK 
               
               
                   
                 QEDNEKHLNWIRNIYNFMTPYVSKNPRLAYLNYRDLDIGINDPKN 
               
               
                   
                 PNNYTQARIWGEKYFGKNFDRLVKVKTLVDPNNFFRNEQSIPPLP 
               
               
                   
                 RHAH* 
               
               
                   
               
               
                 SEQ ID NO: 229 
                 ATGAAATGCTCCACTTTCTC&#39;TTTCTGGTTCGTTTGTAAGATTAT 
               
               
                 CBDA Synthase, 
                 CTTCTTCTTCTTTTCTTTCAACATCCAAACTTCCATTGCCAACCC 
               
               
                 R543E variant 
                 TCGTGAGAACTTCTTGAAATGTTTTTCTCAATATATCCCAAATAA 
               
               
                 Artificial Sequence 
                 CGCTACTAACTTGAAGTTAGTCTATACTCAAAACAACCCATTATA 
               
               
                 Codon optimized 
                 TATGTCTGTCTTAAACTCTACCATTCACAACTTACGTTTCACTTC 
               
               
                   
                 TGATACTACTCCAAAACCTTTGGTCATCGTCACCCCATCCCACGT 
               
               
                   
                 TTCTCACATCCAAGGTACCATCTTGTGTTCCAAAAAGGTTGGTTT 
               
               
                   
                 ACAAATCCGTACTAGATCCGGTGGTCATGACTCCGAAGGTATGTC 
               
               
                   
                 TTACATTTCCCAAGTCCCTTTCGTCATCGTCGACTTAAGAAATAT 
               
               
                   
                 GCGTTCCATCAAGATTGATGTCCATTCCCAAACTGCTTGGGTTGA 
               
               
                   
                 AGCCGGTGCCACTTTAGGTGAAGTCTATTACTGGGTTAACGAGAA 
               
               
                   
                 GAATGAGAACTTATCTTTGGCTGCCGGTTACTGTCCAACTGTTTG 
               
               
                   
                 TGCTGGTGGTCATTTCGGTGGTGGTGGTTACGGTCCATTAATGCG 
               
               
                   
                 TAACTACGGTTTGGCTGCCGATAACATCATTGATGCCCACTTAGT 
               
               
                   
                 CAACGTTCATGGTAAGGTCTTGGACCGTAAGTCTATGGGTGAGGA 
               
               
                   
                 TTTATTCTGGGCTTTGAGAGGTGGTGGTGCTGAATCTTTCGGTAT 
               
               
                   
                 TATCGTCGCTTGGAAGATTAGATTAGTTGCTGTTCCAAAGTCTAC 
               
               
                   
                 TATGTTCTCTGTTAAGAAGATCATGGAAATTCACGAGTTGGTTAA 
               
               
                   
                 ATTAGTTAACAAATGGCAAAACATTGCCTACAAGTACGATAAAGA 
               
               
                   
                 TTTGTTATTAATGACTCACTTTATCACTAGAAACATTACTGATAA 
               
               
                   
                 CCAAGGTAAGAATAAGACTGCCATTCACACTTACTTCTCTTCTGT 
               
               
                   
                 TTTCTTGGGTGGTGTTGATTCCTTGGTCGATTTGATGAACAAGTC 
               
               
                   
                 TTTTCCAGAATTAGGTATTAAGAAGACCGATTGTCGTCAATTATC 
               
               
                   
                 TTGGATTGATACCATTATTTTTTACTCCGGTGTTGTCAACTACGA 
               
               
                   
                 CACTGATAATTTTAATAAGGAGATTTTGTTAGATAGATCTGCTGG 
               
               
                   
                 TCAAAATGGTGCCTTTAAAATCAAATTGGACTACGTTAAGAAGCC 
               
               
                   
                 TATTCCAGAATCCGTCTTTGTTCAAATTTTGGAGAAGTTATACGA 
               
               
                   
                 AGAAGATATTGGTGCTGGTATGTACGCCTTGTATCCATATGGTGG 
               
               
                   
                 TATTATGGATGAAATTTCTGAATCCGCCATCCCTTTCCCTCATCG 
               
               
                   
                 TGCTGGTATCTTATACGAGTTGTGGTACATCTGTTCTTGGGAAAA 
               
               
                   
                 GCAAGAAGATAATGAAAAGCATTTGAACTGGATCCGTAACATCTA 
               
               
                   
                 TAACTTCATGACTCCATACGTTTCCAAAAACCCTAGATTGGCTTA 
               
               
                   
                 CTTAAATTACAGAGACTTAGATATTGGTATTAACGACCCTAAGAA 
               
               
                   
                 CCCAAACAATTACACTCAAGCTAGAATCTGGGGTGAAAAGTACTT 
               
               
                   
                 CGGTAAGAATTTCGACAGATTAGTTAAGGTCAAGACTTTAGTTGA 
               
               
                   
                 CCCAAATAACTTCTTCAGAAACGAACAATCTATCCCACCATTGCC 
               
               
                   
                 TAGACATgaaCACTAG 
               
               
                   
               
               
                 SEQ ID NO: 230 
                 MKCSTFSFWFVCKIIFFFFSFNIQTSIANPRENFLKCFSQYIPNN 
               
               
                 CBDA Synthase, 
                 ATNLKLVYTQNNPLYMSVLNSTIHNLRFTSDTTPKPLVIVTPSHV 
               
               
                 R543E variant 
                 SHIQGTILCSKKVGLQIRTRSGGHDSEGMSYISQVPFVIVDLRNM 
               
               
                 Artificial Sequence 
                 RSIKIDVHSQTAWVEAGATLGEVYYWVNEKNENLSLAAGYCPTVC 
               
               
                   
                 AGGHFGGGGYGPLMRNYGLAADNIIDAHLVNVHGKVLDRKSMGED 
               
               
                   
                 LFWALRGGGAESFGIIVAWKIRLVAVPKSTMFSVKKIMEIHELVK 
               
               
                   
                 LVNKWQNIAYKYDKDLLLMTHFITRNITDNQGKNKTAIHTYFSSV 
               
               
                   
                 FLGGVDSLVDLMNKSFPELGIKKTDCRQLSWIDTIIFYSGWNYDT 
               
               
                   
                 DNFNKEILLDRSAGQNGAFKIKLDYVKKPIPESVFVQILEKLYEE 
               
               
                   
                 DIGAGMYALYPYGGIMDEISESAIPFPHRAGILYELWYICSWEKQ 
               
               
                   
                 EDNEKHLNWIRNIYNFMTPYVSKNPRLAYLNYRDLDIGINDPKNP 
               
               
                   
                 NNYTQARIWGEKYFGKNFDRLVKVKTLVDPNNFFRNEQSIPPLPR 
               
               
                   
                 HEH* 
               
               
                   
               
               
                 SEQ ID NO: 231 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                 CBDA Synthase, 
                 TTCTTCTTCTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 H544E variant 
                 CGTGAGAACTTCTTGAAATGTTTTTCTCAATATATCCCAAATAAC 
               
               
                 Artificial Sequence 
                 GCTACTAACTTGAAGTTAGTCTATACTCAAAACAACCCATTATAT 
               
               
                 Codon optimized 
                 ATGTCTGTCTTAAACTCTACCATTCACAACTTACGTTTCACTTCT 
               
               
                   
                 GATACTACTCCAAAACCTTTGGTCATCGTCACCCCATCCCACGTT 
               
               
                   
                 TCTCACATCCAAGGTACCATCTTGTGTTCCAAAAAGGTTGGTTTA 
               
               
                   
                 CAAATCCGTACTAGATCCGGTGGTCATGACTCCGAAGGTATGTCT 
               
               
                   
                 TACATTTCCCAAGTCCCTTTCGTCATCGTCGACTTAAGAAATATG 
               
               
                   
                 CGTTCCATCAAGATTGATGTCCATTCCCAAACTGCTTGGGTTGAA 
               
               
                   
                 GCCGGTGCCACTTTAGGTGAAGTCTATTACTGGGTTAACGAGAAG 
               
               
                   
                 AATGAGAACTTATCTTTGGCTGCCGGTTACTGTCCAACTGTTTGT 
               
               
                   
                 GCTGGTGGTCATTTCGGTGGTGGTGGTTACGGTCCATTAATGCGT 
               
               
                   
                 AACTACGGTTTGGCTGCCGATAACATCATTGATGCCCACTTAGTC 
               
               
                   
                 AACGTTCATGGTAAGGTCTTGGACCGTAAGTCTATGGGTGAGGAT 
               
               
                   
                 TTATTCTGGGCTTTGAGAGGTGGTGGTGCTGAATCTTTCGGTATT 
               
               
                   
                 ATCGTCGCTTGGAAGATTAGATTAGTTGCTGTTCCAAAGTCTACT 
               
               
                   
                 ATGTTCTCTGTTAAGAAGATCATGGAAATTCACGAGTTGGTTAAA 
               
               
                   
                 TTAGTTAACAAATGGCAAAACATTGCCTACAAGTACGATAAAGAT 
               
               
                   
                 TTGTTATTAATGACTCACTTTATCACTAGAAACATTACTGATAAC 
               
               
                   
                 CAAGGTAAGAATAAGACTGCCATTCACACTTACTTCTCTTCTGTT 
               
               
                   
                 TTCTTGGGTGGTGTTGATTCCTTGGTCGATTTGATGAACAAGTCT 
               
               
                   
                 TTTCCAGAATTAGGTATTAAGAAGACCGATTGTCGTCAACTGATA 
               
               
                   
                 ATTTTAATAAGGAGATTTTGTTAGATAGATCTGCTGGTCAAAATG 
               
               
                   
                 GTGCCTTTAAAATCAAATTGGACTACGTTAAGAAGCCTATTCCAG 
               
               
                   
                 AATCCGTCTTTGTTCAAATTTTGGAGAAGTTATACGAAGAAGATA 
               
               
                   
                 TTGGTGCTGGTATGTACGCCTTGTATCCATATGGTGGTATTATGG 
               
               
                   
                 ATGAAATTTCTGAATCCGCCATCCCTTTCCCTCATCGTGCTGGTA 
               
               
                   
                 TCTTATACGAGTTGTGGTACATCTGTTCTTGGGAAAAGCAAGAAG 
               
               
                   
                 ATAATGAAAAGCATTTGAACTGGATCCGTAACATCTATAACTTCA 
               
               
                   
                 TGACTCCATACGTTTCCAAAAACCCTAGATTGGCTTACTTAAATT 
               
               
                   
                 ACAGAGACTTAGATATTGGTATTAACGACCCTAAGAACCCAAACA 
               
               
                   
                 ATTACACTCAAGCTAGAATCTGGGGTGAAAAGTACTTCGGTAAGA 
               
               
                   
                 ATTTCGACAGATTAGTTAAGGTCAAGACTTTAGTTGACCCAAATA 
               
               
                   
                 ACTTCTTCAGAAACGAACAATCTATCCCACCATTGCCTAGACATA 
               
               
                   
                 GAgaaTAG 
               
               
                   
               
               
                 SEQ ID NO: 232 
                 MKCSTFSFWFVCKIIFFFFSFNIQTSIANPRENFLKCFSQYIPNN 
               
               
                 CBDA Synthase, 
                 ATNLKLVYTQNNPLYMSVLNSTIHNLRFTSDTTPKPLVIVTPSHV 
               
               
                 H544E variant 
                 SHIQGTILCSKKVGLQIRTRSGGHDSEGMSYISQVPFVIVDLRNM 
               
               
                 Artificial Sequence 
                 RSIKIDVHSQTAWVEAGATLGEVYYWVNEKNENLSLAAGYCPTVC 
               
               
                   
                 AGGHFGGGGYGPLMRNYGLAADNIIDAHLVNVHGKVLDRKSMGED 
               
               
                   
                 LFWALRGGGAESFGIIVAWKIRLVAVPKSTMFSVKKIMEIHELVK 
               
               
                   
                 LVNKWQNIAYKYDKDLLLMTHFITRNITDNQGKNKTAIHTYFSSV 
               
               
                   
                 FLGGVDSLVDLMNKSFPELGIKKTDCRQLSWIDTIIFYSGWNYDT 
               
               
                   
                 DNFNKEILLDRSAGQNGAFKIKLDYVKKPIPESVFVQILEKLYEE 
               
               
                   
                 DIGAGMYALYPYGGIMDEISESAIPFPHRAGILYELWYICSWEKQ 
               
               
                   
                 EDNEKHLNWIRNIYNFMTPYVSKNPRLAYLNYRDLDIGINDPKNP 
               
               
                   
                 NNYTQARIWGEKYFGKNFDRLVKVKTLVDPNNFFRNEQSIPPLPR 
               
               
                   
                 HRE* 
               
               
                   
               
               
                 SEQ ID NO: 233 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                 CBDA Synthase, 
                 TTCTTCTTCTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 H544D variant 
                 CGTGAGAACTTCTTGAAATGTTTTTCTCAATATATCCCAAATAAC 
               
               
                 Artificial Sequence 
                 GCTACTAACTTGAAGTTAGTCTATACTCAAAACAACCCATTATAT 
               
               
                 Codon optimized 
                 ATGTCTGTCTTAAACTCTACCATTCACAACTTACGTTTCACTTCT 
               
               
                   
                 GATACTACTCCAAAACCTTTGGTCATCGTCACCCCATCCCACGTT 
               
               
                   
                 TCTCACATCCAAGGTACCATCTTGTGTTCCAAAAAGGTTGGTTTA 
               
               
                   
                 CAAATCCGTACTAGATCCGGTGGTCATGACTCCGAAGGTATGTCT 
               
               
                   
                 TACATTTCCCAAGTCCCTTTCGTCATCGTCGACTTAAGAAATATG 
               
               
                   
                 CGTTCCATCAAGATTGATGTCCATTCCCAAACTGCTTGGGTTGAA 
               
               
                   
                 GCCGGTGCCACTTTAGGTGAAGTCTATTACTGGGTTAACGAGAAG 
               
               
                   
                 AATGAGAACTTATCTTTGGCTGCCGGTTACTGTCCAACTGTTTGT 
               
               
                   
                 GCTGGTGGTCATTTCGGTGGTGGTGGTTACGGTCCATTAATGCGT 
               
               
                   
                 AACTACGGTTTGGCTGCCGATAACATCATTGATGCCCACTTAGTC 
               
               
                   
                 AACGTTCATGGTAAGGTCTTGGACCGTAAGTCTATGGGTGAGGAT 
               
               
                   
                 TTATTCTGGGCTTTGAGAGGTGGTGGTGCTGAATCTTTCGGTATT 
               
               
                   
                 ATCGTCGCTTGGAAGATTAGATTAGTTGCTGTTCCAAAGTCTACT 
               
               
                   
                 ATGTTCTCTGTTAAGAAGATCATGGAAATTCACGAGTTGGTTAAA 
               
               
                   
                 TTAGTTAACAAATGGCAAAACATTGCCTACAAGTACGATAAAGAT 
               
               
                   
                 TTGTTATTAATGACTCACTTTATCACTAGAAACATTACTGATAAC 
               
               
                   
                 CAAGGTAAGAATAAGACTGCCATTCACACTTACTTCTCTTCTGTT 
               
               
                   
                 TTCTTGGGTGGTGTTGATTCCTTGGTCGATTTGATGAACAAGTCT 
               
               
                   
                 TTTCCAGAATTAGGTATTAAGAAGACCGATTGTCGTCAACTGATA 
               
               
                   
                 ATTTTAATAAGGAGATTTTGTTAGATAGATCTGCTGGTCAAAATG 
               
               
                   
                 GTGCCTTTAAAATCAAATTGGACTACGTTAAGAAGCCTATTCCAG 
               
               
                   
                 AATCCGTCTTTGTTCAAATTTTGGAGAAGTTATACGAAGAAGATA 
               
               
                   
                 TTGGTGCTGGTATGTACGCCTTGTATCCATATGGTGGTATTATGG 
               
               
                   
                 ATGAAATTTCTGAATCCGCCATCCCTTTCCCTCATCGTGCTGGTA 
               
               
                   
                 TCTTATACGAGTTGTGGTACATCTGTTCTTGGGAAAAGCAAGAAG 
               
               
                   
                 ATAATGAAAAGCATTTGAACTGGATCCGTAACATCTATAACTTCA 
               
               
                   
                 TGACTCCATACGTTTCCAAAAACCCTAGATTGGCTTACTTAAATT 
               
               
                   
                 ACAGAGACTTAGATATTGGTATTAACGACCCTAAGAACCCAAACA 
               
               
                   
                 ATTACACTCAAGCTAGAATCTGGGGTGAAAAGTACTTCGGTAAGA 
               
               
                   
                 ATTTCGACAGATTAGTTAAGGTCAAGACTTTAGTTGACCCAAATA 
               
               
                   
                 ACTTCTTCAGAAACGAACAATCTATCCCACCATTGCCTAGACATA 
               
               
                   
                 GAgatTAG 
               
               
                   
               
               
                 SEQ ID NO: 234 
                 MKCSTFSFWFVCKIIFFFFSFNIQTSIANPRENFLKCFSQYIPNN 
               
               
                 CBDA Synthase, 
                 ATNLKLVYTQNNPLYMSVLNSTIHNLRFTSDTTPKPLVIVTPSHV 
               
               
                 H544D variant 
                 SHIQGTILCSKKVGLQIRTRSGGHDSEGMSYISQVPFVIVDLRNM 
               
               
                 Artificial Sequence 
                 RSIKIDVHSQTAWVEAGATLGEVYYWVNEKNENLSLAAGYCPTVC 
               
               
                   
                 AGGHFGGGGYGPLMRNYGLAADNIIDAHLVNVHGKVLDRKSMGED 
               
               
                   
                 LFWALRGGGAESFGIIVAWKIRLVAVPKSTMFSVKKIMEIHELVK 
               
               
                   
                 LVNKWQNIAYKYDKDLLLMTHFITRNITDNQGKNKTAIHTYFSSV 
               
               
                   
                 FLGGVDSLVDLMNKSFPELGIKKTDCRQLSWIDTIIFYSGVVNYD 
               
               
                   
                 TDNFNKEILLDRSAGQNGAFKIKLDYVKKPIPESVFVQILEKLYE 
               
               
                   
                 EDIGAGMYALYPYGGIMDEISESAIPFPHRAGILYELWYICSWEK 
               
               
                   
                 QEDNEKHLNVVIRNIYNFMTPYVSKNPRLAYLNYRDLDIGINDPK 
               
               
                   
                 NPNNYTQARIWGEKYFGKNFDRLVKVKTLVDPNNFFRNEQSIPPL 
               
               
                   
                 PRHRD* 
               
               
                   
               
               
                 SEQ ID NO: 293 
                 ATGTCTGAGGCGGCAGACGTAGAGAGAGTATACGCTGCTATGGAG 
               
               
                 Artificial aromatic 
                 GAAGCGGCTGGATTATTGGGGGTGGCTTGTGCCAGAGACAAGATA 
               
               
                 prenyltransferase 
                 TATCCGTTACTGTCTACTTTCCAGGACACTCTTGTAGAAGGAGGG 
               
               
                 (NphB-ScCO) 
                 AGTGTGGTGGTGTTTAGTATGGCATCAGGCCGTCATTCAACAGAG 
               
               
                 nucleotide sequence 
                 CTAGATTTCAGTATATCTGTGCCAACAAGTCACGGTGATCCATAC 
               
               
                   
                 GCAACCGTAGTCGAGAAGGGTCTTTTCCCGGCAACAGGGCATCCT 
               
               
                   
                 GTAGATGATTTGCTTGCCGACACACAGAAGCACCTGCCCGTCTCC 
               
               
                   
                 ATGTTCGCAATCGATGGTGAGGTGACCGGAGGATTTAAAAAGACT 
               
               
                   
                 TACGCTTTCTTCCCGACTGACAATATGCCAGGAGTTGCCGAGTTG 
               
               
                   
                 AGTGCAATACCATCCATGCCGCCAGCAGTCGCGGAGAACGCCGAA 
               
               
                   
                 TTGTTCGCCCGTTACGGCTTGGACAAAGTCCAAATGACTAGTATG 
               
               
                   
                 GACTATAAAAAGAGGCAGGTGAATCTATATTTCAGCGAACTTTCT 
               
               
                   
                 GCCCAAACCTTGGAGGCGGAGAGCGTTTTAGCCCTTGTTAGGGAG 
               
               
                   
                 TTAGGGCTACACGTCCCGAATGAGTTGGGTTTGAAATTTTGTAAG 
               
               
                   
                 CGTAGCTTTTCAGTATATCCGACGCTGAACTGGGAAACTGGAAAG 
               
               
                   
                 ATTGACAGGCTATGCTTTGCAGTGATTTCTAATGACCCTACGCTT 
               
               
                   
                 GTACCTTCCTCAGACGAGGGCGACATCGAGAAATTCCACAACTAT 
               
               
                   
                 GCCACAAAAGCTCCGTATGCCTACGTCGGCGAAAAACGTACTCTA 
               
               
                   
                 GTATACGGTTTGACTCTGAGTCCCAAGGAAGAGTATTACAAGCTA 
               
               
                   
                 GGAGCGTACTATCATATCACTGATGTGCAACGTGGCTTGCTGAAA 
               
               
                   
                 GCCTTCGACTCCTTAGAGGAC 
               
               
                   
               
               
                 SEQ ID NO: 294 
                 MSEAADVERVYAAMEEAAGLLGVACARDKIYPLLSTFQDTLVEGG 
               
               
                 Aromatic 
                 SVWFSMASGRHSTELDFSISVPTSHGDPYATVVEKGLFPATGHPV 
               
               
                 prenyltransferase 
                 DDLLADTQKHLPVSMFAIDGEVTGGFKKTYAFFPTDNMPGVAELS 
               
               
                 NphB-ScCO 
                 AIPSMPPAVAENAELFARYGLDKVQMTSMDYKKRQVNLYFSELSA 
               
               
                 ( Streptomyces  sp.) 
                 QTLEAESVLALVRELGLHVPNELGLKFCKRSFSVYPTLNWETGKI 
               
               
                   
                 DRLCFAVISNDPTLVPSSDEGDIEKFHNYATKAPYAYVGEKRTLV 
               
               
                   
                 YGLTLSPKEEYYKLGAYYHITDVQRGLLKAFDSLED 
               
               
                   
               
               
                 SEQ ID NO: 295 
                 ATGCGGTCTACTTCGAAGAAACATGTTAGTATTGACACTGCTCGT 
               
               
                 IREI fragment 
                 TTGTGTGTTTTCATCCATCATTTCATGCTCAATCCCATTGTCGTC 
               
               
                 Artificial Sequence 
                 TCGCACCTCAAGGCGGCAGATAGTGGAAGATGAAGTTGCCTCCAC 
               
               
                   
                 TAAAAAGCTCAATTTCAACTATGGTGTGGATAAAAATATAAACTC 
               
               
                   
                 GCCCATTCCTGCTCCAAGAACCACTGAAGGTTTACCAAATATGAA 
               
               
                   
                 ACTCAGCTCATATCCAACTCCTAACTTATTGAATACTGCTGATAA 
               
               
                   
                 TCGACGTGCTAACAAAAAAGGACGTAGGGCTGCCAATTCTATAAG 
               
               
                   
                 TGTACCCTATTTGGAGAATCGTTCCTTGAACGAACTGAGTTTATC 
               
               
                   
                 AGATATACTAATCGCAGCCGACGTTGAGGGTGGACTTCATGCTGT 
               
               
                   
                 AGATAGAAGAAATGGTCATATCATATGGTCAATCGAACCAGAAAA 
               
               
                   
                 TTTTCAACCTCTGATAGAAATACAAGAACCTTCGAGGTTAGAAAC 
               
               
                   
                 ATATGAAACGTTGATTATAGAACCTTTCGGTGATGGGAACATTTA 
               
               
                   
                 CTACTTTAACGCCCATCAAGGGTTACAAAAACTGCCTTTATCCAT 
               
               
                   
                 ACGACAACTTGTATCAACTTCCCCGCTGCACTTGAAAACAAATAT 
               
               
                   
                 TGTGGTTAATGACTCTGGAAAAATTGTTGAAGATGAAAAGGTCTA 
               
               
                   
                 CACTGGATCGATGAGAACTATAATGTATACTATAAACATGTTGAA 
               
               
                   
                 TGGTGAAATTATATCAGCGTTCGGACCTGGTTCAAAAAACGGGTA 
               
               
                   
                 TTTCGGGAGCCAGAGTGTGGATTGCTCACCTGAGGAGAAGATAAA 
               
               
                   
                 ACTTCAGGAATGTGAAAATATGATTGTAATAGGCAAAACTATTTT 
               
               
                   
                 TGAGCTGGGAATTCACTCTTATGATGGAGCAAGCTACAATGTCAC 
               
               
                   
                 TTACTCTACATGGCAGCAAAATGTTTTAGATGTTCCCCTAGCGCT 
               
               
                   
                 TCAGAATACATTTTCAAAGGACGGCATGTGCATAGCGCCTTTCCG 
               
               
                   
                 TGATAAATCATTGCTAGCAAGCGATTTAGATTTTAGAATTGCTAG 
               
               
                   
                 ATGGGTTTCTCCGACATTCCCCGGAATTATTGTTGGGCTTTTCGA 
               
               
                   
                 TGTGTTTAATGATCTCCGCACCAATGAAAATATACTGGTACCGCA 
               
               
                   
                 TCCCTTTAATCCTGGTGATCATGAAAGTATATCGAGTAACAAAGT 
               
               
                   
                 TTACTTGGATCAGACTTCGAACCTCTCCTGGTTTGCATTATCTAG 
               
               
                   
                 TCAGAATTTTCCATCTTTAGTCGAATCAGCTCCCATATCAAGATA 
               
               
                   
                 CGCTTCCAGTGACCGTTGGAGGGTGTCTTCAATTTTTGAAGATGA 
               
               
                   
                 GACTTTATTCAAGAACGCAATCATGGGTGTTCATCAGATATATAA 
               
               
                   
                 TAATGAATATGATCACCTTTATGAAAACTATGAAAAAACGAATAG 
               
               
                   
                 TTTGGACACTACGCACAAATATCCACCTCTGATGATTGATTCGTC 
               
               
                   
                 CGTTGATACAACCGATTTACATCAGAATAACGAGATGAATTCACT 
               
               
                   
                 AAAGGAATACATGTCACCAGAAGACCTTGAGGCATATAGAAAAAA 
               
               
                   
                 GATACACGAGCAAATATCGAGAGAATTAGATGAAAAGAACCAAAA 
               
               
                   
                 TTCTTTGCTACTGAAGTTTGGAAGTCTAGTATATCGAATTATAGA 
               
               
                   
                 GACTGGAGTATTTCTGTTGTTATTTCTCATTTTTTGTGCAATACT 
               
               
                   
                 ACAAAGATTCAAAATTTTGCCGCCACTATATGTATTATTATCCAA 
               
               
                   
                 AATTGGATTTATGCCTGAAAAGGAAATCCCCATAGTTGAGTCGAA 
               
               
                   
                 ATCGCTAAATTGTCCCTCTTCATCGGAAAATGTAACCAAGCCATT 
               
               
                   
                 CGATATGAAATCAGGGAAGCAAGTTGTTTTTGAAGGTGCTGTGAA 
               
               
                   
                 CGATGGAAGTCTAAAATCTGAAAAAGATAACGATGATGCTGATGA 
               
               
                   
                 AGATGATGAAAAATCACTAGATTTAACCACAGAAAAGAAGAAGAG 
               
               
                   
                 GAAAAGAGGTTCGAGAGGAGGCAAAAAGGGCCGAAAATCACGCAT 
               
               
                   
                 TGCAAATATACCAAACTTTGAGCAATCTTTAAAAAATTTGGTAGT 
               
               
                   
                 ATCCGAAAAAATTTTAGGTTACGGTTCATCAGGAACAGTAGTTTT 
               
               
                   
                 TCAGGGAAGTTTTCAAGGAAGACCTGTTGCGGTAAAGAGAATGTT 
               
               
                   
                 AATTGATTTTTGTGACATAGCTTTAATGGAAATAAAACTTTTGAC 
               
               
                   
                 TGAAAGCGATGATCACCCTAACGTCATACGATACTACTGTTCAGA 
               
               
                   
                 AACAACAGACAGATTTTTGTATATTGCTTTAGAGCTCTGCAATTT 
               
               
                   
                 GAACCTTCAAGATTTGGTGGAGTCTAAGAATGTATCAGATGAAAA 
               
               
                   
                 CCTGAAATTACAGAAAGAGTATAATCCAATTTCGTTATTGAGACA 
               
               
                   
                 AATAGCGTCCGGGGTAGCACATTTACATTCTTTAAAGATTATCCA 
               
               
                   
                 TCGAGATTTAAAGCCTCAAAATATTCTCGTTTCTACTTCGAGTAG 
               
               
                   
                 GTTTACTGCCGATCAGCAAACAGGAGCAGAAAATCTTCGAATTTT 
               
               
                   
                 GATATCAGACTTTGGTCTTTGCAAAAAACTAGACTCTGGTCAGTC 
               
               
                   
                 TTCATTTAGAACAAATTTGAATAACCCTTCTGGCACAAGTGGTTG 
               
               
                   
                 GAGGGCCCCAGAGCTGCTTGAAGAATCAAACAATTTGCAGTGCCA 
               
               
                   
                 AGTCGAAACGGAACACTCTTCTAGTAGGCATACAGTAGTTTCATC 
               
               
                   
                 TGATTCTTTTTATGATCCGTTCACCAAGAGGAGGCTAACAAAGGG 
               
               
                   
                 AAGCATCCATTTGGAGATAAATATTCACGTGAAAGCAATATCATA 
               
               
                   
                 AGAGGAATATTCAGTCTTGATGAAATGAAATGTCTACATGATAGA 
               
               
                   
                 TCCTTAATTGCAGAAGCTACAGATCTGATCTCCCAAATGATTGAT 
               
               
                   
                 CACGATCCGTTAAAAAGACCTACTGCTATGAAAGTTCTAAGGCAT 
               
               
                   
                 CCGTTGTTTTGGCCAAAGTCGAAAAAATTGGAGTTCCTTTTAAAA 
               
               
                   
                 GTTAGTGATAGGCTTGAAATTGAAAACAGAGACCCTCCAAGTGCC 
               
               
                   
                 CTGTTAATGAAATTTGACGCCGGTTCTGACTTTGTAATACCCAGT 
               
               
                   
                 GGAGATTGGACTGTCAAGTTTGATAAAACATTCATGGACAACCTT 
               
               
                   
                 GAAAGGTACAGAAAATACCATTCATCAAAGTTAATGGATCTATTA 
               
               
                   
                 AGAGCACTTAGGAATAAATATCATCATTTTATGGATTTACCTGAA 
               
               
                   
                 GATATAGCAGAACTAATGGGGCCGGTACCCGATGGATTTTACGAT 
               
               
                   
                 TACTTCACCAAGCGTTTTCCAAACCTATTAATAGGTGTTTATATG 
               
               
                   
                 ATTGTCAAGGAAAATTTAAGTGACGATCAAATTTTACGTGAATTT 
               
               
                   
                 TTGTATTCATAA 
               
               
                   
               
               
                 SEQ ID NO: 296 
                 MLVLTLLVCVFSSIISCSIPLSSRTSRRQIVEDEVASTKKLNFNY 
               
               
                 IRE1 fragment 
                 GVDKNINSPIPAPRTTEGLPNMKLSSYPTPNLLNTADNRRANKKG 
               
               
                 Artificial Sequence 
                 RRAANSISVPYLENRSLNELSLSDILIAADVEGGLHAVDRRNGHI 
               
               
                   
                 IWSIEPENFQPLIEIQEPSRLETYETLIIEPFGDGNIYYFNAHQG 
               
               
                   
                 LQKLPLSIRQLVSTSPLHLKTNIWNDSGKIVEDEKVYTGSMRTIM 
               
               
                   
                 YTINMLNGEIISAFGPGSKNGYFGSQSVDCSPEEKIKLQECENMI 
               
               
                   
                 VIGKTIFELGIHSYDGASYNVTYSTWQQNVLDVPLALQNTFSKDG 
               
               
                   
                 MCIAPFRDKSLLASDLDFRIARWVSPTFPGIIVGLFDVFNDLRTN 
               
               
                   
                 ENILVPHPFNPGDHESISSNKVYLDQTSNLSWFALSSQNFPSLVE 
               
               
                   
                 SAPISRYASSDRWRVSSIFEDETLFKNAIMGVHQIYNNEYDHLYE 
               
               
                   
                 NYEKTNSLDTTHKYPPLMIDSSVDTTDLHQNNEMNSLKEYMSP 
               
               
                   
                 EDLEAYRKKIHEQISRELDEKNQNSLLLKFGSLVYRIIETGVFLL 
               
               
                   
                 LFLIFCAILQRFKILPPLYVLLSKIGFMPEKEIPIVESKSLNCPS 
               
               
                   
                 SSENVTKPFDMKSGKQVVFEGAVNDGSLKSEKDNDDADEDDEKSL 
               
               
                   
                 DLTTEKKKRKRGSRGGKKGRKSRIANIPNFEQSLKNLWSEKILGY 
               
               
                   
                 GSSGTWFQGSFQGRPVAVKRMLIDFCDIALMEIKLLTESDDHPNV 
               
               
                   
                 IRYYCSETTDRFLYIALELCNLNLQDLVESKNVSDENLKLQKEYN 
               
               
                   
                 PISLLRQIASGVAHLHSLKIIHRDLKPQNILVSTSSRFTADQQTG 
               
               
                   
                 AENLRILISDFGLCKKLDSGQSSFRTNLNNPSGTSGWRAPELLEE 
               
               
                   
                 SNNLQCQVETEHSSSRHTWSSDSFYDPFTKRRLTRSIDIFSMGCV 
               
               
                   
                 FYYILSKGKHPFGDKYSRESNIIRGIFSLDEMKCLHDRSLIAEAT 
               
               
                   
                 DLISQMIDHDPLKRPTAMKVLRHPLFWPKSKKLEFLLKVSDRLEI 
               
               
                   
                 ENRDPPSALLMKFDAGSDFVIPSGDWTVKFDKTFMDNLERYRKYH 
               
               
                   
                 SSKLMDLLRALRNKYHHFMDLPEDIAELMGPVPDGFYDYFTKRFP 
               
               
                   
                 NLLIGVYMIVKENLSDDQILREFLYS* 
               
               
                   
               
               
                 SEQ ID NO: 297 
                 ATGCAGTTGAGCAAGGCTGCTGAGATGTGTTATGAGATAACAAAC 
               
               
                 FAD1 
                 TCTTACTTACACATAGACCAGAAATCTCAGATAATAGCAAGTACA 
               
               
                   Saccharomyces  sp. 
                 CAAGAAGCGATACGGTTGACAAGAAAATACTTACTAAGTGAAATT 
               
               
                   
                 TTTGTACGTTGGAGTCCACTGAATGGGGAAATATCATTCTCGTAC 
               
               
                   
                 AACGGAGGAAAAGATTGCCAGGTATTACTACTGTTATATCTGAGT 
               
               
                   
                 TGCTTATGGGAATATTTCTTCATTAAGGCTCAAAATTCCCAATTC 
               
               
                   
                 GATTTCGAGTTTCAAAGCTTCCCCATGCAAAGACTTCCAACTGTT 
               
               
                   
                 TTCATTGATCAAGAAGAAACTTTCCCTACATTAGAGAATTTTGTA 
               
               
                   
                 CTGGAAACCTCAGAGCGATATTGCCTTTCCTTATACGAATCACAA 
               
               
                   
                 AGGCAATCTGGTGCATCGGTCAATATGGCAGACGCATTTAGAGAT 
               
               
                   
                 TTTATAAAGATATACCCTGAGACCGAAGCTATAGTGATAGGTATT 
               
               
                   
                 AGACACACAGACCCATTTGGTGAAGCATTAAAGCCTATTCAAAGA 
               
               
                   
                 ACAGATTCTAACTGGCCTGATTTTATGAGGTTGCAACCTCTCTTA 
               
               
                   
                 CACTGGGACTTAACCAATATATGGAGTTTCTTACTGTATTCTAAT 
               
               
                   
                 GAGCCAATTTGTGGACTATATGGTAAAGGTTTCACATCAATCGGC 
               
               
                   
                 GGAATTAACAACTCATTGCCTAACCCACACTTGAGAAAGGACTCC 
               
               
                   
                 AATAATCCAGCCTTGCATTTTGAATGGGAAATCATTCATGCATTT 
               
               
                   
                 GGCAAGGACGCAGAAGGCGAACGTAGTTCCGCTATAAACACGTCA 
               
               
                   
                 CCTATTTCCGTGGTGGATAAGGAAAGATTCAGCAAATACCATGAC 
               
               
                   
                 AATTACTATCCTGGCTGGTATTTGGTTGATGACACTTTAGAGAGA 
               
               
                   
                 GCAGGCAGGATCAAGAATTAA 
               
               
                   
               
               
                 SEQ ID NO: 298 
                 MQLSKAAEMCYEITNSYLHIDQKSQIIASTQEAIRLTRKYLLSEI 
               
               
                 FAD1 
                 FVRWSPLNGEISFSYNGGKDCQVLLLLYLSCLWEYFFIKAQNSQF 
               
               
                   Saccharomyces  sp. 
                 DFEFQSFPMQRLPTVFIDQEETFPTLENFVLETSERYCLSLYESQ 
               
               
                   
                 RQSGASVNMADAFRDFIKIYPETEAIVIGIRHTDPFGEALKPIQR 
               
               
                   
                 TDSNWPDFMRLQPLLHWDLTNIWSFLLYSNEPICGLYGKGFTSIG 
               
               
                   
                 GINNSLPNPHLRKDSNNPALHFEWEIIHAFGKDAEGERSSAINTS 
               
               
                   
                 PISVVDKERFSKYHDNYYPGWYLVDDTLERAGRIKN* 
               
               
                   
               
               
                 SEQ ID NO: 299 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                 CBDA Synthase, 
                 TTCTTCTTCTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 I445M variant 
                 CGTGAGAACTTCTTGAAATGTTTTTCTCAATATATCCCAAATAAC 
               
               
                 Artificial Sequence 
                 GCTACTAACTTGAAGTTAGTCTATACTCAAAACAACCCATTATAT 
               
               
                   
                 ATGTCTGTCTTAAACTCTACCATTCACAACTTACGTTTCACTTCT 
               
               
                   
                 GATACTACTCCAAAACCTTTGGTCATCGTCACCCCATCCCACGTT 
               
               
                   
                 TCTCACATCCAAGGTACCATCTTGTGTTCCAAAAAGGTTGGTTTA 
               
               
                   
                 CAAATCCGTACTAGATCCGGTGGTCATGACTCCGAAGGTATGTCT 
               
               
                   
                 TACATTTCCCAAGTCCCTTTCGTCATCGTCGACTTAAGAAATATG 
               
               
                   
                 CGTTCCATCAAGATTGATGTCCATTCCCAAACTGCTTGGGTTGAA 
               
               
                   
                 GCCGGTGCCACTTTAGGTGAAGTCTATTACTGGGTTAACGAGAAG 
               
               
                   
                 AATGAGAACTTATCTTTGGCTGCCGGTTACTGTCCAACTGTTTGT 
               
               
                   
                 GCTGGTGGTCATTTCGGTGGTGGTGGTTACGGTCCATTAATGCGT 
               
               
                   
                 AACTACGGTTTGGCTGCCGATAACATCATTGATGCCCACTTAGTC 
               
               
                   
                 AACGTTCATGGTAAGGTCTTGGACCGTAAGTCTATGGGTGAGGAT 
               
               
                   
                 TTATTCTGGGCTTTGAGAGGTGGTGGTGCTGAATCTTTCGGTATT 
               
               
                   
                 ATCGTCGCTTGGAAGATTAGATTAGTTGCTGTTCCAAAGTCTACT 
               
               
                   
                 ATGTTCTCTGTTAAGAAGATCATGGAAATTCACGAGTTGGTTAAA 
               
               
                   
                 TTAGTTAACAAATGGCAAAACATTGCCTACAAGTACGATAAAGAT 
               
               
                   
                 TTGTTATTAATGACTCACTTTATCACTAGAAACATTACTGATAAC 
               
               
                   
                 CAAGGTAAGAATAAGACTGCCATTCACACTTACTTCTCTTCTGTT 
               
               
                   
                 TTCTTGGGTGGTGTTGATTCCTTGGTCGATTTGATGAACAAGTCT 
               
               
                   
                 TTTCCAGAATTAGGTATTAAGAAGACCGATTGTCGTCAACTGATA 
               
               
                   
                 ATTTTAATAAGGAGATTTTGTTAGATAGATCTGCTGGTCAAAATG 
               
               
                   
                 GTGCCTTTAAAATCAAATTGGACTACGTTAAGAAGCCTATTCCAG 
               
               
                   
                 AATCCGTCTTTGTTCAAATTTTGGAGAAGTTATACGAAGAAGATA 
               
               
                   
                 TTGGTGCTGGTATGTACGCCTTGTATCCATATGGTGGTATTATGG 
               
               
                   
                 ATGAAATTTCTGAATCCGCCATCCCTTTCCCTCATCGTGCTGGTA 
               
               
                   
                 TCTTATACGAGTTGTGGTACatgTGTTCTTGGGAAAAGCAAGAAG 
               
               
                   
                 ATAATGAAAAGCATTTGAACTGGATCCGTAACATCTATAACTTCA 
               
               
                   
                 TGACTCCATACGTTTCCAAAAACCCTAGATTGGCTTACTTAAATT 
               
               
                   
                 ACAGAGACTTAGATATTGGTATTAACGACCCTAAGAACCCAAACA 
               
               
                   
                 ATTACACTCAAGCTAGAATCTGGGGTGAAAAGTACTTCGGTAAGA 
               
               
                   
                 ATTTCGACAGATTAGTTAAGGTCAAGACTTTAGTTGACCCAAATA 
               
               
                   
                 ACTTCTTCAGAAACGAACAATCTATCCCACCATTGCCTAGACATA 
               
               
                   
                 GACACTAG 
               
               
                   
               
               
                 SEQ ID NO: 300 
                 MKCSTFSFWFVCKIIFFFFSFNIQTSIANPRENFLKCFSQYIPNN 
               
               
                 CBDA Synthase, 
                 ATNLKLVYTQNNPLYMSVLNSTIHNLRFTSDTTPKPLVIVTPSHV 
               
               
                 I445M variant 
                 SHIQGTILCSKKVGLQIRTRSGGHDSEGMSYISQVPFVIVDLRNM 
               
               
                 Artificial Sequence 
                 RSIKIDVHSQTAWVEAGATLGEVYYWVNEKNENLSLAAGYCPTVC 
               
               
                   
                 AGGHFGGGGYGPLMRNYGLAADNIIDAHLVNVHGKVLDRKSMGED 
               
               
                   
                 LFWALRGGGAESFGIIVAWKIRLVAVPKSTMFSVKKIMEIHELVK 
               
               
                   
                 LVNKWQNIAYKYDKDLLLMTHFITRNITDNQGKNKTAIHTYFSSV 
               
               
                   
                 FLGGVDSLVDLMNKSFPELGIKKTDCRQLSWIDTIIFYSGWNYDT 
               
               
                   
                 DNFNKEILLDRSAGQNGAFKIKLDYVKKPIPESVFVQILEKLYEE 
               
               
                   
                 DIGAGMYALYPYGGIMDEISESAIPFPHRAGILYELWYMCSWEKQ 
               
               
                   
                 EDNEKHLNWIRNIYNFMTPYVSKNPRLAYLNYRDLDIGINDPKNP 
               
               
                   
                 NNYTQARIWGEKYFGKNFDRLVKVKTLVDPNNFFRNEQSIPPLPR 
               
               
                   
                 HRH* 
               
               
                   
               
               
                 SEQ ID NO: 301 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                 CBDA Synthase, 
                 TTCTTCTTCTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 M412Q variant 
                 CGTGAGAACTTCTTGAAATGTTTTTCTCAATATATCCCAAATAAC 
               
               
                 Artificial Sequence 
                 GCTACTAACTTGAAGTTAGTCTATACTCAAAACAACCCATTATAT 
               
               
                   
                 ATGTCTGTCTTAAACTCTACCATTCACAACTTACGTTTCACTTCT 
               
               
                   
                 GATACTACTCCAAAACCTTTGGTCATCGTCACCCCATCCCACGTT 
               
               
                   
                 TCTCACATCCAAGGTACCATCTTGTGTTCCAAAAAGGTTGGTTTA 
               
               
                   
                 CAAATCCGTACTAGATCCGGTGGTCATGACTCCGAAGGTATGTCT 
               
               
                   
                 TACATTTCCCAAGTCCCTTTCGTCATCGTCGACTTAAGAAATATG 
               
               
                   
                 CGTTCCATCAAGATTGATGTCCATTCCCAAACTGCTTGGGTTGAA 
               
               
                   
                 GCCGGTGCCACTTTAGGTGAAGTCTATTACTGGGTTAACGAGAAG 
               
               
                   
                 AATGAGAACTTATCTTTGGCTGCCGGTTACTGTCCAACTGTTTGT 
               
               
                   
                 GCTGGTGGTCATTTCGGTGGTGGTGGTTACGGTCCATTAATGCGT 
               
               
                   
                 AACTACGGTTTGGCTGCCGATAACATCATTGATGCCCACTTAGTC 
               
               
                   
                 AACGTTCATGGTAAGGTCTTGGACCGTAAGTCTATGGGTGAGGAT 
               
               
                   
                 TTATTCTGGGCTTTGAGAGGTGGTGGTGCTGAATCTTTCGGTATT 
               
               
                   
                 ATCGTCGCTTGGAAGATTAGATTAGTTGCTGTTCCAAAGTCTACT 
               
               
                   
                 ATGTTCTCTGTTAAGAAGATCATGGAAATTCACGAGTTGGTTAAA 
               
               
                   
                 TTAGTTAACAAATGGCAAAACATTGCCTACAAGTACGATAAAGAT 
               
               
                   
                 TTGTTATTAATGACTCACTTTATCACTAGAAACATTACTGATAAC 
               
               
                   
                 CAAGGTAAGAATAAGACTGCCATTCACACTTACTTCTCTTCTGTT 
               
               
                   
                 TTCTTGGGTGGTGTTGATTCCTTGGTCGATTTGATGAACAAGTCT 
               
               
                   
                 TTTCCAGAATTAGGTATTAAGAAGACCGATTGTCGTCAACTGATA 
               
               
                   
                 ATTTTAATAAGGAGATTTTGTTAGATAGATCTGCTGGTCAAAATG 
               
               
                   
                 GTGCCTTTAAAATCAAATTGGACTACGTTAAGAAGCCTATTCCAG 
               
               
                   
                 AATCCGTCTTTGTTCAAATTTTGGAGAAGTTATACGAAGAAGATA 
               
               
                   
                 TTGGTGCTGGTcaaTACGCCTTGTATCCATATGGTGGTATTATGG 
               
               
                   
                 ATGAAATTTCTGAATCCGCCATCCCTTTCCCTCATCGTGCTGGTA 
               
               
                   
                 TCTTATACGAGTTGTGGTACATCTGTTCTTGGGAAAAGCAAGAAG 
               
               
                   
                 ATAATGAAAAGCATTTGAACTGGATCCGTAACATCTATAACTTCA 
               
               
                   
                 TGACTCCATACGTTTCCAAAAACCCTAGATTGGCTTACTTAAATT 
               
               
                   
                 ACAGAGACTTAGATATTGGTATTAACGACCCTAAGAACCCAAACA 
               
               
                   
                 ATTACACTCAAGCTAGAATCTGGGGTGAAAAGTACTTCGGTAAGA 
               
               
                   
                 ATTTCGACAGATTAGTTAAGGTCAAGACTTTAGTTGACCCAAATA 
               
               
                   
                 ACTTCTTCAGAAACGAACAATCTATCCCACCATTGCCTAGACATA 
               
               
                   
                 GACACTAG 
               
               
                   
               
               
                 SEQ ID NO: 302 
                 MKCSTFSFWFVCKIIFFFFSFNIQTSIANPRENFLKCFSQYIPNN 
               
               
                 CBDA Synthase, 
                 ATNLKLVYTQNNPLYMSVLNSTIHNLRFTSDTTPKPLVIVTPSHV 
               
               
                 M412Q variant 
                 SHIQGTILCSKKVGLQIRTRSGGHDSEGMSYISQVPFVIVDLRNM 
               
               
                 Artificial Sequence 
                 RSIKIDVHSQTAWVEAGATLGEVYYWVNEKNENLSLAAGYCPTVC 
               
               
                   
                 AGGHFGGGGYGPLMRNYGLAADNIIDAHLVNVHGKVLDRKSMGED 
               
               
                   
                 LFWALRGGGAESFGIIVAWKIRLVAVPKSTMFSVKKIMEIHELVK 
               
               
                   
                 LVNKWQNIAYKYDKDLLLMTHFITRNITDNQGKNKTAIHTYFSSV 
               
               
                   
                 FLGGVDSLVDLMNKSFPELGIKKTDCRQLSWIDTIIFYSGWNYDT 
               
               
                   
                 DNFNKEILLDRSAGQNGAFKIKLDYVKKPIPESVFVQILEKLYEE 
               
               
                   
                 DIGAGQYALYPYGGIMDEISESAIPFPHRAGILYELWYICSWEKQ 
               
               
                   
                 EDNEKHLNVVIRNIYNFMTPYVSKNPRLAYLNYRDLDIGINDPKN 
               
               
                   
                 PNNYTQARIWGEKYFGKNFDRLVKVKTLVDPNNFFRNEQSIPPLP 
               
               
                   
                 RHRH* 
               
               
                   
               
               
                 SEQ ID NO: 303 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                 CBDA Synthase, 
                 TTCTTCTTCTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 L415M variant 
                 CGTGAGAACTTCTTGAAATGTTTTTCTCAATATATCCCAAATAAC 
               
               
                 Artificial Sequence 
                 GCTACTAACTTGAAGTTAGTCTATACTCAAAACAACCCATTATAT 
               
               
                   
                 ATGTCTGTCTTAAACTCTACCATTCACAACTTACGTTTCACTTCT 
               
               
                   
                 GATACTACTCCAAAACCTTTGGTCATCGTCACCCCATCCCACGTT 
               
               
                   
                 TCTCACATCCAAGGTACCATCTTGTGTTCCAAAAAGGTTGGTTTA 
               
               
                   
                 CAAATCCGTACTAGATCCGGTGGTCATGACTCCGAAGGTATGTCT 
               
               
                   
                 TACATTTCCCAAGTCCCTTTCGTCATCGTCGACTTAAGAAATATG 
               
               
                   
                 CGTTCCATCAAGATTGATGTCCATTCCCAAACTGCTTGGGTTGAA 
               
               
                   
                 GCCGGTGCCACTTTAGGTGAAGTCTATTACTGGGTTAACGAGAAG 
               
               
                   
                 AATGAGAACTTATCTTTGGCTGCCGGTTACTGTCCAACTGTTTGT 
               
               
                   
                 GCTGGTGGTCATTTCGGTGGTGGTGGTTACGGTCCATTAATGCGT 
               
               
                   
                 AACTACGGTTTGGCTGCCGATAACATCATTGATGCCCACTTAGTC 
               
               
                   
                 AACGTTCATGGTAAGGTCTTGGACCGTAAGTCTATGGGTGAGGAT 
               
               
                   
                 TTATTCTGGGCTTTGAGAGGTGGTGGTGCTGAATCTTTCGGTATT 
               
               
                   
                 ATCGTCGCTTGGAAGATTAGATTAGTTGCTGTTCCAAAGTCTACT 
               
               
                   
                 ATGTTCTCTGTTAAGAAGATCATGGAAATTCACGAGTTGGTTAAA 
               
               
                   
                 TTAGTTAACAAATGGCAAAACATTGCCTACAAGTACGATAAAGAT 
               
               
                   
                 TTGTTATTAATGACTCACTTTATCACTAGAAACATTACTGATAAC 
               
               
                   
                 CAAGGTAAGAATAAGACTGCCATTCACACTTACTTCTCTTCTGTT 
               
               
                   
                 TTCTTGGGTGGTGTTGATTCCTTGGTCGATTTGATGAACAAGTCT 
               
               
                   
                 TTTCCAGAATTAGGTATTAAGAAGACCGATTGTCGTCAATTATCT 
               
               
                   
                 TGGATTGATACCATTATTTTTTACTCCGGTGTTGTCAACTACGAC 
               
               
                   
                 ACTGATAATTTTAATAAGGAGATTTTGTTAGATAGATCTGCTGGT 
               
               
                   
                 CAAAATGGTGCCTTTAAAATCAAATTGGACTACGTTAAGAAGCCT 
               
               
                   
                 ATTCCAGAATCCGTCTTTGTTCAAATTTTGGAGAAGTTATACGAA 
               
               
                   
                 GAAGATATTGGTGCTGGTATGTACGCCatgTATCCATATGGTGGT 
               
               
                   
                 ATTATGGATGAAATTTCTGAATCCGCCATCCCTTTCCCTCATCGT 
               
               
                   
                 GCTGGTATCTTATACGAGTTGTGGTACATCTGTTCTTGGGAAAAG 
               
               
                   
                 CAAGAAGATAATGAAAAGCATTTGAACTGGATCCGTAACATCTAT 
               
               
                   
                 AACTTCATGACTCCATACGTTTCCAAAAACCCTAGATTGGCTTAC 
               
               
                   
                 TTAAATTACAGAGACTTAGATATTGGTATTAACGACCCTAAGAAC 
               
               
                   
                 CCAAACAATTACACTCAAGCTAGAATCTGGGGTGAAAAGTACTTC 
               
               
                   
                 GGTAAGAATTTCGACAGATTAGTTAAGGTCAAGACTTTAGTTGAC 
               
               
                   
                 CCAAATAACTTCTTCAGAAACGAACAATCTATCCCACCATTGCCT 
               
               
                   
                 AGACATAGACACTAG 
               
               
                   
               
               
                 SEQ ID NO: 304 
                 MKCSTFSFWFVCKIIFFFFSFNIQTSIANPRENFLKCFSQYIPNN 
               
               
                 CBDA Synthase, 
                 ATNLKLVYTQNNPLYMSVLNSTIHNLRFTSDTTPKPLVIVTPSHV 
               
               
                 L415M variant 
                 SHIQGTILCSKKVGLQIRTRSGGHDSEGMSYISQVPFVIVDLRNM 
               
               
                 Artificial Sequence 
                 RSIKIDVHSQTAWVEAGATLGEVYYVVVNEKNENLSLAAGYCPTV 
               
               
                   
                 CAGGHFGGGGYGPLMRNYGLAADNIIDAHLVNVHGKVLDRKSMGE 
               
               
                   
                 DLFWALRGGGAESFGIIVAWKIRLVAVPKSTMFSVKKIMEIHELV 
               
               
                   
                 KLVNKWQNIAYKYDKDLLLMTHFITRNITDNQGKNKTAIHTYFSS 
               
               
                   
                 VFLGGVDSLVDLMNKSFPELGIKKTDCRQLSWIDTIIFYSGVVNY 
               
               
                   
                 DTDNFNKEILLDRSAGQNGAFKIKLDYVKKPIPESVFVQILEKLY 
               
               
                   
                 EEDIGAGMYAMYPYGGIMDEISESAIPFPHRAGILYELVVYICSV 
               
               
                   
                 VEKQEDNEKHLNWIRNIYNFMTPYVSKNPRLAYLNYRDLDIGIND 
               
               
                   
                 PKNPNNYTQARIWGEKYFGKNFDRLVKVKTLVDPNNFFRNEQSIP 
               
               
                   
                 PLPRHRH* 
               
               
                   
               
               
                 SEQ ID NO: 305 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                 CBDA Synthase, 
                 TTCTTCTTCTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 D115N variant 
                 CGTGAGAACTTCTTGAAATGTTTTTCTCAATATATCCCAAATAAC 
               
               
                 Artificial Sequence 
                 GCTACTAACTTGAAGTTAGTCTATACTCAAAACAACCCATTATAT 
               
               
                   
                 ATGTCTGTCTTAAACTCTACCATTCACAACTTACGTTTCACTTCT 
               
               
                   
                 GATACTACTCCAAAACCTTTGGTCATCGTCACCCCATCCCACGTT 
               
               
                   
                 TCTCACATCCAAGGTACCATCTTGTGTTCCAAAAAGGTTGGTTTA 
               
               
                   
                 CAAATCCGTACTAGATCCGGTGGTCATaatTCCGAAGGTATGTCT 
               
               
                   
                 TACATTTCCCAAGTCCCTTTCGTCATCGTCGACTTAAGAAATATG 
               
               
                   
                 CGTTCCATCAAGATTGATGTCCATTCCCAAACTGCTTGGGTTGAA 
               
               
                   
                 GCCGGTGCCACTTTAGGTGAAGTCTATTACTGGGTTAACGAGAAG 
               
               
                   
                 AATGAGAACTTATCTTTGGCTGCCGGTTACTGTCCAACTGTTTGT 
               
               
                   
                 GCTGGTGGTCATTTCGGTGGTGGTGGTTACGGTCCATTAATGCGT 
               
               
                   
                 AACTACGGTTTGGCTGCCGATAACATCATTGATGCCCACTTAGTC 
               
               
                   
                 AACGTTCATGGTAAGGTCTTGGACCGTAAGTCTATGGGTGAG 
               
               
                   
                 GATTTATTCTGGGCTTTGAGAGGTGGTGGTGCTGAATCTTTCGGT 
               
               
                   
                 ATTATCGTCGCTTGGAAGATTAGATTAGTTGCTGTTCCAAAGTCT 
               
               
                   
                 ACTATGTTCTCTGTTAAGAAGATCATGGAAATTCACGAGTTGGTT 
               
               
                   
                 AAATTAGTTAACAAATGGCAAAACATTGCCTACAAGTACGATAAA 
               
               
                   
                 GATTTGTTATTAATGACTCACTTTATCACTAGAAACATTACTGAT 
               
               
                   
                 AACCAAGGTAAGAATAAGACTGCCATTCACACTTACTTCTCTTCT 
               
               
                   
                 GTTTTCTTGGGTGGTGTTGATTCCTTGGTCGATTTGATGAACAAG 
               
               
                   
                 TCTTTTCCAGAATTAGGTATTAAGAAGACCGATTGTCGTCAATTG 
               
               
                   
                 ATAATTTTAATAAGGAGATTTTGTTAGATAGATCTGCTGGTCAAA 
               
               
                   
                 ATGGTGCCTTTAAAATCAAATTGGACTACGTTAAGAAGCCTATTC 
               
               
                   
                 CAGAATCCGTCTTTGTTCAAATTTTGGAGAAGTTATACGAAGAAG 
               
               
                   
                 ATATTGGTGCTGGTATGTACGCCTTGTATCCATATGGTGGTATTA 
               
               
                   
                 TGGATGAAATTTCTGAATCCGCCATCCCTTTCCCTCATCGTGCTG 
               
               
                   
                 GTATCTTATACGAGTTGTGGTACATCTGTTCTTGGGAAAAGCAAG 
               
               
                   
                 AAGATAATGAAAAGCATTTGAACTGGATCCGTAACATCTATAACT 
               
               
                   
                 TCATGACTCCATACGTTTCCAAAAACCCTAGATTGGCTTACTTAA 
               
               
                   
                 ATTACAGAGACTTAGATATTGGTATTAACGACCCTAAGAACCCAA 
               
               
                   
                 ACAATTACACTCAAGCTAGAATCTGGGGTGAAAAGTACTTCGGTA 
               
               
                   
                 AGAATTTCGACAGATTAGTTAAGGTCAAGACTTTAGTTGACCCAA 
               
               
                   
                 ATAACTTCTTCAGAAACGAACAATCTATCCCACCATTGCCTAGAC 
               
               
                   
                 ATAGACACTAG 
               
               
                   
               
               
                 SEQ ID NO: 306 
                 MKCSTFSFWFVCKIIFFFFSFNIQTSIANPRENFLKCFSQYIPNN 
               
               
                 CBDA Synthase, 
                 ATNLKLVYTQNNPLYMSVLNSTIHNLRFTSDTTPKPLVIVTPSHV 
               
               
                 D115N variant 
                 SHIQGTILCSKKVGLQIRTRSGGHNSEGMSYISQVPFVIVDLRNM 
               
               
                 Artificial Sequence 
                 RSIKIDVHSQTAWVEAGATLGEVYYWVNEKNENLSLAAGYCPTVC 
               
               
                   
                 AGGHFGGGGYGPLMRNYGLAADNIIDAHLVNVHGKVLDRKSMGED 
               
               
                   
                 LFWALRGGGAESFGIIVAWKIRLVAVPKSTMFSVKKIMEIHELVK 
               
               
                   
                 LVNKWQNIAYKYDKDLLLMTHFITRNITDNQGKNKTAIHTYFSSV 
               
               
                   
                 FLGGVDSLVDLMNKSFPELGIKKTDCRQLSWIDTIIFYSGVVNYD 
               
               
                   
                 TDNFNKEILLDRSAGQNGAFKIKLDYVKKPIPESVFVQILEKLYE 
               
               
                   
                 EDIGAGMYALYPYGGIMDEISESAIPFPHRAGILYELWYICSWEK 
               
               
                   
                 QEDNEKHLNWIRNIYNFMTPYVSKNPRLAYLNYRDLDIGINDPKN 
               
               
                   
                 PNNYTQARIWGEKYFGKNFDRLVKVKTLVDPNNFFRNEQSIPPLP 
               
               
                   
                 RHRH* 
               
               
                   
               
               
                 SEQ ID NO: 307 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                 CBDA Synthase, 
                 TTCTTCTTCTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 A4I4T variant 
                 CGTGAGAACTTCTTGAAATGTTTTTCTCAATATATCCCAAATAAC 
               
               
                 Artificial Sequence 
                 GCTACTAACTTGAAGTTAGTCTATACTCAAAACAACCCATTATAT 
               
               
                   
                 ATGTCTGTCTTAAACTCTACCATTCACAACTTACGTTTCACTTCT 
               
               
                   
                 GATACTACTCCAAAACCTTTGGTCATCGTCACCCCATCCCACGTT 
               
               
                   
                 TCTCACATCCAAGGTACCATCTTGTGTTCCAAAAAGGTTGGTTTA 
               
               
                   
                 CAAATCCGTACTAGATCCGGTGGTCATGACTCCGAAGGTATGTCT 
               
               
                   
                 TACATTTCCCAAGTCCCTTTCGTCATCGTCGACTTAAGAAATATG 
               
               
                   
                 CGTTCCATCAAGATTGATGTCCATTCCCAAACTGCTTGGGTTGAA 
               
               
                   
                 GCCGGTGCCACTTTAGGTGAAGTCTATTACTGGGTTAACGAGAAG 
               
               
                   
                 AATGAGAACTTATCTTTGGCTGCCGGTTACTGTCCAACTGTTTGT 
               
               
                   
                 GCTGGTGGTCATTTCGGTGGTGGTGGTTACGGTCCATTAATGCGT 
               
               
                   
                 AACTACGGTTTGGCTGCCGATAACATCATTGATGCCCACTTAGTC 
               
               
                   
                 AACGTTCATGGTAAGGTCTTGGACCGTAAGTCTATGGGTGAGGAT 
               
               
                   
                 TTATTCTGGGCTTTGAGAGGTGGTGGTGCTGAATCTTTCGGTATT 
               
               
                   
                 ATCGTCGCTTGGAAGATTAGATTAGTTGCTGTTCCAAAGTCTACT 
               
               
                   
                 ATGTTCTCTGTTAAGAAGATCATGGAAATTCACGAGTTGGTTAAA 
               
               
                   
                 TTAGTTAACAAATGGCAAAACATTGCCTACAAGTACGATAAAGAT 
               
               
                   
                 TTGTTATTAATGACTCACTTTATCACTAGAAACATTACTGATAAC 
               
               
                   
                 CAAGGTAAGAATAAGACTGCCATTCACACTTACTTCTCTTCTGTT 
               
               
                   
                 TTCTTGGGTGGTGTTGATTCCTTGGTCGATTTGATGAACAAGTCT 
               
               
                   
                 TTTCCAGAATTAGGTATTAAGAAGACCGATTGTCGTCAACTGATA 
               
               
                   
                 ATTTTAATAAGGAGATTTTGTTAGATAGATCTGCTGGTCAAAATG 
               
               
                   
                 GTGCCTTTAAAATCAAATTGGACTACGTTAAGAAGCCTATTCCAG 
               
               
                   
                 AATCCGTCTTTGTTCAAATTTTGGAGAAGTTATACGAAGAAGATA 
               
               
                   
                 TTGGTGCTGGTATGTACACTTTGTATCCATATGGTGGTATTATGG 
               
               
                   
                 ATGAAATTTCTGAATCCGCCATCCCTTTCCCTCATCGTGCTGGTA 
               
               
                   
                 TCTTATACGAGTTGTGGTACATCTGTTCTTGGGAAAAGCAAGAAG 
               
               
                   
                 ATAATGAAAAGCATTTGAACTGGATCCGTAACATCTATAACTTCA 
               
               
                   
                 TGACTCCATACGTTTCCAAAAACCCTAGATTGGCTTACTTAAATT 
               
               
                   
                 ACAGAGACTTAGATATTGGTATTAACGACCCTAAGAACCCAAACA 
               
               
                   
                 ATTACACTCAAGCTAGAATCTGGGGTGAAAAGTACTTCGGTAAGA 
               
               
                   
                 ATTTCGACAGATTAGTTAAGGTCAAGACTTTAGTTGACCCAAATA 
               
               
                   
                 ACTTCTTCAGAAACGAACAATCTATCCCACCATTGCCTAGACATA 
               
               
                   
                 GACACTAG 
               
               
                   
               
               
                 SEQ ID NO: 308 
                 MKCSTFSFWFVCKIIFFFFSFNIQTSIANPRENFLKCFSQYIPNN 
               
               
                 CBDA Synthase, 
                 ATNLKLVYTQNNPLYMSVLNSTIHNLRFTSDTTPKPLVIVTPSHV 
               
               
                 A414T variant 
                 SHIQGTILCSKKVGLQIRTRSGGHDSEGMSYISQVPFVIVDLRNM 
               
               
                 Artificial Sequence 
                 RSIKIDVHSQTAWVEAGATLGEVYYWVNEKNENLSLAAGYCPTVC 
               
               
                   
                 AGGHFGGGGYGPLMRNYGLAADNIIDAHLVNVHGKVLDRKSMGED 
               
               
                   
                 LFWALRGGGAESFGIIVAWKIRLVAVPKSTMFSVKKIMEIHELVK 
               
               
                   
                 LVNKWQNIAYKYDKDLLLMTHFITRNITDNQGKNKTAIHTYFSSV 
               
               
                   
                 FLGGVDSLVDLMNKSFPELGIKKTDCRQLSWIDTIIFYSGVVNYD 
               
               
                   
                 TDNFNKEILLDRSAGQNGAFKIKLDYVKKPIPESVFVQILEKLYE 
               
               
                   
                 EDIGAGMYTLYPYGGIMDEISESAIPFPHRAGILYELWYICSWEK 
               
               
                   
                 QEDNEKHLNWIRNIYNFMTPYVSKNPRLAYLNYRDLDIGINDPKN 
               
               
                   
                 PNNYTQARIWGEKYFGKNFDRLVKVKTLVDPNNFFRNEQSIPPLP 
               
               
                   
                 RHRH* 
               
               
                   
               
               
                 SEQ ID NO: 309 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                 CBDA Synthase, 
                 TTCTTCTTCTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 A414V variant 
                 CGTGAGAACTTCTTGAAATGTTTTTCTCAATATATCCCAAATAAC 
               
               
                 Artificial Sequence 
                 GCTACTAACTTGAAGTTAGTCTATACTCAAAACAACCCATTATAT 
               
               
                   
                 ATGTCTGTCTTAAACTCTACCATTCACAACTTACGTTTCACTTCT 
               
               
                   
                 GATACTACTCCAAAACCTTTGGTCATCGTCACCCCATCCCACGTT 
               
               
                   
                 TCTCACATCCAAGGTACCATCTTGTGTTCCAAAAAGGTTGGTTTA 
               
               
                   
                 CAAATCCGTACTAGATCCGGTGGTCATGACTCCGAAGGTATGTCT 
               
               
                   
                 TACATTTCCCAAGTCCCTTTCGTCATCGTCGACTTAAGAAATATG 
               
               
                   
                 CGTTCCATCAAGATTGATGTCCATTCCCAAACTGCTTGGGTTGAA 
               
               
                   
                 GCCGGTGCCACTTTAGGTGAAGTCTATTACTGGGTTAACGAGAAG 
               
               
                   
                 AATGAGAACTTATCTTTGGCTGCCGGTTACTGTCCAACTGTTTGT 
               
               
                   
                 GCTGGTGGTCATTTCGGTGGTGGTGGTTACGGTCCATTAATGCGT 
               
               
                   
                 AACTACGGTTTGGCTGCCGATAACATCATTGATGCCCACTTAGTC 
               
               
                   
                 AACGTTCATGGTAAGGTCTTGGACCGTAAGTCTATGGGTGAGGAT 
               
               
                   
                 TTATTCTGGGCTTTGAGAGGTGGTGGTGCTGAATCTTTCGGTATT 
               
               
                   
                 ATCGTCGCTTGGAAGATTAGATTAGTTGCTGTTCCAAAGTCTACT 
               
               
                   
                 ATGTTCTCTGTTAAGAAGATCATGGAAATTCACGAGTTGGTTAAA 
               
               
                   
                 TTAGTTAACAAATGGCAAAACATTGCCTACAAGTACGATAAAGAT 
               
               
                   
                 TTGTTATTAATGACTCACTTTATCACTAGAAACATTACTGATAAC 
               
               
                   
                 CAAGGTAAGAATAAGACTGCCATTCACACTTACTTCTCTTCTGTT 
               
               
                   
                 TTCTTGGGTGGTGTTGATTCCTTGGTCGATTTGATGAACAAGTCT 
               
               
                   
                 TTTCCAGAATTAGGTATTAAGAAGACCGATTGTCGTCAATTATCT 
               
               
                   
                 TGGATTGATACCATTATTTTTTACTCCGGTGTTGTCAACTACGAC 
               
               
                   
                 ACTGATAATTTTAATAAGGAGATTTTGTTAGATAGATCTGCTGGT 
               
               
                   
                 CAAAATGGTGCCTTTAAAATCAAATTGGACTACGTTAAGAAGCCT 
               
               
                   
                 ATTCCAGAATCCGTCTTTGTTCAAATTTTGGAGAAGTTATACGAA 
               
               
                   
                 GAAGATATTGGTGCTGGTATGTACGttTTGTATCCATATGGTGGT 
               
               
                   
                 ATTATGGATGAAATTTCTGAATCCGCCATCCCTTTCCCTCATCGT 
               
               
                   
                 GCTGGTATCTTATACGAGTTGTGGTACATCTGTTCTTGGGAAAAG 
               
               
                   
                 CAAGAAGATAATGAAAAGCATTTGAACTGGATCCGTAACATCTAT 
               
               
                   
                 AACTTCATGACTCCATACGTTTCCAAAAACCCTAGATTGGCTTAC 
               
               
                   
                 TTAAATTACAGAGACTTAGATATTGGTATTAACGACCCTAAGAAC 
               
               
                   
                 CCAAACAATTACACTCAAGCTAGAATCTGGGGTGAAAAGTACTTC 
               
               
                   
                 GGTAAGAATTTCGACAGATTAGTTAAGGTCAAGACTTTAGTTGAC 
               
               
                   
                 CCAAATAACTTCTTCAGAAACGAACAATCTATCCCACCATTGCCT 
               
               
                   
                 AGACATAGACACTAG 
               
               
                   
               
               
                 SEQ ID NO: 310 
                 MKCSTFSFWFVCKIIFFFFSFNIQTSIANPRENFLKCFSQYIPNN 
               
               
                 CBDA Synthase, 
                 ATNLKLVYTQNNPLYMSVLNSTIHNLRFTSDTTPKPLVIVTPSHV 
               
               
                 A414V variant 
                 SHIQGTILCSKKVGLQIRTRSGGHDSEGMSYISQVPFVIVDLRNM 
               
               
                 Artificial Sequence 
                 RSIKIDVHSQTAWVEAGATLGEVYYWVNEKNENLSLAAGYCPTVC 
               
               
                   
                 AGGHFGGGGYGPLMRNYGLAADNIIDAHLVNVHGKVLDRKSMGED 
               
               
                   
                 LFWALRGGGAESFGIIVAWKIRLVAVPKSTMFSVKKIMEIHELVK 
               
               
                   
                 LVNKWQNIAYKYDKDLLLMTHFITRNITDNQGKNKTAIHTYFSSV 
               
               
                   
                 FLGGVDSLVDLMNKSFPELGIKKTDCRQLSWIDTIIFYSGWNYDT 
               
               
                   
                 DNFNKEILLDRSAGQNGAFKKLDYVKKPIPESVFVQILEKLYEED 
               
               
                   
                 IGAGMYVLYPYGGIMDEISESAIPFPHRAGILYELWYICSWEKQE 
               
               
                   
                 DNEKHLNWIRNIYNFMTPYVSKNPRLAYLNYRDLDIGINDPKNPN 
               
               
                   
                 NYTQARIWGEKYFGKNFDRLVKVKTLVDPNNFFRNEQSIPPLPRH 
               
               
                   
                 RH* 
               
               
                   
               
               
                 SEQ ID NO: 311 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                 CBDA Synthase, 
                 TTCTTCTTCTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 A414M variant 
                 CGTGAGAACTTCTTGAAATGTTTTTCTCAATATATCCCAAATAAC 
               
               
                 Artificial Sequence 
                 GCTACTAACTTGAAGTTAGTCTATACTCAAAACAACCCATTATAT 
               
               
                   
                 ATGTCTGTCTTAAACTCTACCATTCACAACTTACGTTTCACTTCT 
               
               
                   
                 GATACTACTCCAAAACCTTTGGTCATCGTCACCCCATCCCACGTT 
               
               
                   
                 TCTCACATCCAAGGTACCATCTTGTGTTCCAAAAAGGTTGGTTTA 
               
               
                   
                 CAAATCCGTACTAGATCCGGTGGTCATGACTCCGAAGGTATGTCT 
               
               
                   
                 TACATTTCCCAAGTCCCTTTCGTCATCGTCGACTTAAGAAATATG 
               
               
                   
                 CGTTCCATCAAGATTGATGTCCATTCCCAAACTGCTTGGGTTGAA 
               
               
                   
                 GCCGGTGCCACTTTAGGTGAAGTCTATTACTGGGTTAACGAGAAG 
               
               
                   
                 AATGAGAACTTATCTTTGGCTGCCGGTTACTGTCCAACTGTTTGT 
               
               
                   
                 GCTGGTGGTCATTTCGGTGGTGGTGGTTACGGTCCATTAATGCGT 
               
               
                   
                 AACTACGGTTTGGCTGCCGATAACATCATTGATGCCCACTTAGTC 
               
               
                   
                 AACGTTCATGGTAAGGTCTTGGACCGTAAGTCTATGGGTGAGGAT 
               
               
                   
                 TTATTCTGGGCTTTGAGAGGTGGTGGTGCTGAATCTTTCGGTATT 
               
               
                   
                 ATCGTCGCTTGGAAGATTAGATTAGTTGCTGTTCCAAAGTCTACT 
               
               
                   
                 ATGTTCTCTGTTAAGAAGATCATGGAAATTCACGAGTTGGTTAAA 
               
               
                   
                 TTAGTTAACAAATGGCAAAACATTGCCTACAAGTACGATAAAGAT 
               
               
                   
                 TTGTTATTAATGACTCACTTTATCACTAGAAACATTACTGATAAC 
               
               
                   
                 CAAGGTAAGAATAAGACTGCCATTCACACTTACTTCTCTTCTGTT 
               
               
                   
                 TTCTTGGGTGGTGTTGATTCCTTGGTCGATTTGATGAACAAGTCT 
               
               
                   
                 TTTCCAGAATTAGGTATTAAGAAGACCGATTGTCGTCAACTGATA 
               
               
                   
                 ATTTTAATAAGGAGATTTTGTTAGATAGATCTGCTGGTCAAAATG 
               
               
                   
                 GTGCCTTTAAAATCAAATTGGACTACGTTAAGAAGCCTATTCCAG 
               
               
                   
                 AATCCGTCTTTGTTCAAATTTTGGAGAAGTTATACGAAGAAGATA 
               
               
                   
                 TTGGTGCTGGTATGTACatgTTGTATCCATATGGTGGTATTATGG 
               
               
                   
                 ATGAAATTTCTGAATCCGCCATCCCTTTCCCTCATCGTGCTGGTA 
               
               
                   
                 TCTTATACGAGTTGTGGTACATCTGTTCTTGGGAAAAGCAAGAAG 
               
               
                   
                 ATAATGAAAAGCATTTGAACTGGATCCGTAACATCTATAACTTCA 
               
               
                   
                 TGACTCCATACGTTTCCAAAAACCCTAGATTGGCTTACTTAAATT 
               
               
                   
                 ACAGAGACTTAGATATTGGTATTAACGACCCTAAGAACCCAAACA 
               
               
                   
                 ATTACACTCAAGCTAGAATCTGGGGTGAAAAGTACTTCGGTAAGA 
               
               
                   
                 ATTTCGACAGATTAGTTAAGGTCAAGACTTTAGTTGACCCAAATA 
               
               
                   
                 ACTTCTTCAGAAACGAACAATCTATCCCACCATTGCCTAGACATA 
               
               
                   
                 GACACTAG 
               
               
                   
               
               
                 SEQ ID NO: 312 
                 MKCSTFSFWFVCKIIFFFFSFNIQTSIANPRENFLKCFSQYIPNN 
               
               
                 CBDA Synthase, 
                 ATNLKLVYTQNNPLYMSVLNSTIHNLRFTSDTTPKPLVIVTPSHV 
               
               
                 A4I4M variant 
                 SHIQGTILCSKKVGLQIRTRSGGHDSEGMSYISQVPFVIVDLRNM 
               
               
                 Artificial Sequence 
                 RSIKIDVHSQTAWVEAGATLGEVYYWVNEKNENLSLAAGYCPTVC 
               
               
                   
                 AGGHFGGGGYGPLMRNYGLAADNIIDAHLVNVHGKVLDRKSMGED 
               
               
                   
                 LFWALRGGGAESFGIIVAWKIRLVAVPKSTMFSVKKIMEIHELVK 
               
               
                   
                 LVNKWQNIAYKYDKDLLLMTHFITRNITDNQGKNKTAIHTYFSSV 
               
               
                   
                 FLGGVDSLVDLMNKSFPELGIKKTDCRQLSWIDTIIFYSGVVNYD 
               
               
                   
                 TDNFNKEILLDRSAGQNGAFKIKLDYVKKPIPESVFVQILEKLYE 
               
               
                   
                 EDIGAGMYMLYPYGGIMDEISESAIPFPHRAGILYELWYICSWEK 
               
               
                   
                 QEDNEKHLNWIRNIYNFMTPYVSKNPRLAYLNYRDLDIGINDPKN 
               
               
                   
                 PNNYTQARIWGEKYFGKNFDRLVKVKTLVDPNNFFRNEQSIPPLP 
               
               
                   
                 RHRH* 
               
               
                   
               
               
                 SEQ ID NO: 313 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTrCGTTTGTAAGATTATC 
               
               
                 CBDA Synthase, 
                 TTCTTCTTCTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 M61W, G378T variant 
                 CGTGAGAACTTCTTGAAATGTTTTTCTCAATATATCCCAAATAAC 
               
               
                 Artificial Sequence 
                 GCTACTAACTTGAAGTTAGTCTATACTCAAAACAACCCATTATAT 
               
               
                   
                 tggTCTGTCTTAAACTCTACCATTCACAACTTACGTTTCACTTCT 
               
               
                   
                 GATACTACTCCAAAACCTTTGGTCATCGTCACCCCATCCCACGTT 
               
               
                   
                 TCTCACATCCAAGGTACCATCTTGTGTTCCAAAAAGGTTGGTTTA 
               
               
                   
                 CAAATCCGTACTAGATCCGGTGGTCATGACTCCGAAGGTATGTCT 
               
               
                   
                 TACATTTCCCAAGTCCCTTTCGTCATCGTCGACTTAAGAAATATG 
               
               
                   
                 CGTTCCATCAAGATTGATGTCCATTCCCAAACTGCTTGGGTTGAA 
               
               
                   
                 GCCGGTGCCACTTTAGGTGAAGTCTATTACTGGGTTAACGAGAAG 
               
               
                   
                 AATGAGAACTTATCTTTGGCTGCCGGTTACTGTCCAACTGTTTGT 
               
               
                   
                 GCTGGTGGTCATTTCGGTGGTGGTGGTTACGGTCCATTAATGCGT 
               
               
                   
                 AACTACGGTTTGGCTGCCGATAACATCATTGATGCCCACTTAGTC 
               
               
                   
                 AACGTTCATGGTAAGGTCTTGGACCGTAAGTCTATGGGTGAGGAT 
               
               
                   
                 TTATTCTGGGCTTTGAGAGGTGGTGGTGCTGAATCTTTCGGTATT 
               
               
                   
                 ATCGTCGCTTGGAAGATTAGATTAGTTGCTGTTCCAAAGTCTACT 
               
               
                   
                 ATGTTCTCTGTTAAGAAGATCATGGAAATTCACGAGTTGGTTAAA 
               
               
                   
                 TTAGTTAACAAATGGCAAAACATTGCCTACAAGTACGATAAAGAT 
               
               
                   
                 TTGTTATTAATGACTCACTTTATCACTAGAAACATTACTGATAAC 
               
               
                   
                 CAAGGTAAGAATAAGACTGCCATTCACACTTACTTCTCTTCTGTT 
               
               
                   
                 TTCTTGGGTGGTGTTGATTCCTTGGTCGATTTGATGAACAAGTCT 
               
               
                   
                 TTTCCAGAATTAGGTATTAAGAAGACCGATTGTCGTCAATTGATA 
               
               
                   
                 ATTTTAATAAGGAGATTTTGTTAGATAGATCTGCTGGTCAAAATa 
               
               
                   
                 ctGCCTTTAAAATCAAATTGGACTACGTTAAGAAGCCTATTCCAG 
               
               
                   
                 AATCCGTCTTTGTTCAAATTTTGGAGAAGTTATACGAAGAAGATA 
               
               
                   
                 TTGGTGCTGGTATGTACGCCTTGTATCCATATGGTGGTATTATGG 
               
               
                   
                 ATGAAATTTCTGAATCCGCCATCCCTTTCCCTCATCGTGCTGGTA 
               
               
                   
                 TCTTATACGAGTTGTGGTACATCTGTTCTTGGGAAAAGCAAGAAG 
               
               
                   
                 ATAATGAAAAGCATTTGAACTGGATCCGTAACATCTATAACTTCA 
               
               
                   
                 TGACTCCATACGTTTCCAAAAACCCTAGATTGGCTTACTTAAATT 
               
               
                   
                 ACAGAGACTTAGATATTGGTATTAACGACCCTAAGAACCCAAACA 
               
               
                   
                 ATTACACTCAAGCTAGAATCTGGGGTGAAAAGTACTTCGGTAAGA 
               
               
                   
                 ATTTCGACAGATTAGTTAAGGTCAAGACTTTAGTTGACCCAAATA 
               
               
                   
                 ACTTCTTCAGAAACGAACAATCTATCCCACCATTGCCTAGACATA 
               
               
                   
                 GACACTAG 
               
               
                   
               
               
                 SEQ ID NO: 314 
                 MKCSTFSFWFVCKIIFFFFSFNIQTSIANPRENFLKCFSQYIPNN 
               
               
                 CBDA Synthase, 
                 ATNLKLVYTQNNPLYWSVLNSTIHNLRFTSDTTPKPLVIVTPSHV 
               
               
                 M61W, G378T variant 
                 SHIQGTILCSKKVGLQIRTRSGGHDSEGMSYISQVPFVIVDLRNM 
               
               
                 Artificial Sequence 
                 RSIKIDVHSQTAWVEAGATLGEVYYWVNEKNENLSLAAGYCPTVC 
               
               
                   
                 AGGHFGGGGYGPLMRNYGLAADNIIDAHLVNVHGKVLDRKSMGED 
               
               
                   
                 LFWALRGGGAESFGIIVAWKIRLVAVPKSTMFSVKKIMEIHELVK 
               
               
                   
                 LVNKWQNIAYKYDKDLLLMTHFITRNITDNQGKNKTAIHTYFSSV 
               
               
                   
                 FLGGVDSLVDLMNKSFPELGIKKTDCRQLSWIDTIIFYSGWNYDT 
               
               
                   
                 DNFNKEILLDRSAGQNTAFKIKLDYVKKPIPESVFVQILEKLYEE 
               
               
                   
                 DIGAGMYALYPYGGIMDEISESAIPFPHRAGILYELWYICSWEKQ 
               
               
                   
                 EDNEKHLNWIRNIYNFMTPYVSKNPRLAYLNYRDLDIGINDPKNP 
               
               
                   
                 NNYTQARIWGEKYFGKNFDRLVKVKTLVDPNNFFRNEQSIPPLPR 
               
               
                   
                 HRH* 
               
               
                   
               
               
                 SEQ ID NO: 3l5 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                 CBDA Synthase, 
                 TTCTTCTTCTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 M61W, K389E variant 
                 CGTGAGAACTTCTTGAAATGTTTTTCTCAATATATCCCAAATAAC 
               
               
                 Artificial Sequence 
                 GCTACTAACTTGAAGTTAGTCTATACTCAAAACAACCCATTATAT 
               
               
                   
                 tggTCTGTCTTAAACTCTACCATTCACAACTTACGTTTCACTTCT 
               
               
                   
                 GATACTACTCCAAAACCTTTGGTCATCGTCACCCCATCCCACGTT 
               
               
                   
                 TCTCACATCCAAGGTACCATCTTGTGTTCCAAAAAGGTTGGTTTA 
               
               
                   
                 CAAATCCGTACTAGATCCGGTGGTCATGACTCCGAAGGTATGTCT 
               
               
                   
                 TACATTTCCCAAGTCCCTTTCGTCATCGTCGACTTAAGAAATATG 
               
               
                   
                 CGTTCCATCAAGATTGATGTCCATTCCCAAACTGCTTGGGTTGAA 
               
               
                   
                 GCCGGTGCCACTTTAGGTGAAGTCTATTACTGGGTTAACGAGAAG 
               
               
                   
                 AATGAGAACTTATCTTTGGCTGCCGGTTACTGTCCAACTGTTTGT 
               
               
                   
                 GCTGGTGGTCATTTCGGTGGTGGTGGTTACGGTCCATTAATGCGT 
               
               
                   
                 AACTACGGTTTGGCTGCCGATAACATCATTGATGCCCACTTAGTC 
               
               
                   
                 AACGTTCATGGTAAGGTCTTGGACCGTAAGTCTATGGGTGAGGAT 
               
               
                   
                 TTATTCTGGGCTTTGAGAGGTGGTGGTGCTGAATCTTTCGGTATT 
               
               
                   
                 ATCGTCGCTTGGAAGATTAGATTAGTTGCTGTTCCAAAGTCTACT 
               
               
                   
                 ATGTTCTCTGTTAAGAAGATCATGGAAATTCACGAGTTGGTTAAA 
               
               
                   
                 TTAGTTAACAAATGGCAAAACATTGCCTACAAGTACGATAAAGAT 
               
               
                   
                 TTGTTATTAATGACTCACTTTATCACTAGAAACATTACTGATAAC 
               
               
                   
                 CAAGGTAAGAATAAGACTGCCATTCACACTTACTTCTCTTCTGTT 
               
               
                   
                 TTCTTGGGTGGTGTTGATTCCTTGGTCGATTTGATGAACAAGTCT 
               
               
                   
                 TTTCCAGAATTAGGTATTAAGAAGACCGATTGTCGTCAATTGATA 
               
               
                   
                 ATTTTAATAAGGAGATTTTGTTAGATAGATCTGCTGGTCAAAATG 
               
               
                   
                 GTGCCTTTAAAATCAAATTGGACTACGTTAAGgaaCCTATTCCAG 
               
               
                   
                 AATCCGTCTTTGTTCAAATTTTGGAGAAGTTATACGAAGAAGATA 
               
               
                   
                 TTGGTGCTGGTATGTACGCCTTGTATCCATATGGTGGTATTATGG 
               
               
                   
                 ATGAAATTTCTGAATCCGCCATCCCTTTCCCTCATCGTGCTGGTA 
               
               
                   
                 TCTTATACGAGTTGTGGTACATCTGTTCTTGGGAAAAGCAAGAAG 
               
               
                   
                 ATAATGAAAAGCATTTGAACTGGATCCGTAACATCTATAACTTCA 
               
               
                   
                 TGACTCCATACGTTTCCAAAAACCCTAGATTGGCTTACTTAAATT 
               
               
                   
                 ACAGAGACTTAGATATTGGTATTAACGACCCTAAGAACCCAAACA 
               
               
                   
                 ATTACACTCAAGCTAGAATCTGGGGTGAAAAGTACTTCGGTAAGA 
               
               
                   
                 ATTTCGACAGATTAGTTAAGGTCAAGACTTTAGTTGACCCAAATA 
               
               
                   
                 ACTTCTTCAGAAACGAACAATCTATCCCACCATTGCCTAGACATA 
               
               
                   
                 GACACTAG 
               
               
                   
               
               
                 SEQ ID NO: 316 
                 MKCSTFSFWFVCKIIFFFFSFNIQTSIANPRENFLKCFSQYIPNN 
               
               
                 CBDA Synthase, 
                 ATNLKLVYTQNNPLYWSVLNSTIHNLRFTSDTTPKPLVIVTPSHV 
               
               
                 M61W, K389E variant 
                 SHIQGTILCSKKVGLQIRTRSGGHDSEGMSYISQVPFVIVDLRNM 
               
               
                 Artificial Sequence 
                 RSIKIDVHSQTAWVEAGATLGEVYYWVNEKNENLSLAAGYCPTVC 
               
               
                   
                 AGGHFGGGGYGPLMRNYGLAADNIIDAHLVNVHGKVLDRKSMGED 
               
               
                   
                 LFWALRGGGAESFGIIVAWKIRLVAVPKSTMFSVKKIMEIHELVK 
               
               
                   
                 LVNKWQNIAYKYDKDLLLMTHFITRNITDNQGKNKTAIHTYFSSV 
               
               
                   
                 FLGGVDSLVDLMNKSFPELGIKKTDCRQLSWIDTIIFYSGWNYDT 
               
               
                   
                 DNFNKEILLDRSAGQNGAFKIKLDYVKEPIPESVFVQILEKLYEE 
               
               
                   
                 DIGAGMYALYPYGGIMDEISESAIPFPHRAGILYELWYICSWEKQ 
               
               
                   
                 EDNEKHLNWIRNIYNFMTPYVSKNPRLAYLNYRDLDIGINDPKNP 
               
               
                   
                 NNYTQARIWGEKYFGKNFDRLVKVKTLVDPNNFFRNEQSIPPLPR 
               
               
                   
                 HRH* 
               
               
                   
               
               
                 SEQ ID NO: 317 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                 CBDA Synthase, 
                 TTCTTCTTCTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 G378T, K389E variant 
                 CGTGAGAACTTCTTGAAATGTTTTTCTCAATATATCCCAAATAAC 
               
               
                 Artificial Sequence 
                 GCTACTAACTTGAAGTTAGTCTATACTCAAAACAACCCATTATAT 
               
               
                   
                 ATGTCTGTCTTAAACTCTACCATTCACAACTTACGTTTCACTTCT 
               
               
                   
                 GATACTACTCCAAAACCTTTGGTCATCGTCACCCCATCCCACGTT 
               
               
                   
                 TCTCACATCCAAGGTACCATCTTGTGTTCCAAAAAGGTTGGTTTA 
               
               
                   
                 CAAATCCGTACTAGATCCGGTGGTCATGACTCCGAAGGTATGTCT 
               
               
                   
                 TACATTTCCCAAGTCCCTTTCGTCATCGTCGACTTAAGAAATATG 
               
               
                   
                 CGTTCCATCAAGATTGATGTCCATTCCCAAACTGCTTGGGTTGAA 
               
               
                   
                 GCCGGTGCCACTTTAGGTGAAGTCTATTACTGGGTTAACGAGAAG 
               
               
                   
                 AATGAGAACTTATCTTTGGCTGCCGGTTACTGTCCAACTGTTTGT 
               
               
                   
                 GCTGGTGGTCATTTCGGTGGTGGTGGTTACGGTCCATTAATGCGT 
               
               
                   
                 AACTACGGTTTGGCTGCCGATAACATCATTGATGCCCACTTAGTC 
               
               
                   
                 AACGTTCATGGTAAGGTCTTGGACCGTAAGTCTATGGGTGAGGAT 
               
               
                   
                 TTATTCTGGGCTTTGAGAGGTGGTGGTGCTGAATCTTTCGGTATT 
               
               
                   
                 ATCGTCGCTTGGAAGATTAGATTAGTTGCTGTTCCAAAGTCTACT 
               
               
                   
                 ATGTTCTCTGTTAAGAAGATCATGGAAATTCACGAGTTGGTTAAA 
               
               
                   
                 TTAGTTAACAAATGGCAAAACATTGCCTACAAGTACGATAAAGAT 
               
               
                   
                 TTGTTATTAATGACTCACTTTATCACTAGAAACATTACTGATAAC 
               
               
                   
                 CAAGGTAAGAATAAGACTGCCATTCACACTTACTTCTCTTCTGTT 
               
               
                   
                 TTCTTGGGTGGTGTTGATTCCTTGGTCGATTTGATGAACAAGTCT 
               
               
                   
                 TTTCCAGAATTAGGTATTAAGAAGACCGATTGTCGTCAATTATCT 
               
               
                   
                 TGGATTGATACCATTATTTTTTACTCCGGTGTTGTCAACTACGAC 
               
               
                   
                 ACTGATAATTTTAATAAGGAGATTTTGTTAGATAGATCTGCTGGT 
               
               
                   
                 CAAAATactGCCTTTAAAATCAAATTGGACTACGTTAAGgaaCCT 
               
               
                   
                 ATTCCAGAATCCGTCTTTGTTCAAATTTTGGAGAAGTTATACGAA 
               
               
                   
                 GAAGATATTGGTGCTGGTATGTACGCCTTGTATCCATATGGTGGT 
               
               
                   
                 ATTATGGATGAAATTTCTGAATCCGCCATCCCTTTCCCTCATCGT 
               
               
                   
                 GCTGGTATCTTATACGAGTTGTGGTACATCTGTTCTTGGGAAAAG 
               
               
                   
                 CAAGAAGATAATGAAAAGCATTTGAACTGGATCCGTAACATCTAT 
               
               
                   
                 AACTTCATGACTCCATACGTTTCCAAAAACCCTAGATTGGCTTAC 
               
               
                   
                 TTAAATTACAGAGACTTAGATATTGGTATTAACGACCCTAAGAAC 
               
               
                   
                 CCAAACAATTACACTCAAGCTAGAATCTGGGGTGAAAAGTACTTC 
               
               
                   
                 GGTAAGAATTTCGACAGATTAGTTAAGGTCAAGACTTTAGTTGAC 
               
               
                   
                 CCAAATAACTTCTTCAGAAACGAACAATCTATCCCACCATTGCCT 
               
               
                   
                 AGACATAGACACTAG 
               
               
                   
               
               
                 SEQ ID NO: 318 
                 MKCSTFSFWFVCKIIFFFFSFNIQTSIANPRENFLKCFSQYIPNN 
               
               
                 CBDA Synthase, 
                 ATNLKLVYTQNNPLYMSVLNSTIHNLRFTSDTTPKPLVIVTPSHV 
               
               
                 G378T, K389E variant 
                 SHIQGTILCSKKVGLQIRTRSGGHDSEGMSYISQVPFVIVDLRNM 
               
               
                 Artificial Sequence 
                 RSIKIDVHSQTAVVVEAGATLGEVYYWVNEKNENLSLAAGYCPTV 
               
               
                   
                 CAGGHFGGGGYGPLMRNYGLAADNIIDAHLVNVFIGKVLDRKSMG 
               
               
                   
                 EDLFWALRGGGAESFGIIVAWKIRLVAVPKSTMFSVKKIVIEIHE 
               
               
                   
                 LVKLVNKVVQNIAYKYDKDLLLMTHFITRNITDNQGKNKTAIHTY 
               
               
                   
                 FSSVFLGGVDSLVDLMNKSFPELGIKKTDCRQLSWIDTIIFYSGV 
               
               
                   
                 VNYDTDNFNKEILLDRSAGQNTAFKIKLDYVKEPIPESVFVQILE 
               
               
                   
                 KLYEEDIGAGMYALYPYGGIMDEISESAIPFPHRAGILYELWYIC 
               
               
                   
                 SWEKQEDNEKHLNWIRNIYNFMTPYVSKNPRLAYLNYRDLDIGIN 
               
               
                   
                 DPKNPNNYTQARIWGEKYFGKNFDRLVKVKTLVDPNNFFRNEQSI 
               
               
                   
                 PPLPRHRH* 
               
               
                   
               
               
                 SEQ ID NO: 319 
                 ATGAAATGCTCCACTTTCTCTTTCTGGTTCGTTTGTAAGATTATC 
               
               
                 CBDA Synthase, 
                 TTCTTCTTCTTTTCTTTCAACATCCAAACTTCCATTGCCAACCCT 
               
               
                 M61W, G378T, K389E 
                 CGTGAGAACTTCTTGAAATGTTTTTCTCAATATATCCCAAATAAC 
               
               
                 variant 
                 GCTACTAACTTGAAGTTAGTCTATACTCAAAACAACCCATTATAT 
               
               
                 Artificial Sequence 
                 tggTCTGTCTTAAACTCTACCATTCACAACTTACGTTTCACTTCT 
               
               
                   
                 GATACTACTCCAAAACCTTTGGTCATCGTCACCCCATCCCACGTT 
               
               
                   
                 TCTCACATCCAAGGTACCATCTTGTGTTCCAAAAAGGTTGGTTTA 
               
               
                   
                 CAAATCCGTACTAGATCCGGTGGTCATGACTCCGAAGGTATGTCT 
               
               
                   
                 TACAT 
               
               
                   
                 TTCCCAAGTCCCTTTCGTCATCGTCGACTTAAGAAATATGCGTTC 
               
               
                   
                 CATCAAGATTGATGTCCATTCCCAAACTGCTTGGGTTGAAGCCGG 
               
               
                   
                 TGCCACTTTAGGTGAAGTCTATTACTGGGTTAACGAGAAGAATGA 
               
               
                   
                 GAACTTATCTTTGGCTGCCGGTTACTGTCCAACTGTTTGTGCTGG 
               
               
                   
                 TGGTCATTTCGGTGGTGGTGGTTACGGTCCATTAATGCGTAACTA 
               
               
                   
                 CGGTTTGGCTGCCGATAACATCATTGATGCCCACTTAGTCAACGT 
               
               
                   
                 TCATGGTAAGGTCTTGGACCGTAAGTCTATGGGTGAGGATTTATT 
               
               
                   
                 CTGGGCTTTGAGAGGTGGTGGTGCTGAATCTTTCGGTATTATCGT 
               
               
                   
                 CGCTTGGAAGATTAGATTAGTTGCTGTTCCAAAGTCTACTATGTT 
               
               
                   
                 CTCTGTTAAGAAGATCATGGAAATTCACGAGTTGGTTAAATTAGT 
               
               
                   
                 TAACAAATGGCAAAACATTGCCTACAAGTACGATAAAGATTTGTT 
               
               
                   
                 ATTAATGACTCACTTTATCACTAGAAACATTACTGATAACCAAGG 
               
               
                   
                 TAAGAATAAGACTGCCATTCACACTTACTTCTCTTCTGTTTTCTT 
               
               
                   
                 GGGTGGTGTTGATTCCTTGGTCGATTTGATGAACAAGTCTTTTCC 
               
               
                   
                 AGAATTAGGTATTAAGAAGACCGATTGTCGTCAATTGATAATTTT 
               
               
                   
                 AATAAGGAGATTTTGTTAGATAGATCTGCTGGTCAAAATactGCC 
               
               
                   
                 TTTAAAATCAAATTGGACTACGTTAAGgaaCCTATTCCAGAATCC 
               
               
                   
                 GTCTTTGTTCAAATTTTGGAGAAGTTATACGAAGAAGATATTGGT 
               
               
                   
                 GCTGGTATGTACGCCTTGTATCCATATGGTGGTATTATGGATGAA 
               
               
                   
                 ATTTCTGAATCCGCCATCCCTTTCCCTCATCGTGCTGGTATCTTA 
               
               
                   
                 TACGAGTTGTGGTACATCTGTTCTTGGGAAAAGCAAGAAGATAAT 
               
               
                   
                 GAAAAGCATTTGAACTGGATCCGTAACATCTATAACTTCATGACT 
               
               
                   
                 CCATACGTTTCCAAAAACCCTAGATTGGCTTACTTAAATTACAGA 
               
               
                   
                 GACTTAGATATTGGTATTAACGACCCTAAGAACCCAAACAATTAC 
               
               
                   
                 ACTCAAGCTAGAATCTGGGGTGAAAAGTACTTCGGTAAGAATTTC 
               
               
                   
                 GACAGATTAGTTAAGGTCAAGACTTTAGTTGACCCAAATAACTTC 
               
               
                   
                 TTCAGAAACGAACAATCTATCCCACCATTGCCTAGACATAGACAC 
               
               
                   
                 TAG 
               
               
                   
               
               
                 SEQ ID NO: 320 
                 MKCSTFSFWFVCKIIFFFFSFNIQTSIANPRENFLKCFSQYIPNN 
               
               
                 CBDA Synthase, 
                 ATNLKLVYTQNNPLYWSVLNSTIHNLRFTSDTTPKPLVIVTPSHV 
               
               
                 M61W, G378T, K389E 
                 SHIQGTILCSKKVGLQIRTRSGGHDSEGMSYISQVPFVIVDLRNM 
               
               
                 variant 
                 RSIKIDVHSQTAWVEAGATLGEVYYWVNEKNENLSLAAGYCPTVC 
               
               
                 Artificial Sequence 
                 AGGHFGGGGYGPLMRNYGLAADNIIDAHLVNVHGKVLDRKSMGED 
               
               
                   
                 LFWALRGGGAESFGIIVAWKIRLVAVPKSTMFSVKKIYIEIHELV 
               
               
                   
                 KLVNKWQNIAYKYDKDLLLMTHFITRNITDNQGKNKTAIHTYFSS 
               
               
                   
                 VFLGGVDSLVDLMNKSFPELGIKKTDCRQLSWIDTIIFYSGWNYD 
               
               
                   
                 TDNFNKEILLDRSAGQNTAFKIKLDYVKEPIPESVFVQILEKLYE 
               
               
                   
                 EDIGAGMYALYPYGGIMDEISESAIPFPHRAGILYELWYICSWEK 
               
               
                   
                 QEDNEKHLNWIRNIYNFMTPYVSKNPRLAYLNYRDLDIGINDPKN 
               
               
                   
                 PNNYTQARIWGEKYFGKNFDRLVKVKTLVDPNNFFRNEQSIPPLP 
               
               
                   
                 RHRH* 
               
               
                   
               
               
                 SEQ ID NO: 323 
                 GTTAACCATTCTGGTTCACTTGCCGTCGTATGTTGCGGACCACCT 
               
               
                 i33 native sequence 
                 ATTTTCGTCGACACCGCTAGAAATCAAACTGCCAAAGCTGTTATC 
               
               
                   Saccharomyces  sp. 
                 AGAAACCCATCAAGAATGATTGAATACTTGGAGGAATACCAAGCC 
               
               
                   
                 TGGTGAACAATTTTTCATATTTAAGTAAACACTCAATGTATAATA 
               
               
                   
                 TCCTCTAACTGTTGTAATTTCATTAACGTAAATGGTTTGCGCCTT 
               
               
                   
                 TTTTAGGGGACCCTTGTTGATTCATTCTAACTACTGAGGCATAAG 
               
               
                   
                 TTGTTTCAAATAACACTTTTTCAGAAAAATAATCGTATTAAAAAG 
               
               
                   
                 CAGAAAAATCATACGTAAGATGACAGAAGCTTCATATTTAGTAAC 
               
               
                   
                 TCTGAATTGTATAACACACCAATTGCCGATAGAATATGAACCAAT 
               
               
                   
                 CGATCTTCAGCGTTCATGTACTTAATTTAACTACCTGTATTTTCT 
               
               
                   
                 TATAAAGATAAAATTGGTGTATAATGTAAGGGCCAAGAGAAAAAG 
               
               
                   
                 GAATCCCGCATCCCAAGCAACTTCTAGTGGACTATTTCTTCAAAA 
               
               
                   
                 AAATAACTGAATAAACACCTATATAATGTTCAGAGGTTATACTTT 
               
               
                   
                 AGTGTTTTAGAATGCAGTACCAAAAGTAATATATTGAATTAATAA 
               
               
                   
                 CTATATGATGTGTAGCTAAGAATTAAATAGTAAACGTCTTCTGAA 
               
               
                   
                 ACCTTTTAAGAGGTAATTATTGGTATTCCAAAGTCATATGTGGAG 
               
               
                   
                 GTAAGGGAGACACAAAATTATCTGGAATGACAGCGTGCTGACACA 
               
               
                   
                 TATAAAGTTCCGTAACTTCAAATGCCTTCATTATTCAACATAGGA 
               
               
                   
                 AAAGTGAAATGTGTGCCTCTAAAATATACGGAACATCGTCGAACT 
               
               
                   
                 AAAAAAATCCATTAAGCAAAGTTAGAAACAGCATGCACTACAAGA 
               
               
                   
                 CATTTGGTTCATCATGAAGAATGCTCAATTGAACCATCAATCACT 
               
               
                   
                 TTCTCTTGTTCGATGTTAGCATTATCCTCACTATCAGTTGAATCC 
               
               
                   
                 TCAATGCTTTCGGTTTCAGTCCTCGCATCTTCCTGAACTT 
               
               
                   
               
            
           
         
       
     
     EXAMPLES 
     The following examples are put forth so as to provide those of ordinary skill in the art with a complete disclosure and description of how to make and use the present disclosure, and are not intended to limit the scope of what the inventors regard as their disclosure nor are they intended to represent that the experiments below are all or the only experiments performed. Efforts have been made to ensure accuracy with respect to numbers used (e.g., amounts, temperature, etc.) but some experimental errors and deviations should be accounted for. Unless indicated otherwise, parts are parts by weight, molecular weight is weight average molecular weight, temperature is in degrees Celsius, and pressure is at or near atmospheric. Standard abbreviations may be used, e.g., bp, base pair(s); kb, kilobase(s); s or sec, second(s); min, minute(s); h or hr, hour(s); aa, amino acid(s); bp, base pair(s); nt, nucleotide(s); and the like. 
     Example 1: CBDAS Library Design, Construction, and Transformations 
     A saturation mutagenesis library of the CBDAS enzyme was synthesized by Twist Biosciences. The library was based on the full-length DNA sequence of CBDASco5 (SEQ ID NO:2), which encodes a wild type CBDAS sequence. Each construct was synthesized with 75 bp homology to the 3′ end of the GAL1 promoter at the 5′ end of the construct, and 75 bp homology to the tTDH1 terminator at the 3′ end of the construct. The library was arrayed in 96 well plate format, where each well contained a mixture of constructs encoding all possible amino acid variants for a single position, excluding the native amino acid and stop codons. All amino acid positions were varied in this way with the exception of the initiating methionine and stop codon. Amino acid variants were encoded by high frequency codons (Table 1). 
     Example 2: Competition Assay Strains 
     To evaluate variant CBDAS constructs in the context of competition with a second cannabinoid synthase, strain S478 was used. Strain S478, described in Table 5 contains all engineering required for production of CBGA from fed olivetolic acid (OA) as well as chaperones and secretory pathway engineering features that support expression of CBDAS. Additionally, Strain S478 contains an integrated THCAS construct under control of the pGAL10 promoter. Library constructs were integrated at a second locus using yeast transformation methods described herein. Single colonies were inoculated directly into the 96 well plate assay. Upon completion, samples were extracted and assayed by LC-MS. Competition assay data are shown in Table 2. 
     Once hits were identified in the initial n=1 screening, they were re-struck from the pre-culture well onto agar, and the variant synthase was PCR amplified and Sanger sequenced to identify the causal mutation. In multiple cases, especially for the most improved enzymes, it was observed that the same mutation was recovered multiple times, with remarkably similar competition ratios. This result increases our confidence in the reliability of the screening system and the efficacy of the identified mutations. 
     In total, 6,528 colonies were screened in the initial n=1 round. Of these colonies, 4,410 showed &gt;50% reduction in CBDA titer. This is a relatively high level of loss of function. Prior studies on three different proteins have shown severe loss of function (&gt;90% reduction in activity) for approximately 33% of mutations. (Crit Rev Biochem Mol Biol. 2007 September-October; 42(5): 10.1080/10409230701597642.). Applying the same metric to the initial CBDAS screening data shows that 45.6% of all clones tested had this severe loss of function. This surprising result is an indication of how difficult engineering this secreted plant enzyme is. The  Cannabis  trichome is a considerably different than the yeast cell, and it is reasonable to speculate that these differences could destabilizes the enzyme, leading to greater sensitivity to mutations. This further highlights the importance of identifying context-dependent gain of function mutations that adapt the CBDAS to the yeast environment. 
     
       
         
           
               
             
               
                 TABLE 2 
               
             
            
               
                   
               
               
                 Competition Assay Data 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                   
                   
                 Ratio 
                 Std 
                 CBDA 
                 Std 
                 THCA 
                 Std 
                   
                 Std 
               
               
                 Strain 
                 Mutation 
                 (mM) 
                 Dev 
                 (mg/L) 
                 Dev 
                 (mg/L) 
                 Dev 
                 OD600 
                 Dev 
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 S562 
                 NA 
                 3.13 
                 0.18 
                 164.91 
                 8.47 
                 52.85 
                 4.52 
                 2.81 
                 0.26 
               
               
                 S606 
                 C12F 
                 3.95 
                 0.25 
                 123.66 
                 27.68 
                 31.35 
                 7.16 
                 2.35 
                 0.58 
               
               
                 S607 
                 F17M 
                 3.81 
                 0.26 
                 154.01 
                 9.35 
                 40.59 
                 3.17 
                 2.36 
                 0.29 
               
               
                 S608 
                 F18T 
                 3.83 
                 0.38 
                 88.12 
                 49.56 
                 22.35 
                 11.91 
                 2.06 
                 0.86 
               
               
                 S609 
                 F18W 
                 3.59 
                 0.57 
                 122.11 
                 20.8 
                 34.39 
                 5.63 
                 2.44 
                 0.42 
               
               
                 S610 
                 S20G 
                 3.98 
                 0.51 
                 117.85 
                 46.79 
                 30.13 
                 12.91 
                 1.98 
                 0.76 
               
               
                 S611 
                 R31Q 
                 4.05 
                 0.16 
                 175.35 
                 1.42 
                 43.31 
                 1.94 
                 2.82 
                 0.1 
               
               
                 S612 
                 N33K 
                 4.05 
                 0.67 
                 81.73 
                 32.22 
                 19.6 
                 6.35 
                 1.65 
                 0.49 
               
               
                 S613 
                 P43E 
                 3.8 
                 0.08 
                 166.75 
                 8.65 
                 43.95 
                 3.21 
                 2.66 
                 0.03 
               
               
                 S614 
                 L49E 
                 4.33 
                 0.46 
                 216.3 
                 7.07 
                 50.33 
                 6.26 
                 2.78 
                 0.04 
               
               
                 S615 
                 L49K 
                 3.39 
                 0.16 
                 179.21 
                 11.72 
                 53 
                 4 
                 2.82 
                 0.07 
               
               
                 S616 
                 L49Q 
                 3.77 
                 0.25 
                 188.45 
                 10.28 
                 50 
                 0.87 
                 2.86 
                 0.08 
               
               
                 S617 
                 K50T 
                 4.2 
                 0.07 
                 197.76 
                 5.93 
                 47.11 
                 1.22 
                 2.56 
                 0.04 
               
               
                 S618 
                 L51I 
                 4.27 
                 0.51 
                 125.52 
                 65.82 
                 31.01 
                 17.98 
                 2.16 
                 0.82 
               
               
                 S619 
                 Q55E 
                 3.88 
                 0.31 
                 162.17 
                 20.67 
                 42.01 
                 5.93 
                 2.53 
                 0.18 
               
               
                 S620 
                 Q55P 
                 4.03 
                 0.36 
                 148.46 
                 26.02 
                 37.41 
                 10.03 
                 2.49 
                 0.59 
               
               
                 S621 
                 N56E 
                 3.9 
                 0.23 
                 172.67 
                 21.29 
                 44.45 
                 6.67 
                 2.64 
                 0.09 
               
               
                 S622 
                 N57D 
                 4.24 
                 0.31 
                 180.09 
                 3.62 
                 42.71 
                 3.98 
                 2.59 
                 0.15 
               
               
                 S623 
                 N57E 
                 4.14 
                 0.37 
                 159.48 
                 5.42 
                 38.77 
                 4.5 
                 2.51 
                 0.2 
               
               
                 S624 
                 L59E 
                 5.18 
                 0.62 
                 96.47 
                 15.62 
                 18.87 
                 3.67 
                 1.57 
                 0.28 
               
               
                 S625 
                 M61H 
                 3.89 
                 0.64 
                 144.99 
                 47.06 
                 39.09 
                 16.77 
                 2.19 
                 0.49 
               
               
                 S626 
                 M61S 
                 4.85 
                 0.23 
                 96.22 
                 6.15 
                 19.89 
                 1.89 
                 1.5 
                 0.38 
               
               
                 S627 
                 M61W 
                 4.86 
                 0.2 
                 60.69 
                 10.62 
                 12.44 
                 1.72 
                 1.25 
                 0.04 
               
               
                 S628 
                 S62N 
                 4.61 
                 0.15 
                 143.94 
                 7.53 
                 31.19 
                 1.15 
                 3.05 
                 0.05 
               
               
                 S629 
                 S62Q 
                 3.77 
                 0.11 
                 147.26 
                 11.3 
                 39.16 
                 4.02 
                 2.55 
                 0.12 
               
               
                 S630 
                 V63M 
                 4.79 
                 0.75 
                 111.97 
                 19.07 
                 23.77 
                 5.52 
                 2.19 
                 0.26 
               
               
                 S631 
                 S66D 
                 4.65 
                 0.42 
                 131.84 
                 34.54 
                 28.4 
                 7.35 
                 2.61 
                 0.53 
               
               
                 S632 
                 L71A 
                 3.68 
                 0.13 
                 177.82 
                 5.26 
                 48.38 
                 3.05 
                 2.52 
                 0.09 
               
               
                 S633 
                 L71H 
                 3.81 
                 0.19 
                 169.03 
                 10.23 
                 44.35 
                 1.37 
                 2.41 
                 0.04 
               
               
                 S634 
                 L71Q 
                 4.08 
                 0.27 
                 179.78 
                 9.3 
                 44.28 
                 4.89 
                 2.58 
                 0.14 
               
               
                 S635 
                 S75D 
                 3.53 
                 0.11 
                 158.12 
                 8.7 
                 44.82 
                 3.8 
                 2.53 
                 0.05 
               
               
                 S636 
                 S75E 
                 3.51 
                 0.17 
                 154.17 
                 3.08 
                 43.96 
                 1.53 
                 2.47 
                 0.05 
               
               
                 S637 
                 I97V 
                 3.94 
                 0.32 
                 161.05 
                 2.53 
                 41.04 
                 3.84 
                 2.67 
                 0.1 
               
               
                 S638 
                 L98V 
                 3.59 
                 0.02 
                 121.38 
                 3.5 
                 33.83 
                 0.87 
                 2.85 
                 0.28 
               
               
                 S639 
                 S100A 
                 4.29 
                 0.21 
                 200.9 
                 3.32 
                 46.93 
                 2.32 
                 2.57 
                 0.04 
               
               
                 S640 
                 V103A 
                 3.51 
                 0.51 
                 177.1 
                 2.63 
                 51.03 
                 6.43 
                 2.76 
                 0.17 
               
               
                 S641 
                 V103F 
                 3.35 
                 0.07 
                 180.18 
                 9.52 
                 53.81 
                 2.31 
                 2.67 
                 0.04 
               
               
                 S642 
                 T109V 
                 3.28 
                 0.2 
                 178.61 
                 7.75 
                 54.61 
                 3.02 
                 2.79 
                 0.01 
               
               
                 S643 
                 Q124D 
                 3.57 
                 0.24 
                 178.35 
                 8.96 
                 50 
                 1.51 
                 2.98 
                 0.37 
               
               
                 S644 
                 Q124E 
                 3.79 
                 0.3 
                 161.39 
                 12.17 
                 42.96 
                 6.39 
                 3.02 
                 0.59 
               
               
                 S645 
                 Q124N 
                 3.44 
                 0.19 
                 161.61 
                 6.09 
                 47 
                 1.08 
                 2.58 
                 0.05 
               
               
                 S646 
                 V125E 
                 4.6 
                 0.32 
                 197.61 
                 11.61 
                 42.97 
                 1.17 
                 2.71 
                 0.03 
               
               
                 S647 
                 V125Q 
                 3.49 
                 0.09 
                 171.93 
                 2.88 
                 49.25 
                 1.51 
                 2.68 
                 0.13 
               
               
                 S648 
                 I129V 
                 3.43 
                 0.31 
                 174.38 
                 0.93 
                 51.2 
                 5.07 
                 2.68 
                 0.06 
               
               
                 S649 
                 L132M 
                 3.79 
                 0.61 
                 182.82 
                 18.8 
                 48.63 
                 3.68 
                 2.39 
                 0.25 
               
               
                 S650 
                 S137G 
                 3.56 
                 0.2 
                 179.33 
                 3.79 
                 50.54 
                 3.85 
                 2.59 
                 0.08 
               
               
                 S651 
                 H143D 
                 4.25 
                 0.07 
                 185.71 
                 3.37 
                 43.75 
                 1.3 
                 2.62 
                 0.05 
               
               
                 S652 
                 V149I 
                 4.38 
                 0.31 
                 125.14 
                 8.33 
                 28.76 
                 3.87 
                 3.75 
                 0.05 
               
               
                 S653 
                 W161K 
                 3.26 
                 0.15 
                 183.12 
                 3.69 
                 56.22 
                 2.82 
                 2.61 
                 0.05 
               
               
                 S654 
                 W161R 
                 3.8 
                 0.06 
                 189.13 
                 9.34 
                 49.73 
                 2.99 
                 2.61 
                 0.06 
               
               
                 S655 
                 W161Y 
                 3.63 
                 0.19 
                 166.6 
                 6.3 
                 45.89 
                 0.67 
                 2.77 
                 0.13 
               
               
                 S656 
                 K165A 
                 4.08 
                 0.46 
                 201.72 
                 5.73 
                 49.91 
                 6.44 
                 2.61 
                 0.1 
               
               
                 S657 
                 E167P 
                 3.85 
                 0.26 
                 183.28 
                 6.04 
                 47.75 
                 2.7 
                 2.67 
                 0.08 
               
               
                 S658 
                 N168S 
                 3.89 
                 0.1 
                 186.1 
                 1.43 
                 47.87 
                 1.03 
                 2.77 
                 0.02 
               
               
                 S659 
                 S170T 
                 5.68 
                 0.15 
                 213.9 
                 9.5 
                 37.69 
                 2.03 
                 2.67 
                 0.02 
               
               
                 S660 
                 L171I 
                 5.58 
                 0.43 
                 212.17 
                 7.02 
                 38.23 
                 4.14 
                 2.6 
                 0.07 
               
               
                 S661 
                 A172V 
                 4.29 
                 0.24 
                 201.53 
                 6.58 
                 47.03 
                 1.4 
                 2.56 
                 0.04 
               
               
                 S662 
                 Y175F 
                 4.4 
                 0.81 
                 180.68 
                 4.74 
                 42.42 
                 8.58 
                 2.74 
                 0.14 
               
               
                 S663 
                 C180A 
                 3.59 
                 0.15 
                 172.49 
                 11.13 
                 47.99 
                 2.51 
                 2.63 
                 0.06 
               
               
                 S664 
                 A181V 
                 4.25 
                 0.19 
                 187.76 
                 6.23 
                 44.32 
                 3.27 
                 2.58 
                 0.07 
               
               
                 S665 
                 N196Q 
                 4.73 
                 0.27 
                 216.45 
                 5.22 
                 45.85 
                 3.21 
                 2.78 
                 0.07 
               
               
                 S666 
                 N196T 
                 4.52 
                 0.29 
                 209.85 
                 4.71 
                 46.56 
                 3.19 
                 2.8 
                 0.06 
               
               
                 S667 
                 N196V 
                 4.57 
                 0.15 
                 206.15 
                 4.38 
                 45.12 
                 1.6 
                 2.89 
                 0.13 
               
               
                 S668 
                 H208T 
                 3.26 
                 0.37 
                 185.74 
                 16.77 
                 57.09 
                 1.94 
                 2.76 
                 0.01 
               
               
                 S669 
                 A235P 
                 4.33 
                 0.19 
                 210.94 
                 1.07 
                 48.74 
                 1.94 
                 2.78 
                 0.05 
               
               
                 S670 
                 A250T 
                 3.4 
                 0.31 
                 181.44 
                 4.49 
                 53.64 
                 5.72 
                 2.79 
                 0.07 
               
               
                 S671 
                 M256V 
                 3.57 
                 0.13 
                 176.82 
                 3.15 
                 49.63 
                 2.03 
                 2.64 
                 0.04 
               
               
                 S672 
                 K260C 
                 4.77 
                 0.6 
                 198.67 
                 3.92 
                 42.04 
                 4.81 
                 2.97 
                 0.13 
               
               
                 S673 
                 K260W 
                 4.42 
                 0.23 
                 202.46 
                 3.69 
                 45.87 
                 2.94 
                 2.71 
                 0.08 
               
               
                 S674 
                 L268I 
                 3.94 
                 0.09 
                 213.24 
                 4.37 
                 54.07 
                 0.08 
                 2.73 
                 0.03 
               
               
                 S675 
                 H309V 
                 4.67 
                 0.53 
                 196.22 
                 2.3 
                 42.4 
                 4.87 
                 2.67 
                 0.08 
               
               
                 S676 
                 T310A 
                 4.91 
                 0.18 
                 207.61 
                 3.77 
                 42.27 
                 1 
                 2.64 
                 0.09 
               
               
                 S677 
                 T310C 
                 3.76 
                 0.04 
                 192.94 
                 1.11 
                 51.25 
                 0.41 
                 2.59 
                 0.03 
               
               
                 S678 
                 F316Y 
                 4.9 
                 0.49 
                 204.15 
                 2.98 
                 41.95 
                 4.01 
                 2.72 
                 0.04 
               
               
                 S679 
                 L326I 
                 4.29 
                 0.51 
                 190.04 
                 7.99 
                 44.71 
                 5.43 
                 2.6 
                 0.05 
               
               
                 S680 
                 G378T 
                 4.59 
                 0.43 
                 181.97 
                 2.09 
                 39.81 
                 3.25 
                 2.59 
                 0.01 
               
               
                 S681 
                 G378S 
                 3.94 
                 0.26 
                 173.32 
                 1.44 
                 44.09 
                 3.26 
                 2.69 
                 0.11 
               
               
                 S682 
                 K389E 
                 4.1 
                 0.14 
                 189.16 
                 3.07 
                 46.17 
                 1.94 
                 2.74 
                 0.02 
               
               
                 S683 
                 E406K 
                 4.48 
                 0.16 
                 199.44 
                 5.43 
                 44.55 
                 1.43 
                 2.61 
                 0.07 
               
               
                 S684 
                 S428L 
                 4.44 
                 0.28 
                 196.94 
                 6.43 
                 44.39 
                 1.53 
                 2.61 
                 0.11 
               
               
                 S685 
                 L439M 
                 3.42 
                 0.28 
                 174.39 
                 2.26 
                 51.16 
                 3.57 
                 2.62 
                 0.01 
               
               
                 S686 
                 N466D 
                 3.74 
                 0.2 
                 184.79 
                 3.73 
                 49.53 
                 1.75 
                 2.57 
                 0.11 
               
               
                 S687 
                 K474S 
                 3.92 
                 0.09 
                 180.41 
                 6.8 
                 46.02 
                 2.84 
                 2.48 
                 0.1 
               
               
                 S688 
                 Y499M 
                 4.32 
                 0.65 
                 183.01 
                 19.13 
                 42.59 
                 3.04 
                 2.58 
                 0.11 
               
               
                 S689 
                 Y499V 
                 4.3 
                 0.11 
                 202.74 
                 5.51 
                 47.11 
                 0.97 
                 2.61 
                 0.09 
               
               
                 S690 
                 N527E 
                 4.54 
                 0.04 
                 221.17 
                 7.69 
                 48.72 
                 1.46 
                 2.7 
                 0.04 
               
               
                 S691 
                 P538T 
                 2.22 
                 0.09 
                 107.31 
                 9.75 
                 48.18 
                 2.44 
                 2.12 
                 0.05 
               
               
                 S692 
                 R541E 
                 4.05 
                 0.49 
                 156.8 
                 57.75 
                 37.88 
                 10.63 
                 2.57 
                 0.16 
               
               
                 S693 
                 R541V 
                 3.5 
                 0.08 
                 180.51 
                 13.23 
                 51.54 
                 2.7 
                 2.5 
                 0.12 
               
               
                 S694 
                 H542V 
                 3.33 
                 0.15 
                 173.59 
                 5.52 
                 52.25 
                 3.51 
                 2.63 
                 0.11 
               
               
                 S695 
                 R543A 
                 3.8 
                 0.16 
                 172.37 
                 1.49 
                 45.46 
                 1.8 
                 2.68 
                 0.15 
               
               
                 S696 
                 R543E 
                 3.49 
                 0.05 
                 173.7 
                 6.64 
                 49.86 
                 2.54 
                 2.63 
                 0.25 
               
               
                 S697 
                 H544E 
                 4.93 
                 0.24 
                 213.7 
                 6.01 
                 43.43 
                 3.14 
                 2.51 
                 0.06 
               
               
                 S698 
                 H544D 
                 5.24 
                 0.19 
                 204.23 
                 9.94 
                 39.07 
                 3.31 
                 2.71 
                 0.18 
               
               
                   
               
            
           
         
       
     
     Example 3: Non-Competition Assay Strains 
     Selected constructs were further evaluated in a non-competition strain background, strain S487. Strain S487, described in Table 5, contains all engineering required for production of CBGA from fed olivetolic acid as well as chaperones and secretory pathway engineering features that support expression of CBDAS. Variant CBDAS constructs were PCR amplified from the selected competition strains and were integrated into S487 using yeast transformation methods described herein. A subset of these constructs were also tested in a strain, S510. Strain S510, described in Table 5, contains all engineering required for production of CBGA from fed olivetolic acid as well as a much more limited set of chaperones and secretory pathway engineering features that support expression of CBDAS. Single colonies from the transformations were inoculated directly into the 96 well plate assay. Upon completion, samples were extracted and assayed by LC-MS. The data for this assay are shown in Tables 3 and 4. 
     In total, 6,528 variants were screened in the competition background and possible hits were replicated to confirm. All validated hits were then tested in the non-competition assay to assess actual performance. 
     Considering strains S699-S791, CBDA titers were improved (outside standard deviation of wild type, S579) in 68 distinct variants covering 53 positions (nearly 10% of all residues). Preliminary mapping to a structural model shows that many mutations increase the hydrophilicity of solvent-exposed residues, which may improve solubility of the enzyme in an aqueous (non-trichome) environment. Additionally, some variants displayed a reduction in undesired THCA production. Moreover, growth, as measured by optical density (OD) was improved in most variants. Expression of wild type CBDAS makes strains sick, so this is a desirable outcome. A subset of the constructs that improved titers in the S487 background were also tested in S510 background, which contains a more limited set of chaperone and secretory pathway engineering features. Of the 20 mutations tested in this strain, 14 improved titer over the wild type strain S1100, and six reduced titer. This result indicates that some but not all mutations identified in the S487 background require the support of more extensive chaperone and secretory pathway engineering to function. 
     
       
         
           
               
             
               
                 TABLE 3 
               
             
            
               
                   
               
               
                 Non-competition Assay 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                   
                   
                 % 
                 Std 
                 CBDA 
                 Std 
                 THCA 
                 Std 
                   
                 Std 
               
               
                 Strain 
                 Mutation 
                 THCA 
                 Dev 
                 (mg/L) 
                 Dev 
                 (mg/L) 
                 Dev 
                 OD 
                 Dev 
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 S579 
                 NA 
                 7.61 
                 0.91 
                 162.07 
                 15.36 
                 14.4 
                 2.32 
                 2.46 
                 0.15 
               
               
                 S699 
                 C12F 
                 8.66 
                 0.81 
                 132.3 
                 0.86 
                 12.55 
                 1.32 
                 3.05 
                 0.4 
               
               
                 S700 
                 F17M 
                 7.91 
                 1.17 
                 160.01 
                 13.13 
                 13.74 
                 2.36 
                 2.67 
                 0.14 
               
               
                 S701 
                 F18T 
                 7.4 
                 0.69 
                 133 
                 11.5 
                 10.62 
                 1.32 
                 2.61 
                 0.14 
               
               
                 S702 
                 F18W 
                 7.77 
                 1.08 
                 145.29 
                 11.91 
                 12.17 
                 1.25 
                 2.43 
                 0.07 
               
               
                 S703 
                 S20G 
                 8.04 
                 1.44 
                 149.93 
                 7.59 
                 13.19 
                 2.94 
                 2.74 
                 0.11 
               
               
                 S704 
                 R31Q 
                 6.78 
                 0.71 
                 186.48 
                 9.37 
                 13.59 
                 1.97 
                 2.64 
                 0.02 
               
               
                 S705 
                 N33K 
                 8.32 
                 1 
                 153.12 
                 9.77 
                 13.89 
                 1.88 
                 2.37 
                 0.14 
               
               
                 S706 
                 P43E 
                 7.78 
                 0.96 
                 198.3 
                 6.67 
                 16.75 
                 2.25 
                 2.71 
                 0.23 
               
               
                 S707 
                 L49E 
                 8.09 
                 0.52 
                 221.28 
                 16.87 
                 19.43 
                 0.93 
                 3.16 
                 0.04 
               
               
                 S708 
                 L49K 
                 7.69 
                 0.27 
                 192.56 
                 10.04 
                 16.02 
                 0.61 
                 2.54 
                 0.1 
               
               
                 S709 
                 L49Q 
                 7.86 
                 0.44 
                 206.98 
                 13 
                 17.71 
                 2.1 
                 2.69 
                 0.12 
               
               
                 S710 
                 K50T 
                 8.17 
                 0.52 
                 205.99 
                 2.22 
                 18.34 
                 1.32 
                 2.66 
                 0.08 
               
               
                 S711 
                 L51I 
                 8.15 
                 0.7 
                 188 
                 12.35 
                 16.72 
                 2.26 
                 2.49 
                 0.32 
               
               
                 S712 
                 Q55E 
                 7.18 
                 0.69 
                 186.5 
                 1.54 
                 14.43 
                 1.49 
                 2.49 
                 0.15 
               
               
                 S713 
                 Q55P 
                 7.3 
                 0.63 
                 182.74 
                 2.85 
                 14.39 
                 1.4 
                 2.61 
                 0.17 
               
               
                 S714 
                 N56E 
                 8 
                 0.32 
                 215.47 
                 6.61 
                 18.73 
                 0.92 
                 2.84 
                 0.05 
               
               
                 S715 
                 N57D 
                 7.05 
                 0.96 
                 223.94 
                 7.72 
                 17.06 
                 3.03 
                 2.73 
                 0.05 
               
               
                 S716 
                 N57E 
                 7.71 
                 0.42 
                 142.47 
                 12 
                 11.86 
                 0.43 
                 2.77 
                 0.16 
               
               
                 S717 
                 L59E 
                 7.61 
                 0.39 
                 160.45 
                 6.03 
                 13.22 
                 0.88 
                 2.31 
                 0.08 
               
               
                 S718 
                 M61H 
                 7.18 
                 0.64 
                 176.09 
                 4.86 
                 13.64 
                 1.47 
                 3.33 
                 0.11 
               
               
                 S719 
                 M61S 
                 7.88 
                 0.79 
                 175.52 
                 4.41 
                 15.33 
                 1.22 
                 2.95 
                 0.22 
               
               
                 S720 
                 M61W 
                 6.83 
                 0.61 
                 180.49 
                 10.73 
                 13.29 
                 1.97 
                 3.15 
                 0.32 
               
               
                 S721 
                 S62N 
                 7.91 
                 1.13 
                 142.05 
                 6.05 
                 12.2 
                 1.83 
                 2.75 
                 0.02 
               
               
                 S722 
                 S62Q 
                 7.29 
                 0.79 
                 188.83 
                 4.51 
                 14.88 
                 1.97 
                 2.77 
                 0.13 
               
               
                 S723 
                 V63M 
                 7.23 
                 0.41 
                 123.49 
                 2.24 
                 9.63 
                 0.76 
                 2.18 
                 0.24 
               
               
                 S724 
                 S66D 
                 8.12 
                 0.61 
                 158.68 
                 6.5 
                 14.03 
                 1.46 
                 2.68 
                 0.11 
               
               
                 S725 
                 L71A 
                 7.27 
                 1.01 
                 179.55 
                 5.46 
                 14.14 
                 2.5 
                 2.6 
                 0.08 
               
               
                 S726 
                 L71H 
                 6.71 
                 0.87 
                 163.52 
                 5.76 
                 11.75 
                 1.33 
                 2.74 
                 0.03 
               
               
                 S727 
                 L71Q 
                 7.68 
                 0.62 
                 172.74 
                 7.9 
                 14.42 
                 1.88 
                 2.74 
                 0.06 
               
               
                 S728 
                 S75D 
                 7.3 
                 1.11 
                 155.85 
                 3.07 
                 12.26 
                 1.8 
                 2.71 
                 0.05 
               
               
                 S729 
                 S75E 
                 8.57 
                 0.59 
                 155.44 
                 8.67 
                 14.57 
                 1.26 
                 2.72 
                 0.07 
               
               
                 S730 
                 I97V 
                 8.28 
                 1.11 
                 172.47 
                 10.43 
                 15.65 
                 2.99 
                 2.68 
                 0.02 
               
               
                 S731 
                 L98V 
                 8.08 
                 0.84 
                 124.45 
                 9.88 
                 10.95 
                 1.51 
                 2.7 
                 0.07 
               
               
                 S732 
                 S100A 
                 7.81 
                 1.76 
                 194.51 
                 4.7 
                 16.53 
                 4.08 
                 2.63 
                 0.07 
               
               
                 S733 
                 V103A 
                 7.53 
                 0.67 
                 171.55 
                 14.95 
                 14.04 
                 2.4 
                 2.8 
                 0.1 
               
               
                 S734 
                 V103F 
                 8.41 
                 0.73 
                 197.08 
                 2.83 
                 18.12 
                 1.81 
                 2.92 
                 0.03 
               
               
                 S735 
                 T109V 
                 7.91 
                 0.43 
                 198.91 
                 0.81 
                 17.08 
                 0.94 
                 2.95 
                 0.03 
               
               
                 S736 
                 Q124D 
                 8.68 
                 0.85 
                 192.12 
                 5.09 
                 18.28 
                 2.04 
                 2.94 
                 0.02 
               
               
                 S737 
                 Q124E 
                 8.6 
                 0.57 
                 175.75 
                 2.64 
                 16.54 
                 1.32 
                 2.84 
                 0.08 
               
               
                 S738 
                 Q124N 
                 8.1 
                 1.51 
                 184.3 
                 2.21 
                 16.29 
                 3.31 
                 2.76 
                 0.03 
               
               
                 S739 
                 V125E 
                 8.11 
                 0.65 
                 214.24 
                 4.01 
                 18.9 
                 1.62 
                 2.83 
                 0.04 
               
               
                 S740 
                 V125Q 
                 8.4 
                 0.21 
                 184.39 
                 8.73 
                 16.92 
                 1.11 
                 2.91 
                 0.02 
               
               
                 S741 
                 I129V 
                 8.35 
                 1.06 
                 183.7 
                 7.44 
                 16.83 
                 2.97 
                 2.71 
                 0.1 
               
               
                 S742 
                 L132M 
                 7.4 
                 1.15 
                 229.74 
                 10.56 
                 18.31 
                 2.54 
                 3.14 
                 0.12 
               
               
                 S743 
                 S137G 
                 7.34 
                 0.58 
                 185.65 
                 6.36 
                 14.74 
                 1.64 
                 2.88 
                 0.04 
               
               
                 S744 
                 H143D 
                 7.95 
                 0.59 
                 187.93 
                 6.86 
                 16.24 
                 1.66 
                 2.87 
                 0.09 
               
               
                 S745 
                 V149I 
                 7.6 
                 1.01 
                 212.1 
                 3.7 
                 17.47 
                 2.51 
                 3.1 
                 0.08 
               
               
                 S746 
                 W161K 
                 8.28 
                 0.78 
                 190.83 
                 2.93 
                 17.23 
                 1.54 
                 2.88 
                 0.18 
               
               
                 S747 
                 W161R 
                 7.16 
                 0.73 
                 211.08 
                 6.64 
                 16.28 
                 1.89 
                 2.89 
                 0.06 
               
               
                 S748 
                 W161Y 
                 7.3 
                 0.82 
                 194.18 
                 5.19 
                 15.27 
                 1.54 
                 2.78 
                 0.06 
               
               
                 S749 
                 K165A 
                 7.43 
                 0.53 
                 221.03 
                 3.43 
                 17.77 
                 1.62 
                 3.08 
                 0.05 
               
               
                 S750 
                 E167P 
                 8.13 
                 1 
                 196.1 
                 3.23 
                 17.39 
                 2.59 
                 2.87 
                 0.03 
               
               
                 S751 
                 N168S 
                 8.05 
                 1.11 
                 197.14 
                 5.78 
                 17.32 
                 2.99 
                 3.07 
                 0.1 
               
               
                 S752 
                 S170T 
                 6.78 
                 0.49 
                 245.1 
                 2.72 
                 17.83 
                 1.33 
                 3.14 
                 0.03 
               
               
                 S753 
                 L171I 
                 7.33 
                 0.75 
                 245.44 
                 7.43 
                 19.46 
                 2.48 
                 3.01 
                 0.03 
               
               
                 S754 
                 A172V 
                 7.07 
                 0.83 
                 205.35 
                 12.64 
                 15.67 
                 2.5 
                 2.75 
                 0.07 
               
               
                 S755 
                 Y175F 
                 6.68 
                 0.67 
                 198.7 
                 1.66 
                 14.25 
                 1.61 
                 3.04 
                 0.04 
               
               
                 S756 
                 C180A 
                 7.54 
                 1.49 
                 184.86 
                 2.91 
                 15.09 
                 3.08 
                 2.82 
                 0.04 
               
               
                 S757 
                 A181V 
                 8.89 
                 0.95 
                 198.25 
                 6.26 
                 19.37 
                 2.42 
                 2.8 
                 0.05 
               
               
                 S758 
                 N196Q 
                 7.5 
                 0.64 
                 234.66 
                 3.74 
                 19.04 
                 1.81 
                 3 
                 0.03 
               
               
                 S759 
                 N196T 
                 7.25 
                 0.81 
                 232.71 
                 1.82 
                 18.2 
                 2.2 
                 3.02 
                 0.11 
               
               
                 S760 
                 N196V 
                 6.65 
                 0.23 
                 221.97 
                 2.92 
                 15.81 
                 0.65 
                 3.04 
                 0.04 
               
               
                 S761 
                 H208T 
                 6.86 
                 0.79 
                 196.07 
                 5.31 
                 14.45 
                 1.91 
                 2.98 
                 0.03 
               
               
                 S762 
                 A235P 
                 7 
                 0.16 
                 218.66 
                 2.12 
                 17.79 
                 1.47 
                 2.95 
                 0.02 
               
               
                 S763 
                 A250T 
                 7.63 
                 0.79 
                 178.38 
                 7.71 
                 14.76 
                 1.96 
                 2.91 
                 0.01 
               
               
                 S764 
                 M256V 
                 14.05 
                 2 
                 196.25 
                 5.09 
                 32.23 
                 5.93 
                 2.83 
                 0.02 
               
               
                 S765 
                 K260C 
                 7.5 
                 1.02 
                 226.92 
                 19.8 
                 18.42 
                 3.11 
                 2.83 
                 0.03 
               
               
                 S766 
                 K260W 
                 6.47 
                 0.51 
                 220.7 
                 11.96 
                 15.22 
                 0.69 
                 2.94 
                 0.07 
               
               
                 S767 
                 L268I 
                 7.59 
                 0.55 
                 233.68 
                 6.98 
                 19.19 
                 1.46 
                 2.78 
                 0.03 
               
               
                 S768 
                 H309V 
                 8.84 
                 0.74 
                 172.01 
                 32.73 
                 16.46 
                 1.8 
                 2.8 
                 0.14 
               
               
                 S769 
                 T310A 
                 9.23 
                 0.85 
                 217.24 
                 4.54 
                 22.07 
                 1.92 
                 2.74 
                 0.06 
               
               
                 S770 
                 T310C 
                 9.62 
                 0.51 
                 213.55 
                 8.72 
                 22.79 
                 2.2 
                 2.76 
                 0.04 
               
               
                 S771 
                 F316Y 
                 8.74 
                 0.71 
                 231.8 
                 8.9 
                 22.23 
                 2.24 
                 2.72 
                 0.07 
               
               
                 S772 
                 L326I 
                 8.73 
                 0.72 
                 213.73 
                 6.82 
                 20.42 
                 1.34 
                 2.75 
                 0.05 
               
               
                 S773 
                 G378T 
                 6.6 
                 0.81 
                 201.39 
                 1.94 
                 14.23 
                 1.78 
                 2.8 
                 0.04 
               
               
                 S774 
                 G378S 
                 7.95 
                 1.38 
                 199.74 
                 6.91 
                 17.3 
                 3.44 
                 2.75 
                 0.03 
               
               
                 S775 
                 K389E 
                 7.09 
                 0.81 
                 191.7 
                 6.09 
                 14.63 
                 1.66 
                 2.91 
                 0.04 
               
               
                 S776 
                 E406K 
                 ND 
                 ND 
                 ND 
                 ND 
                 ND 
                 ND 
                 ND 
                 ND 
               
               
                 S777 
                 S428L 
                 8.5 
                 0.52 
                 206.13 
                 1.8 
                 19.16 
                 1.41 
                 2.74 
                 0.02 
               
               
                 S778 
                 L439M 
                 7.43 
                 1.06 
                 180.84 
                 5.67 
                 14.54 
                 2.36 
                 2.89 
                 0.06 
               
               
                 S779 
                 N466D 
                 8.21 
                 0.96 
                 190.55 
                 5.45 
                 17.05 
                 2.23 
                 2.84 
                 0.07 
               
               
                 S780 
                 K474S 
                 7.21 
                 0.75 
                 172.35 
                 3.06 
                 13.41 
                 1.64 
                 2.79 
                 0.09 
               
               
                 S781 
                 Y499M 
                 7.5 
                 0.2 
                 203.87 
                 4.24 
                 16.54 
                 0.52 
                 2.83 
                 0.05 
               
               
                 S782 
                 Y499V 
                 7.98 
                 1.34 
                 221.74 
                 4.21 
                 19.23 
                 3.2 
                 2.9 
                 0.03 
               
               
                 S783 
                 N527E 
                 8.08 
                 0.46 
                 213.24 
                 2.57 
                 18.76 
                 1.17 
                 3.18 
                 0.16 
               
               
                 S784 
                 P538T 
                 7.11 
                 1.97 
                 171.35 
                 5.64 
                 13.14 
                 3.83 
                 2.88 
                 0.03 
               
               
                 S785 
                 R541E 
                 8.12 
                 1.04 
                 184.17 
                 1.51 
                 16.27 
                 2.16 
                 2.92 
                 0.03 
               
               
                 S786 
                 R541V 
                 8.07 
                 0.3 
                 190.64 
                 8.32 
                 16.72 
                 0.11 
                 2.87 
                 0.06 
               
               
                 S787 
                 H542V 
                 7.87 
                 1.72 
                 181.8 
                 3.47 
                 15.63 
                 3.92 
                 2.84 
                 0.05 
               
               
                 S788 
                 R543A 
                 8.82 
                 0.25 
                 179.82 
                 1.17 
                 17.39 
                 0.48 
                 2.87 
                 0.13 
               
               
                 S789 
                 R543E 
                 6.92 
                 1.02 
                 201.49 
                 2.72 
                 14.98 
                 2.28 
                 2.93 
                 0.04 
               
               
                 S790 
                 H544E 
                 7.89 
                 0.6 
                 200.67 
                 4.27 
                 17.23 
                 1.76 
                 3.01 
                 0.05 
               
               
                 S791 
                 H544D 
                 7.93 
                 0.17 
                 194.86 
                 16.01 
                 16.78 
                 1.53 
                 3.03 
                 0.11 
               
               
                 S1100 
                 NA (WT) 
                 8.43 
                 0.86 
                 51.81 
                 8.72 
                 4.76 
                 8.72 
                 3.23 
                 0.18 
               
               
                 S1101 
                 R31Q 
                 8.33 
                 1.07 
                 69.58 
                 6.39 
                 6.36 
                 6.39 
                 3.2 
                 0.15 
               
               
                 S1102 
                 L49E 
                 8.58 
                 0.85 
                 86.97 
                 9.15 
                 8.11 
                 9.15 
                 3.35 
                 0.06 
               
               
                 S1103 
                 L71H 
                 7.92 
                 0.8 
                 44 
                 5.9 
                 3.79 
                 5.9 
                 3.37 
                 0.3 
               
               
                 S1104 
                 M61H 
                 8.97 
                 1.46 
                 36.4 
                 2.91 
                 3.6 
                 2.91 
                 3.46 
                 0.26 
               
               
                 S1105 
                 M61W 
                 9.01 
                 0.53 
                 42.06 
                 4.75 
                 4.18 
                 4.75 
                 3.6 
                 0.21 
               
               
                 S1106 
                 L132M 
                 9.37 
                 1.6 
                 60.99 
                 11.57 
                 6.26 
                 11.57 
                 3.55 
                 0.4 
               
               
                 S1107 
                 V149I 
                 8.17 
                 1.68 
                 40.67 
                 6.74 
                 3.64 
                 6.74 
                 3.33 
                 0.19 
               
               
                 S1108 
                 S170T 
                 7.91 
                 0.93 
                 141.99 
                 10.56 
                 12.19 
                 10.56 
                 3.41 
                 0.26 
               
               
                 S1109 
                 L171I 
                 7.96 
                 0.96 
                 126.11 
                 12.35 
                 10.9 
                 12.35 
                 3.51 
                 0.14 
               
               
                 S1110 
                 Y175F 
                 7.84 
                 0.8 
                 103.07 
                 12.66 
                 8.75 
                 12.66 
                 3.39 
                 0.26 
               
               
                 S1111 
                 N196Q 
                 8.47 
                 0.79 
                 88.61 
                 18.38 
                 8.1 
                 18.38 
                 3.5 
                 0.26 
               
               
                 S1112 
                 N196T 
                 8 
                 0.66 
                 73.5 
                 10.73 
                 6.4 
                 10.73 
                 3.73 
                 0.23 
               
               
                 S1113 
                 N196V 
                 7.51 
                 1.34 
                 86.16 
                 11.2 
                 7.15 
                 11.2 
                 4.29 
                 0.68 
               
               
                 S1114 
                 H208T 
                 8.96 
                 1.82 
                 40.13 
                 5.26 
                 3.92 
                 5.26 
                 3.28 
                 0.3 
               
               
                 S1115 
                 K260W 
                 7.83 
                 1.11 
                 100.95 
                 14.49 
                 8.54 
                 14.49 
                 3.42 
                 0.14 
               
               
                 S1116 
                 L268I 
                 8.4 
                 0.66 
                 62.7 
                 8.31 
                 5.74 
                 8.31 
                 3.47 
                 0.06 
               
               
                 S1117 
                 F316Y 
                 8.22 
                 0.78 
                 93.97 
                 9.12 
                 8.41 
                 9.12 
                 3.47 
                 0.28 
               
               
                 S1118 
                 G378T 
                 6.58 
                 1.16 
                 106.8 
                 12.83 
                 7.5 
                 12.83 
                 3.36 
                 0.17 
               
               
                 S1119 
                 N527E 
                 7.3 
                 0.82 
                 90.02 
                 9.59 
                 7.1 
                 9.59 
                 3.33 
                 0.18 
               
               
                 S1120 
                 R543E 
                 8.69 
                 1.17 
                 47.9 
                 7.48 
                 4.54 
                 7.48 
                 3.28 
                 0.28 
               
               
                   
               
               
                 (ND = Not Done) 
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 4 
               
             
            
               
                   
               
               
                 Non-competition Assay 
               
            
           
           
               
               
               
               
               
               
            
               
                   
                 CBDA mg/L 
                 THCA mg/L 
                 THCA % 
                 CBCA mg/L 
                 CBCA % 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 Exp* 
                 Strain** 
                 Mutation 
                 Avg 
                 StdDev 
                 Avg 
                 StdDev 
                 Avg 
                 Avg 
                 StdDev 
                 Avg 
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 1 
                 S579 
                 NA 
                 204.03 
                 9.82 
                 24.07 
                 2.36 
                 10.54 
                 ND 
                 ND 
                 ND 
               
               
                 1 
                 S935 
                 I445M 
                 94.42 
                 6.67 
                 6.48 
                 1.34 
                 6.42 
                 ND 
                 ND 
                 ND 
               
               
                 1 
                 S938 
                 M412Q 
                 88.52 
                 17.46 
                 9.01 
                 2.41 
                 9.21 
                 ND 
                 ND 
                 ND 
               
               
                 1 
                 S940 
                 L415M 
                 173.12 
                 6.85 
                 17.2 
                 1.77 
                 9.04 
                 ND 
                 ND 
                 ND 
               
               
                 1 
                 S941 
                 D115N 
                 61.26 
                 8.32 
                 13.09 
                 1.53 
                 17.66 
                 ND 
                 ND 
                 ND 
               
               
                 1 
                 S942 
                 A414T 
                 68.63 
                 3.55 
                 23.32 
                 1.99 
                 25.34 
                 ND 
                 ND 
                 ND 
               
               
                 1 
                 S943 
                 A414T 
                 75.63 
                 8.2 
                 26.77 
                 4.04 
                 26.11 
                 ND 
                 ND 
                 ND 
               
               
                 1 
                 S944 
                 A414V 
                 188.19 
                 20.16 
                 81.2 
                 13.23 
                 30.05 
                 ND 
                 ND 
                 ND 
               
               
                 1 
                 S945 
                 A414M 
                 73.07 
                 7.2 
                 40.3 
                 2.61 
                 35.64 
                 ND 
                 ND 
                 ND 
               
               
                 1 
                 S946 
                 A414M 
                 66.57 
                 3.37 
                 42.35 
                 4.07 
                 38.83 
                 ND 
                 ND 
                 ND 
               
               
                 2 
                 S579 
                 NA 
                 211.17 
                 14 
                 19.23 
                 2.24 
                 8.33 
                 ND 
                 ND 
                 ND 
               
               
                 2 
                 S935 
                 I445M 
                 105.31 
                 6.27 
                 4.98 
                 0.75 
                 4.51 
                 ND 
                 ND 
                 ND 
               
               
                 3 
                 S1205 
                 M61W, G378T 
                 174.13 
                 26.9 
                 10.97 
                 2.17 
                 5.9 
                 33.36 
                 4.66 
                 15.27 
               
               
                 3 
                 S1206 
                 M61W, K389E 
                 186.82 
                 13.84 
                 15.56 
                 1.11 
                 7.7 
                 17.78 
                 1.52 
                 8.08 
               
               
                 3 
                 S1207 
                 G378T, K389E 
                 199.96 
                 9.91 
                 12.91 
                 1.41 
                 6.06 
                 35.4 
                 1.75 
                 14.26 
               
               
                 3 
                 S1208 
                 M61W, G378T, 
                 192.82 
                 7.36 
                 12.88 
                 1.16 
                 6.26 
                 38.35 
                 1.9 
                 15.71 
               
               
                   
                   
                 K389E 
               
               
                 3 
                 S579 
                 NA 
                 173.53 
                 5.9 
                 14.49 
                 0.66 
                 7.71 
                 13.72 
                 1.4 
                 6.80 
               
               
                 3 
                 S935 
                 I445M 
                 85.24 
                 7.62 
                 3.1 
                 0.65 
                 3.51 
                 4.56 
                 0.72 
                 4.91 
               
               
                 3 
                 S975 
                 L171I 
                 228.93 
                 11.96 
                 18.48 
                 0.86 
                 ND 
                 20.91 
                 2.22 
                 7.79 
               
               
                 4 
                 S579 
                 NA 
                 198.61 
                 12.07 
                 16.66 
                 1.41 
                 ND 
                 17.54 
                 1.6 
                 7.53 
               
               
                 4 
                 S935 
                 I445M 
                 99 
                 13.2 
                 3.43 
                 1.26 
                 ND 
                 4.98 
                 1.23 
                 4.64 
               
               
                 4 
                 S975 
                 L171I 
                 257.02 
                 19.41 
                 22.13 
                 2.78 
                 ND 
                 25.63 
                 3.38 
                 8.41 
               
               
                   
               
               
                 (n = 4 or greater for all data in Table 4; ND = Not Done) 
               
               
                 *Absolute values and %THCA can vary by experiment, so values should be compared to their same experiment control. Four separate experiments were conducted and each group is indicated in the “Exp” column. 
               
               
                 **Where multiple strains have the same mutation (e.g., S942, S943), they represent different transformation clones that were compared 
               
            
           
         
       
     
     GENERAL METHODS OF THE EXAMPLES 
     Yeast Transformation Methods 
     Each DNA construct comprising one or more heterologous nucleic acids disclosed herein (e.g., constructs detailed in Table 5) was integrated into  Saccharomyces cerevisiae  (CEN.PK2, Strain S4) with standard molecular biology techniques in an optimized lithium acetate (LiAc) transformation. Briefly, cells were grown overnight in yeast extract peptone dextrose (YPD) media at 30° C. with shaking (200 rpm), diluted to an OD600 of 0.175 in YPD, and grown to an OD600 of 0.6-0.8. Transformations were conducted in 96 well plate format, using 1.67 mL of culture per well. The total culture volume was harvested by centrifugation, washed in equivalent volume of sterile water, spun down again, and washed in equivalent volume 100 mM LiAc. Cells were spun down again, the supernatant was removed, and the cells were resuspended in a transformation mix consisting of 80 μL 50% PEG, 12 μL 1M LiAc, 3.3 μL boiled salmon sperm DNA, 5 μL of PCR amplified library DNA, and 19.7 μL of water (scaled by number of transformations). Following a heat shock at 42° C. for 40 minutes, cells were recovered overnight in YPD media before plating on selective media. DNA integration was confirmed by colony PCR with primers specific to the integrations for a sample of colonies to confirm high rates of integration. 
     Yeast Culturing Conditions 
     Yeast colonies comprising library construct nucleic acids disclosed herein, modified host cells, were picked into 96-well microtiter plates containing 360 μL of YPD (10 g/L yeast extract, 20 g/L Bacto peptone, 20 g/L dextrose (glucose)) and sealed with a breathable film seal. Cells were cultured at 30° C. in a high capacity microtiter plate incubator shaking at 1000 rpm and 80% humidity for 2 days (termed “pre-culture”) until the cultures reached carbon exhaustion. The growth-saturated cultures were subcultured into fresh plates containing YPGAL and either olivetolic acid or hexanoic acid, or an olivetolic acid derivative or a carboxylic acid other than hexanoic acid (10 g/L yeast extract, 20 g/L Bacto peptone, 20 or 40 g/L galactose, 1 g/L glucose and either 1 mM olivetolic acid or 2 mM hexanoic acid, or 1 mM of an olivetolic acid derivative or 2 mM of a carboxylic acid other than hexanoic acid), by taking 15 μL from the saturated cultures and diluting into 360 of fresh media and sealed with a breathable film seal. Modified host cells in the production media were cultured at 30° C. in a high capacity microtiter plate shaker at 1000 rpm and 80% humidity for an additional 5 days prior to extraction and analysis. Upon completion, 25 μL of whole cell broth was diluted into 975 μL of methanol, sealed with a foil seal, and shaken at 1200 rpm for 60 seconds to extract the cannabinoids or cannabinoid derivatives. After shaking, the plate was centrifuged at 1000×g for 60 seconds to remove any solids. After centrifugation, the seal was removed and 10 μL of supernatant was transferred to a fresh assay plate containing 240 μL of methanol, sealed with a foil seal, shaken for 60 seconds at 900 rpm, and analyzed by LC-MS. 
     Analytical Methods 
     Samples were analyzed by LC-MS mass spectrometer (Agilent 6470) using a Phenomenex Kinetex Phenyl-Hexyl 2.1×30 mm, 2.6 μm analytical column with the following gradient (Mobile Phase A: LC-MS grade water with 0.1% formic acid; Mobile Phase B: LC-MS grade acetonitrile with 0.1% formic acid): 
     
       
         
           
               
               
               
             
               
                   
                   
               
               
                   
                 Time (minutes) 
                 % B 
               
               
                   
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                   
                 0 
                 40 
               
               
                   
                 0.1 
                 40 
               
               
                   
                 0.55 
                 58 
               
               
                   
                 1.45 
                 58 
               
               
                   
                 1.46 
                 40 
               
               
                   
                 1.75 
                 40 
               
               
                   
                   
               
            
           
         
       
     
     The mass spectrometer was operated in negative ion multiple reaction-monitoring mode. Each cannabinoid or cannabinoid derivative was identified by retention time, determined from an authentic standard, and multiple reaction monitoring (MRM) transition: 
     
       
         
           
               
               
               
               
               
             
               
                   
                   
               
               
                   
                 Compound  
                 Q1 Mass  
                 Q3 Mass  
                 Collision  
               
               
                   
                 Name 
                 (Da) 
                 (Da) 
                 Energy (V) 
               
               
                   
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
            
               
                   
                 CBGA 
                 359.2 
                 341.1 
                 22 
               
               
                   
                 CBGA 
                 359.2 
                 315.2 
                 22 
               
               
                   
                 CBDA 
                 357.2 
                 339.1 
                 22 
               
               
                   
                 CBDA 
                 357.2 
                 245.1 
                 30 
               
               
                   
                 CBCA 
                 357.2 
                 203.0 
                 40 
               
               
                   
                 CBCA 
                 357.2 
                 191.0 
                 30 
               
               
                   
                 THCA 
                 357.0 
                 245.0 
                 35 
               
               
                   
                 THCA 
                 357.0 
                 191.0 
                 35 
               
               
                   
                   
               
            
           
         
       
     
     Recovery and Purifications 
     Whole-cell broth from cultures comprising modified host cells of the disclosure are extracted with a suitable organic solvent to afford cannabinoids or cannabinoid derivatives. Suitable organic solvents include, but are not limited to, hexane, heptane, ethyl acetate, petroleum ether, and di-ethyl ether, chloroform, and ethyl acetate. The suitable organic solvent, such as hexane, is added to the whole-cell broth from fermentations comprising modified host cells of the disclosure at a 10:1 ratio (10 parts whole-cell broth−1 part organic solvent) and stirred for 30 minutes. The organic fraction is separated and extracted twice with an equal volume of acidic water (pH 2.5). The organic layer is then separated and dried in a concentrator (rotary evaporator or thin film evaporator under reduced pressure) to obtain crude cannabinoid or cannabinoid derivative crystals. The crude crystals may then be heated to 105° C. for 15 minutes followed by 145° C. for 55 minutes to decarboxylate the crude cannabinoid or cannabinoid derivative. The crude crystalline product is re-dissolved and recrystallized in a suitable solvent (e.g., n-pentane) and filtered through a 1 μm filter to remove any insoluble material. The solvent is then removed e.g., by rotary evaporation, to produce pure crystalline product. 
     In Vitro Enzyme Assay and Cell-Free Production of Cannabinoids or Cannabinoid Derivatives 
     In some embodiments, modified host cells, e.g., modified yeast cells are cultured in 96-well microtiter plates containing 360 μL of YPD (10 g/L yeast extract, 20 g/L Bacto peptone, 20 g/L dextrose (glucose)) and sealed with a breathable film seal. Cells are then cultured at 30° C. in a high capacity microtiter plate incubator shaking at 1000 rpm and 80% humidity for 3 days until the cultures reach carbon exhaustion. The growth-saturated cultures are then subcultured into 200 mL of YPGAL media to an OD600 of 0.2 and incubated with shaking for 20 hours at 30° C. Cells are then harvested by centrifugation at 3000×g for 5 minutes at 4° C. Harvested cells are then resuspended in 50 mL buffer (50 mM Tris-HCl, 1 mM EDTA, 0.1 M KCl, pH 7.4, 125 units Benzonase) and then lysed (Emulsiflex C3, Avestin, INC., 60 bar, 10 min). Cells debris is removed by centrifugation (10,000×g, 10 min, 4° C.). Subsequently, the supernatant is then subjected to ultracentrifugation (150,000×g, 1 h, 4° C., Beckman Coulter L-90K, TI-70). The resulting membrane fractions are then resuspended in 3.3 mL buffer (10 mM Tris-HCl, 10 mM MgCl 2 , pH 8.0, 10% glycerol) and solubilized with a tissue grinder. Then, 0.02% (v/v) of the respective membrane preparations are then dissolved in reaction buffer (50 mM Tris-HCl, 10 mM MgCl2, pH 8.5) and substrate (500 μM olivetolic acid, 500 μM GPP) to a total volume of 50 μL and incubated for 1 hour at 30° C. Assays are then extracted by adding two reaction volumes of ethyl acetate followed by vortexing and centrifugation. The organic layer is evaporated for 30 minutes, resuspended in acetonitrile/H20/formic acid (80:20:0.05%) and filtered with Ultrafree®-MC columns (0.22 μm pore size, PVDF membrane material). Cannabinoids or cannabinoid derivatives are then detected via LC-MS and/or recovered and purified. 
     Yeast Cultivation in a Bioreactor 
     Single yeast colonies comprising modified host cells disclosed herein are grown in 15 mL of Verduyn medium (originally described by Verduyn et al, Yeast 8(7): 501-17) with 50 mM succinate (pH 5.0) and 2% glucose in a 125 mL flask at 30° C., with shaking at 200 rpm to an OD600 between 4 to 9. Glycerol is then added to the culture to a concentration of 20% and 1 mL vials of the modified host cell suspension are stored at −80° C. One to two vials of modified host cells are thawed and grown in Verduyn medium with 50 mM succinate (pH 5.0) and 4% sucrose for 24 hours, then sub-cultured to an OD600 reading of 0.1 in the same media. After 24 hours of growth at 30° C. with shaking, 65 mL of culture is used to inoculate a 1.3-liter fermenter (Eppendorf DASGIP Bioreactor) with 585 mL of Verduyn fermentation media containing 20 g/L galactose supplemented with hexanoic acid (2 mM), a carboxylic acid other than hexanoic acid (2 mM), olivetolic acid (1 mM), or an olivetolic acid derivative (1 mM). A poly-alpha-olefin may be added to the fermenter as an extractive agent. The fermenter is maintained at 30° C. and pH 5.0 with addition of NH 4 OH. In an initial batch phase, the fermenter is aerated at 0.5 volume per volume per minute air (VVM) and agitation ramped to maintain 30% dissolved oxygen. After the initial sugar is consumed, the rise in dissolved oxygen triggers feeding of galactose+hexanoic acid (800 g galactose per liter+9.28 g hexanoic acid per liter) at 10 g galactose per liter per hour in pulses of 10 g galactose per liter doses (alternatively, rather than feeding the modified host cells disclosed herein hexanoic acid, olivetolic acid, an olivetolic acid derivative, or a carboxylic acid other than hexanoic acid is fed to the modified host cells). 
     Between pulses, the feed rate is lowered to 5 g galactose per liter per hour. Upon a 10% rise in dissolved oxygen, the feed rate is resumed at 10 g L −1  hour −1 . As modified host cell density increases, dissolved oxygen is allowed to reach 0%, and the pulse dose is increased to 50 g galactose per liter. Oxygen transfer rate is maintained at rates representative of full-scale conditions of 100 mM per liter per hour by adjusting agitation as volume increased. Feed rate is adjusted dynamically to meet demand using an algorithm that alternates between a high feed rate and low feed rate. During the low feed rate, modified host cells should consume galactose and hexanoic acid, or, alternatively, olivetolic acid, an olivetolic acid derivative, or a carboxylic acid other than hexanoic acid, and any overflow metabolites accumulated during the high feed rate. A rise in dissolved oxygen triggers the high feed rate to resume. The length of time spent in the low feed rate reflects the extent to which modified host cells are over- or under-fed in the prior high feed rate pulse; this information is then monitored and used to tune the high feed rate up or down, keeping the low feed rate within a defined range. 
     Over time, the feed rate matches sugar and hexanoic acid, or, alternatively, olivetolic acid, an olivetolic acid derivative, or a carboxylic acid other than hexanoic acid, demand from modified host cells. This algorithm ensures minimal net accumulation of fermentation products other than cannabinoids or cannabinoid derivatives; biomass; and CO 2 . In some embodiments, the process continues for 5 to 14 days. In certain such embodiments, accumulated broth is removed daily and assayed for biomass and cannabinoid, or cannabinoid derivative concentration. A concentrated solution of NH 4 H 2 PO 4 , trace metals and vitamins are added periodically to maintain steady state concentrations. 
     
       
         
           
               
             
               
                 TABLE 5 
               
             
            
               
                   
               
               
                 Constructs and strains used in the Examples 
               
            
           
           
               
               
               
            
               
                 Strain  
                 Parent 
                 Polypeptide SEQ ID NOs  
               
               
                 (Constructs) 
                 Strain* 
                 (Nucleotide SEQ ID NOs) 
               
               
                   
               
               
                 S29 (FIGS.  
                 S4** 
                 Sc_tHMG1 (tHMGR): SEQ ID  
               
               
                 1A, 1B, 
                   
                 NO: 27 (SEQ ID NO: 26) 
               
               
                 and 1C) 
                   
                 Sc_ERG13 (HMGS): SEQ ID  
               
               
                   
                   
                 NO: 29 (SEQ ID NO: 28) 
               
               
                   
                   
                 Sc_ERG10 (acetoacetyl CoA  
               
               
                   
                   
                 thiolase): SEQ ID NO: 31 (SEQ 
               
               
                   
                   
                 ID NO: 30) 
               
               
                   
                   
                 Sc_MVD1 (Sc_ERG19): SEQ ID  
               
               
                   
                   
                 NO: 33 (SEQ ID NO: 32) 
               
               
                   
                   
                 Sc_IDI1: SEQ ID NO: 25 (SEQ ID NO: 24) 
               
               
                   
                   
                 Zm_PDC: SEQ ID NO: 35 (SEQ ID NO: 34) 
               
               
                   
                   
                 Sc_ERG8 (PMK): SEQ ID NO: 37  
               
               
                   
                   
                 (SEQ ID NO: 36) 
               
               
                   
                   
                 Sc_ERG12 (MK): SEQ ID NO: 39  
               
               
                   
                   
                 (SEQ ID NO: 38) 
               
               
                   
                   
                 Cs_PT4 (GOT): SEQ ID NO: 17  
               
               
                   
                   
                 (SEQ ID NO: 16) 
               
               
                   
                   
                 Sc_ERG20mut (GPPS): SEQ ID NO:  
               
               
                   
                   
                 41 (SEQ ID NO: 40) 
               
               
                 S61 (FIG. 5) 
                 S29 
                 GFP: SEQ ID NO: 43 (SEQ ID NO: 42) 
               
               
                 S122 (FIG. 6) 
                 S61 
                 CBDAS Codon opt 2: SEQ ID NO:  
               
               
                   
                   
                 3 (SEQ ID NO: 1) 
               
               
                 S171 (FIG. 7) 
                 S122 
                 KAR2: SEQ ID NO: 5 (SEQ ID NO: 4) 
               
               
                 S181 (FIG. 2) 
                 S171 
                 PDI1: SEQ ID NO: 9 (SEQ ID NO: 8) 
               
               
                   
                   
                 pep4: SEQ ID NO: 15  
               
               
                   
                   
                 (SEQ ID NO: 14); Deletion or 
               
               
                   
                   
                 downregulation of 
               
               
                 S206  
                 S29 
                 PDI1: SEQ ID NO: 9 (SEQ ID NO: 8) 
               
               
                 (FIGS. 13A 
                   
                 KAR2: SEQ ID NO: 5 (SEQ ID NO: 4) 
               
               
                 and 13B) 
                   
                 FAD1: SEQ ID NO: 298 (SEQ ID NO: 297) 
               
               
                   
                   
                 ERO1: SEQ ID NO: 7 (SEQ ID NO: 6) 
               
               
                 S220 (FIG. 3) 
                 S181 
                 rot2: SEQ ID NO: 13  
               
               
                   
                   
                 (SEQ ID NO: 12); Deletion or 
               
               
                   
                   
                 downregulation of 
               
               
                 S241 (FIG. 4) 
                 S220 
                 KAR2: SEQ ID NO: 5 (SEQ ID NO: 4) 
               
               
                   
                   
                 IRE1: SEQ ID NO: 296 (SEQ ID NO: 295) 
               
               
                 S270 (FIG. 8) 
                 S241 
                 ERO1: SEQ ID NO: 7 (SEQ ID NO: 6) 
               
               
                 S478 (FIG. 9)  
                 S270 
                 pGAL1_tTDH1: (SEQ ID NO: 46) 
               
               
                 *** 
                   
                 THCAScol: SEQ ID NO: 44 (SEQ ID NO: 45) 
               
               
                 S487 (FIG. 10)  
                 S270 
                 pGAL1_tTDH1: (SEQ ID NO: 46) 
               
               
                 **** 
                   
                 i33: deletion of CBDAS and  
               
               
                   
                   
                 reversion to native sequence 
               
               
                   
                   
                 (SEQ ID NO: 323) 
               
               
                 S510 (FIG. 14)  
                 S206 
                 pGAL1_tTDH1: (SEQ ID NO: 46) 
               
               
                 ****  
                   
                   
               
               
                 S562 (FIG. 11) 
                 S478 
                 CBDASco5: SEQ ID NO: 3 (SEQ ID NO: 2) 
               
               
                 S579 (FIG. 11) 
                 S487 
                 CBDASco5: SEQ ID NO: 3 (SEQ ID NO: 2) 
               
               
                 S606 (FIG. 12) 
                 S478 
                 CBDA Synthase C12F: SEQ ID  
               
               
                   
                   
                 NO: 50 (SEQ ID NO: 49) 
               
               
                 S607 (FIG. 12) 
                 S478 
                 CBDA Synthase F17M: SEQ ID  
               
               
                   
                   
                 NO: 52 (SEQ ID NO: 51) 
               
               
                 S608 (FIG. 12) 
                 S478 
                 CBDA Synthase F18T: SEQ ID  
               
               
                   
                   
                 NO: 54 (SEQ ID NO: 53) 
               
               
                 S609 (FIG. 12) 
                 S478 
                 CBDA Synthase F18W: SEQ ID  
               
               
                   
                   
                 NO: 56 (SEQ ID NO: 55) 
               
               
                 S610 (FIG. 12) 
                 S478 
                 CBDA Synthase S20G: SEQ ID  
               
               
                   
                   
                 NO: 58 (SEQ ID NO: 57) 
               
               
                 S611 (FIG. 12) 
                 S478 
                 CBDA Synthase R31Q: SEQ ID  
               
               
                   
                   
                 NO: 60 (SEQ ID NO: 59) 
               
               
                 S612 (FIG. 12) 
                 S478 
                 CBDA Synthase N33K: SEQ ID  
               
               
                   
                   
                 NO: 62 (SEQ ID NO: 61) 
               
               
                 S613 (FIG. 12) 
                 S478 
                 CBDA Synthase P43E: SEQ ID  
               
               
                   
                   
                 NO: 64 (SEQ ID NO: 63) 
               
               
                 S614 (FIG. 12) 
                 S478 
                 CBDA Synthase L49E: SEQ ID  
               
               
                   
                   
                 NO: 66 (SEQ ID NO: 65) 
               
               
                 S615 (FIG. 12) 
                 S478 
                 CBDA Synthase L49K: SEQ ID  
               
               
                   
                   
                 NO: 68 (SEQ ID NO: 67) 
               
               
                 S616 (FIG. 12) 
                 S478 
                 CBDA Synthase L49Q: SEQ ID  
               
               
                   
                   
                 NO: 70 (SEQ ID NO: 69) 
               
               
                 S617 (FIG. 12) 
                 S478 
                 CBDA Synthase K5OT: SEQ ID  
               
               
                   
                   
                 NO: 72 (SEQ ID NO: 71) 
               
               
                 S618 (FIG. 12) 
                 S478 
                 CBDA Synthase L51I: SEQ ID  
               
               
                   
                   
                 NO: 74 (SEQ ID NO: 73) 
               
               
                 S619 (FIG. 12) 
                 S478 
                 CBDA Synthase Q55E: SEQ ID  
               
               
                   
                   
                 NO: 76 (SEQ ID NO: 75) 
               
               
                 S620 (FIG. 12) 
                 S478 
                 CBDA Synthase Q55P: SEQ ID  
               
               
                   
                   
                 NO: 78 (SEQ ID NO: 77) 
               
               
                 S621 (FIG. 12) 
                 S478 
                 CBDA Synthase N56E: SEQ ID  
               
               
                   
                   
                 NO: 80 (SEQ ID NO: 79) 
               
               
                 S622 (FIG. 12) 
                 S478 
                 CBDA Synthase N57D: SEQ ID  
               
               
                   
                   
                 NO: 82 (SEQ ID NO: 81) 
               
               
                 S623 (FIG. 12) 
                 S478 
                 CBDA Synthase N57E: SEQ ID  
               
               
                   
                   
                 NO: 84 (SEQ ID NO: 83) 
               
               
                 S624 (FIG. 12) 
                 S478 
                 CBDA Synthase L59E: SEQ ID  
               
               
                   
                   
                 NO: 86 (SEQ ID NO: 85) 
               
               
                 S625 (FIG. 12) 
                 S478 
                 CBDA Synthase M61H: SEQ ID  
               
               
                   
                   
                 NO: 88 (SEQ ID NO: 87) 
               
               
                 S626 (FIG. 12) 
                 S478 
                 CBDA Synthase M61S: SEQ ID  
               
               
                   
                   
                 NO: 90 (SEQ ID NO: 89) 
               
               
                 S627 (FIG. 12) 
                 S478 
                 CBDA Synthase M61W: SEQ ID  
               
               
                   
                   
                 NO: 92 (SEQ ID NO: 91) 
               
               
                 S628 (FIG. 12) 
                 S478 
                 CBDA Synthase S62N: SEQ ID  
               
               
                   
                   
                 NO: 94 (SEQ ID NO: 93) 
               
               
                 S629 (FIG. 12) 
                 S478 
                 CBDA Synthase S62Q: SEQ ID  
               
               
                   
                   
                 NO: 96 (SEQ ID NO: 95) 
               
               
                 S630 (FIG. 12) 
                 S478 
                 CBDA Synthase V63M: SEQ ID  
               
               
                   
                   
                 NO: 98 (SEQ ID NO: 97) 
               
               
                 S631 (FIG. 12) 
                 S478 
                 CBDA Synthase S66D: SEQ ID  
               
               
                   
                   
                 NO: 100 (SEQ ID NO: 99) 
               
               
                 S632 (FIG. 12) 
                 S478 
                 CBDA Synthase L71A: SEQ ID  
               
               
                   
                   
                 NO: 102 (SEQ ID NO: 101) 
               
               
                 S633 (FIG. 12) 
                 S478 
                 CBDA Synthase L71H: SEQ ID  
               
               
                   
                   
                 NO: 104 (SEQ ID NO: 103) 
               
               
                 S634 (FIG. 12) 
                 S478 
                 CBDA Synthase L71Q: SEQ ID  
               
               
                   
                   
                 NO: 106 (SEQ ID NO: 105) 
               
               
                 S635 (FIG. 12) 
                 S478 
                 CBDA Synthase S75D: SEQ ID  
               
               
                   
                   
                 NO: 108 (SEQ ID NO: 107) 
               
               
                 S636 (FIG. 12) 
                 S478 
                 CBDA Synthase S75E: SEQ ID  
               
               
                   
                   
                 NO: 110 (SEQ ID NO: 109) 
               
               
                 S637 (FIG. 12) 
                 S478 
                 CBDA Synthase I97V: SEQ ID  
               
               
                   
                   
                 NO: 112 (SEQ ID NO: 111) 
               
               
                 S638 (FIG. 12) 
                 S478 
                 CBDA Synthase L98V: SEQ ID  
               
               
                   
                   
                 NO: 114 (SEQ ID NO: 113) 
               
               
                 S639 (FIG. 12) 
                 S478 
                 CBDA Synthase S100A: SEQ ID  
               
               
                   
                   
                 NO: 116 (SEQ ID NO: 115) 
               
               
                 S640 (FIG. 12) 
                 S478 
                 CBDA Synthase V103A: SEQ ID  
               
               
                   
                   
                 NO: 118 (SEQ ID NO: 117) 
               
               
                 S641 (FIG. 12) 
                 S478 
                 CBDA Synthase V103F: SEQ ID  
               
               
                   
                   
                 NO: 120 (SEQ ID NO: 119) 
               
               
                 S642 (FIG. 12) 
                 S478 
                 CBDA Synthase T109V: SEQ ID  
               
               
                   
                   
                 NO: 122 (SEQ ID NO: 121) 
               
               
                 S643 (FIG. 12) 
                 S478 
                 CBDA Synthase Q124D: SEQ ID  
               
               
                   
                   
                 NO: 124 (SEQ ID NO: 123) 
               
               
                 S644 (FIG. 12) 
                 S478 
                 CBDA Synthase Q124E: SEQ ID  
               
               
                   
                   
                 NO: 126 (SEQ ID NO: 125) 
               
               
                 S645 (FIG. 12) 
                 S478 
                 CBDA Synthase Q124N: SEQ ID  
               
               
                   
                   
                 NO: 128 (SEQ ID NO: 127) 
               
               
                 S646 (FIG. 12) 
                 S478 
                 CBDA Synthase V125E: SEQ ID  
               
               
                   
                   
                 NO: 130 (SEQ ID NO: 129) 
               
               
                 S647 (FIG. 12) 
                 S478 
                 CBDA Synthase V125Q: SEQ ID  
               
               
                   
                   
                 NO: 132 (SEQ ID NO: 131) 
               
               
                 S648 (FIG. 12) 
                 S478 
                 CBDA Synthase I129V: SEQ ID  
               
               
                   
                   
                 NO: 134 (SEQ ID NO: 133) 
               
               
                 S649 (FIG. 12) 
                 S478 
                 CBDA Synthase L132M: SEQ ID  
               
               
                   
                   
                 NO: 136 (SEQ ID NO: 135) 
               
               
                 S650 (FIG. 12) 
                 S478 
                 CBDA Synthase S137G: SEQ ID  
               
               
                   
                   
                 NO: 138 (SEQ ID NO: 137) 
               
               
                 S651 (FIG. 12) 
                 S478 
                 CBDA Synthase H143D: SEQ ID  
               
               
                   
                   
                 NO: 140 (SEQ ID NO: 139) 
               
               
                 S652 (FIG. 12) 
                 S478 
                 CBDA Synthase V149I: SEQ ID  
               
               
                   
                   
                 NO: 142 (SEQ ID NO: 141) 
               
               
                 S653 (FIG. 12) 
                 S478 
                 CBDA Synthase W161K: SEQ ID  
               
               
                   
                   
                 NO: 144 (SEQ ID NO: 143) 
               
               
                 S654 (FIG. 12) 
                 S478 
                 CBDA Synthase W161R: SEQ ID  
               
               
                   
                   
                 NO: 146 (SEQ ID NO: 145) 
               
               
                 S655 (FIG. 12) 
                 S478 
                 CBDA Synthase W161Y: SEQ ID  
               
               
                   
                   
                 NO: 148 (SEQ ID NO: 147) 
               
               
                 S656 (FIG. 12) 
                 S478 
                 CBDA Synthase K165A: SEQ ID  
               
               
                   
                   
                 NO: 150 (SEQ ID NO: 149) 
               
               
                 S657 (FIG. 12) 
                 S478 
                 CBDA Synthase E167P: SEQ ID  
               
               
                   
                   
                 NO: 152 (SEQ ID NO: 151) 
               
               
                 S658 (FIG. 12) 
                 S478 
                 CBDA Synthase N168S: SEQ ID  
               
               
                   
                   
                 NO: 154 (SEQ ID NO: 153) 
               
               
                 S659 (FIG. 12) 
                 S478 
                 CBDA Synthase S170T: SEQ ID  
               
               
                   
                   
                 NO: 156 (SEQ ID NO: 155) 
               
               
                 S660 (FIG. 12) 
                 S478 
                 CBDA Synthase L171I: SEQ ID  
               
               
                   
                   
                 NO: 158 (SEQ ID NO: 157) 
               
               
                 S661 (FIG. 12) 
                 S478 
                 CBDA Synthase A172V: SEQ ID  
               
               
                   
                   
                 NO: 160 (SEQ ID NO: 159) 
               
               
                 S662 (FIG. 12) 
                 S478 
                 CBDA Synthase Y175F: SEQ ID  
               
               
                   
                   
                 NO: 162 (SEQ ID NO: 161) 
               
               
                 S663 (FIG. 12) 
                 S478 
                 CBDA Synthase C180A: SEQ ID  
               
               
                   
                   
                 NO: 164 (SEQ ID NO: 163) 
               
               
                 S664 (FIG. 12) 
                 S478 
                 CBDA Synthase A181V: SEQ ID  
               
               
                   
                   
                 NO: 166 (SEQ ID NO: 165) 
               
               
                 S665 (FIG. 12) 
                 S478 
                 CBDA Synthase N196Q: SEQ ID  
               
               
                   
                   
                 NO: 168 (SEQ ID NO: 167) 
               
               
                 S666 (FIG. 12) 
                 S478 
                 CBDA Synthase N196T: SEQ ID  
               
               
                   
                   
                 NO: 170 (SEQ ID NO: 169) 
               
               
                 S667 (FIG. 12) 
                 S478 
                 CBDA Synthase N196V: SEQ ID  
               
               
                   
                   
                 NO: 172 (SEQ ID NO: 171) 
               
               
                 S668 (FIG. 12) 
                 S478 
                 CBDA Synthase H208T: SEQ ID  
               
               
                   
                   
                 NO: 174 (SEQ ID NO: 173) 
               
               
                 S669 (FIG. 12) 
                 S478 
                 CBDA Synthase A235P: SEQ ID  
               
               
                   
                   
                 NO: 176 (SEQ ID NO: 175) 
               
               
                 S670 (FIG. 12) 
                 S478 
                 CBDA Synthase A250T: SEQ ID  
               
               
                   
                   
                 NO: 178 (SEQ ID NO: 177) 
               
               
                 S671 (FIG. 12) 
                 S478 
                 CBDA Synthase M256V: SEQ ID  
               
               
                   
                   
                 NO: 180 (SEQ ID NO: 179) 
               
               
                 S672 (FIG. 12) 
                 S478 
                 CBDA Synthase K260C: SEQ ID  
               
               
                   
                   
                 NO: 182 (SEQ ID NO: 181) 
               
               
                 S673 (FIG. 12) 
                 S478 
                 CBDA Synthase K260W: SEQ ID  
               
               
                   
                   
                 NO: 184 (SEQ ID NO: 183) 
               
               
                 S674 (FIG. 12) 
                 S478 
                 CBDA Synthase L268I: SEQ ID  
               
               
                   
                   
                 NO: 186 (SEQ ID NO: 185) 
               
               
                 S675 (FIG. 12) 
                 S478 
                 CBDA Synthase H309V: SEQ ID  
               
               
                   
                   
                 NO: 188 (SEQ ID NO: 187) 
               
               
                 S676 (FIG. 12) 
                 S478 
                 CBDA Synthase T310A: SEQ ID  
               
               
                   
                   
                 NO: 190 (SEQ ID NO: 189) 
               
               
                 S677 (FIG. 12) 
                 S478 
                 CBDA Synthase T310C: SEQ ID  
               
               
                   
                   
                 NO: 192 (SEQ ID NO: 191) 
               
               
                 S678 (FIG. 12) 
                 S478 
                 CBDA Synthase F316Y: SEQ ID  
               
               
                   
                   
                 NO: 194 (SEQ ID NO: 193) 
               
               
                 S679 (FIG. 12) 
                 S478 
                 CBDA Synthase L326I: SEQ ID  
               
               
                   
                   
                 NO: 196 (SEQ ID NO: 195) 
               
               
                 S680 (FIG. 12) 
                 S478 
                 CBDA Synthase G378T: SEQ ID  
               
               
                   
                   
                 NO: 198 (SEQ ID NO: 197) 
               
               
                 S681 (FIG. 12) 
                 S478 
                 CBDA Synthase G378S: SEQ ID  
               
               
                   
                   
                 NO: 200 (SEQ ID NO: 199) 
               
               
                 S682 (FIG. 12) 
                 S478 
                 CBDA Synthase K389E: SEQ ID  
               
               
                   
                   
                 NO: 202 (SEQ ID NO: 201) 
               
               
                 S683 (FIG. 12) 
                 S478 
                 CBDA Synthase E406K: SEQ ID  
               
               
                   
                   
                 NO: 204 (SEQ ID NO: 203) 
               
               
                 S684 (FIG. 12) 
                 S478 
                 CBDA Synthase S428L: SEQ ID  
               
               
                   
                   
                 NO: 206 (SEQ ID NO: 205) 
               
               
                 S685 (FIG. 12) 
                 S478 
                 CBDA Synthase L439M: SEQ ID  
               
               
                   
                   
                 NO: 208 (SEQ ID NO: 207) 
               
               
                 S686 (FIG. 12) 
                 S478 
                 CBDA Synthase N466D: SEQ ID  
               
               
                   
                   
                 NO: 210 (SEQ ID NO: 209) 
               
               
                 S687 (FIG. 12) 
                 S478 
                 CBDA Synthase K474S: SEQ ID  
               
               
                   
                   
                 NO: 212 (SEQ ID NO: 211) 
               
               
                 S688 (FIG. 12) 
                 S478 
                 CBDA Synthase Y499M: SEQ ID  
               
               
                   
                   
                 NO: 214 (SEQ ID NO: 213) 
               
               
                 S689 (FIG. 12) 
                 S478 
                 CBDA Synthase Y499V: SEQ ID  
               
               
                   
                   
                 NO: 216 (SEQ ID NO: 215) 
               
               
                 S690 (FIG. 12) 
                 S478 
                 CBDA Synthase N527E: SEQ ID  
               
               
                   
                   
                 NO: 218 (SEQ ID NO: 217) 
               
               
                 S691 (FIG. 12) 
                 S478 
                 CBDA Synthase P538T: SEQ ID  
               
               
                   
                   
                 NO: 220 (SEQ ID NO: 219) 
               
               
                 S692 (FIG. 12) 
                 S478 
                 CBDA Synthase R541E: SEQ ID  
               
               
                   
                   
                 NO: 222 (SEQ ID NO: 221) 
               
               
                 S693 (FIG. 12) 
                 S478 
                 CBDA Synthase R541V: SEQ ID  
               
               
                   
                   
                 NO: 224 (SEQ ID NO: 223) 
               
               
                 S694 (FIG. 12) 
                 S478 
                 CBDA Synthase H542V: SEQ ID  
               
               
                   
                   
                 NO: 226 (SEQ ID NO: 225) 
               
               
                 S695 (FIG. 12) 
                 S478 
                 CBDA Synthase R543A: SEQ ID  
               
               
                   
                   
                 NO: 228 (SEQ ID NO: 227) 
               
               
                 S696 (FIG. 12) 
                 S478 
                 CBDA Synthase R543E: SEQ ID  
               
               
                   
                   
                 NO: 230 (SEQ ID NO: 229) 
               
               
                 S697 (FIG. 12) 
                 S478 
                 CBDA Synthase H544E: SEQ ID  
               
               
                   
                   
                 NO: 232 (SEQ ID NO: 231) 
               
               
                 S698 (FIG. 12) 
                 S478 
                 CBDA Synthase H544D: SEQ ID  
               
               
                   
                   
                 NO: 234 (SEQ ID NO: 233) 
               
               
                 S699 (FIG. 12) 
                 S487 
                 CBDA Synthase C12F: SEQ ID  
               
               
                   
                   
                 NO: 50 (SEQ ID NO: 49) 
               
               
                 S700 (FIG. 12) 
                 S487 
                 CBDA Synthase F17M: SEQ ID  
               
               
                   
                   
                 NO: 52 (SEQ ID NO: 51) 
               
               
                 S701 (FIG. 12) 
                 S487 
                 CBDA Synthase F18T: SEQ ID  
               
               
                   
                   
                 NO: 54 (SEQ ID NO: 53) 
               
               
                 S702 (FIG. 12) 
                 S487 
                 CBDA Synthase F18W: SEQ ID  
               
               
                   
                   
                 NO: 56 (SEQ ID NO: 55) 
               
               
                 S703 (FIG. 12) 
                 S487 
                 CBDA Synthase S20G: SEQ ID  
               
               
                   
                   
                 NO: 58 (SEQ ID NO: 57) 
               
               
                 S704 (FIG. 12) 
                 S487 
                 CBDA Synthase R31Q: SEQ ID  
               
               
                   
                   
                 NO: 60 (SEQ ID NO: 59) 
               
               
                 S705 (FIG. 12) 
                 S487 
                 CBDA Synthase N33K: SEQ ID 
               
               
                   
                   
                 NO: 62 (SEQ ID NO: 61) 
               
               
                 S706 (FIG. 12) 
                 S487 
                 CBDA Synthase P43E: SEQ ID 
               
               
                   
                   
                 NO: 64 (SEQ ID NO: 63) 
               
               
                 S707 (FIG. 12) 
                 S487 
                 CBDA Synthase L49E: SEQ ID 
               
               
                   
                   
                 NO: 66 (SEQ ID NO: 65) 
               
               
                 S708 (FIG. 12) 
                 S487 
                 CBDA Synthase L49K: SEQ ID 
               
               
                   
                   
                 NO: 68 (SEQ ID NO: 67) 
               
               
                 S709 (FIG. 12) 
                 S487 
                 CBDA Synthase L49Q: SEQ ID 
               
               
                   
                   
                 NO: 70 (SEQ ID NO: 69) 
               
               
                 S710 (FIG. 12) 
                 S487 
                 CBDA Synthase K50T: SEQ ID 
               
               
                   
                   
                 NO: 72 (SEQ ID NO: 71) 
               
               
                 S711 (FIG. 12) 
                 S487 
                 CBDA Synthase L51I: SEQ ID 
               
               
                   
                   
                 NO: 74 (SEQ ID NO: 73) 
               
               
                 S712 (FIG. 12) 
                 S487 
                 CBDA Synthase Q55E: SEQ ID 
               
               
                   
                   
                 NO: 76 (SEQ ID NO: 75) 
               
               
                 S713 (FIG. 12) 
                 S487 
                 CBDA Synthase Q55P: SEQ ID 
               
               
                   
                   
                 NO: 78 (SEQ ID NO: 77) 
               
               
                 S714 (FIG. 12) 
                 S487 
                 CBDA Synthase N56E: SEQ ID 
               
               
                   
                   
                 NO: 80 (SEQ ID NO: 79) 
               
               
                 S715 (FIG. 12) 
                 S487 
                 CBDA Synthase N57D: SEQ ID 
               
               
                   
                   
                 NO: 82 (SEQ ID NO: 81) 
               
               
                 S716 (FIG. 12) 
                 S487 
                 CBDA Synthase N57E: SEQ ID 
               
               
                   
                   
                 NO: 84 (SEQ ID NO: 83) 
               
               
                 S717 (FIG. 12) 
                 S487 
                 CBDA Synthase L59E: SEQ ID 
               
               
                   
                   
                 NO: 86 (SEQ ID NO: 85) 
               
               
                 S718 (FIG. 12) 
                 S487 
                 CBDA Synthase M61H: SEQ ID 
               
               
                   
                   
                 NO: 88 (SEQ ID NO: 87) 
               
               
                 S719 (FIG. 12) 
                 S487 
                 CBDA Synthase M61S: SEQ ID 
               
               
                   
                   
                 NO: 90 (SEQ ID NO: 89) 
               
               
                 S720 (FIG. 12) 
                 S487 
                 CBDA Synthase M61W: SEQ ID 
               
               
                   
                   
                 NO: 92 (SEQ ID NO: 91) 
               
               
                 S721 (FIG. 12) 
                 S487 
                 CBDA Synthase S62N: SEQ ID 
               
               
                   
                   
                 NO: 94 (SEQ ID NO: 93) 
               
               
                 S722 (FIG. 12) 
                 S487 
                 CBDA Synthase S62Q: SEQ ID 
               
               
                   
                   
                 NO: 96 (SEQ ID NO: 95) 
               
               
                 S723 (FIG. 12) 
                 S487 
                 CBDA Synthase V63M: SEQ ID 
               
               
                   
                   
                 NO: 98 (SEQ ID NO: 97) 
               
               
                 S724 (FIG. 12) 
                 S487 
                 CBDA Synthase S66D: SEQ ID 
               
               
                   
                   
                 NO: 100 (SEQ ID NO: 99) 
               
               
                 S725 (FIG. 12) 
                 S487 
                 CBDA Synthase L71A: SEQ ID 
               
               
                   
                   
                 NO: 102 (SEQ ID NO: 101) 
               
               
                 S726 (FIG. 12) 
                 S487 
                 CBDA Synthase L71H: SEQ ID 
               
               
                   
                   
                 NO: 104 (SEQ ID NO: 103) 
               
               
                 S727 (FIG. 12) 
                 S487 
                 CBDA Synthase L71Q: SEQ ID 
               
               
                   
                   
                 NO: 106 (SEQ ID NO: 105) 
               
               
                 S728 (FIG. 12) 
                 S487 
                 CBDA Synthase S75D: SEQ ID 
               
               
                   
                   
                 NO: 108 (SEQ ID NO: 107) 
               
               
                 S729 (FIG. 12) 
                 S487 
                 CBDA Synthase S75E: SEQ ID  
               
               
                   
                   
                 NO: 110 (SEQ ID NO: 109) 
               
               
                 S730 (FIG. 12) 
                 S487 
                 CBDA Synthase I97V: SEQ ID 
               
               
                   
                   
                 NO: 112 (SEQ ID NO: 111) 
               
               
                 S731 (FIG. 12) 
                 S487 
                 CBDA Synthase L98V: SEQ ID 
               
               
                   
                   
                 NO: 114 (SEQ ID NO: 113) 
               
               
                 S732 (FIG. 12) 
                 S487 
                 CBDA Synthase S100A: SEQ ID 
               
               
                   
                   
                 NO: 116 (SEQ ID NO: 115) 
               
               
                 S733 (FIG. 12) 
                 S487 
                 CBDA Synthase V103A: SEQ ID 
               
               
                   
                   
                 NO: 118 (SEQ ID NO: 117) 
               
               
                 S734 (FIG. 12) 
                 S487 
                 CBDA Synthase V103F: SEQ ID 
               
               
                   
                   
                 NO: 120 (SEQ ID NO: 119) 
               
               
                 S735 (FIG. 12) 
                 S487 
                 CBDA Synthase T109V: SEQ ID 
               
               
                   
                   
                 NO: 122 (SEQ ID NO: 121) 
               
               
                 S736 (FIG. 12) 
                 S487 
                 CBDA Synthase Q124D: SEQ ID 
               
               
                   
                   
                 NO: 124 (SEQ ID NO: 123) 
               
               
                 S737 (FIG. 12) 
                 S487 
                 CBDA Synthase Q124E: SEQ ID 
               
               
                   
                   
                 NO: 126 (SEQ ID NO: 125) 
               
               
                 S738 (FIG. 12) 
                 S487 
                 CBDA Synthase Q124N: SEQ ID 
               
               
                   
                   
                 NO: 128 (SEQ ID NO: 127) 
               
               
                 S739 (FIG. 12) 
                 S487 
                 CBDA Synthase V125E: SEQ ID 
               
               
                   
                   
                 NO: 130 (SEQ ID NO: 129) 
               
               
                 S740 (FIG. 12) 
                 S487 
                 CBDA Synthase V125Q: SEQ ID 
               
               
                   
                   
                 NO: 132 (SEQ ID NO: 131) 
               
               
                 S741 (FIG. 12) 
                 S487 
                 CBDA Synthase I129V: SEQ ID 
               
               
                   
                   
                 NO: 134 (SEQ ID NO: 133) 
               
               
                 S742 (FIG. 12) 
                 S487 
                 CBDA Synthase L132M: SEQ ID 
               
               
                   
                   
                 NO: 136 (SEQ ID NO: 135) 
               
               
                 S743 (FIG. 12) 
                 S487 
                 CBDA Synthase S137G: SEQ ID 
               
               
                   
                   
                 NO: 138 (SEQ ID NO: 137) 
               
               
                 S744 (FIG. 12) 
                 S487 
                 CBDA Synthase H143D: SEQ ID 
               
               
                   
                   
                 NO: 140 (SEQ ID NO: 139) 
               
               
                 S745 (FIG. 12) 
                 S487 
                 CBDA Synthase V149I: SEQ ID 
               
               
                   
                   
                 NO: 142 (SEQ ID NO: 141) 
               
               
                 S746 (FIG. 12) 
                 S487 
                 CBDA Synthase W161K: SEQ ID 
               
               
                   
                   
                 NO: 144 (SEQ ID NO: 143) 
               
               
                 S747 (FIG. 12) 
                 S487 
                 CBDA Synthase W161R: SEQ ID 
               
               
                   
                   
                 NO: 146 (SEQ ID NO: 145) 
               
               
                 S748 (FIG. 12) 
                 S487 
                 CBDA Synthase W161Y: SEQ ID 
               
               
                   
                   
                 NO: 148 (SEQ ID NO: 147) 
               
               
                 S749 (FIG. 12) 
                 S487 
                 CBDA Synthase K165A: SEQ ID 
               
               
                   
                   
                 NO: 150 (SEQ ID NO: 149) 
               
               
                 S750 (FIG. 12) 
                 S487 
                 CBDA Synthase E167P: SEQ ID 
               
               
                   
                   
                 NO: 152 (SEQ ID NO: 151) 
               
               
                 S751 (FIG. 12) 
                 S487 
                 CBDA Synthase N168S: SEQ ID 
               
               
                   
                   
                 NO: 154 (SEQ ID NO: 153) 
               
               
                 S752 (FIG. 12) 
                 S487 
                 CBDA Synthase S170T: SEQ ID 
               
               
                   
                   
                 NO: 156 (SEQ ID NO: 155) 
               
               
                 S753 (FIG. 12) 
                 S487 
                 CBDA Synthase L171I: SEQ ID  
               
               
                   
                   
                 NO: 158 (SEQ ID NO: 157) 
               
               
                 S754 (FIG. 12) 
                 S487 
                 CBDA Synthase A172V: SEQ ID  
               
               
                   
                   
                 NO: 160 (SEQ ID NO: 159) 
               
               
                 S755 (FIG. 12) 
                 S487 
                 CBDA Synthase Y175F: SEQ ID 
               
               
                   
                   
                 NO: 162 (SEQ ID NO: 161) 
               
               
                 S756 (FIG. 12) 
                 S487 
                 CBDA Synthase C180A: SEQ ID 
               
               
                   
                   
                 NO: 164 (SEQ ID NO: 163) 
               
               
                 S757 (FIG. 12) 
                 S487 
                 CBDA Synthase A181V: SEQ ID 
               
               
                   
                   
                 NO: 166 (SEQ ID NO: 165) 
               
               
                 S758 (FIG. 12) 
                 S487 
                 CBDA Synthase N196Q: SEQ ID 
               
               
                   
                   
                 NO: 168 (SEQ ID NO: 167) 
               
               
                 S759 (FIG. 12) 
                 S487 
                 CBDA Synthase N196T: SEQ ID 
               
               
                   
                   
                 NO: 170 (SEQ ID NO: 169) 
               
               
                 S760 (FIG. 12) 
                 S487 
                 CBDA Synthase N196V: SEQ ID 
               
               
                   
                   
                 NO: 172 (SEQ ID NO: 171) 
               
               
                 S761 (FIG. 12) 
                 S487 
                 CBDA Synthase H208T: SEQ ID  
               
               
                   
                   
                 NO: 174 (SEQ ID NO: 173) 
               
               
                 S762 (FIG. 12) 
                 S487 
                 CBDA Synthase A235P: SEQ ID 
               
               
                   
                   
                 NO: 176 (SEQ ID NO: 175) 
               
               
                 S763 (FIG. 12) 
                 S487 
                 CBDA Synthase A250T: SEQ ID 
               
               
                   
                   
                 NO: 178 (SEQ ID NO: 177) 
               
               
                 S764 (FIG. 12) 
                 S487 
                 CBDA Synthase M256V: SEQ ID 
               
               
                   
                   
                 NO: 180 (SEQ ID NO: 179) 
               
               
                 S765 (FIG. 12) 
                 S487 
                 CBDA Synthase K260C: SEQ ID 
               
               
                   
                   
                 NO: 182 (SEQ ID NO: 181) 
               
               
                 S766 (FIG. 12) 
                 S487 
                 CBDA Synthase K260W: SEQ ID 
               
               
                   
                   
                 NO: 184 (SEQ ID NO: 183) 
               
               
                 S767 (FIG. 12) 
                 S487 
                 CBDA Synthase L268I: SEQ ID 
               
               
                   
                   
                 NO: 186 (SEQ ID NO: 185) 
               
               
                 S768 (FIG. 12) 
                 S487 
                 CBDA Synthase H309V: SEQ ID 
               
               
                   
                   
                 NO: 188 (SEQ ID NO: 187) 
               
               
                 S769 (FIG. 12) 
                 S487 
                 CBDA Synthase T310A: SEQ ID 
               
               
                   
                   
                 NO: 190 (SEQ ID NO: 189) 
               
               
                 S770 (FIG. 12) 
                 S487 
                 CBDA Synthase T310C: SEQ ID 
               
               
                   
                   
                 NO: 192 (SEQ ID NO: 191) 
               
               
                 S771 (FIG. 12) 
                 S487 
                 CBDA Synthase F316Y: SEQ ID 
               
               
                   
                   
                 NO: 194 (SEQ ID NO: 193) 
               
               
                 S772 (FIG. 12) 
                 S487 
                 CBDA Synthase L326I: SEQ ID 
               
               
                   
                   
                 NO: 196 (SEQ ID NO: 195) 
               
               
                 S773 (FIG. 12) 
                 S487 
                 CBDA Synthase G378T: SEQ ID 
               
               
                   
                   
                 NO: 198 (SEQ ID NO: 197) 
               
               
                 S774 (FIG. 12) 
                 S487 
                 CBDA Synthase G378S: SEQ ID 
               
               
                   
                   
                 NO: 200 (SEQ ID NO: 199) 
               
               
                 S775 (FIG. 12) 
                 S487 
                 CBDA Synthase K389E: SEQ ID 
               
               
                   
                   
                 NO: 202 (SEQ ID NO: 201) 
               
               
                 S776 (FIG. 12) 
                 S487 
                 CBDA Synthase E406K: SEQ ID 
               
               
                   
                   
                 NO: 204 (SEQ ID NO: 203) 
               
               
                 S777 (FIG. 12) 
                 S487 
                 CBDA Synthase S428L: SEQ ID 
               
               
                   
                   
                 NO: 206 (SEQ ID NO: 205) 
               
               
                 S778 (FIG. 12) 
                 S487 
                 CBDA Synthase L439M: SEQ ID 
               
               
                   
                   
                 NO: 208 (SEQ ID NO: 207) 
               
               
                 S779 (FIG. 12) 
                 S487 
                 CBDA Synthase N466D: SEQ ID 
               
               
                   
                   
                 NO: 210 (SEQ ID NO: 209) 
               
               
                 S780 (FIG. 12) 
                 S487 
                 CBDA Synthase K474S: SEQ ID 
               
               
                   
                   
                 NO: 212 (SEQ ID NO: 211) 
               
               
                 S781 (FIG. 12) 
                 S487 
                 CBDA Synthase Y499M: SEQ ID 
               
               
                   
                   
                 NO: 214 (SEQ ID NO: 213) 
               
               
                 S782 (FIG. 12) 
                 S487 
                 CBDA Synthase Y499V: SEQ ID 
               
               
                   
                   
                 NO: 216 (SEQ ID NO: 215) 
               
               
                 S783 (FIG. 12) 
                 S487 
                 CBDA Synthase N527E: SEQ ID 
               
               
                   
                   
                 NO: 218 (SEQ ID NO: 217) 
               
               
                 S784 (FIG. 12) 
                 S487 
                 CBDA Synthase P538T: SEQ ID 
               
               
                   
                   
                 NO: 220 (SEQ ID NO: 219) 
               
               
                 S785 (FIG. 12) 
                 S487 
                 CBDA Synthase R541E: SEQ ID 
               
               
                   
                   
                 NO: 222 (SEQ ID NO: 221) 
               
               
                 S786 (FIG. 12) 
                 S487 
                 CBDA Synthase R541V: SEQ ID 
               
               
                   
                   
                 NO: 224 (SEQ ID NO: 223) 
               
               
                 S787 (FIG. 12) 
                 S487 
                 CBDA Synthase H542V: SEQ ID  
               
               
                   
                   
                 NO: 226 (SEQ ID NO: 225) 
               
               
                 S788 (FIG. 12) 
                 S487 
                 CBDA Synthase R543A: SEQ ID  
               
               
                   
                   
                 NO: 228 (SEQ ID NO: 227) 
               
               
                 S789 (FIG. 12) 
                 S487 
                 CBDA Synthase R543E: SEQ ID  
               
               
                   
                   
                 NO: 230 (SEQ ID NO: 229) 
               
               
                 S790 (FIG. 12) 
                 S487 
                 CBDA Synthase H544E: SEQ ID 
               
               
                   
                   
                 NO: 232 (SEQ ID NO: 231) 
               
               
                 S791 (FIG. 12) 
                 S487 
                 CBDA Synthase H544D: SEQ ID 
               
               
                   
                   
                 NO: 234 (SEQ ID NO: 233) 
               
               
                 S935 (FIG. 12) 
                 S487 
                 CBDA Synthase I445M: SEQ ID 
               
               
                   
                   
                 NO: 300 (SEQ ID NO: 299) 
               
               
                 S938 (FIG. 12) 
                 S487 
                 CBDA Synthase M412Q: SEQ ID  
               
               
                   
                   
                 NO: 302 (SEQ ID NO: 301) 
               
               
                 S940 (FIG. 12) 
                 S487 
                 CBDA Synthase L415M: SEQ ID 
               
               
                   
                   
                 NO: 304 (SEQ ID NO: 303) 
               
               
                 S941 (FIG. 12) 
                 S487 
                 CBDA Synthase D115N: SEQ ID 
               
               
                   
                   
                 NO: 306 (SEQ ID NO: 305) 
               
               
                 S942 (FIG. 12) 
                 S487 
                 CBDA Synthase A414T: SEQ ID 
               
               
                   
                   
                 NO: 308 (SEQ ID NO: 307) 
               
               
                 S943 (FIG. 12) 
                 S487 
                 CBDA Synthase A414T: SEQ ID 
               
               
                   
                   
                 NO: 308 (SEQ ID NO: 307) 
               
               
                 S944 (FIG. 12) 
                 S487 
                 CBDA Synthase A414V: SEQ ID 
               
               
                   
                   
                 NO: 310 (SEQ ID NO: 309) 
               
               
                 S945 (FIG. 12) 
                 S487 
                 CBDA Synthase A414M: SEQ ID 
               
               
                   
                   
                 NO: 312 (SEQ ID NO: 311) 
               
               
                 S946 (FIG. 12) 
                 S487 
                 CBDA Synthase A414M: SEQ ID 
               
               
                   
                   
                 NO: 312 (SEQ ID NO: 311) 
               
               
                 S1100 (FIG. 11) 
                 S510 
                 CBDASco5: SEQ ID 
               
               
                   
                   
                 NO: 3 (SEQ ID NO: 2) 
               
               
                 S1101 (FIG. 12) 
                 S510 
                 CBDA Synthase R31Q: SEQ ID 
               
               
                   
                   
                 NO: 60 (SEQ ID NO: 59) 
               
               
                 S1102 (FIG. 12) 
                 S510 
                 CBDA Synthase L49E: SEQ ID 
               
               
                   
                   
                 NO: 66 (SEQ ID NO: 65) 
               
               
                 S1103 (FIG. 12) 
                 S510 
                 CBDA Synthase L71H: SEQ ID 
               
               
                   
                   
                 NO: 104 (SEQ ID NO: 103) 
               
               
                 S1104 (FIG. 12) 
                 S510 
                 CBDA Synthase M61H: SEQ ID 
               
               
                   
                   
                 NO: 88 (SEQ ID NO: 87) 
               
               
                 S1105 (FIG. 12) 
                 S510 
                 CBDA Synthase M61W: SEQ ID  
               
               
                   
                   
                 NO: 92 (SEQ ID NO: 91) 
               
               
                 S1106 (FIG. 12) 
                 S510 
                 CBDA Synthase L132M: SEQ ID 
               
               
                   
                   
                 NO: 136 (SEQ ID NO: 135) 
               
               
                 S1107 (FIG. 12) 
                 S510 
                 CBDA Synthase V149I: SEQ ID 
               
               
                   
                   
                 NO: 142 (SEQ ID NO: 141) 
               
               
                 S1108 (FIG. 12) 
                 S510 
                 CBDA Synthase S170T: SEQ ID 
               
               
                   
                   
                 NO: 156 (SEQ ID NO: 155) 
               
               
                 S1109 (FIG. 12) 
                 S510 
                 CBDA Synthase L171I: SEQ ID 
               
               
                   
                   
                 NO: 158 (SEQ ID NO: 157) 
               
               
                 S1110 (FIG. 12) 
                 S510 
                 CBDA Synthase Y175F: SEQ ID 
               
               
                   
                   
                 NO: 162 (SEQ ID NO: 161) 
               
               
                 S1111 (FIG. 12) 
                 S510 
                 CBDA Synthase N196Q: SEQ ID 
               
               
                   
                   
                 NO: 168 (SEQ ID NO: 167) 
               
               
                 S1112 (FIG. 12) 
                 S510 
                 CBDA Synthase N196T: SEQ ID 
               
               
                   
                   
                 NO: 170 (SEQ ID NO: 169) 
               
               
                 S1113 (FIG. 12) 
                 S510 
                 CBDA Synthase N196V: SEQ ID 
               
               
                   
                   
                 NO: 172 (SEQ ID NO: 171) 
               
               
                 S1114 (FIG. 12) 
                 S510 
                 CBDA Synthase H208T: SEQ ID 
               
               
                   
                   
                 NO: 174 (SEQ ID NO: 173) 
               
               
                 S1115 (FIG. 12) 
                 S510 
                 CBDA Synthase K260W: SEQ ID 
               
               
                   
                   
                 NO: 184 (SEQ ID NO: 183) 
               
               
                 S1116 (FIG. 12) 
                 S510 
                 CBDA Synthase L268I: SEQ ID 
               
               
                   
                   
                 NO: 186 (SEQ ID NO: 185) 
               
               
                 S1117 (FIG. 12) 
                 S510 
                 CBDA Synthase F316Y: SEQ ID 
               
               
                   
                   
                 NO: 194 (SEQ ID NO: 193) 
               
               
                 S1118 (FIG. 12) 
                 S510 
                 CBDA Synthase G378T: SEQ ID 
               
               
                   
                   
                 NO: 198 (SEQ ID NO: 197) 
               
               
                 S1119 (FIG. 12) 
                 S510 
                 CBDA Synthase N527E: SEQ ID 
               
               
                   
                   
                 NO: 218 (SEQ ID NO: 217) 
               
               
                 S1120 (FIG. 12) 
                 S510 
                 CBDA Synthase R543E: SEQ ID  
               
               
                   
                   
                 NO: 230 (SEQ ID NO: 229) 
               
               
                 S1205 (FIG. 12) 
                 S487 
                 CBDA Synthase M61W, G378T:  
               
               
                   
                   
                 SEQ ID NO: 314 (SEQ ID 
               
               
                   
                   
                 NO: 313) 
               
               
                 S1206 (FIG. 12) 
                 S487 
                 CBDA Synthase M61W, K389E:  
               
               
                   
                   
                 SEQ ID NO: 316 (SEQ ID 
               
               
                   
                   
                 NO: 315) 
               
               
                 S1207 (FIG. 12) 
                 S487 
                 CBDA Synthase G378T, K389E:  
               
               
                   
                   
                 SEQ ID NO: 318 (SEQ ID 
               
               
                   
                   
                 NO: 317) 
               
               
                 S1208 (FIG. 12) 
                 S487 
                 CBDA Synthase M61W, G378T,  
               
               
                   
                   
                 K389E: SEQ ID NO: 320 
               
               
                   
                   
                 (SEQ ID NO: 319) 
               
               
                   
               
               
                 *If a strain has a parent strain, it is a child strain. All of the constructs present in the parent strain are also all present in the child strain. 
               
               
                 **S4 is CEN.PK113-1A with genotype MATalpha; URA3; TRP1; LEU2; HIS3; MAL2-8C; SUC2 
               
               
                 *** S478 is the competition assay base strain used to test the library of CBDA synthase constructs. In this strain, the nucleotide sequence encoding a pGAL1_tTDH1 empty expression cassette is added and the CBDA synthase polypeptide in parent S270 is deleted, creating a strain without synthase. A THCA synthase is added at a second locus. 
               
               
                 **** S487 and S510 are the non-competition assay base strains used to test CBDA synthase constructs selected by competition assay result. S487 has extensive chaperone and secretory pathway engineering while S510 has a more minimal set of engineering. In these strains, the nucleotide sequence encoding a pGAL1_tTDH1 empty expression cassette is added and the CBDA synthase polypeptide in parent S270 is deleted, creating a strain without synthase. There is no THCA synthase. 
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 6 
               
             
            
               
                   
               
               
                 List of Regulatory and Other Elements 
               
            
           
           
               
               
               
            
               
                 SEQ ID 
                   
                   
               
               
                 and Type 
                 Name 
                 Sequence 
               
               
                   
               
               
                 SEQ ID 
                 ui1 
                 GCTTGTACTGAAATTAACGAGAAGATTGCTTTGTCGAGACGTATCGAAAA 
               
               
                 NO: 235 
                   
                 GCATTGGCGTTTGATTGGTTGGGCAACCATTAAAAAGGGTACTACATTGGA 
               
               
                 Flanking 
                   
                 ACCCATCGCTTAAGGAACCAATAAAACCACTGCAAAGACAAAAATTTCAT 
               
               
                 homology 
                   
                 AATTAATCTGAAAGAAAGTGAAGATAAGAAACGGGCTAGGAGGAAGGGA 
               
               
                   
                   
                 AACTGACACTTCTGGTTATTGCAATATGCTCATATACATTGATGCGTAATG 
               
               
                   
                   
                 ACATTGATGATCTTTATTCTCTTTTTATAACGTTTTCTTTCTTTTTTTTTCCTT 
               
               
                   
                   
                 CTTACATAGTATTCAACTGTATATTTAACATGTTTTACGTATTTTTAAGAAA 
               
               
                   
                   
                 AAATTACTAAACGCGATAATATTAAGCAAATATTTATCTCATAGTTCTCGA 
               
               
                   
                   
                 ACTCATTTATTTCCCATTGATGCCATGAAAACCTCTCAAACCTTTATCGTCT 
               
               
                   
                   
                 AGTTACACCAGTAGTCAATAAACTGCCTTTCTTTTTTTAC 
               
               
                   
               
               
                 SEQ ID 
                 di1 
                 ACAATTGCACAAAGATAATGAAGCTCCAAAATTATTCAGTATCTATTGAGT 
               
               
                 NO: 236 
                   
                 ATATATAACCTTGAAAAGGTTTTATTTTATATAAGTTCGCCATCTTAGTATA 
               
               
                 Flanking 
                   
                 GTGGTTAGTACACATCGTTGTGGCCGATGAAACCCTGGTTCGATTCTAGGA 
               
               
                 homology 
                   
                 GATGGCATATTTATTTTTTATATTCTTAATATACAAAGAATGTCGTGTGAA 
               
               
                   
                   
                 GCTGTAGGCACAGGTAATTTTGTAACCATAGTCAGATGTGGTGATCATGAG 
               
               
                   
                   
                 AGCGAATTATAATTTTATACCAGCTGGCAAGAATTGAGTAATATTTAGACC 
               
               
                   
                   
                 AGCATATAAAAGTAGAATAAAAAGTTATATGTACAAATTTTTTTTGACGCC 
               
               
                   
                   
                 AGGCATGAACAAAAACTACTATGGCTTTGGAATTTTCAAGCTCTTCGAAAT 
               
               
                   
                   
                 CATTCCACACCCATGGATAAAAAATACTAGAATAATTGGATGAAATTCCA 
               
               
                   
                   
                 ATATTTGGTCTTCTCTAAAAATGCCGAATGGGATGTTATCA 
               
               
                   
               
               
                 SEQ ID 
                 ui2 
                 AGTTTTGCCGCTTTGCTTGATCACTGTTAGTATTTCGGCAAATTATATGGTA 
               
               
                 NO: 237 
                   
                 TTGGTCGCCTTGCCAGGTTCTTTAGGAAGTTCATCATAAACTAACGCTTTC 
               
               
                 Flanking 
                   
                 AAGAATTTACGGAAATGATAGGGTTTATAGTTTTTATAACAGTAGTGGACC 
               
               
                 homology 
                   
                 TAGAAAACACCGATAGCTGGCGGCGGTTATATCTCATTACTACTATGAAAA 
               
               
                   
                   
                 CTGTGGCTCCTGAGTAGCTACTGAAGGATGTGCCCATCTTAATCCAGACCT 
               
               
                   
                   
                 AGTCAATACAATCAATACAACTGTCTAGCTGAAAACTGACAAAAAAGTTT 
               
               
                   
                   
                 GTCGATGTCTCTAGTATATTCACTATAACACTAAATTTTATTGTAAATTATT 
               
               
                   
                   
                 ACACAAGTTTTCAAGAAGAAAAACAATATTAAACACAATAACTAGATTAT 
               
               
                   
                   
                 GCGAGGCACGGCAAAAGGAGTGAAGAGGGCAAAATACGGAGAAGACAAT 
               
               
                   
                   
                 ATAGAATAAATTTCTTTTTTTGATTAGAGAAGATTGTTTGCCA 
               
               
                   
               
               
                 SEQ ID 
                 di2 
                 ATAGTCTTACCATGATGATCAGTCGGATTCTGACGACGTTGGGTATTTTAA 
               
               
                 NO: 238 
                   
                 AACACGCGTAATTGAAAGGGTGATGTTGAGAATGGACCACTTCAAGATAT 
               
               
                 Flanking 
                   
                 GCTCGAAAATGTAGCTATATTTCACGGATGAATAACTCGTAAGAATGTGCA 
               
               
                 homology 
                   
                 GTAGCTGATGGACCTAGGAACGATCAAGTCAACGTTGTATTTTGGTTCGGC 
               
               
                   
                   
                 AAACAATTGATATGATGTTGACAAGAAAACCATCTGCGCTCTAATCTCTAA 
               
               
                   
                   
                 GTACACGTGCATTTGGACCTATCATCAAAAGAGAATAAGAGGATACTTTC 
               
               
                   
                   
                 AAGAGAAGTTCAAAAAAGAATCATTATTATGATCCAATGACAGTGACAAT 
               
               
                   
                   
                 AAGATCAACATAAAAAAGAAAAGTCAGAAGTATAAATCTGGGTCTTTTTC 
               
               
                   
                   
                 TCTAAAATAATTATAGTCTGTTAATTTATAAAACTGCCTAAAAAATATACT 
               
               
                   
                   
                 TAAAATATGTCTACAGATTATGCAGCTGGAAAAAATCAAGCAAAA 
               
               
                   
               
               
                 SEQ ID 
                 ui3 
                 CCAGTTATCCTAGGCAATTACTTTATTTGAGTCTTATATGACGTCACTAGA 
               
               
                 NO: 239 
                   
                 AGCTCAGTAAGAGCAACCGAGACCTGAACATCCTTTTTTTTTTTTGCTTCTT 
               
               
                 Flanking 
                   
                 TATTTGGCAGCATTTTTCAAAAATAATAAAATGGAAGCCGCGAGTACGAA 
               
               
                 homology 
                   
                 CAATGATGTGTTCTGGGAATACCTCGTCAAAACAAGACAATGGTAAGGAT 
               
               
                   
                   
                 TTTCTTTCATCAGGCAGAAAGATCTGGATCTGAATGGCATCATTTTGTGAT 
               
               
                   
                   
                 GTGTAAAAGCGGGACCTTGTTATTTCGACTTTTTGCATCATGTTGATGCAA 
               
               
                   
                   
                 TTTGCTACTTTTCCGACGGTGCGCTCCAACGGATGGGTATTTCCTTAATAAC 
               
               
                   
                   
                 AAGGCATTTCTCTGGAAGTTGGCTTACTGTTTGAAATCACAGCCGGTCACA 
               
               
                   
                   
                 AAATAAAGTAAAAAAACTATCTCTCTCCACAAGAAGTAATTACAGGTTGT 
               
               
                   
                   
                 ATACTACGTGTGATCGTATTTCTTTATGAACACTAAGGAGTT 
               
               
                   
               
               
                 SEQ ID 
                 di3 
                 CGTGTCTGAAAAATCTTGAATTTTCAGAAAAGAATAAGCCCCAAATGTCA 
               
               
                 NO: 240 
                   
                 GTGATGGTAGTAGCAGTACTCCCCTACGATTTTAGATACTTTAGAGAGCCC 
               
               
                 Flanking 
                   
                 ACCTTCAGAATCGGAAGGAGGATAATTTTGTAAAGCCCTTCTGTTTTTTCT 
               
               
                 homology 
                   
                 CTTGCATAACTTATATTTCCACATCAAAAAGTAGTGTGCTAAGAAAAAGGA 
               
               
                   
                   
                 GACGAGAAAAAGGATTACGGCACTCTCTGCATCTAGACATATACCAAAAG 
               
               
                   
                   
                 TTGGGTTTGCTCACGAAAATACCATAATTGTGGTGTCAAAAAAATCCTGCC 
               
               
                   
                   
                 TCATAATACCACTGCAGCAATTGTGGATGACTAAAAAATAACTTGCATTCC 
               
               
                   
                   
                 ACGATGTTATTTTACTTTATAAAGCACCTGCAATTTTTTTTTTTGTATTAAC 
               
               
                   
                   
                 TCATCGAGTATGTCTGATGTGTAAACTGAACCAGGCTTAATATCGTTTCTA 
               
               
                   
                   
                 ATTCTTGTTGTGAGAAAACTTTCCTGCCTAATGTATTTCGTC 
               
               
                   
               
               
                 SEQ ID 
                 ui7 
                 TAAAATTTTACTCATAGTAGATAATGGCATAAATCAGTGGTAAAAAAAGA 
               
               
                 NO: 241 
                   
                 ATACGCATGACAAATTTTGAAAACCGTACGTGACATAAAATACCTATAAT 
               
               
                 Flanking 
                   
                 AAGATGAAGACATCAATTCTCAAGTTCCACTTTTCGCCGGTTGAGTGTATC 
               
               
                 homology 
                   
                 GGTCATAGTACAAAGGCAGAAATGAATAATAGTAATATTAATCGCAGTTT 
               
               
                   
                   
                 CCTGTTGTTTAGAGAACTGAAACGCTTTGTGGGCATCAGGTTTAGATTAAC 
               
               
                   
                   
                 TGCTACCCTTCTTCTGTATTTGTCTGGCCATGCTTCTCAAATAAACCGCTGC 
               
               
                   
                   
                 GGATAACATTTCAAGTGGTTTCTCAAGGGAGAATCATAGTTTAGCTTAACA 
               
               
                   
                   
                 TACAGCAAATCGTCACTATCTTGACTGATGCCCGGTGTATAGAGAATGGGT 
               
               
                   
                   
                 AGTTAATATCATCTAGATGGGGTTTCTTTGAAAACACCAGTTTCTTTGAGG 
               
               
                   
                   
                 ACACCAGTTTCAGTGCTTCTCTCTACCCCATCAACTATTGCAC 
               
               
                   
               
               
                 SEQ ID 
                 di7 
                 CGTCTTGCTTTTTTCGGTAGTTTTTCGTTTCGATAAAGGCAACAATGCTGTA 
               
               
                 NO: 242 
                   
                 TATTGTATGCAGGAAGTTCTTAAGGAAAATACAGGAATCTTTAGAAAAAG 
               
               
                 Flanking 
                   
                 AATAAATAGCTTTCCATTGTATCATGAACAAGTCACTCTTCATATTATATGT 
               
               
                 homology 
                   
                 CGTCGCTTCTTATCCCTTTAAGTTATGAATTGTTGAGCTTAGGATTTTACCA 
               
               
                   
                   
                 CAACTGAATAACATTTTCTTTATTCTAATAATCGATTTTTTTTAATAAGATT 
               
               
                   
                   
                 AGACTTGAGTGCCATCAGCAAAGAAAAATACTTTTAATGTCCTTTTTTTAA 
               
               
                   
                   
                 CTCTACACAGAATTTAGTTGGCTGTTTCATTGATTTACAAAAATATAAATA 
               
               
                   
                   
                 TATACCGTTAAAATTATAGCGATAAACTGAGTATGTGGTCTCTCTTTTCCC 
               
               
                   
                   
                 GCAGAATATGAAAGCTTTTCTTTTATAAATCTTATAATATTGGTCTCTTTTT 
               
               
                   
                   
                 GGTACGTTTGGCAAATTGGCATTCATTTATCATGAAA 
               
               
                   
               
               
                 SEQ ID 
                 ui10 
                 AGGACCACTTCATCAAGTTTCGAAAGTGAAATTAAATCCATTTCAGAAAAT 
               
               
                 NO: 243 
                   
                 TTCAAGAACTCTATTCCAGAATCTTCCATACTCTTCAGGATATCATATAAT 
               
               
                 Flanking 
                   
                 AACAACTCTAATAATACCTCTAGTAGCGAGATCTTCACACTTTTGGTAGAA 
               
               
                 homology 
                   
                 AAAGTTTGGAATTTTGACGACTTGATAATGGCGATCAATTCTAAAATTTCG 
               
               
                   
                   
                 AATACACATAATAACAACATTTCACCAATCACCAAGATCAAATATCAGGA 
               
               
                   
                   
                 CGAAGATGGGGATTTTGTTGTGTTAGGTAGCGATGAAGATTGGAATGTTGC 
               
               
                   
                   
                 TAAAGAAATGTTGGCGGAAAACAATGAGAAATTCTTGAACATTCGTCTGT 
               
               
                   
                   
                 ATTGATAAATAAAACTAGTATACAGCAAATACTAAATAATTCAAGAAAAA 
               
               
                   
                   
                 AACATTAGATAGAGAGGGGCAGATGTTCAAGCTATACCCATTATATTGATC 
               
               
                   
                   
                 CACACTTAGTATTAAGATACGTCTGTGAAGGATGAAAAAAAATGTAT 
               
               
                   
               
               
                 SEQ ID 
                 di10 
                 TTGTGCGTTTTTATAATTTTTTTTTTTTTGTAATTCTATGCAAATGTAATATA 
               
               
                 NO: 244 
                   
                 AGTATATTTAAAGAAATAATGAGTCCTGTGAAAACAAAAAGAAAAAAAGA 
               
               
                 Flanking 
                   
                 TCATTAATGTATGTTAACGTATTTGCTTTGCAAATTTTAATTTATTTGTTGTT 
               
               
                 homology 
                   
                 AAATGCATTTTTTTTTTGTCGTTTCAGCGAGTTTTCTTGAGGTTGCTACTAT 
               
               
                   
                   
                 CATTAAAATCACAATCCACAGAGGAAGTTGATCTCTTTTTCAGTTGGGTGG 
               
               
                   
                   
                 GGGCAGAGCATGGGTGAGCAGTGGCCATGGGTCTAACAGGAAATAATCTT 
               
               
                   
                   
                 TTTGAACGCACAGATAAATTTTGTAATAATTTTCTATTTGACATTAGAGAT 
               
               
                   
                   
                 GGGGTGGTGGGAGTTAGTGGGCTTGGCCAAAAGATGCTTGAATTTTGTGG 
               
               
                   
                   
                 GATGCTCAGTGACCTTTTAAAAGAATTTTGGGTAGAAGAGAACGAACCTG 
               
               
                   
                   
                 AATGTGAATGGTGTGATGCAGAGTC 
               
               
                   
               
               
                 SEQ ID 
                 ui21 
                 CCATCTATCCTTCGCCTCTCCTTCGCTCTGTAATTTTTTTTACTCGCGCGCTT 
               
               
                 NO: 245 
                   
                 CCGACTTTTGAAAGAAGGAGCAATAAAGTTAAATAAATGTAATTAAATTA 
               
               
                 Flanking 
                   
                 TGCTTTTTTAGGCAAGTTCGGGACTTTGTTGCCACGTATTGCTCTTCTATGC 
               
               
                 homology 
                   
                 AAGCACTTCACTCCTTTTCTTTCATCTCTGTTTTCTTCCACTGGCTGGAAGC 
               
               
                   
                   
                 TTGAGGGTTGCCTCTTGATTCTTTATCGCCTGCAACCATTGCCTTGTTCCGT 
               
               
                   
                   
                 CCTCTCAAGGCGTTCCTTCCGTGCTTTTTAAATACTAGAATCATTCGAGAC 
               
               
                   
                   
                 GTATTTATGAGCATGTTACTTCTTGATGTTTATCTAAGAGGGTTGTTTAGGT 
               
               
                   
                   
                 TATCCGCATTATTTTTAAAGTTTTAAGGTTACATCATTTATTCAGACGCGTT 
               
               
                   
                   
                 CGGAGGAGAGTGCATTCACCAAGATGTAAATTTCTTCAGTTTTCCGGATTA 
               
               
                   
                   
                 GGATTGGAAAAATGAAGAAAAATAG 
               
               
                   
               
               
                 SEQ ID 
                 di21 
                 CTAAAGTAATTGTAGCAGTTGTTATTAAGGAGTTCTTTAAATCATATTGCTT 
               
               
                 NO: 246 
                   
                 GCTTGTATCAGACCATTGGAAACTTCAATGTTTAAACTCTAGAAAGGTTGA 
               
               
                 Flanking 
                   
                 TCTGCTCAAATATTTTCATATTTACGGCATGTCCTAACTTGAACATTTGTAG 
               
               
                 homology 
                   
                 AAGAGAGACATATTTCTTAGTGTAGGCAAGATATTTGAATGACATTGTCTG 
               
               
                   
                   
                 CCGAAATATACTCGACTTGCAGTGGAACTGCAAGTCGAAAAGGATATCGC 
               
               
                   
                   
                 TTTAGCCAAACAAAAATTTGTTGTGCTATTCAGTGAGCATGCATTGGCTAT 
               
               
                   
                   
                 AGAGGCCGCACCTAAATTGTATCTTTTGATTTATGTAACTGCCACACTTTCT 
               
               
                   
                   
                 CTAGCACAGTCATGATACGGCTTTTTTTCATTTAGCCACCAAATACTGTAA 
               
               
                   
                   
                 ATATCGTTTTAGAACGTTATGAAAAAATGCTCATCCACTTAAAAACCTCTC 
               
               
                   
                   
                 CGTATTCTGAAAGTTGGTATAATCTTGCACTTTAAGTGT 
               
               
                   
               
               
                 SEQ ID 
                 ui33 
                 TCTGTTAACCATTCTGGTTCACTTGCCGTCGTATGTTGCGGACCACCTATTT 
               
               
                 NO: 247 
                   
                 TCGTCGACACCGCTAGAAATCAAACTGCCAAAGCTGTTATCAGAAACCCA 
               
               
                 Flanking 
                   
                 TCAAGAATGATTGAATACTTGGAGGAATACCAAGCCTGGTGAACAATTTTT 
               
               
                 homology 
                   
                 CATATTTAAGTAAACACTCAATGTATAATATCCTCTAACTGTTGTAATTTCA 
               
               
                   
                   
                 TTAACGTAAATGGTTTGCGCCTTTTTTAGGGGACCCTTGTTGATTCATTCTA 
               
               
                   
                   
                 ACTACTGAGGCATAAGTTGTTTCAAATAACACTTTTTCAGAAAAATAATCG 
               
               
                   
                   
                 TATTAAAAAGCAGAAAAATCATACGTAAGATGACAGAAGCTTCATATTTA 
               
               
                   
                   
                 GTAACTCTGAATTGTATAACACACCAATTGCCGATAGAATATGAACCAATC 
               
               
                   
                   
                 GATCTTCAGCGTTCATGTACTTAATTTAACTACCTGTATTTTCTTATAAAGA 
               
               
                   
                   
                 TAAAATTGGTGTATAATGTAAGGGCCAAGAGAAAAAGGAATC 
               
               
                   
               
               
                 SEQ ID 
                 di33 
                 ATTTCTTCAAAAAAATAACTGAATAAACACCTATATAATGTTCAGAGGTTA 
               
               
                 NO: 248 
                   
                 TACTTTAGTGTTTTAGAATGCAGTACCAAAAGTAATATATTGAATTAATAA 
               
               
                 Flanking 
                   
                 CTATATGATGTGTAGCTAAGAATTAAATAGTAAACGTCTTCTGAAACCTTT 
               
               
                 homology 
                   
                 TAAGAGGTAATTATTGGTATTCCAAAGTCATATGTGGAGGTAAGGGAGAC 
               
               
                   
                   
                 ACAAAATTATCTGGAATGACAGCGTGCTGACACATATAAAGTTCCGTAACT 
               
               
                   
                   
                 TCAAATGCCTTCATTATTCAACATAGGAAAAGTGAAATGTGTGCCTCTAAA 
               
               
                   
                   
                 ATATACGGAACATCGTCGAACTAAAAAAATCCATTAAGCAAAGTTAGAAA 
               
               
                   
                   
                 CAGCATGCACTACAAGACATTTGGTTCATCATGAAGAATGCTCAATTGAAC 
               
               
                   
                   
                 CATCAATCACTTTCTCTTGTTCGATGTTAGCATTATCCTCACTATCAGTTGA 
               
               
                   
                   
                 ATCCTCAATGCTTTCGGTTTCAGTCCTCGCATCTTC 
               
               
                   
               
               
                 SEQ ID 
                 ui34 
                 TGAGCAACCAATCACTTCTGAAACCGCTATGAAGAAGGTTGAAGATGGTA 
               
               
                 NO: 249 
                   
                 ACATTTTGGTTTTCCAAGTTTCCATGAAAGCTAACAAATACCAAATCAAGA 
               
               
                 Flanking 
                   
                 AGGCCGTCAAGGAATTATACGAAGTTGACGTATTGAAGGTTAACACTTTG 
               
               
                 homology 
                   
                 GTTAGACCAAACGGTACCAAGAAGGCTTACGTTAGATTGACTGCTGACTA 
               
               
                   
                   
                 CGATGCTTTGGACATTGCTAACAGAATCGGTTACATTTAATCTAATTGGTT 
               
               
                   
                   
                 TAATTAATAAATTTAATATTATTTTTAAATTTTTCTTTAAATATACAATAAA 
               
               
                   
                   
                 TCTTTCATAACATGTTAAATTCATGATTAAGCGTAAATAAAGTGTAGTGGC 
               
               
                   
                   
                 AGAGTGCACGGGGTTTCCTGTGCCTTACAAAGTAGGTACCAATTTGCGTAT 
               
               
                   
                   
                 TGCAGCGAGGGTTCCGGTTACTATTTATAATTACGTGTTAGTGTACTGTGA 
               
               
                   
                   
                 TTTTATTGAGGCTATAACAAGAAAAGGATCTGTGAAGGTTTTGAG 
               
               
                   
               
               
                 SEQ ID 
                 di34 
                 CCCTTTTCTTTTCGCAAGATGAGAGTAAAGAGTTGTACATCAGGTAAGAAT 
               
               
                 NO: 250 
                   
                 GTTATTATTTAAATTCGAAGTGATAAATTCTTTTCATGATGAATCACTCGCT 
               
               
                 Flanking 
                   
                 TATATGGGGTAGAATATATATATATGTGTGTGTGTGTGTGTGTTTGTGTAT 
               
               
                 homology 
                   
                 GTAGGGATGGTGCGCGTTTGTTGTGTGACATTTGCTACTCATTCTTTTCCTT 
               
               
                   
                   
                 TTCCTACGACTGGCTTAACGGGAATATTATCAATTTGCTGCATTCTTATGCT 
               
               
                   
                   
                 TCGGTCCGATGCTCATTAAGATGATGCAGATCTCGATGCAACGAATTCCAA 
               
               
                   
                   
                 GCCCTTATCGATATTTTTCTTTAACTGGGAGACGCAAATTGGCAACATTTG 
               
               
                   
                   
                 GTTGCGTTCCATGTCGTTCATCCTATTAACGATGTCATAATCCACATAGGA 
               
               
                   
                   
                 AACACCCTTTGTAGTAATAGTTAATGGTATGGCAAAGTAGTCTGCACCGTC 
               
               
                   
                   
                 CACCAGAGGCAATAATTGATCTGCCCCAGG 
               
               
                   
               
               
                 SEQ ID 
                 ui1001 
                 ATGAGTTAACGTAGATTACTTTCCGTTAGTGTAACGGACAAGATGACACAG 
               
               
                 NO: 251 
                   
                 TATTGAAACGCTCCTCTATCTTTGTGGGTGTTGAGGGAGGAGAGAGTTATT 
               
               
                 Flanking 
                   
                 AGTCTAGACGCTATATATCACAGAGTCGAGTGCCCAATAATATAGCAGGT 
               
               
                 homology 
                   
                 AGACGCCAACTTAACTACTGGATGTGAGTTAGAGAGGAATATACTGTTTTA 
               
               
                   
                   
                 TTAACTCGTACCGTAGTGGTTTCTGGCGAGAATTCGCCGGCTTAAAATCTA 
               
               
                   
                   
                 TTGACTAACTAGAATTAGCTTAAAGTGGACCTTATTGAATCTCACCGGGTT 
               
               
                   
                   
                 ATCGCGACATTTATATTATCGAAGGGTCCAGCTTGGGGTTTGTTTGGAAGG 
               
               
                   
                   
                 TTGACTTGTTGTTGTAGTTGTATCACTAATAATTACGATTCTCAACGACCGG 
               
               
                   
                   
                 CCCAAAGATTGCCTGGGTTAAATTCAGCGTCTGATGTATACTTAGCTCTTC 
               
               
                   
                   
                 GCAAGTAGTGTTCTAATTAAAGATCACTTCAACTTATCTTC 
               
               
                   
               
               
                 SEQ ID 
                 di1001 
                 AAGGTAACTTAGGCTGACGACGCAATAATGCACGCTCGCGTGTGATGAGA 
               
               
                 NO: 252 
                   
                 TTACATCAGTAAGAATTCATATCTCGATATGGGATAATTACGGGCTCACAC 
               
               
                 Flanking 
                   
                 TCTAGGAATACCAAGAACAGTAATGTTTCCTTATTAATATGTAGATAAGGA 
               
               
                 homology 
                   
                 TCTTCTTAAAGTTTAATTGATGGCGAATTCCAAATAGTGACTTAACTTTCGC 
               
               
                   
                   
                 GCAGAGTATCGCAGGACAAGGTTAGCTTTTCGTAAGCCTGATGTTATGCCA 
               
               
                   
                   
                 TAACTAGCCACCTTGTAATCCCCGCGCTCAGTAAATCTATCTACTTATTTGC 
               
               
                   
                   
                 TTCACTTCTTCACGGAGAGTACTGATTTTCTTCTCTCAATACTACTGACTAC 
               
               
                   
                   
                 CTTAGGGCGACATACTTTAGTTCTGCATAAGCGTCAACCTCTTGCCTAAGG 
               
               
                   
                   
                 GTATGGATCCTTGTTAAGCCTTATTCCATATAGTTGAGCTGAAGAACAGAT 
               
               
                   
                   
                 CCCTCAACTCGAGTGCGACTAGTAGCTAGTTACGAACAC 
               
               
                   
               
               
                 SEQ ID 
                 uPEP4 
                 TGTTAATCCGTTTTCAATATCTTGAGCTCCTCAATTGTATTTGCTGAGGTCT 
               
               
                 NO: 253 
                   
                 GATTATTTCTATAACCAAAAGCGGTTATTGAATCTATGGAGAGGCTGTAAC 
               
               
                 Flanking 
                   
                 CCGTCTTATGCCTTCCGGGTACTATATTTCATTTGCGGGTGTCGATGGATTA 
               
               
                 homology 
                   
                 AGGGGCGGAGGCGGCCCTTTTTAGGATTTATATAAAAAGCCATACTTCCGT 
               
               
                   
                   
                 ACTTCGTAACCTCTTATCAACTGGTTAAGGGAACAGAGTAAAGAAGTTTGG 
               
               
                   
                   
                 GTAATTCGCTGCTATTTATTCATTCCACCTTCTTCTTTTTTGAGCGAAGCCT 
               
               
                   
                   
                 TTATAATCAAATTTTAGTGGTCTTTTCTATTTTTATTTGAGAAGCCTACCAC 
               
               
                   
                   
                 GTAAGGGAAGAATAACAAAAAGTATATCTCACCCTACTGTATTCATAAAA 
               
               
                   
                   
                 AGTTTTTTCTATTAGAATTCTATAAGAAAAGAAAAAAAAAAAGCCTAGTG 
               
               
                   
                   
                 ACCTAGTATTTAATCCAAATAAAATTCAAACAAAAACCAAAACTAAC 
               
               
                   
               
               
                 SEQ ID 
                 dPEP4 
                 GCTAAACTTTTCTTACTTCTCCGCCCTATCCTTTTCTGCCATCTAGAGAGCT 
               
               
                 NO: 254 
                   
                 TTTATAAGTAGATAACAATAAAAAAAACTATAGTATATTTAAAAAAAAAA 
               
               
                 Flanking 
                   
                 AACAAGACAAACCATCTTGTCCTCAGTTTTAGAATCCATTGTTCTATGCTG 
               
               
                 homology 
                   
                 CTGCCCATAATGTCATTATATGCGGGTAGCCCGATGATGCGGCTCGAGAAT 
               
               
                   
                   
                 TTCCTTGTTTATCCTTTTCCAATAGCGGAACAATTGATAATAAAGCAATGT 
               
               
                   
                   
                 AAGCAGAAGCGAAAAATAAAAAGAAATAGGCTGCAGAGATTCACAGGCT 
               
               
                   
                   
                 GCGCTCTAGAAACATTTGAAATCAAGGCAAACATAGAACACTTGATAAAA 
               
               
                   
                   
                 TTCTTACCATAATACCACCATTGATGATTCAAAAAATGAGCCCAAGCTTAA 
               
               
                   
                   
                 GGAGGCCATCAACGAGGTCTAGTTCTGGTTCAAGTAATATCCCACAATCGC 
               
               
                   
                   
                 CCTCTGTACGATCAACTTCATCGTTTTCTAATCTGACAAGAAACTCCATAC 
               
               
                   
                   
                 GG 
               
               
                   
               
               
                 SEQ ID 
                 uROT2 
                 GCTGCATTCTTCAGTGGTATGTTATTTATGTAACGGGTATGCGAACCACAA 
               
               
                 NO: 255 
                   
                 CGCCAGATTCTTGAAGGGGAAACCTAACTACACAGTCTTAGCAACAACCG 
               
               
                 Flanking 
                   
                 CCGGCGCTCTGGGTCTTTTGACGCTGGACGGTATAATTTCAAAGAAATACT 
               
               
                 homology 
                   
                 ACTCCAGATACGACAAGAAATAATAACATACTATTTAATAACATCCTTTTC 
               
               
                   
                   
                 ACACACTCACACACTCACATACTTTATATACATATATTTTTATAACTATTAC 
               
               
                   
                   
                 TGCTGATTTATTTGTAAGGAAACGTGCTTTCCTCTTCATCGGTCAAGTGATA 
               
               
                   
                   
                 AGTTTCTATAATATAATAGCTTTTCTGTCTACTATCATTCTTTTTTCATTTCA 
               
               
                   
                   
                 AGTACCCTTAATTTGTTTTACCCGGACCACGAAATTTTCTCACTACGGCACT 
               
               
                   
                   
                 TGAGAGCTATAACTCAATGAACATGTTGCTTGGAGTGATTTGATTGCTCTG 
               
               
                   
                   
                 CGTATCTTAAAATAGCGGTCTCGAATCAACCGTATGCAAC 
               
               
                   
               
               
                 SEQ ID 
                 dROT2 
                 GGGAAAAAAACGAAGGGGTATCTTTACATCTTTTTAGCTCTTTCTTGCAAA 
               
               
                 NO: 256 
                   
                 TTAAACGTAAAAATATCCGTAAATATAACATATAACCATTATCTATAGAAA 
               
               
                 Flanking 
                   
                 AAAAGAACCGAAAATTGTGTCAGGCCCTACTTCCCGTGAGCTAACTTCATT 
               
               
                 homology 
                   
                 CTTGTCGAAAACTTGACTAGGGTCGTCCAGTCGCAAAACGTATCACATTTC 
               
               
                   
                   
                 GGACATTTCCCACCTCGAGGTATCAAGTTTCTTCTCCCTACTATCAACTGTT 
               
               
                   
                   
                 CATCATCTAGAAAGTACCTGTGAAGACATTTCAAGTGGTTAACAGACCCGC 
               
               
                   
                   
                 AGTCTTTATTATTGCAAAGCGCTACAAACGGCTTCAGATTTTGCTCTTCAG 
               
               
                   
                   
                 ACGTGTAGTCAATTTCTTTCTCACAAATTTCACATCGCACTACCCCTGTAGT 
               
               
                   
                   
                 TAGTTTCTTTTCGAAAGTTTCGAATATGTTTCTTTCATTTTCAATGACTTTA 
               
               
                   
                   
                 GTGTATACAGCTTCTACCACTTTTAAATTCTCATCAC 
               
               
                   
               
               
                 SEQ ID 
                 D0 
                 ATCGACGGGCCGGCCAGTGTCTCTCGTTTAAACTTG 
               
               
                 NO: 257 
                   
                   
               
               
                 Linker 
                   
                   
               
               
                   
               
               
                 SEQ ID 
                 D2 
                 ATGAGTATGCTATACTCCCACTAATGGCATCACGCT 
               
               
                 NO: 258 
                   
                   
               
               
                 Linker 
                   
                   
               
               
                   
               
               
                 SEQ ID 
                 D3 
                 TAGGCAAGAATAGCGGAGCACTAGGTTTCGACTTAA 
               
               
                 NO: 259 
                   
                   
               
               
                 Linker 
                   
                   
               
               
                   
               
               
                 SEQ ID 
                 D4 
                 ACGATCCACGGCTTCTAAAGACTGACAATTGCTTTC 
               
               
                 NO: 260 
                   
                   
               
               
                 Linker 
                   
                   
               
               
                   
               
               
                 SEQ ID 
                 D9 
                 CAAAGCTAGGCCGGCCCTTAGTACTAGTTTAAACCG 
               
               
                 NO: 261 
                   
                   
               
               
                 Linker 
                   
                   
               
               
                   
               
               
                 SEQ ID 
                 D20 
                 TCGGAGCAAATGAAACGATTCCGATAAGTGTTGCAA 
               
               
                 NO: 262 
                   
                   
               
               
                 Linker 
                   
                   
               
               
                   
               
               
                 SEQ ID 
                 D21 
                 TTGTGGGTGAAAGAAGGAGAGGTACGTTTCTATCGT 
               
               
                 NO: 263 
                   
                   
               
               
                 Linker 
                   
                   
               
               
                   
               
               
                 SEQ ID 
                 D22 
                 AGACAGACCCGCCTTAATCTACAAGATTCGTGACAT 
               
               
                 NO: 264 
                   
                   
               
               
                 Linker 
                   
                   
               
               
                   
               
               
                 SEQ ID 
                 D23 
                 CATTATATTTCCTACGGAGTCGGAAGCAGGGACGTA 
               
               
                 NO: 265 
                   
                   
               
               
                 Linker 
                   
                   
               
               
                   
               
               
                 SEQ ID 
                 D30 
                 GGACCACCAGTAACACTCCAATTCTGGGTGATTTAC 
               
               
                 NO: 266 
                   
                   
               
               
                 Linker 
                   
                   
               
               
                   
               
               
                 SEQ ID 
                 DH7 
                 CTCTTATTACCCTATCCTATGGTACTTTCTCGGCAG 
               
               
                 NO: 267 
                   
                   
               
               
                 Linker 
                   
                   
               
               
                   
               
               
                 SEQ ID 
                 G1 
                 ACCTCTATACTTTAACGTCAAGGAGAAAAAACTATA 
               
               
                 NO: 268 
                   
                   
               
               
                 Linker 
                   
                   
               
               
                   
               
               
                 SEQ ID 
                 G7 
                 CATGATAAAAAAAAACAGTTGAATATTCCCTCAAAA 
               
               
                 NO: 269 
                   
                   
               
               
                 Linker 
                   
                   
               
               
                   
               
               
                 SEQ ID 
                 G10 
                 AAAAAAAAAGTAAGAATTTTTGAAAATTCAATATAA 
               
               
                 NO: 270 
                   
                   
               
               
                 Linker 
                   
                   
               
               
                   
               
               
                 SEQ ID 
                 RG1 
                 TATAGTTTTTTCTCCTTGACGTTAAAGTATAGAGGT 
               
               
                 NO: 271 
                   
                   
               
               
                 Linker 
                   
                   
               
               
                   
               
               
                 SEQ ID 
                 LTTDH1 
                 ATAAAGCAATCTTGATGAGGATAATGATTTTTTTTT 
               
               
                 NO: 272 
                   
                   
               
               
                 Linker 
                   
                   
               
               
                   
               
               
                 SEQ ID 
                 pGAL1 
                 TTTGGATGGACGCAAAGAAGTTTAATAATCATATTACATGGCAATACCACC 
               
               
                 NO: 273 
                   
                 ATATACATATCCATATCTAATCTTACTTATATGTTGTGGAAATGTAAAGAG 
               
               
                 Promoter 
                   
                 CCCCATTATCTTAGCCTAAAAAAACCTTCTCTTTGGAACTTTCAGTAATAC 
               
               
                   
                   
                 GCTTAACTGCTCATTGCTATATTGAAGTACGGATTAGAAGCCGCCGAGCGG 
               
               
                   
                   
                 GCGACAGCCCTCCGACGGAAGACTCTCCTCCGTGCGTCCTGGTCTTCACCG 
               
               
                   
                   
                 GTCGCGTTCCTGAAACGCAGATGTGCCTCGCGCCGCACTGCTCCGAACAAT 
               
               
                   
                   
                 AAAGATTCTACAATACTAGCTTTTATGGTTATGAAGAGGAAAAATTGGCA 
               
               
                   
                   
                 GTAACCTGGCCCCACAAACCTTCAAATCAACGAATCAAATTAACAACCAT 
               
               
                   
                   
                 AGGATAATAATGCGATTAGTTTTTTAGCCTTATTTCTGGGGTAATTAATCA 
               
               
                   
                   
                 GCGAAGCGATGATTTTTGATCTATTAACAGATATATAAATGCAAAAGCTGC 
               
               
                   
                   
                 ATAACCACTTTAACTAATACTTTCAACATTTTCGGTTTGTATTACTTCTTAT 
               
               
                   
                   
                 TCAAATGTCATAAAAGTATCAACAAAAAATTGTTAATATACCTCTATACTT 
               
               
                   
                   
                 TAACGTCAAGGAGAAAAAACTATA 
               
               
                   
               
               
                 SEQ ID 
                 pGAL1- 
                 TATAGTTTTTTCTCCTTGACGTTAAAGTATAGAGGTATATTAACAATTTTTT 
               
               
                 NO: 274 
                 10 
                 GTTGATACTTTTATGACATTTGAATAAGAAGTAATACAAACCGAAAATGTT 
               
               
                 Promoter 
                   
                 GAAAGTATTAGTTAAAGTGGTTATGCAGCTTTTGCATTTATATATCTGTTA 
               
               
                   
                   
                 ATAGATCAAAAATCATCGCTTCGCTGATTAATTACCCCAGAAATAAGGCTA 
               
               
                   
                   
                 AAAAACTAATCGCATTATTATCCTATGGTTGTTAATTTGATTCGTTGATTTG 
               
               
                   
                   
                 AAGGTTTGTGGGGCCAGGTTACTGCCAATTTTTCCTCTTCATAACCATAAA 
               
               
                   
                   
                 AGCTAGTATTGTAGAATCTTTATTGTTCGGAGCAGTGCGGCGCGAGGCACA 
               
               
                   
                   
                 TCTGCGTTTCAGGAACGCGACCGGTGAAGACCAGGACGCACGGAGGAGAG 
               
               
                   
                   
                 TCTTCCGTCGGAGGGCTGTCGCCCGCTCGGCGGCTTCTAATCCGTACTTCA 
               
               
                   
                   
                 ATATAGCAATGAGCAGTTAAGCGTATTACTGAAAGTTCCAAAGAGAAGGT 
               
               
                   
                   
                 TTTTTTAGGCTAAGATAATGGGGCTCTTTACATTTCCACAACATATAAGTA 
               
               
                   
                   
                 AGATTAGATATGGATATGTATATGGTGGTATTGCCATGTAATATGATTATT 
               
               
                   
                   
                 AAACTTCTTTGCGTCCATCCAAAAAAAAAGTAAGAATTTTTGAAAATTCAA 
               
               
                   
                   
                 TATAA 
               
               
                   
               
               
                 SEQ ID 
                 pGAL7 
                 GGACGGTAGCAACAAGAATATAGCACGAGCCGCGAAGTTCATTTCGTTAC 
               
               
                 NO: 275 
                   
                 TTTTGATATCGCTCACAACTATTGCGAAGCGCTTCAGTGAAAAAATCATAA 
               
               
                 Promoter 
                   
                 GGAAAAGTTGTAAATATTATTGGTAGTATTCGTTTGGTAAAGTAGAGGGG 
               
               
                   
                   
                 GTAATTTTTCCCCTTTATTTTGTTCATACATTCTTAAATTGCTTTGCCTCTCC 
               
               
                   
                   
                 TTTTGGAAAGCTATACTTCGGAGCACTGTTGAGCGAAGGCTCATTAGATAT 
               
               
                   
                   
                 ATTTTCTGTCATTTTCCTTAACCCAAAAATAAGGGAAAGGGTCCAAAAAGC 
               
               
                   
                   
                 GCTCGGACAACTGTTGACCGTGATCCGAAGGACTGGCTATACAGTGTTCAC 
               
               
                   
                   
                 AAAATAGCCAAGCTGAAAATAATGTGTAGCTATGTTCAGTTAGTTTGGCTA 
               
               
                   
                   
                 GCAAAGATATAAAAGCAGGTCGGAAATATTTATGGGCATTATTATGCAGA 
               
               
                   
                   
                 GCATCAA 
               
               
                   
               
               
                 SEQ ID 
                 pTDH3 
                 TTAGTCAAAAAATTAGCCTTTTAATTCTGCTGTAACCCGTACATGCCCAAA 
               
               
                 NO: 276 
                   
                 ATAGGGGGCGGGTTACACAGAATATATAACATCGTAGGTGTCTGGGTGAA 
               
               
                 Promoter 
                   
                 CAGTTTATTCCTGGCATCCACTAAATATAATGGAGCCCGCTTTTTAAGCTG 
               
               
                   
                   
                 GCATCCAGAAAAAAAAAGAATCCCAGCACCAAAATATTGTTTTCTTCACC 
               
               
                   
                   
                 AACCATCAGTTCATAGGTCCATTCTCTTAGCGCAACTACAGAGAACAGGG 
               
               
                   
                   
                 GCACAAACAGGCAAAAAACGGGCACAACCTCAATGGAGTGATGCAACCTG 
               
               
                   
                   
                 CCTGGAGTAAATGATGACACAAGGCAATTGACCCACGCATGTATCTATCTC 
               
               
                   
                   
                 ATTTTCTTACACCTTCTATTACCTTCTGCTCTCTCTGATTTGGAAAAAGCTG 
               
               
                   
                   
                 AAAAAAAAGGTTGAAACCAGTTCCCTGAAATTATTCCCCTACTTGACTAAT 
               
               
                   
                   
                 AAGTATATAAAGACGGTAGGTATTGATTGTAATTCTGTAAATCTATTTCTT 
               
               
                   
                   
                 AAACTTCTTAAATTCTACTTTTATAGTTAGTCTTTTTTTTAGTTTTAAAACA 
               
               
                   
                   
                 CCAAGAACTTAGTTTCGAATAAACACACATAAACAAACAAA 
               
               
                   
               
               
                 SEQ ID 
                 pTEF1 
                 GACAGCCTAGACATCAATAGTCATACAACAGAAAGCGACCACCCAACTTT 
               
               
                 NO: 277 
                   
                 GGCTGATAATAGCGTATAAACAATGCATACTTTGTACGTTCAAAATACAAT 
               
               
                 Promoter 
                   
                 GCAGTAGATATATTTATGCATATTACATATAATACATATCACATAGGAAGC 
               
               
                   
                   
                 AACAGGCGCGTTGGACTTTTAATTTTCGAGGACCGCGAATCCTTACATCAC 
               
               
                   
                   
                 ACCCAATCCCCCACAAGTGATCCCCCACACACCATAGCTTCAAAATGTTTC 
               
               
                   
                   
                 TACTCCTTTTTTACTCTTCCAGATTTTCTCGGACTCCGCGCATCGCCGTACC 
               
               
                   
                   
                 ACTTCAAAACACCCAAGCACAGCATACTAAATTTCCCCTCTTTCTTCCTCTA 
               
               
                   
                   
                 GGGTGTCGTTAATTACCCGTACTAAAGGTTTGGAAAAGAAAAAAGAGACC 
               
               
                   
                   
                 GCCTCGTTTCTTTTTCTTCGTCGAAAAAGGCAATAAAAATTTTTATCACGTT 
               
               
                   
                   
                 TCTTTTTCTTGAAAATTTTTTTTTTTGATTTTTTTCTCTTTCGATGACCTCCC 
               
               
                   
                   
                 ATTGATATTTAAGTTAATAAACGGTCTTCAATTTCTCAAGTTTCAGTTTCAT 
               
               
                   
                   
                 TTTTCTTGTTCTATTACAACTTTTTTTACTTCTTGCTCATTAGAAAGAAAGC 
               
               
                   
                   
                 ATAGCAATCTAATCTAAGTTTTAATTACAAA 
               
               
                   
               
               
                 SEQ ID 
                 SRS_A 
                 GAGATCCCCAAACAGTTTAATCTCTGATTAACTCTTGCGTCGTATAGTCGG 
               
               
                 NO: 278 
                   
                 GCTTAACTCTATACTCAAAATCACTAACAAGACGTAGACGCAAGACGATA 
               
               
                 SRS 
                   
                 AGACCGGGCAGGATACTATCACTCAATACAGTTCAGATATCTCCATCTAAC 
               
               
                   
                   
                 TGTACTCTACTCAAAAACGTCTTACTAAAGAAGAACGTCTCCCCAACACAT 
               
               
                   
                   
                 GTAGGAAGGAAGTGATTACTTATCTTTTGGCTAAATCTACATAATTAGTCA 
               
               
                   
                   
                 GCGAACATTCTAGACAGAGAGTGAAATCTGACACGTGAGATTAGTGCTTA 
               
               
                   
                   
                 TACTCTGATTAGGCTCAGTGAAACTAGCTGTGCATGTACCGTGATTATTAG 
               
               
                   
                   
                 GTTGACATAGGAATTTAGTGCCTAATATCGGCTCGATTATAAATATCAGTA 
               
               
                   
                   
                 ATTCGATATCGTCATGTCTTTATGCTTACAGGTATAGTAATTTGGCCTTAGT 
               
               
                   
                   
                 GGAACGATCAATCGGCTTCTGTAATATTATTCAACCTTCCCT 
               
               
                   
               
               
                 SEQ ID 
                 SRS_B 
                 ATCAATTTGTGATTACTTTGCTAGGTAACGCCACTACTGGTGTTATAATTGC 
               
               
                 NO: 279 
                   
                 TGTTACTTAAGCGCCTTGTAATCGATATAAGTGAAAATACAAAACGCAGCC 
               
               
                 SRS 
                   
                 TACTGTTCAATCGGAACTTTAGTATATTCGCTGAGGACTAGTACGTGGCAG 
               
               
                   
                   
                 AATCCAGTTATAATGTTTTGAATCGCTTTTAAGGTACTGAAGTAATCCACA 
               
               
                   
                   
                 GGACGCCAAGCTCTTATAGCACAGTGGGATATATTTGCACGTGATTATTGC 
               
               
                   
                   
                 AAAAGAGCTAAGGGTCGTACTTCACGTCTTTTAACTGAGTACAACCCAAAT 
               
               
                   
                   
                 TTGGTTCGCTTCGCAAGTTGATAGCGTAGCGACACGTACAGTTGGTTTGAA 
               
               
                   
                   
                 ACAGTAGTACTTCCTTTTAATTCGGAGGCTTATTGTACGGAAAGTGTTCTG 
               
               
                   
                   
                 TTAATTAAGGTAGACCAGCAGAACACCGCGCACCAGGGATTGCATATCTTT 
               
               
                   
                   
                 AGGGTATTTCGAGATTGCATCCCATTGAAATCGTACCTTT 
               
               
                   
               
               
                 SEQ ID 
                 SRS_C 
                 GAAGACTAACGAACGAGGTGGTATATAGTTACCCTATGTAAAATCGTTAA 
               
               
                 NO: 280 
                   
                 TTGTCATTAGACAATGTTTCAGGAGTAGAATTCAGCTAGCTGTTAGCCCAC 
               
               
                 SRS 
                   
                 TGGCACACGCTAGGACGCTATCAGGACGGTCTTTGAACCTATAACTCAGTA 
               
               
                   
                   
                 TATGGTTTTAGACCTATAATCTGCTTCTAAGGCACGCGGGGGAGTAACTTA 
               
               
                   
                   
                 GATACTAGTGCTTCCAGGAAAATCTGGCGCGATAATAGCCCGATCTTCTAA 
               
               
                   
                   
                 TAGACTATCCCTACCAAAAGTTATAAATCATTGTTCTCTTGACGTTAACAT 
               
               
                   
                   
                 CACTTGCTGAAAATTAGAATGTGAAGAAAACCATAAACAAATTAGCCTGG 
               
               
                   
                   
                 CAGACAGTGAATATACTCTACGTTGAACATATACAAAAATAGAAGCGCCG 
               
               
                   
                   
                 GAAAGAAGATCCTTCCCAGTAGAGTCCGTTAAACTAATTTCCTAATTGCTA 
               
               
                   
                   
                 AATACTGTATCTACCTGATAATGGGGTCGGTTACTTCAGTTTAT 
               
               
                   
               
               
                 SEQ ID 
                 SRS_D 
                 CTCGTAACTTGATTTAATAACGGAGGCTATTGAACTTAAAATCGCATCTGG 
               
               
                 NO: 281 
                   
                 CTGTTAAATTCAATAAACTTGCTTTCAGGTTAACTTCCTTTGATTAAGTCGT 
               
               
                 SRS 
                   
                 GAATTAAGATCTTATTACAACTCTGGTACGTCCTAAGTTAGATTAAAGTAC 
               
               
                   
                   
                 TGTTGGAGGAACGGAATAATATTTCTTGTGTTACGCAGCTAGTGAACCAGT 
               
               
                   
                   
                 GTCACAGGAGGTGTAACAACCGGTTGAAATTCTAACTTTTGAAGCTTTACC 
               
               
                   
                   
                 TAAGGGTACTGTATAAGGATCACATTGTTAGTACAACGCTAGTTCGTAGGC 
               
               
                   
                   
                 GTTCAAACTTAATTGTTTAGTAGTCCGCACTTGACTAACTGACGCTCCTTG 
               
               
                   
                   
                 GTCTGCTCTTCGTAATTAGGCTTTCGAAAGGTACGATGGAATACTAAGTAT 
               
               
                   
                   
                 AATAACAGTTGTCTGACAACTACGGTACGTATTTGATGTTGAGGCAGTGAG 
               
               
                   
                   
                 CTAACTCCACTTAGTGTGTAACCTTACGTATCATATA 
               
               
                   
               
               
                 SEQ ID 
                 SRS_G 
                 ATGAGTTAACGTAGATTACTTTCCGTTAGTGTAACGGACAAGATGACACAG 
               
               
                 NO: 282 
                   
                 TATTGAAACGCTCCTCTATCTTTGTGGGTGTTGAGGGAGGAGAGAGTTATT 
               
               
                 SRS 
                   
                 AGTCTAGACGCTATATATCACAGAGTCGAGTGCCCAATAATATAGCAGGT 
               
               
                   
                   
                 AGACGCCAACTTAACTACTGGATGTGAGTTAGAGAGGAATATACTGTTTTA 
               
               
                   
                   
                 TTAACTCGTACCGTAGTGGTTTCTGGCGAGAATTCGCCGGCTTAAAATCTA 
               
               
                   
                   
                 TTGACTAACTAGAATTAGCTTAAAGTGGACCTTATTGAATCTCACCGGGTT 
               
               
                   
                   
                 ATCGCGACATTTATATTATCGAAGGGTCCAGCTTGGGGTTTGTTTGGAAGG 
               
               
                   
                   
                 TTGACTTGTTGTTGTAGTTGTATCACTAATAATTACGATTCTCAACGACCGG 
               
               
                   
                   
                 CCCAAAGATTGCCTGGGTTAAATTCAGCGTCTGATGTATACTTAGCTCTTC 
               
               
                   
                   
                 GCAAGTAGTGTTCTAATTAAAGATCACTTCAACTTATCTTC 
               
               
                   
               
               
                 SEQ ID 
                 SRS_H 
                 AAGGTAACTTAGGCTGACGACGCAATAATGCACGCTCGCGTGTGATGAGA 
               
               
                 NO: 283 
                   
                 TTACATCAGTAAGAATTCATATCTCGATATGGGATAATTACGGGCTCACAC 
               
               
                 SRS 
                   
                 TCTAGGAATACCAAGAACAGTAATGTTTCCTTATTAATATGTAGATAAGGA 
               
               
                   
                   
                 TCTTCTTAAAGTTTAATTGATGGCGAATTCCAAATAGTGACTTAACTTTCGC 
               
               
                   
                   
                 GCAGAGTATCGCAGGACAAGGTTAGCTTTTCGTAAGCCTGATGTTATGCCA 
               
               
                   
                   
                 TAACTAGCCACCTTGTAATCCCCGCGCTCAGTAAATCTATCTACTTATTTGC 
               
               
                   
                   
                 TTCACTTCTTCACGGAGAGTACTGATTTTCTTCTCTCAATACTACTGACTAC 
               
               
                   
                   
                 CTTAGGGCGACATACTTTAGTTCTGCATAAGCGTCAACCTCTTGCCTAAGG 
               
               
                   
                   
                 GTATGGATCCTTGTTAAGCCTTATTCCATATAGTTGAGCTGAAGAACAGAT 
               
               
                   
                   
                 CCCTCAACTCGAGTGCGACTAGTAGCTAGTTACGAACAC 
               
               
                   
               
               
                 SEQ ID 
                 SRS_J 
                 GGTCATTGAGGCGGTAAGAATCTGATTTATCTAGATCTATAGCAACGTCAA 
               
               
                 NO: 284 
                   
                 ATAATTCAAATCCCGTACTTTTCAAGATTCTGAGGGTTAAGGTCTTGATTG 
               
               
                 SRS 
                   
                 TGATTCTAAATACTTGTAGGTACCGAGTAATAGACGCGCACTCAGATTTGG 
               
               
                   
                   
                 TCTAATACGATTATTTACCCATAGAGAGAGTAATCGTCTATGGCCCGTAGT 
               
               
                   
                   
                 TAGCAAGGTTCAACGTGTATTATGTACTGAGTACGCAGATCTGATTACCCT 
               
               
                   
                   
                 ATAATTTCCAAGATATTAGTGATTCTAACGGATATAGTCAATACCTCCCAA 
               
               
                   
                   
                 TTCCCCACGCTTCGATTGTAGTATTTGATTCGGCTGACAAACGCCGACAAG 
               
               
                   
                   
                 ATTCGCTGTAACTCTTTGGCTAATAGAAAAGTAAATCAACACGCGTTCTTA 
               
               
                   
                   
                 AATTCTTGACATGTAAGTACTTGGAACAATCTTACCTGTTATCCATTATCTG 
               
               
                   
                   
                 TTTATCGATCTTACCTAACCATCCAGTTTGCCTGAGTGGG 
               
               
                   
               
               
                 SEQ ID 
                 tTDH1 
                 ATAAAGCAATCTTGATGAGGATAATGATTTTTTTTTGAATATACATAAATA 
               
               
                 NO: 285 
                   
                 CTACCGTTTTTCTGCTAGATTTTGTGAAGACGTAAATAAGTACATATTACTT 
               
               
                 Terminator 
                   
                 TTTAAGCCAAGACAAGATTAAGCATTAACTTTACCCTTTTCTCTTCTAAGTT 
               
               
                   
                   
                 TCAATACTAGTTATCACTGTTTAAAAGTTATGGCGAGAACGTCGGCGGTTA 
               
               
                   
                   
                 AAATATATTACCCTGAACGTGGTGAATTGAAGTTCTAGGATGGT 
               
               
                   
               
               
                 SEQ ID 
                 tENO1 
                 AGCTTTTGATTAAGCCTTCTAGTCCAAAAAACACGTTTTTTTGTCATTTATT 
               
               
                 NO: 286 
                   
                 TCATTTTCTTAGAATAGTTTAGTTTATTCATTTTATAGTCACGAATGTTTTA 
               
               
                 Terminator 
                   
                 TGATTCTATATAGGGTTGCAAACAAGCATTTTTCATTTTATGTTAAAACAA 
               
               
                   
                   
                 TTTCAGGTTTACCTTTTATTCTGCTTGTGGTGACGCGTGTATCCGCCCGCTC 
               
               
                   
                   
                 TTTTGGTCACCCATGTATTTAATTGCATAAATAATTCTTAAAAGTGGAGCT 
               
               
                   
                   
                 AGTCTATTTCTATTTACATACCTCTCATTTCTCATTTCCTCCT 
               
               
                   
               
               
                 SEQ ID 
                 tSSA1 
                 GCCAATTGGTGCGGCAATTGATAATAACGAAAATGTCTTTTAATGA 
               
               
                 NO: 287 
                   
                 TCTGGGTATAATGAGGAATTTTCCGAACGTTTTTACTTTATATATAT 
               
               
                 Terminator 
                   
                 ATATACATGTAACATATATTCTATACGCTATAGAGAAAGGAAATTT 
               
               
                   
                   
                 TTCAATTAAAAAAAAAATAGAGAAAGAGTTTCACTTCTTGATTATC 
               
               
                   
                   
                 GCTAACACTAATGGTTGAAGTACTGCTACTTTAATTTTATAGATAG 
               
               
                   
                   
                 GCAAAAAAAAATTATTCGGGGCGAGCTGGGAATTGAACCCAGGGC 
               
               
                   
                   
                 CTCTCGCATGCTTTGTCTTC 
               
               
                   
               
               
                 SEQ ID 
                 tADH1 
                 GCGAATTTCTTATGATTTATGATTTTTATTATTAAATAAGTTATAAAAAAA 
               
               
                 NO: 288 
                   
                 ATAAGTGTATACAAATTTTAAAGTGACTCTTAGGTTTTAAAACGAAAATTC 
               
               
                 Terminator 
                   
                 TTATTCTTGAGTAACTCTTTCCTGTAGGTCAGGTTGCTTTCTCAGGTATAGC 
               
               
                   
                   
                 ATGAGGTCGCTCTTATTGACCACACCTCTACCGGCATGCCGAGCAAATGCC 
               
               
                   
                   
                 TGCAAATCGCTCCCCATTTCACCCAATTGTAGATATGCTAACTCC 
               
               
                   
               
               
                 SEQ ID 
                 tCYC1 
                 ATCATGTAATTAGTTATGTCACGCTTACATTCACGCCCTCCCCCCACATCCG 
               
               
                 NO: 289 
                   
                 CTCTAACCGAAAAGGAAGGAGTTAGACAACCTGAAGTCTAGGTCCCTATT 
               
               
                 Terminator 
                   
                 TATTTTTTTATAGTTATGTTAGTATTAAGAACGTTATTTATATTTCAAATTTT 
               
               
                   
                   
                 TCTTTTTTTTCTGTACAGACGCGTGTACGCATGTAACATTATACTGAAAACC 
               
               
                   
                   
                 TTGCTTGAGAAGGTTTTGGGACGCTCGAAGGCTTTAATTTGC 
               
               
                   
               
               
                 SEQ ID 
                 tHUG1 
                 AGTATGCTTCTCTTTTTTTTTGTAGGCCAGTGATAGGAAAGAACAATAGAA 
               
               
                 NO: 290 
                   
                 TATAAATACGTCAGAATATAATAGATATGTTTTTATATTTAGACCTCGTAC 
               
               
                 Terminator 
                   
                 ATAGGAATAATTGACGTTTTTTTTGGCCAACATTTGAAATTTTTTTTTGTTA 
               
               
                   
                   
                 CCTCGCGCTGAGCCCAAACGGGCTCCACTACCCGCCGCGGTCGCCATTTTG 
               
               
                   
                   
                 GGAAGTCATCCGTCCCAAAAAGGAAATAGCCATAACATGTCGTTACTGTTT 
               
               
                   
                   
                 TGGAACATCGCCCGTTTCGCCCGATTCCGCCTCAGCGGGTATAAAAAGAG 
               
               
                   
                   
                 ATCTTTTTTTTTCCTGGCTGTCCCTTCCCATTTTTAAATGTCTTATCTGCTCC 
               
               
                   
                   
                 TTTGTGATCTTACGGTCTCACTAACCTCTCTTCAACTGCTCAATAATTTCCC 
               
               
                   
                   
                 GCTATGCAAAATTCCCAAGACTACTTTTACGCTCAAAATCGCTCCCAACAA 
               
               
                   
                   
                 CAACAAGCCCCTTCCACATTGCGTACCGTGACCATGGCGGAATTTAG 
               
               
                   
               
               
                 SEQ ID 
                 tSPG5 
                 AAAGACGTTGTTTCATCGCGCTATTACCAAGAAGGTTACTTTACTTGTTCTT 
               
               
                 NO: 291 
                   
                 GCACATGGACGCACGTTGTGTGTTCATATATATATATATATATATATATAT 
               
               
                 Terminator 
                   
                 ATATTTGTGCTTGTTTTCATTGTCTCTATAGTTAATACATTCTATTTTTATCG 
               
               
                   
                   
                 TTATATTTGCATTCTCTTCGCATAAAAACTTCATGAAAATTCGGCAGAAAA 
               
               
                   
                   
                 TAAGCCATATATGTACTTTATCCATAGGCAAAGAAAAGCACTTAACGAGA 
               
               
                   
                   
                 ATATACAACAATTGCACTAGTACTGCATGTATATACTCTTATGATTATAGC 
               
               
                   
                   
                 GGCAAGAAAACAAATATAAACACACTAACAGATGAATTCGAATGAAGATA 
               
               
                   
                   
                 TACATGAAGAACGCATTGAAGTTCCACGAACTCCCCATCAAACCCAGCCA 
               
               
                   
                   
                 GAGAAAGACTCTGATCGCATCGCTCTCAGGGATGAAATATCAGTACCAGA 
               
               
                   
                   
                 AGGCGATGAAAAAGCATATTCGGATGAGAAAGTAGAAATGGCAACCA 
               
               
                   
               
               
                 SEQ ID 
                 pGAL10 
                 ATCTGTTAATAGATCAAAAATCATCGCTTCGCTGATTAATTACCCCAGAAA 
               
               
                 NO: 292 
                   
                 TAAGGCTAAAAAACTAATCGCATTATTATCCTATGGTTGTTAATTTGATTC 
               
               
                 Promoter 
                   
                 GTTGATTTGAAGGTTTGTGGGGCCAGGTTACTGCCAATTTTTCCTCTTCATA 
               
               
                   
                   
                 ACCATAAAAGCTAGTATTGTAGAATCTTTATTGTTCGGAGCAGTGCGGCGC 
               
               
                   
                   
                 GAGGCACATCTGCGTTTCAGGAACGCGACCGGTGAAGACCAGGACGCACG 
               
               
                   
                   
                 GAGGAGAGTCTTCCGTCGGAGGGCTGTCGCCCGCTCGGCGGCTTCTAATCC 
               
               
                   
                   
                 GTACTTCAATATAGCAATGAGCAGTTAAGCGTATTACTGAAAGTTCCAAAG 
               
               
                   
                   
                 AGAAGGTTTTTTTAGGCTAAGATAATGGGGCTCTTTACATTTCCACAACAT 
               
               
                   
                   
                 ATAAGTAAGATTAGATATGGATATGTATATGGTGGTATTGCCATGTAATAT 
               
               
                   
                   
                 GATTATTAAACTTCTTTGCGTCCATCCAAAAAAAAAGTAAGAATTTTTGAA 
               
               
                   
                   
                 AATTCAATATAA 
               
               
                   
               
               
                 SEQ ID 
                 ui12 
                 TCCTACAACGATATCATTCACTTGAAGGAATACAAAATTGATAATGATCCA 
               
               
                 NO: 321 
                   
                 ATTGAAAAGTACGTTAAGAACAGCGGCAATAATTTGGGGATTTGTTTCTAC 
               
               
                 Flanking 
                   
                 AAAGAATAAAAATTCATGTTCGACATATAGATAGCAGGGTAATGTACGTG 
               
               
                 homology 
                   
                 TATATTTTAATGTAATAAAGAGGCCTTACTAGACGGTAAAGTTAAGAATAT 
               
               
                   
                   
                 CGAGTGAACTTTTCCTTAAGATAAAGGTAAATATAGTCGAGTATTTATTTA 
               
               
                   
                   
                 TTATTCTTTTCCACTATACAGTATTTAAAATTCTGTAAGAAATTGATTCTAC 
               
               
                   
                   
                 ATACATAAGACAAACGAACAGGTCAGAGAGAATCAGATTTTTGGTTAGCA 
               
               
                   
                   
                 AGAATACATTTTGGAGAAGAAAGACATTAACTCCACCTTACTGTATCATCT 
               
               
                   
                   
                 TATTTGCTTTTTCACTCCTTCCTAATATTTTTTTTATTTTATTTTGAATTTCTT 
               
               
                   
                   
                 CCTATTTCTGATGCATTGAACAGATCGTAATCTGTAAGTAAATA 
               
               
                   
               
               
                 SEQ ID 
                 di12 
                 AAATCTTGGCTCCGTTGTGTACAAAACTTCTTAATGAATATATATATATTTT 
               
               
                 NO: 322 
                   
                 TCCCTTATTTTATCTTTTTTTTTCGAATTTTTTATGTAAACATTCTTATACTG 
               
               
                 Flanking 
                   
                 GAACAATAGATGGCTAATGAGTCCCTATAATTTCGATTTTAGATGTTAACG 
               
               
                 homology 
                   
                 CTTCATTTCTTTTCATATAAAAGACTACCTGCCAAATGTATTTTCTCCTGAG 
               
               
                   
                   
                 TAAGTGACATACAAAAACCCGTCCTTATCCTTGTGTTCTTGATATATGGCA 
               
               
                   
                   
                 GACATCAACGCCGCAGTAGGTGGCAAAGTATCATTGACAAAAATGAAGAT 
               
               
                   
                   
                 GGCCTTCTCAGGGGGTAGCATAATTCTCTTTCTTATAACATAAACAAATTG 
               
               
                   
                   
                 CCCTACGGTAAGGTCAGCAGGAACTAGATATTTACGCTTATCAATCTCTGG 
               
               
                   
                   
                 AATATCTGACTTTTCAGCTTTTTCGCAAATCACAGGTATCCTATTCTTGAAC 
               
               
                   
                   
                 CTGTCAGCAATCC 
               
               
                   
               
               
                 Table 6 Legend: Non-coding DNA regions (regulatory and other) referenced in the FIGURES 
               
               
                 are listed in Table 6. Flanking Homology regions direct recombination at specific genomic 
               
               
                 loci. Flanking homology upstream sequences are denoted with a “u”, and downstream with a 
               
               
                 ″d′″. “I” indicates an intergenic integration site, e.g., ui7, di7 are the regions flanking 
               
               
                 intergenic region 7. Integrations that delete an open reading frame have flanking homology 
               
               
                 with the deleted gene indicated, e.g., uPEP4, dPEP4 are the regions flanking the PEP4 gene. 
               
               
                 Synthetic Recombination Sequences (SRS) direct internal recombination of two DNA 
               
               
                 constructs targeted for integration at the same locus. Linkers are short sequences used in 
               
               
                 assembly the DNA constructs, they are intervening between the indicated parts. Linkers G1, 
               
               
                 G7, G10, RG1 and LTTDH1 contain the last 36 bp of the upstream DNA part; in cases 
               
               
                 where these linkers are used assume that the linker reconstitutes sequence omitted from the 
               
               
                 upstream part to create a seamless junction with the downstream part. Linkers D0 and D9 
               
               
                 are terminal linkers that direct entry of the DNA constructs into cloning vectors and are not 
               
               
                 integrated into the genome. Where no linker is shown between parts, the junction is also 
               
               
                 seamless. 
               
            
           
         
       
     
     Although the present disclosure has been described with reference to the specific embodiments thereof, it should be understood by those skilled in the art that various changes may be made and equivalents may be substituted without departing from the true spirit and scope of the disclosure. In addition, many modifications may be made to adapt a particular situation, material, composition of matter, process, process step or steps, to the objective, spirit and scope of the present disclosure. All such modifications are intended to be within the scope of the claims appended hereto.