Patent Publication Number: US-2023148463-A9

Title: Method for producing albicanol and/or drimenol

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
     This application is a divisional application of U.S. patent application Ser. No. 16/618,737, filed Dec. 2, 2019, which is a U.S. National Phase Application of International Patent Application No. PCT/EP2018/064344, filed May 31, 2018, which claims the benefit of priority to European Patent Application No. 17174399.0, filed Jun. 2, 2017, the entire contents of which are hereby incorporated by reference herein. 
    
    
     REFERENCE TO AN ELECTRONIC SEQUENCE LISTING 
     The contents of the electronic sequence listing (10200PCT SequenceListingAsFiled.txt; Size: 180,406 bytes; and Date of Creation: Feb. 16, 2022) is herein incorporated by reference in its entirety. 
     TECHNICAL FIELD 
     Provided herein are biochemical methods of producing albicanol, drimenol and related compounds and derivatives, which method comprises the use of novel polypeptides. 
     BACKGROUND 
     Terpenes are found in most organisms (microorganisms, animals and plants). These compounds are made up of five carbon units called isoprene units and are classified by the number of these units present in their structure. Thus monoterpenes, sesquiterpenes and diterpenes are terpenes containing 10, 15 and 20 carbon atoms, respectively. Sesquiterpenes, for example, are widely found in the plant kingdom. Many sesquiterpene molecules are known for their flavor and fragrance properties and their cosmetic, medicinal and antimicrobial effects. Numerous sesquiterpene hydrocarbons and sesquiterpenoids have been identified. Chemical synthesis approaches have been developed but are still complex and not always cost-effective. 
     Biosynthetic production of terpenes involves enzymes called terpene synthases. There are numerous sesquiterpene synthases present in the plant kingdom, all using the same substrate (farnesyl diphosphate, FPP), but having different product profiles. Genes and cDNAs encoding sesquiterpene synthases have been cloned and the corresponding recombinant enzymes characterized. 
     Many of the main sources for sesquiterpenes, for example drimenol, are plants naturally containing the sesquiterpene; however, the content of sesquiterpenes in these natural sources can be low. There still remains a need for the discovery of new terpenes, terpene synthases and more cost-effective methods of producing sesquiterpenes such as albicanol and/or drimenol and derivatives therefrom. 
     SUMMARY 
     Provided herein is a method for producing a drimane sesquiterpene comprising:
         a. contacting an acyclic farnesyl diphosphate (FPP) precursor with a polypeptide comprising aHaloacid dehalogenase (HAD)-like hydrolase domain and having bifunctional terpene synthase activity to produce a drimane sesquiterpene, wherein the polypeptide comprises
           i. a class I terpene synthase-like motif as set forth in SEQ ID NO: 53 (DDxx(D/E)); and   ii. a class II terpene synthase-like motifas set forth in SEQ ID NO: 56 (DxD(T/S)T); and   
           b. optionally isolating the drimane sesquiterpene or a mixture comprising the drimane sesquiterpene.       

     In one aspect, the drimane sesquiterpene comprises albicanol and/or drimenol. 
     In a further aspect, in the above method, the polypeptide having bifunctional terpene synthase activity comprises
         a. an amino acid sequence having at least 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99% sequence identity to SEQ ID NO: 1, SEQ ID NO: 5, SEQ ID NO: 9, SEQ ID NO: 12, SEQ ID NO: 15, SEQ ID NO: 17, SEQ ID NO: 20, SEQ ID NO: 23, SEQ ID NO: 26, SEQ ID NO: 29, SEQ ID NO: 32, SEQ ID NO: 35, SEQ ID NO: 38, SEQ ID NO: 41, SEQ ID NO: 44, SEQ ID NO: 47, SEQ ID NO: 50, or SEQ ID NO: 63; and   b. the sequence as set forth in SEQ ID NO: 53, SEQ ID NO: 54, or SEQ ID NO: 55; and   c. the sequence as set forth in SEQ ID NO: 56, SEQ ID NO: 57, or SEQ ID NO: 58.       

     In one embodiment, the above method comprises contacting the drimane sesquiterpene with at least one enzyme to produce a drimane sesquiterpene derivative. In another embodiment, the above method comprises converting the drimane sesquiterpene to a drimane sesquiterpene derivative using chemical synthesis or biochemical synthesis. 
     In one aspect, the above method comprises transforming a host cell or non-human host organism with a nucleic acid encoding the above polypeptide. 
     In one aspect, the method further comprises culturing a non-human host organism or a host cell capable of producing FPP and transformed to express a polypeptide comprising a HAD-like hydrolase domain under conditions that allow for the production of the polypeptide, wherein the polypeptide
         a. comprises the amino acid sequence of SEQ ID NO: 1, SEQ ID NO: 5, SEQ ID NO: 9, SEQ ID NO: 12, SEQ ID NO: 15, SEQ ID NO: 17, SEQ ID NO: 20, SEQ ID NO: 23, SEQ ID NO: 26, SEQ ID NO: 29, SEQ ID NO: 32, SEQ ID NO: 35, SEQ ID NO: 38, SEQ ID NO: 41, SEQ ID NO: 44, SEQ ID NO: 47, SEQ ID NO: 50, or SEQ ID NO: 63; or   b. comprises
           i. an amino acid sequence having at least 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% sequence identity to SEQ ID NO: 1, SEQ ID NO: 5, SEQ ID NO: 9, SEQ ID NO: 12, SEQ ID NO: 15, SEQ ID NO: 17, SEQ ID NO: 20, SEQ ID NO: 23, SEQ ID NO: 26, SEQ ID NO: 29, SEQ ID NO: 32, SEQ ID NO: 35, SEQ ID NO: 38, SEQ ID NO: 41, SEQ ID NO: 44, SEQ ID NO: 47, SEQ ID NO: 50, or SEQ ID NO: 63; and   ii. the sequence as set forth in SEQ ID NO: 53, SEQ ID NO: 54, or SEQ ID NO: 55; and   iii. the sequence as set forth in SEQ ID NO: 56, SEQ ID NO: 57, or SEQ ID NO: 58.   
               

     In a further aspect, in the above method, the polypeptide comprises one or more conserved motif as set forth in SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61, and/or SEQ ID NO: 62. 
     In one embodiment, the class I terpene synthase-like motif of the above method comprises SEQ ID NO: 54 (DD(K/Q/R)(L/I/T)(D/E)), the class II terpene synthase-like motif comprises SEQ ID NO: 57 (D(V/M/L)DTT), and the drimane sesquiterpene is albicanol. 
     In a one embodiment, in the above method the polypeptide comprises
         a. an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 1, SEQ ID NO: 5, SEQ ID NO: 9, SEQ ID NO: 12, SEQ ID NO: 15, SEQ ID NO: 17, SEQ ID NO: 20, SEQ ID NO: 23, SEQ ID NO: 26, SEQ ID NO: 29, or SEQ ID NO: 32, and   b. the sequence of SEQ ID NO: 54 (DD(K/Q/R)(L/I/T)(D/E)), and   c. the sequence of SEQ ID NO: 57 (D(V/M/L/F)DTTS); and   the drimane sesquiterpene is albicanol.       

     In a further embodiment, in the above method the polypeptide comprises
         a. an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 35, SEQ ID NO: 38, SEQ ID NO: 41, SEQ ID NO: 44, SEQ ID NO: 47, SEQ ID NO: 50, or SEQ ID NO: 63, and   b. the sequence of SEQ ID NO: 55, and   c. the sequence of SEQ ID NO: 58; and   the drimane sesquiterpene is drimenol.       

     Also provided is an isolated polypeptide comprising a HAD-like hydrolase domains and having bifunctional terpene synthase activity comprising the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 5 or comprising
         a. an amino acid sequence having at least 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99% sequence identity to SEQ ID NO: 1 or SEQ ID NO: 5; and   b. the sequence as set forth in SEQ ID NO: 53, SEQ ID NO: 54, or SEQ ID NO: 55; and   c. the sequence as set forth in SEQ ID NO: 56, SEQ ID NO: 57, or SEQ ID NO: 48.       

     In one aspect, the isolated polypeptide further comprises one or more conserved motif as set forth in SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61, and/or SEQ ID NO: 62. 
     Provided herein is an isolated nucleic acid molecule
         a. comprising a nucleotide sequence encoding the polypeptide of claim  13  or  14 ; or   b. comprising a nucleotide sequence having at least 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99% sequence identity to the nucleotide sequence of SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 7, SEQ ID NO: 8, or SEQ ID NO: 68, or the reverse complement thereof; or   c. comprising a nucleotide molecule that hybridizes under stringent conditions to SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 7, SEQ ID NO: 8, or SEQ ID NO: 68; or   d. comprising the nucleotide sequence of SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 16, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67, SEQ ID NO: 68, SEQ ID NO: 69, or SEQ ID NO: 70, or the reverse complement thereof.       

     Also provided is a vector comprising the above nucleic acid molecule or a nucleic acid encoding the above polypeptide. In one aspect, the vector is an expression vector. In another aspect, the vector is a prokaryotic vector, viral vector or a eukaryotic vector. 
     Further provided is a host cell or non-human organism comprising the above nucleic acid or above vector. 
     In one aspect, the host cell or non-human organism is a prokaryotic cell or a eukaryotic cell or a microorganism or fungal cell. 
     In one aspect, the prokaryotic cell is a bacterial cell. In a further aspect, the bacterial cell is  E. coli.    
     In another aspect, the host cell or non-human organism is a eukaryotic cell. In one aspect, the eukaryotic cell is a yeast cell or plant cell. In a further aspect, the yeast cell is  Saccharomyces cerevisiae.    
     Provided herein is the use of the above polypeptide for producing a drimane sesquiterpene or a mixture comprising a drimane sesquiterpene and one or more terpenes. 
     In one aspect, in the above use of the polypeptide, the drimane sesquiterpene is albicanol. In another aspect, in the above use of the polypeptide, the drimane sesquiterpene is drimenol. 
    
    
     
       DESCRIPTION OF THE DRAWINGS 
         FIG.  1   : Structure of drimane, (+)-albicanol and (−)-drimenol. 
         FIG.  2   : Mechanism of cyclization of farnesyl-diphosphate by a class II terpene synthase and class I terpene synthase enzymatic activity. 
         FIG.  3   : GCMS analysis of the sesquiterpenes produced in-vivo by the recombinant CvTps1 enzyme in bacteria cells modified to overproduce farnesyl-diphosphate. A. Total ion chromatogram of an extract of  E. coli  cells expressing CvTps1 and the mevalonate pathway enzymes. B. Total ion chromatogram of an authentic standard of albicanol. C. Total ion chromatogram of an extract of  E. coli  cells expressing only the mevalonate pathway enzymes. 1, albicanol; 2, trans-farnesol (from hydrolysis of FPP by endogenous phosphatase enzymes). 
         FIG.  4   : Comparison of the mass spectra of the product of CvTps1 and of an authentic standard of albicanol. A. Mass spectra of peak 1 in  FIG.  3 A  (product of CvTps1). B. Mass spectra of peak 1 in  FIG.  3 B  (authentic standard of albicanol). 
         FIG.  5   : GCMS analysis of the sesquiterpenes produced by the LoTps1 and CvTps1 recombinant protein. Total ion chromatogram of an extract of  E. coli  cells expressing LoTpsl (A) and CvTps1 (B). The peak labeled ‘1’ is (+)-albicanol. 
         FIG.  6 A-C : Amino acid sequences alignment of putative terpene synthases containing class I and class II motifs: CvTps1 (SEQ ID NO: 1), LoTps1 (SEQ ID NO: 5), OCH93767.1 (SEQ ID NO: 9), EMD37666.1 (SEQ ID NO: 12), EMD37666-B (SEQ ID NO: 15), XP_001217376.1 (SEQ ID NO: 17), OJJ98394.1 (SEQ ID NO: 20), GA087501.1 (SEQ ID NO: 23), XP_008034151.1 (SEQ ID NO: 26), XP_007369631.1 (SEQ ID NO: 29), ACg006372 (SEQ ID NO: 32), KIA75676.1 (SEQ ID NO: 35), XP_001820867.2 (SEQ ID NO: 38), CEN60542.1 (SEQ ID NO: 41), XP_009547469.1 (SEQ ID NO: 44), KLO09124.1 (SEQ ID NO: 47), and OJI95797.1 (SEQ ID NO: 50). 
         FIG.  7   . GCMS chromatograms of the sesquiterpenes produced by the LoTps1, CvTps1, OCH93767.1, EMD37666.1, EMD37666-B, and XP_001217376.1, recombinant proteins. The peak labeled ‘1’ is (+)-albicanol. 
         FIG.  8   . GCMS chromatograms of the sesquiterpenes produced by the OJJ98394.1, GAO87501.1, XP_008034151.1, XP_007369631.1, and ACg006372 recombinant proteins. The peak labeled ‘1’ is (+)-albicanol. 
         FIG.  9   . GCMS chromatograms of the sesquiterpenes produced by the KIA75676.1, XP_001820867.2, CEN60542.1, XP_009547469.1, KLO09124.1 and OJI95797.1 recombinant proteins. The peak labeled ‘1’ is (−)-drimenol and the peak labeled ‘2’ is farnesol. 
         FIG.  10   . GCMS chromatograms of the sesquiterpenes produced by CvTps1 and AstC expressed in  E. coli  cells with and without the AstI and AstK phosphatases. The major peak obtained with AstC is drim-8-ene-11-ol and the major peak obtained with CvTps1 is (+)-albicanol. 
         FIG.  11   . GCMS analysis of the sesquiterpenes produced in-vivo by the recombinant XP_006461126.1 enzyme in bacteria cells modified to overproduce farnesyl-diphosphate. A. Total ion chromatogram of an extract of  E. coli  cells expressing XP_006461126.1 and the mevalonate pathway enzymes. B. Mass spectra of peak 13.1 minutes identified as drimenol. 
         FIG.  12   . GC-FID analysis of drimane sesquiterpenes produced using the modified  S. cereviciae  strain YST045 expressing five different synthases: XP_007369631.1 from  Dichomitus squalens , XP_006461126 from  Agaricus bisporus , LoTps1 from  Laricifomes officinalis , EMD37666.1 from  Gelatoporia subvermispora  and XP_001217376.1 from  Aspergillus terreus.    
       Abbreviations Used 
       
           
           bp base pair 
           kb kilo base 
           DNA deoxyribonucleic acid 
           cDNA complementary DNA 
           DTT dithiothreitol 
           FPP farnesyl diphosphate 
           GC gas chromatograph 
           HAD Haloacid dehalogenase 
           IPTG isopropyl-D-thiogalacto-pyranoside 
           LB lysogeny broth 
           MS mass spectrometer/mass spectrometry 
           MVA mevalonic acid 
           PCR polymerase chain reaction 
           RNA ribonucleic acid 
           mRNA messenger ribonucleic acid 
           miRNA micro RNA 
           siRNA small interfering RNA 
           rRNA ribosomal RNA 
           tRNA transfer RNA 
         
      
       Definitions 
       The term “polypeptide” means an amino acid sequence of consecutively polymerized amino acid residues, for instance, at least 15 residues, at least 30 residues, at least 50 residues. In some embodiments herein, a polypeptide comprises an amino acid sequence that is an enzyme, or a fragment, or a variant thereof. 
       The term “protein” refers to an amino acid sequence of any length wherein amino acids are linked by covalent peptide bonds, and includes oligopeptide, peptide, polypeptide and full length protein whether naturally occurring or synthetic. 
       The term “isolated” polypeptide refers to an amino acid sequence that is removed from its natural environment by any method or combination of methods known in the art and includes recombinant, biochemical and synthetic methods. 
       The terms “bifunctional terpene synthase” or “polypeptide having bifunctional terpene synthase activity” relate to a polypeptide that comprises class I and class II terpene synthase domains and has bifunctional terpene synthase activity of protonation-initiated cyclization and ionization-initiated cyclization catalytic activities. A bifunctional terpene synthase as described herein comprises a HAD-like hydrolase domain which is characteristic of polypeptides belonging to the Haloacid dehalogenase (HAD)-like hydrolase superfamily (Interpro protein superfamily IPR023214, www.ebi.ac.uk/interpro/entry/IPR023214; Pfam protein superfamily PF13419, pfam.xfam.org/family/PF13419). A HAD-like hydrolase domain is a portion of a polypeptide having amino acid sequence similarities with the members of the HAD-like hydrolase family and related function. A HAD-like hydrolase domain can be identified in a polypeptide by searching for amino acid motifs or signatures characteristic of this protein family. Tools for performing such searches are available at the following web sites: ebi.ac.uk/interpro/ or ebi.ac.uk/Tools/hmmer/. Proteins are generally composed of one or more functional regions or domains. Different combinations of domains give rise to the diverse range of proteins found in nature. The identification of domains that occur within proteins can therefore provide insights into their function. A polypeptide which comprises a HAD-like hydrolase domain and/or characteristic HAD-like hydrolase motifs functions in binding and cleavage of phosphate or diphosphate groups of a ligand. A bifunctional terpene synthase may also comprise one or more of conserved motifs A, B, C, and/or D as depicted in SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61, and/or SEQ ID NO: 62. 
       The term “drimane sesquiterpene” relates to a terpene having a drimane-like carbon skeleton structure as depicted in  FIG.  1   . 
       The term “class I terpene synthase” relates to a terpene synthase that catalyses ionization-initiated reactions, for example, monoterpene and sesquiterpene synthases. 
       The term “class I terpene synthase motif” or “class I terpene synthase-like motif” relates to an active site of a terpene synthase that comprises the conserved DDxx(D/E) motif. The aspartic acid residues of this class I motif bind, for example, a divalent metal ion (most often Mg 2+ ) involved in the binding of the diphosphate group and catalyze the ionization and cleavage of the allylic diphosphate bond of the substrate. 
       The term “class II terpene synthase” relates to a terpene synthase that catalyses protonation-initiated cyclization reactions, for example, typically involved in the biosynthesis of triterpenes and labdane diterpenes. In class II terpene synthases, the protonation-initiated reaction may involve, for example, acidic amino acids donating a proton to the terminal double-bond. 
       The term “class II terpene synthase motif” or “class II terpene synthase-like motif” relates to an active site of a terpene synthase that comprises the conserved DxDD or DxD(T/S)T motif. 
       The terms “albicanol synthase” or “polypeptide having albicanol synthase activity” or “albicanol synthase protein” relate to a polypeptide capable of catalyzing the synthesis of albicanol, in the form of any of its stereoisomers or a mixture thereof, starting from an acyclic terpene pyrophosphate, particularly farnesyl diphosphate (FPP). Albicanol may be the only product or may be part of a mixture of sesquiterpenes. 
       The terms “drimenol synthase” or “polypeptide having a drimenol synthase activity” or “drimenol synthase protein” relate to a polypeptide capable of catalyzing the synthesis of drimenol, in the form of any of its stereoisomers or a mixture thereof, starting from an acyclic terpene pyrophosphate, particularly farnesyl diphosphate (FPP). Drimenol may be the only product or may be part of a mixture of sesquiterpenes. 
       The terms “biological function,” “function,” “biological activity” or “activity” refer to the ability of the bifunctional terpene synthase to catalyze the formation of albicanol and/or drimenol or a mixture of compounds comprising albicanol and/or drimenol and one or more terpenes. 
       The terms “mixture of terpenes” or “mixture of sesquiterpenes” refer to a mixture of terpenes or sesquiterpenes that comprises albicanol and/or drimenol, and may also comprise one or more additional terpenes or sesquiterpenes. 
       The terms “nucleic acid sequence,” “nucleic acid,” “nucleic acid molecule” and “polynucleotide” are used interchangeably meaning a sequence of nucleotides. A nucleic acid sequence may be a single-stranded or double-stranded deoxyribonucleotide, or ribonucleotide of any length, and include coding and non-coding sequences of a gene, exons, introns, sense and anti-sense complimentary sequences, genomic DNA, cDNA, miRNA, siRNA, mRNA, rRNA, tRNA, recombinant nucleic acid sequences, isolated and purified naturally occurring DNA and/or RNA sequences, synthetic DNA and RNA sequences, fragments, primers and nucleic acid probes. The skilled artisan is aware that the nucleic acid sequences of RNA are identical to the DNA sequences with the difference of thymine (T) being replaced by uracil (U). The term “nucleotide sequence” should also be understood as comprising a polynucleotide molecule or an oligonucleotide molecule in the form of a separate fragment or as a component of a larger nucleic acid. 
       An “isolated nucleic acid” or “isolated nucleic acid sequence” relates to a nucleic acid or nucleic acid sequence that is in an environment different from that in which the nucleic acid or nucleic acid sequence naturally occurs and can include those that are substantially free from contaminating endogenous material. The term “naturally-occurring” as used herein as applied to a nucleic acid refers to a nucleic acid that is found in a cell of an organism in nature and which has not been intentionally modified by a human in the laboratory. 
       “Recombinant nucleic acid sequences” are nucleic acid sequences that result from the use of laboratory methods (for example, molecular cloning) to bring together genetic material from more than on source, creating or modifying a nucleic acid sequence that does not occur naturally and would not be otherwise found in biological organisms. 
       “Recombinant DNA technology” refers to molecular biology procedures to prepare a recombinant nucleic acid sequence as described, for instance, in Laboratory Manuals edited by Weigel and Glazebrook, 2002, Cold Spring Harbor Lab Press; and Sambrook et al, 1989, Cold Spring Harbor, N.Y., Cold Spring Harbor Laboratory Press. 
       The term “gene” means a DNA sequence comprising a region, which is transcribed into a RNA molecule, e.g., an mRNA in a cell, operably linked to suitable regulatory regions, e.g., a promoter. A gene may thus comprise several operably linked sequences, such as a promoter, a 5′ leader sequence comprising, e.g., sequences involved in translation initiation, a coding region of cDNA or genomic DNA, introns, exons, and/or a 3′non-translated sequence comprising, e.g., transcription termination sites. 
       A “chimeric gene” refers to any gene which is not normally found in nature in a species, in particular, a gene in which one or more parts of the nucleic acid sequence are present that are not associated with each other in nature. For example the promoter is not associated in nature with part or all of the transcribed region or with another regulatory region. The term “chimeric gene” is understood to include expression constructs in which a promoter or transcription regulatory sequence is operably linked to one or more coding sequences or to an antisense, i.e., reverse complement of the sense strand, or inverted repeat sequence (sense and antisense, whereby the RNA transcript forms double stranded RNA upon transcription). The term “chimeric gene” also includes genes obtained through the combination of portions of one or more coding sequences to produce a new gene. 
       A “3′ UTR” or “3′ non-translated sequence” (also referred to as “3′ untranslated region,” or “3′end”) refers to the nucleic acid sequence found downstream of the coding sequence of a gene, which comprises, for example, a transcription termination site and (in most, but not all eukaryotic mRNAs) a polyadenylation signal such as AAUAAA or variants thereof. After termination of transcription, the mRNA transcript may be cleaved downstream of the polyadenylation signal and a poly(A) tail may be added, which is involved in the transport of the mRNA to the site of translation, e.g., cytoplasm. 
       “Expression of a gene” encompasses “heterologous expression” and “over-expression” and involves transcription of the gene and translation of the mRNA into a protein. Overexpression refers to the production of the gene product as measured by levels of mRNA, polypeptide and/or enzyme activity in transgenic cells or organisms that exceeds levels of production in non-transformed cells or organisms of a similar genetic background. 
       “Expression vector” as used herein means a nucleic acid molecule engineered using molecular biology methods and recombinant DNA technology for delivery of foreign or exogenous DNA into a host cell. The expression vector typically includes sequences required for proper transcription of the nucleotide sequence. The coding region usually codes for a protein of interest but may also code for an RNA, e.g., an antisense RNA, siRNA and the like. 
       An “expression vector” as used herein includes any linear or circular recombinant vector including but not limited to viral vectors, bacteriophages and plasmids. The skilled person is capable of selecting a suitable vector according to the expression system. In one embodiment, the expression vector includes the nucleic acid of an embodiment herein operably linked to at least one regulatory sequence, which controls transcription, translation, initiation and termination, such as a transcriptional promoter, operator or enhancer, or an mRNA ribosomal binding site and, optionally, including at least one selection marker. Nucleotide sequences are “operably linked” when the regulatory sequence functionally relates to the nucleic acid of an embodiment herein. 
       “Regulatory sequence” refers to a nucleic acid sequence that determines expression level of the nucleic acid sequences of an embodiment herein and is capable of regulating the rate of transcription of the nucleic acid sequence operably linked to the regulatory sequence. Regulatory sequences comprise promoters, enhancers, transcription factors, promoter elements and the like. 
       “Promoter” refers to a nucleic acid sequence that controls the expression of a coding sequence by providing a binding site for RNA polymerase and other factors required for proper transcription including without limitation transcription factor binding sites, repressor and activator protein binding sites. The meaning of the term promoter also includes the term “promoter regulatory sequence”. Promoter regulatory sequences may include upstream and downstream elements that may influences transcription, RNA processing or stability of the associated coding nucleic acid sequence. Promoters include naturally-derived and synthetic sequences. The coding nucleic acid sequences is usually located downstream of the promoter with respect to the direction of the transcription starting at the transcription initiation site. 
       The term “constitutive promoter” refers to an unregulated promoter that allows for continual transcription of the nucleic acid sequence it is operably linked to. 
       As used herein, the term “operably linked” refers to a linkage of polynucleotide elements in a functional relationship. A nucleic acid is “operably linked” when it is placed into a functional relationship with another nucleic acid sequence. For instance, a promoter, or rather a transcription regulatory sequence, is operably linked to a coding sequence if it affects the transcription of the coding sequence. Operably linked means that the DNA sequences being linked are typically contiguous. The nucleotide sequence associated with the promoter sequence may be of homologous or heterologous origin with respect to the plant to be transformed. The sequence also may be entirely or partially synthetic. Regardless of the origin, the nucleic acid sequence associated with the promoter sequence will be expressed or silenced in accordance with promoter properties to which it is linked after binding to the polypeptide of an embodiment herein. The associated nucleic acid may code for a protein that is desired to be expressed or suppressed throughout the organism at all times or, alternatively, at a specific time or in specific tissues, cells, or cell compartment. Such nucleotide sequences particularly encode proteins conferring desirable phenotypic traits to the host cells or organism altered or transformed therewith. More particularly, the associated nucleotide sequence leads to the production of albicanol and/or drimenol or a mixture comprising albicanol and/or drimenol or a mixture comprising albicanol and/or drimenol and one or more terpenes in the cell or organism. Particularly, the nucleotide sequence encodes a bifunctional terpene synthase. 
       “Target peptide” refers to an amino acid sequence which targets a protein, or polypeptide to intracellular organelles, i.e., mitochondria, or plastids, or to the extracellular space (secretion signal peptide). A nucleic acid sequence encoding a target peptide may be fused to the nucleic acid sequence encoding the amino terminal end, e.g., N-terminal end, of the protein or polypeptide, or may be used to replace a native targeting polypeptide. 
       The term “primer” refers to a short nucleic acid sequence that is hybridized to a template nucleic acid sequence and is used for polymerization of a nucleic acid sequence complementary to the template. 
       As used herein, the term “host cell” or “transformed cell” refers to a cell (or organism) altered to harbor at least one nucleic acid molecule, for instance, a recombinant gene encoding a desired protein or nucleic acid sequence which upon transcription yields a bifunctional terpene synthase protein useful to produce albicanol and/or drimenol. The host cell is particularly a bacterial cell, a fungal cell or a plant cell. The host cell may contain a recombinant gene which has been integrated into the nuclear or organelle genomes of the host cell. Alternatively, the host may contain the recombinant gene extra-chromosomally. 
       Homologous sequences include orthologous or paralogous sequences. Methods of identifying orthologs or paralogs including phylogenetic methods, sequence similarity and hybridization methods are known in the art and are described herein. 
       Paralogs result from gene duplication that gives rise to two or more genes with similar sequences and similar functions. Paralogs typically cluster together and are formed by duplications of genes within related plant species. Paralogs are found in groups of similar genes using pair-wise Blast analysis or during phylogenetic analysis of gene families using programs such as CLUSTAL. In paralogs, consensus sequences can be identified characteristic to sequences within related genes and having similar functions of the genes. 
       Orthologs, or orthologous sequences, are sequences similar to each other because they are found in species that descended from a common ancestor. For instance, plant species that have common ancestors are known to contain many enzymes that have similar sequences and functions. The skilled artisan can identify orthologous sequences and predict the functions of the orthologs, for example, by constructing a polygenic tree for a gene family of one species using CLUSTAL or BLAST programs. A method for identifying or confirming similar functions among homologous sequences is by comparing of the transcript profiles in host cells or organisms, such as plants or microorganisms, overexpressing or lacking (in knockouts/knockdowns) related polypeptides. 
       The skilled person will understand that genes having similar transcript profiles, with greater than 50% regulated transcripts in common, or with greater than 70% regulated transcripts in common, or greater than 90% regulated transcripts in common will have similar functions. Homologs, paralogs, orthologs and any other variants of the sequences herein are expected to function in a similar manner by making the host cells, organism such as plants or microorganisms producing bifunctional terpene synthase proteins. 
       The term “selectable marker” refers to any gene which upon expression may be used to select a cell or cells that include the selectable marker. Examples of selectable markers are described below. The skilled artisan will know that different antibiotic, fungicide, auxotrophic or herbicide selectable markers are applicable to different target species. 
       “Drimenol” for purposes of this application relates to (−)-drimenol (CAS: 468-68-8). 
       “Albicanol” for the purpose of this application relates to (+)-albicanol (CAS: 54632-04-1). 
       The term “organism” refers to any non-human multicellular or unicellular organisms such as a plant, or a microorganism. Particularly, a micro-organism is a bacterium, a yeast, an algae or a fungus. 
       The term “plant” is used interchangeably to include plant cells including plant protoplasts, plant tissues, plant cell tissue cultures giving rise to regenerated plants, or parts of plants, or plant organs such as roots, stems, leaves, flowers, pollen, ovules, embryos, fruits and the like. Any plant can be used to carry out the methods of an embodiment herein. 
       A particular organism or cell is meant to be “capable of producing FPP” when it produces FPP naturally or when it does not produce FPP naturally but is transformed to produce FPP, either prior to the transformation with a nucleic acid as described herein or together with said nucleic acid. Organisms or cells transformed to produce a higher amount of FPP than the naturally occurring organism or cell are also encompassed by the “organisms or cells capable of producing FPP”. 
       For the descriptions herein and the appended claims, the use of “or” means “and/or” unless stated otherwise. Similarly, “comprise,” “comprises,” “comprising”, “include,” “includes,” and “including” are interchangeable and not intended to be limiting. 
       It is to be further understood that where descriptions of various embodiments use the term “comprising,” those skilled in the art would understand that in some specific instances, an embodiment can be alternatively described using language “consisting essentially of” or “consisting of.” 
     
    
    
     DETAILED DESCRIPTION 
     Provided herein is a nucleic acid molecule comprising a nucleotide sequence having at least 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99% sequence identity to the nucleotide sequence of SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 7, SEQ ID NO: 8, or SEQ ID NO: 68 or comprising the nucleotide sequence of SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 16, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67, SEQ ID NO: 68, SEQ ID NO: 69, or SEQ ID NO: 70, or the reverse complement thereof. 
     According to one embodiment, the nucleic acid molecule consists of the nucleotide sequence SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 16, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67, SEQ ID NO: 68, SEQ ID NO: 69, or SEQ ID NO: 70, or the reverse complement thereof. 
     In one embodiment, the nucleic acid of an embodiment herein can be either present naturally in  Cryptoporus  or  Laricifomes  or in other fungal species, or be obtained by modifying SEQ ID NO: 3 or SEQ ID NO: 7 or the reverse complement thereof. 
     In another embodiment, the nucleic acid is isolated or is derived from fungi of the genus  Cryptoporus  or  Laricifomes . In a further embodiment the nucleic acid is isolated or derived from  Cryptoporus volvatus  or  Laricifomes officinalis.    
     Further provided is a nucleotide sequence obtained by modifying SEQ ID NO: 3 or SEQ ID NO: 7 or the reverse complement thereof which encompasses any sequence that has been obtained by modifying the sequence of SEQ ID NO: 3 or SEQ ID NO: 7, or of the reverse complement thereof using any method known in the art, for example, by introducing any type of mutations such as deletion, insertion and/or substitution mutations. The nucleic acids comprising a sequence obtained by mutation of SEQ ID NO: 3 or SEQ ID NO: 7 or the reverse complement thereof are encompassed by an embodiment herein, provided that the sequences they comprise share at least the defined sequence identity of SEQ ID NO: 3 or SEQ ID NO: 7 as defined in any of the above embodiments or the reverse complement thereof and provided that they encode a polypeptide comprising a HAD-like hydrolase domain and having a bifunctional terpene synthase activity to produce a drimane sesquiterpene, wherein the polypeptide comprises (1) a class I terpene synthase-like motif as set forth in SEQ ID NO: 53 (DDxx(D/E)) and (2) a class II terpene synthase-like motif as set forth in SEQ ID NO: 56 (DxD(T/S)T). The polypeptide having bifunctional terpene synthase activity may further comprise one or more conserved motif as set forth in SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61, and/or SEQ ID NO: 62. Mutations may be any kind of mutations of these nucleic acids, for example, point mutations, deletion mutations, insertion mutations and/or frame shift mutations of one or more nucleotides of the DNA sequence of SEQ ID NO: 3 or SEQ ID NO: 7. In one embodiment, the nucleic acid of an embodiment herein may be truncated provided that it encodes a polypeptide as described herein. 
     A variant nucleic acid may be prepared in order to adapt its nucleotide sequence to a specific expression system. For example, bacterial expression systems are known to more efficiently express polypeptides if amino acids are encoded by particular codons. 
     Due to the degeneracy of the genetic code, more than one codon may encode the same amino acid sequence, multiple nucleic acid sequences can code for the same protein or polypeptide, all these DNA sequences being encompassed by an embodiment herein. Where appropriate, the nucleic acid sequences encoding the bifunctional terpene synthase may be optimized for increased expression in the host cell. For example, nucleotides of an embodiment herein may be synthesized using codons particular to a host for improved expression. In one embodiment, the nucleic acid molecule comprises the nucleotide sequence of SEQ ID NO: 4, SEQ ID NO: 8, SEQ ID NO: 11, SEQ ID NO: 14, SEQ ID NO: 16, SEQ ID NO: 19, SEQ ID NO: 22, SEQ ID NO: 25, SEQ ID NO: 28, SEQ ID NO: 31, SEQ ID NO: 34, SEQ ID NO: 37, SEQ ID NO: 40, SEQ ID NO: 43, SEQ ID NO: 46, SEQ ID NO: 49, SEQ ID NO: 52, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67, SEQ ID NO: 68, SEQ ID NO: 69, or SEQ ID NO: 70, or the reverse complement thereof. 
     In one embodiment provided herein is an isolated, recombinant or synthetic nucleic acid sequence comprising the nucleotide sequence of SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 16, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67, SEQ ID NO: 68, SEQ ID NO: 69, or SEQ ID NO: 70, encoding for a bifunctional terpene synthase comprising the amino acid sequence of SEQ ID NO: 1, SEQ ID NO: 5, SEQ ID NO: 9, SEQ ID NO: 12, SEQ ID NO: 15, SEQ ID NO: 17, SEQ ID NO: 20, SEQ ID NO: 23, SEQ ID NO: 26, SEQ ID NO: 29, SEQ ID NO: 32, SEQ ID NO: 35, SEQ ID NO: 38, SEQ ID NO: 41, SEQ ID NO: 44, SEQ ID NO: 47, SEQ ID NO: 50, or SEQ ID NO: 63 or functional fragments thereof that catalyze production of a drimane sesquiterpene in a cell from a FPP precursor. In a further embodiment, the drimane sesquiterpene comprises albicanol and/or drimenol. 
     Provided herein are also cDNA, genomic DNA and RNA sequences. Any nucleic acid sequence encoding the bifunctional terpene synthase or variants thereof is referred herein as a bifunctional terpene synthase encoding sequence. 
     According to one embodiment, the nucleic acid of SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 7, SEQ ID NO: 8, or SEQ ID NO: 68 is the coding sequence of a bifunctional terpene synthase gene encoding a bifunctional terpene synthase obtained as described in the Examples. 
     A fragment of a polynucleotide of SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 7, SEQ ID NO: 8, or SEQ ID NO: 68 refers to contiguous nucleotides that is particularly at least 15 bp, at least 30 bp, at least 40 bp, at least 50 bp and/or at least 60 bp in length of the polynucleotide of an embodiment herein. Particularly the fragment of a polynucleotide comprises at least 25, more particularly at least 50, more particularly at least 75, more particularly at least 100, more particularly at least 150, more particularly at least 200, more particularly at least 300, more particularly at least 400, more particularly at least 500, more particularly at least 600, more particularly at least 700, more particularly at least 800, more particularly at least 900, more particularly at least 1000 contiguous nucleotides of the polynucleotide of an embodiment herein. 
     Without being limited, the fragment of the polynucleotides herein may be used as a PCR primer, and/or as a probe, or for anti-sense gene silencing or RNAi. 
     It is clear to the person skilled in the art that genes, including the polynucleotides of an embodiment herein, can be cloned on basis of the available nucleotide sequence information, such as found in the attached sequence listing, by methods known in the art. These include e.g. the design of DNA primers representing the flanking sequences of such gene of which one is generated in sense orientations and which initiates synthesis of the sense strand and the other is created in reverse complementary fashion and generates the antisense strand. Thermo stable DNA polymerases such as those used in polymerase chain reaction are commonly used to carry out such experiments. Alternatively, DNA sequences representing genes can be chemically synthesized and subsequently introduced in DNA vector molecules that can be multiplied by e.g. compatible bacteria such as e.g.  E. coli.    
     In a related embodiment provided herein, PCR primers and/or probes for detecting nucleic acid sequences encoding a polypeptide having bifunctional terpene synthase activity are provided. 
     The skilled artisan will be aware of methods to synthesize degenerate or specific PCR primer pairs to amplify a nucleic acid sequence encoding the bifunctional terpene synthase or functional fragments thereof, based on SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 7, SEQ ID NO: 8, or SEQ ID NO: 68. A detection kit for nucleic acid sequences encoding the bifunctional terpene synthase may include primers and/or probes specific for nucleic acid sequences encoding the bifunctional terpene synthase, and an associated protocol to use the primers and/or probes to detect nucleic acid sequences encoding the bifunctional terpene synthase in a sample. Such detection kits may be used to determine whether a plant, organism, microorganism or cell has been modified, i.e., transformed with a sequence encoding the bifunctional terpene synthase. 
     To test a function of variant DNA sequences according to an embodiment herein, the sequence of interest is operably linked to a selectable or screenable marker gene and expression of the reporter gene is tested in transient expression assays, for example, with microorganisms or with protoplasts or in stably transformed plants. The skilled artisan will recognize that DNA sequences capable of driving expression are built as modules. Accordingly, expression levels from shorter DNA fragments may be different than the one from the longest fragment and may be different from each other. Provided herein are also functional equivalents of the nucleic acid sequence coding the bifunctional terpene synthase proteins provided herein, i.e., nucleotide sequences that hybridize under stringent conditions to the nucleic acid sequence of SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 7, SEQ ID NO: 8, or SEQ ID NO: 68. 
     As used herein, the term hybridization or hybridizes under certain conditions is intended to describe conditions for hybridization and washes under which nucleotide sequences that are significantly identical or homologous to each other remain bound to each other. The conditions may be such that sequences, which are at least about 70%, such as at least about 80%, and such as at least about 85%, 90%, or 95% identical, remain bound to each other. Definitions of low stringency, moderate, and high stringency hybridization conditions are provided herein. 
     Appropriate hybridization conditions can be selected by those skilled in the art with minimal experimentation as exemplified in Ausubel et al. (1995,  Current Protocols in Molecular Biology , John Wiley &amp; Sons, sections 2, 4, and 6). Additionally, stringency conditions are described in Sambrook et al. (1989,  Molecular Cloning: A Laboratory Manual,  2nd ed., Cold Spring Harbor 
     Press, chapters 7, 9, and 11). As used herein, defined conditions of low stringency are as follows. Filters containing DNA are pretreated for 6 h at 40° C. in a solution containing 35% formamide, 5× SSC, 50 mM Tris-HCl (pH 7.5), 5 mM EDTA, 0.1% PVP, 0.1% Ficoll, 1% BSA, and 500 μg/ml denatured salmon sperm DNA. Hybridizations are carried out in the same solution with the following modifications: 0.02% PVP, 0.02% Ficoll, 0.2% BSA, 100 μg/ml salmon sperm DNA, 10% (wt/vol) dextran sulfate, and 5-20×106 32P-labeled probe is used. Filters are incubated in hybridization mixture for 18-20 h at 40° C., and then washed for 1.5 h at 55° C. In a solution containing 2× SSC, 25 mM Tris-HCl (pH 7.4), 5 mM EDTA, and 0.1% SDS. The wash solution is replaced with fresh solution and incubated an additional 1.5 h at 60° C. Filters are blotted dry and exposed for autoradiography. 
     As used herein, defined conditions of moderate stringency are as follows. Filters containing DNA are pretreated for 7 h at 50° C. in a solution containing 35% formamide, 5× SSC, 50 mM Tris-HCl (pH 7.5), 5 mM EDTA, 0.1% PVP, 0.1% Ficoll, 1% BSA, and 500 μg/ml denatured salmon sperm DNA. Hybridizations are carried out in the same solution with the following modifications: 0.02% PVP, 0.02% Ficoll, 0.2% BSA, 100 μg/ml salmon sperm DNA, 10% (wt/vol) dextran sulfate, and 5-20×106 32P-labeled probe is used. Filters are incubated in hybridization mixture for 30 h at 50° C., and then washed for 1.5 h at 55° C. In a solution containing 2× SSC, 25 mM Tris-HCl (pH 7.4), 5 mM EDTA, and 0.1% SDS. The wash solution is replaced with fresh solution and incubated an additional 1.5 h at 60° C. Filters are blotted dry and exposed for autoradiography. 
     As used herein, defined conditions of high stringency are as follows. Prehybridization of filters containing DNA is carried out for 8 h to overnight at 65° C. in buffer composed of 6× SSC, 50 mM Tris-HCl (pH 7.5), 1 mM EDTA, 0.02% PVP, 0.02% Ficoll, 0.02% BSA, and 500 μg/ml denatured salmon sperm DNA. Filters are hybridized for 48 h at 65° C. in the prehybridization mixture containing 100 μg/ml denatured salmon sperm DNA and 5-20×106 cpm of 32P-labeled probe. Washing of filters is done at 37° C. for 1 h in a solution containing 2× SSC, 0.01% PVP, 0.01% Ficoll, and 0.01% BSA. This is followed by a wash in 0.1× SSC at 50° C. for 45 minutes. Other conditions of low, moderate, and high stringency well known in the art (e.g., as employed for cross-species hybridizations) may be used if the above conditions are inappropriate (e.g., as employed for cross-species hybridizations). 
     The skilled artisan will be aware of methods to identify homologous sequences in other organisms and methods to determine the percentage of sequence identity between homologous sequences. Such newly identified DNA molecules then can be sequenced and the sequence can be compared with the nucleic acid sequence of SEQ ID NO: 3 or SEQ ID NO: 7. 
     The percentage of identity between two peptide or nucleotide sequences is a function of the number of amino acids or nucleotide residues that are identical in the two sequences when an alignment of these two sequences has been generated. Identical residues are defined as residues that are the same in the two sequences in a given position of the alignment. The percentage of sequence identity, as used herein, is calculated from the optimal alignment by taking the number of residues identical between two sequences dividing it by the total number of residues in the shortest sequence and multiplying by 100. The optimal alignment is the alignment in which the percentage of identity is the highest possible. Gaps may be introduced into one or both sequences in one or more positions of the alignment to obtain the optimal alignment. These gaps are then taken into account as non-identical residues for the calculation of the percentage of sequence identity. Alignment for the purpose of determining the percentage of amino acid or nucleic acid sequence identity can be achieved in various ways using computer programs and for instance publicly available computer programs available on the world wide web. Preferably, the BLAST program (Tatiana et al,  FEMS Microbiol Lett.,  1999, 174:247-250, 1999) set to the default parameters, available from the National Center for Biotechnology Information (NCBI) website at ncbi.nlm.nih.gov/BLAST/b12seq/wblast2.cgi, can be used to obtain an optimal alignment of protein or nucleic acid sequences and to calculate the percentage of sequence identity. 
     A related embodiment provided herein provides a nucleic acid sequence which is complementary to the nucleic acid sequence according to SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 7, SEQ ID NO: 8, or SEQ ID NO: 68 such as inhibitory RNAs, or nucleic acid sequence which hybridizes under stringent conditions to at least part of the nucleotide sequence according to SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 7, SEQ ID NO: 8, or SEQ ID NO: 68. An alternative embodiment of an embodiment herein provides a method to alter gene expression in a host cell. For instance, the polynucleotide of an embodiment herein may be enhanced or overexpressed or induced in certain contexts (e.g. upon exposure to certain temperatures or culture conditions) in a host cell or host organism. 
     Alteration of expression of a polynucleotide provided herein may also result in ectopic expression which is a different expression pattern in an altered and in a control or wild-type organism. Alteration of expression occurs from interactions of polypeptide of an embodiment herein with exogenous or endogenous modulators, or as a result of chemical modification of the polypeptide. The term also refers to an altered expression pattern of the polynucleotide of an embodiment herein which is altered below the detection level or completely suppressed activity. 
     In one embodiment, provided herein is also an isolated, recombinant or synthetic polynucleotide encoding a polypeptide or variant polypeptide provided herein. 
     In one embodiment is provided an isolated nucleic acid molecule encoding a polypeptide comprising a domain of the HAD-like hydrolase superfamily having bifunctional terpene synthase activity and comprising an amino acid sequence having at least 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% sequence identity to SEQ ID NO: 1, SEQ ID NO: 5, SEQ ID NO: 9, SEQ ID NO: 12, SEQ ID NO: 15, SEQ ID NO: 17, SEQ ID NO: 20, SEQ ID NO: 23, SEQ ID NO: 26, SEQ ID NO: 29, SEQ ID NO: 32, SEQ ID NO: 35, SEQ ID NO: 38, SEQ ID NO: 41, SEQ ID NO: 44, SEQ ID NO: 47, SEQ ID NO: 50, or SEQ ID NO: 63; and the sequence as set forth in SEQ ID NO: 53, SEQ ID NO: 54, or SEQ ID NO: 55; and the sequence as set forth in SEQ ID NO: 56, SEQ ID NO: 57, or SEQ ID NO: 58 or comprising the amino acid sequence of SEQ ID NO: 1, SEQ ID NO: 5, SEQ ID NO: 9, SEQ ID NO: 12, SEQ ID NO: 15, SEQ ID NO: 17, SEQ ID NO: 20, SEQ ID NO: 23, SEQ ID NO: 26, SEQ ID NO: 29, SEQ ID NO: 32, SEQ ID NO: 35, or SEQ ID NO: 38, SEQ ID NO: 41, SEQ ID NO: 44, SEQ ID NO: 47, SEQ ID NO: 50, or SEQ ID NO: 63. 
     In one embodiment provided herein is an isolated polypeptide comprising a HAD-like hydrolase domain having bifunctional terpene synthase activity and comprising an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% sequence identity to SEQ ID NO: 1 or SEQ ID NO: 5 or comprising the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 5. 
     According to one embodiment, the polypeptide consists of the amino acid sequence of SEQ ID NO: 1 or 5. 
     In one embodiment, the polypeptide of an embodiment herein can be present naturally in  Cryptoporus  or  Laricifomes  fungi or in other fungi species, or comprises an amino acid sequence that is a variant of SEQ ID NO: 1 or SEQ ID NO: 5, either obtained by genetic engineering or found naturally in  Cryptoporus  or  Laricifomes  fungi or in other fungi species. 
     According to another embodiment, the polypeptide is isolated or derived from fungi of the genus  Cryptoporus  or  Laricifomes . In a further embodiment, the polypeptide is isolated or derived from  Cryptoporus volvatus  or  Laricifomes officinalis.    
     In one embodiment, the at least one polypeptide having a bifunctional terpene synthase activity used in any of the herein-described embodiments or encoded by the nucleic acid used in any of the herein-described embodiments comprises an amino acid sequence that is a variant of SEQ ID NO: 1 or SEQ ID NO: 5, obtained by genetic engineering. In one embodiment the polypeptide comprises an amino acid sequence encoded by a nucleotide sequence that has been obtained by modifying SEQ ID NO: 3 or SEQ ID NO: 7 or the reverse complement thereof. 
     Polypeptides are also meant to include variants and truncated polypeptides provided that they have bifunctional terpene synthase activity. 
     According to another embodiment, the at least one polypeptide having a bifunctional terpene synthase activity used in any of the herein-described embodiments or encoded by the nucleic acid used in any of the herein-described embodiments comprises an amino acid sequence that is a variant of SEQ ID NO: 1 or SEQ ID NO: 5, obtained by genetic engineering, provided that said variant has bifunctional terpene synthase activity to produce a drimane sesquiterpene and has the required percentage of identity to SEQ ID NO: 1 or SEQ ID NO: 5 as described in any of the above embodiments and comprises (1) a class I terpene synthase-like motif as set forth in SEQ ID NO: 53 (DDxx(D/E)) and (2) a class II terpene synthase-like motif as set forth in SEQ ID NO: 56 (DxD(T/S)T) and comprises domains corresponding to Pfam domains PF13419.5 and PF13242.5. The polypeptide having bifunctional terpene synthase activity may further comprise one or more conserved motifs as set forth in SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61, and/or SEQ ID NO: 62. 
     According to another embodiment, the at least one polypeptide having a bifunctional terpene synthase activity used in any of the herein-described embodiments or encoded by the nucleic acid used in any of the herein-described embodiments is a variant of SEQ ID NO: 1 or SEQ ID NO: 5 that can be found naturally in other organisms, such as other fungal species, provided that it has bifunctional terpene synthase activity and comprises domains corresponding to Pfam domains PF13419.5 and PF13242.5. As used herein, the polypeptide includes a polypeptide or peptide fragment that encompasses the amino acid sequences identified herein, as well as truncated or variant polypeptides provided that they have bifunctional terpene synthase activity and that they share at least the defined percentage of identity with the corresponding fragment of SEQ ID NO: 1 or SEQ ID NO: 5 and comprise (1) a class I terpene synthase-like motif as set forth in SEQ ID NO: 53 (DDxx(D/E)) and (2) a class II terpene synthase-like motif as set forth in SEQ ID NO: 56 (DxD(T/S)T) and comprises domains corresponding to Pfam domains PF13419.5 and PF13242.5. 
     Examples of variant polypeptides are naturally occurring proteins that result from alternate mRNA splicing events or from proteolytic cleavage of the polypeptides described herein. Variations attributable to proteolysis include, for example, differences in the N- or C-termini upon expression in different types of host cells, due to proteolytic removal of one or more terminal amino acids from the polypeptides of an embodiment herein. Polypeptides encoded by a nucleic acid obtained by natural or artificial mutation of a nucleic acid of an embodiment herein, as described thereafter, are also encompassed by an embodiment herein. 
     Polypeptide variants resulting from a fusion of additional peptide sequences at the amino and carboxyl terminal ends can also be used in the methods of an embodiment herein. In particular such a fusion can enhance expression of the polypeptides, be useful in the purification of the protein or improve the enzymatic activity of the polypeptide in a desired environment or expression system. Such additional peptide sequences may be signal peptides, for example. Another aspect encompasses methods using variant polypeptides, such as those obtained by fusion with other oligo- or polypeptides and/or those which are linked to signal peptides. Polypeptides resulting from a fusion with another functional protein, such as another protein from the terpene biosynthesis pathway, can also be advantageously used in the methods of an embodiment herein. 
     A variant may also differ from the polypeptide of an embodiment herein by attachment of modifying groups which are covalently or non-covalently linked to the polypeptide backbone. The variant also includes a polypeptide which differs from the polypeptide provided herein by introduced N-linked or O-linked glycosylation sites, and/or an addition of cysteine residues. The skilled artisan will recognize how to modify an amino acid sequence and preserve biological activity. 
     In addition to the gene sequences shown in the sequences disclosed herein, it will be apparent for the person skilled in the art that DNA sequence polymorphisms may exist within a given population, which may lead to changes in the amino acid sequence of the polypeptides disclosed herein. Such genetic polymorphisms may exist in cells from different populations or within a population due to natural allelic variation. Allelic variants may also include functional equivalents. 
     Further embodiments also relate to the molecules derived by such sequence polymorphisms from the concretely disclosed nucleic acids. These natural variations usually bring about a variance of about 1 to 5% in the nucleotide sequence of a gene or in the amino acid sequence of the polypeptides disclosed herein. As mentioned above, the nucleic acid encoding the polypeptide or variants thereof of an embodiment herein is a useful tool to modify non-human host organisms, microorganisms or cells and to modify non-human host organisms, microorganisms or cells intended to be used in the methods described herein. 
     An embodiment provided herein provides amino acid sequences of bifunctional terpene synthase proteins including orthologs and paralogs as well as methods for identifying and isolating orthologs and paralogs of the bifunctional terpene synthases in other organisms. Particularly, so identified orthologs and paralogs of the bifunctional terpene synthase retain bifunctional terpene synthase activity, may be considered a polypeptide of the HAD-like hydrolase superfamily (Interpro protein superfamily IPR023214 or Pfam protein superfamily PF13419) and which comprises a HAD-like hydrolase domain and are capable of producing a drimane sesquiterpene, such as albicanol and/or drimenol, starting from an acyclic terpene pyrophosphate precursor, e.g. FPP. 
     The polypeptide to be contacted with an acyclic terpene pyrophosphate, e.g. FPP, in vitro can be obtained by extraction from any organism expressing it, using standard protein or enzyme extraction technologies. If the host organism is an unicellular organism or cell releasing the polypeptide of an embodiment herein into the culture medium, the polypeptide may simply be collected from the culture medium, for example by centrifugation, optionally followed by washing steps and re-suspension in suitable buffer solutions. If the organism or cell accumulates the polypeptide within its cells, the polypeptide may be obtained by disruption or lysis of the cells and optionally further extraction of the polypeptide from the cell lysate. The cell lysate or the extracted polypeptide can be used to contact the acyclic terpene pyrophosphate for production of a terpene or a mixture of terpenes. 
     The polypeptide having a bifunctional terpene synthase activity, either in an isolated form or together with other proteins, for example in a crude protein extract obtained from cultured cells or microorganisms, may then be suspended in a buffer solution at optimal pH. If adequate, salts, DTT, inorganic cations and other kinds of enzymatic co-factors, may be added in order to optimize enzyme activity. The precursor FPP is added to the polypeptide suspension, which is then incubated at optimal temperature, for example between 15 and 40° C., particularly between 25 and 35° C., more particularly at 30° C. After incubation, the drimane sesquiterpene, such as albicanol and/or drimenol, produced may be isolated from the incubated solution by standard isolation procedures, such as solvent extraction and distillation, optionally after removal of polypeptides from the solution. 
     According to another embodiment, the at least one polypeptide having a bifunctional terpene synthase activity can be used for production of a drimane sesquiterpene comprising albicanol and/or drimenol or mixtures of terpenes comprising albicanol and/or drimenol. 
     One particular tool to carry out the method of an embodiment herein is the polypeptide itself as described herein. 
     According to a particular embodiment, the polypeptide is capable of producing a mixture of sesquiterpenes wherein albicanol and/or drimenol represents at least 20%, particularly at least 30%, particularly at least 35%, particularly at least 90%, particularly at least 95%, more particularly at least 98% of the sesquiterpenes produced. In another aspect provided here, the albicanol and/or drimenol is produced with greater than or equal to 95%, more particularly 98% selectivity. 
     The functionality or activity of any bifunctional terpene synthase protein, variant or fragment, may be determined using various methods. For example, transient or stable overexpression in plant, bacterial or yeast cells can be used to test whether the protein has activity, i.e., produces albicanol and/or drimenol from FPP precursors. Bifunctional terpene synthase activity may be assessed in a microbial expression system, such as the assay described in Example 3 herein on the production of albicanol and/or drimenol, indicating functionality. A variant or derivative of a bifunctional terpene synthase polypeptide of an embodiment herein retains an ability to produce a drimane sesquiterpene such as albicanol and/or drimenol from FPP precursors. Amino acid sequence variants of the bifunctional terpene synthases provided herein may have additional desirable biological functions including, e.g., altered substrate utilization, reaction kinetics, product distribution or other alterations. 
     The ability of a polypeptide to catalyze the synthesis of a particular sesquiterpene (for example albicanol and/or drimenol) can be simply confirmed, for example, by performing the enzyme assay as detailed in Examples 3, 4 and 6. 
     Further provided is at least one vector comprising the nucleic acid molecules described herein. 
     Also provided herein is a vector selected from the group of a prokaryotic vector, viral vector and a eukaryotic vector. 
     Further provided here is a vector that is an expression vector. 
     In one embodiment, several bifunctional terpene synthases encoding nucleic acid sequences are co-expressed in a single host, particularly under control of different promoters. In another embodiment, several bifunctional terpene synthase proteins encoding nucleic acid sequences can be present on a single transformation vector or be co-transformed at the same time using separate vectors and selecting transformants comprising both chimeric genes. Similarly, one or more bifunctional terpene synthase encoding genes may be expressed in a single plant, cell, microorganism or organism together with other chimeric genes. 
     The nucleic acid sequences of an embodiment herein encoding bifunctional terpene synthase proteins can be inserted in expression vectors and/or be contained in chimeric genes inserted in expression vectors, to produce bifunctional terpene synthase proteins in a host cell or non-human host organism. The vectors for inserting transgenes into the genome of host cells are well known in the art and include plasmids, viruses, cosmids and artificial chromosomes. Binary or co-integration vectors into which a chimeric gene is inserted can also be used for transforming host cells. 
     An embodiment provided herein provides recombinant expression vectors comprising a nucleic acid sequence of a bifunctional terpene synthase gene, or a chimeric gene comprising a nucleic acid sequence of a bifunctional terpene synthase gene, operably linked to associated nucleic acid sequences such as, for instance, promoter sequences. For example, a chimeric gene comprising a nucleic acid sequence of SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 16, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67, SEQ ID NO: 68, SEQ ID NO: 69, or SEQ ID NO: 70 or a variant thereof may be operably linked to a promoter sequence suitable for expression in plant cells, bacterial cells or fungal cells, optionally linked to a 3′ non-translated nucleic acid sequence. 
     Alternatively, the promoter sequence may already be present in a vector so that the nucleic acid sequence which is to be transcribed is inserted into the vector downstream of the promoter sequence. Vectors can be engineered to have an origin of replication, a multiple cloning site, and a selectable marker. 
     In one embodiment, an expression vector comprising a nucleic acid as described herein can be used as a tool for transforming non-human host organisms or host cells suitable to carry out the method of an embodiment herein in vivo. 
     The expression vectors provided herein may be used in the methods for preparing a genetically transformed non-human host organism and/or host cell, in non-human host organisms and/or host cells harboring the nucleic acids of an embodiment herein and in the methods for making polypeptides having a bifunctional terpene synthase activity, as described herein. 
     Recombinant non-human host organisms and host cells transformed to harbor at least one nucleic acid of an embodiment herein so that it heterologously expresses or over-expresses at least one polypeptide of an embodiment herein are also very useful tools to carry out the method of an embodiment herein. Such non-human host organisms and host cells are therefore provided herein. 
     In one embodiment is provided a host cell, microorganism or non-human host organism comprising at least one of the nucleic acid molecules described herein or comprising at least one vector comprising at least one of the nucleic acid molecules. 
     A nucleic acid according to any of the above-described embodiments can be used to transform the non-human host organisms and cells and the expressed polypeptide can be any of the above-described polypeptides. 
     In one embodiment, the non-human host organism or host cell is a prokaryotic cell. In another embodiment, the non-human host organism or host cell is a bacterial cell. In a further embodiment, the non-human host organism or host cell is  Escherichia coli.    
     In one embodiment, the non-human host organism or host cell is a eukaryotic cell. In another embodiment, the non-human host organism or host cell is a yeast cell. In a further embodiment, the non-human host organism or cell is  Saccharomyces cerevisiae.    
     In a further embodiment, the non-human organism or host cell is a plant cell or a fungal cell. 
     In one embodiment the non-human host organism or host cell expresses a polypeptide, provided that the organism or cell is transformed to harbor a nucleic acid encoding said polypeptide, this nucleic acid is transcribed to mRNA and the polypeptide is found in the host organism or cell. Suitable methods to transform a non-human host organism or a host cell have been previously described and are also provided herein. 
     To carry out an embodiment herein in vivo, the host organism or host cell is cultivated under conditions conducive to the production of a drimane sesquiterpene such as albicanol and/or drimenol. Accordingly, if the host is a transgenic plant, optimal growth conditions can be provided, such as optimal light, water and nutrient conditions, for example. If the host is a unicellular organism, conditions conducive to the production of a drimane sesquiterpene such as albicanol and/or drimenol may comprise addition of suitable cofactors to the culture medium of the host. In addition, a culture medium may be selected, so as to maximize drimane sesquiterpene, such as albicanol and/or drimenol, synthesis. Examples of optimal culture conditions are described in a more detailed manner in the Examples. 
     Non-human host organisms suitable to carry out the method of an embodiment herein in vivo may be any non-human multicellular or unicellular organisms. In one embodiment, the non-human host organism used to carry out an embodiment herein in vivo is a plant, a prokaryote or a fungus. Any plant, prokaryote or fungus can be used. Particularly useful plants are those that naturally produce high amounts of terpenes. In another embodiment the non-human host organism used to carry out the method of an embodiment herein in vivo is a microorganism. Any microorganism can be used, for example, the microorganism can be a bacteria or yeast, such as  E. coli  or  Saccharomyces cerevisiae.    
     Some of these organisms do not produce FPP naturally. To be suitable to carry out the method of an embodiment herein, organisms or cells that do not produce an acyclic terpene pyrophosphate precursor, e.g. FPP, naturally are transformed to produce said precursor. They can be so transformed either before the modification with the nucleic acid described according to any of the above embodiments or simultaneously, as explained above. Methods to transform organisms, for example microorganisms, so that they produce an acyclic terpene pyrophosphate precursor, e.g. FPP, are already known in the art. 
     Isolated higher eukaryotic cells can also be used, instead of complete organisms, as hosts to carry out the method of an embodiment herein in vivo. Suitable eukaryotic cells may be any non-human cell, such as plant or fungal cells. 
     Further provided herein is a method of producing a drimane sesquiterpene comprising: contacting an acyclic terpene pyrophosphate, particularly farnesyl diphosphate (FPP) with a polypeptide which comprises a HAD-like hydrolase domain and having bifunctional terpene synthase activity to produce a drimane sesquiterpene, wherein the polypeptide comprises (1) a class I terpene synthase-like motif as set forth in SEQ ID NO: 53 (DDxx(D/E)); and (2) a class II terpene synthase-like motif as set forth in SEQ ID NO: 56 (DxD(T/S)T); and optionally isolating the drimane sesquiterpene. 
     Also provided is the above method wherein the drimane sesquiterpene comprises albicanol and/or drimenol. 
     Additionally provided is the above method, wherein the polypeptide comprises an amino acid sequence having at least 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% sequence identity to SEQ ID NO: 1, SEQ ID NO: 5, SEQ ID NO: 9, SEQ ID NO: 12, SEQ ID NO: 15, SEQ ID NO: 17, SEQ ID NO: 20, SEQ ID NO: 23, SEQ ID NO: 26, SEQ ID NO: 29, SEQ ID NO: 32, SEQ ID NO: 35, SEQ ID NO: 38, SEQ ID NO: 41, SEQ ID NO: 44, SEQ ID NO: 47, SEQ ID NO: 50, or SEQ ID NO: 63 and (1) the sequence as set forth in SEQ ID NO: 53, SEQ ID NO: 54, or SEQ ID NO: 55; and (2) the sequence as set forth in SEQ ID NO: 56, SEQ ID NO: 57, or SEQ ID NO: 58 or comprising the amino acid sequence of SEQ ID NO: 1, SEQ ID NO: 5, SEQ ID NO: 9, SEQ ID NO: 12, SEQ ID NO: 15, SEQ ID NO: 17, SEQ ID NO: 20, SEQ ID NO: 23, SEQ ID NO: 26, SEQ ID NO: 29, SEQ ID NO: 32, SEQ ID NO: 35, SEQ ID NO: 38, SEQ ID NO: 41, SEQ ID NO: 44, SEQ ID NO: 47, SEQ ID NO: 50, or SEQ ID NO: 63 to produce a drimane sesquiterpene ; and optionally isolating the drimane sesquiterpene. In another aspect, the polypeptide further comprises one or more conserved motif as set forth in SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61, and/or SEQ ID NO: 62. 
     In one aspect, the drimane sesquiterpene is albicanol and/or drimenol. In another aspect, the drimane sesquiterpene is isolated. 
     In another aspect provided here, the albicanol and/or drimenol is produced with greater than or equal to, 60%, 80%, or 90% or even 95% selectivity. In a further aspect the drimane sesquiterpene is albicanol. 
     Further provided here is a method comprising transforming a host cell, microorganism or a non-human host organism with a nucleic acid encoding a polypeptide comprising a HAD-like hydrolase domain having bifunctional terpene synthase activity and comprising an amino acid sequence having at least 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99% sequence identity to SEQ ID NO: 1, SEQ ID NO: 5, SEQ ID NO: 9, SEQ ID NO: 12, SEQ ID NO: 15, SEQ ID NO: 17, SEQ ID NO: 20, SEQ ID NO: 23, SEQ ID NO: 26, SEQ ID NO: 29, SEQ ID NO: 32, SEQ ID NO: 35, or SEQ ID NO: 38, SEQ ID NO: 41, SEQ ID NO: 44, SEQ ID NO: 47, SEQ ID NO: 50, or SEQ ID NO: 63; and comprising (1) the sequence as set forth in SEQ ID NO: 53, SEQ ID NO: 54, or SEQ ID NO: 55; and (2) the sequence as set forth in SEQ ID NO: 56, SEQ ID NO: 57, or SEQ ID NO: 58 or comprising the amino acid sequence of SEQ ID NO: 1, SEQ ID NO: 5, SEQ ID NO: 9, SEQ ID NO: 12, SEQ ID NO: 15, SEQ ID NO: 17, SEQ ID NO: 20, SEQ ID NO: 23, SEQ ID NO: 26, SEQ ID NO: 29, SEQ ID NO: 32, SEQ ID NO: 35, or SEQ ID NO: 38, SEQ ID NO: 41, SEQ ID NO: 44, SEQ ID NO: 47, SEQ ID NO: 50, or SEQ ID NO: 63. 
     In one embodiment, a method provided herein comprises cultivating a non-human host organism or a host cell capable of producing FPP and transformed to express a polypeptide wherein the polypeptide comprises a sequence of amino acids that has at least 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99% or 100% sequence identity to SEQ ID NO: 1 or SEQ ID NO: 5 under conditions that allow for the production of the polypeptide. 
     In a another embodiment, a method provided herein comprises contacting a sesquiterpene such as albicanol and/or drimenol with at least one enzyme to produce a sesquiterpene derivative. In one embodiment, the sesquiterpene derivative can be obtained biochemically or chemically. In one embodiment, a drimenol derivative is provided. Examples of such derivatives of drimenol include but not limited to drimenyl acetate (CAS 40266-93-1), drimenal (CAS 105426-71-9), drimenic acid (CAS 111319-84-7). 
     In one embodiment, an albicanol derivative is provided. Examples of such derivatives of albicanol include cryptoporic acid E (CAS 120001-10-7), cryptoporic acid D (CAS 119979-95-2), cryptoporic acid B (CAS 113592-88-4), cryptoporic acid A (CAS 113592-87-3), laricinolic acid (CAS 302355-23-3), albicanyl acetate (CAS 83679-71-4). 
     The albicanol and/or drimenol produced in any of the method described herein can be converted to derivatives such as, but not limited to hydrocarbons, esters, amides, glycosides, ethers, epoxides, aldehydes, ketons, alcohols, diols, acetals or ketals. 
     The albicanol and/or drimenol derivatives can be obtained by a chemical method such as, but not limited to oxidation, reduction, alkylation, acylation and/or rearrangement. 
     Alternatively, the albicanol and/or drimenol derivatives can be obtained using a biochemical method by contacting the albicanol and/or drimenol with an enzyme such as, but not limited to an oxidoreductase, a monooxygenase, a dioxygenase, a transferase. The biochemical conversion can be performed in-vitro using isolated enzymes, enzymes from lysed cells or in-vivo using whole cells. 
     According to another particularly embodiment, the method of any of the above-described embodiments is carried out in vivo. In such a case, step a) comprises cultivating a non-human host organism or a host cell capable of producing FPP and transformed to express at least one polypeptide comprising an amino acid comprising SEQ ID NO: 1 or SEQ ID NO: 5 or a functional variant thereof which may be considered a polypeptide of the HAD-like hydrolase superfamily (Interpro protein superfamily IPR023214 or Pfam protein superfamily PF13419) and which comprises a HAD-like hydrolase domain and having a bifunctional terpene synthase activity, under conditions conducive to the production of drimane synthase, for example, albicanol and/or drimenol. In one embodiment, albicanol may be the only product or may be part of a mixture of sesquiterpenes. In another aspect, drimenol may be the only product or may be part of a mixture of sesquiterpenes. 
     According to a further embodiment, the method further comprises, prior to step a), transforming a non-human organism or cell capable of producing FPP with at least one nucleic acid encoding a polypeptide comprising an amino acid comprising SEQ ID NO: 1 or SEQ ID NO: 5 or encoding a polypeptide having bifunctional terpene synthase activity and comprising an amino acid sequence having at least 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99% sequence identity to SEQ ID NO: 1, SEQ ID NO: 5, SEQ ID NO: 9, SEQ ID NO: 12, SEQ ID NO: 15, SEQ ID NO: 17, SEQ ID NO: 20, SEQ ID NO: 23, SEQ ID NO: 26, SEQ ID NO: 29, SEQ ID NO: 32, SEQ ID NO: 35, or SEQ ID NO: 38, SEQ ID NO: 41, SEQ ID NO: 44, SEQ ID NO: 47, SEQ ID NO: 50, or SEQ ID NO: 63; and (1) the sequence as set forth in SEQ ID NO: 53, SEQ ID NO: 54, or SEQ ID NO: 55; and (2) the sequence as set forth in SEQ ID NO: 56, SEQ ID NO: 57, or SEQ ID NO: 58, so that said organism expresses said polypeptide. The polypeptide may further comprise one or more conserved motif as set forth in SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61, and/or SEQ ID NO: 62. 
     These embodiments of an embodiment herein are particularly advantageous since it is possible to carry out the method in vivo without previously isolating the polypeptide. The reaction occurs directly within the organism or cell transformed to express said polypeptide. 
     An embodiment herein provides polypeptides of an embodiment herein to be used in a method to produce a drimane sesquiterpene such as albicanol and/or drimenol contacting an FPP precursor with the polypeptides of an embodiment herein either in vitro or in vivo. 
     Further provided is the use of a polypeptide as described herein for producing a drimane sesquiterpene, for example, albicanol and/or drimenol. 
     The following examples are illustrative only and are not intended to limit the scope of the claims an embodiments described herein. 
     EXAMPLES 
     Example 1 
     Microorganism Cultivation and DNA and RNA Extraction. 
     Drimane sesquiterpenoids are widespread in nature (Jansen and Groot, 2004,  Nat. Prod. Rep.,  21, 449-477). The compounds in the drimane sesquiterpeneoid family contain the sesquiterpene structure with the drimane carbon skeleton depicted in  FIG.  1   . For example, commonly found drimane sesquiterpene are drimenol and albicanol ( FIG.  1   ) and compounds derived from drimenol and albicanol by enzymatic reactions such as oxidations, reduction, acylation, alkylation or rearrangement. The drimane sesquiterpenoid family contains also compounds were the drimane sesquiterpene is bound to a molecule derived from another biosynthetic pathway (Jansen and Groot, 2004,  Nat. Prod. Rep.,  21, 449-477). 
     Cryptoporic acids A-H are drimane sequiterpenoid ethers of isocitric acid found in the fungus  Cryptoporus volvatus  (Hashimoto et al, 1987,  Tetrahedron Let.  28, 6303-6304; Asakawa et al, 1992,  Phytochemistry  31(2), 579-592; Hirotani et al, 1991,  Phytochemistry  30(5), 1555-1559). In crypotoporic acids, the sesquiterpene moiety has the structure of albicanol and thus these compounds are putatively derived biosynthetically from albicanol. Laricinolic acid is a drimane type sesquiterpene which can be isolated from the wood-rotting fungus  Laricifomes officinalis  (Erb et al, 2000,  J. Chem. Soc., Perkin Trans.  1, 2307-2309). Laricinolic acid is most likely derived from albicanol following several oxidative enzymatic steps. 
     We undertook to characterize albicanol synthases and to identify nucleotide sequences encoding for albicanol synthases from  Cryptoporus volvatus  and  Laricifomes officinalis . Strains of  Laricifomes officinalis  (ATCC® 64430™) and  Cryptoporus volvatus  (ATCC® 12212™) are conserved at the American Type Culture Collection (ATCC) under the collection numbers ATCC-64430 and ATCC-12212, respectively. The  Laricifomes officinalis  (ATCC® 64430™) and  Cryptoporus volvatus  (ATCC® 12212™) strains were purchased from LGC Standards GmbH (46485 Wesel, Germany). The cells were grown in Yeast Mold (YM) medium (Wickerham, 1939,  J. Tropical Med. Hyg.  42, 176). 
     For each of the two strains, genomic DNA and total RNA were extracted in order to sequence the full genome and a transcriptome. Cells propagated on YM-agar plates were used to inoculate 100 ml liquid YM medium in glass tubes. The cultures were incubated for 6 days with at 25° C. and 180 rpm agitation. For RNA extraction 0.5 ml of culture was taken, the cells (Approximately 100 mg) were recovered by centrifugation frozen in liquid nitrogen and grinded using a mortar and pestle. The total RNA pool was extracted using the ZR Fungal/Bacterial RNA MiniPrep™ from Zymo Research Corp (Irvine, Calif. 92614, U.S.A). From 100 mg of cells 18 and 23 micrograms of total RNA were obtained for ATCC-12212 and ATCC-64430, respectively. Genomic DNA was extracted using the NucleoSpin® Soil Kit from Machery-Nagel (Duren, Germany). Cells were recovered from the culture by centrifugation and the genomic DNA was extracted following the manufacturer protocol. From 500 mg of cells 1.05 and 0.93 micrograms of genomic DNA was extracted from ATCC-12212 and ATCC-64430, respectively. 
     Example 2 
     Genome and Transcriptome Sequencing. 
     The genomic DNA was sequenced using a paired read protocol (Illumina). The libraries were prepared to select insert sizes between 250 and 350 bp. The sequencing was performed on a HiSeq 2500 Illumina sequencer. The length of the reads was 125 bases. A total of 21.3 and 30.4 millions of paired-reads (clusters) were sequenced for ATCC-12212 and ATCC-64430, respectively. 
     For the transcriptomes the library was prepared from the total RNA using the TruSeq Stranded mRNA Library Preparation Kit (Illumina). An additional insert size selection step (160-240 bp) was performed. The libraries were sequenced in 2×125 bases paired-ends on a HiSeq 2500 Illumina sequencer. For ATCC-12212 and ATCC-64430, 19.9 million and 126 millions of reads were sequences, respectively. 
     For assembly of the  C. volvatus  transcriptome, the reads were first joined on their overlapping ends. The joined paired reads were then assembled using the Velvet V1.2.10 assembler (Zerbino D. R. and Birney E. 2008,  Genome Res.  18(5), 821-829; www.ebi.ac.uk/˜zerbino/velvet/) and the Oases software (Schulz M. H et al., 2012,  Bioinformatics  28(8), 1086-1092; www.ebi.ac.uk/˜zerbino/oases/). A total of 25′866 contigs with an average length of 1,792 bases was obtained for the  C. volvatus  transcriptome. 
     The  C. volvatus  genome was assembled using the Velvet V1.2.10 assembler (Zerbino D. R. and Birney E., 2008,  Genome Res.  18(5), 821-829; www.ebi.ac.uk/˜zerbino/velvet/). The genome could be assembled in 1′266 contigs with an average size 20,000 bases and a total size of 25′320′421 bases. An ab-initio gene prediction in the  C. volvatus  genomic contigs was performed by Progenus S A (Gembloux, Belgium) using the Augustus software (Stanke et al.,  Nucleic Acids Res . (2004) 32, W309-W312). A total of 7738 genes were predicted. Functional annotation was performed combining a Pfam domain search (Finn, R. D. et al., 2016,  Nucleic Acids Research  Database Issue 44:D279-D285) and a Blast search (Altschul et al., 1990,  J. Mol. Biol.  215, 403-410). 
     The genome and transcriptome of  L. officinalis  were assembled using the CLC Genomic Workbench (Qiagen). The genome was assembled in 16′831 contigs for a total genome size of 90′591′190 bases. The transcriptome assembly provided 28′633 contigs with an average length of 1′962 bases. 
     Example 3 
     Identification of Drimane Sesquiterpene Synthases. 
     Using a tBlastn search (Altschul et al., 1990,  J. Mol. Biol.  215, 403-410) with the amino acid sequences of known sesquiterpene synthases as query sequences, 6 and 10 putative sesquiterpene synthases sequences were identified in the  C. volvatus  genome and  L. officinalis  genome, respectively. The sequences were manually corrected, in particular for the intro-exon junction localizations, using a mapping of the RNA sequencing reads on the genomic contigs. The corresponding cDNAs were then codon-optimized for optimal  E. coli  expression, synthesized and cloned in an expression plasmid (pJ401, ATUM, Newark, Calif.). Functional expression  E coli  cells and enzyme characterization assay showed sesquiterpene synthase activities but did not reveal any formation of albicanol from FPP. 
     Drimane sesquiterpene are presumably produced from farnesyl-diphosphate (FPP) by an enzymatic mechanism involving a protonation-initiated cyclization followed by an ionization-initiated reaction (Henquet et al., 2017,  Plant J . Mar 4. doi: 10.1111/tpj.13527; Kwon, M.et al., 2014,  FEBS Letters  588, 4597-4603) ( FIG.  2   ). This implies that the drimane synthases are composed of two catalytic domains, a protonation-initiated cyclization catalytic domain and an ionization-initiated cyclization catalytic domain. 
     Terpene synthases catalyzing protonation-initiated cyclization reaction are called class II (or type II) terpene synthases and are typically involved in the biosynthesis of triterpenes and labdane diterpenes. In class II terpene synthases the protonation-initiated reaction involves acidic amino acids donating a proton to the terminal double-bond. These residues, usually aspartic acids, are part of a conserved DxDD motif located in the active site of the enzyme. 
     Terpene synthases catalyzing ionization-initiated reactions are called class I (or type I) terpene synthases, generally monoterpene and sesquiterpene synthases, and the catalytic center contains a conserved DDxxD (part of SEQ ID NO: 53) motif. The aspartic acid residues of this class I motif bind a divalent metal ion (most often Mg 2+ ) involved in the binding of the diphosphate group and catalyze the ionization and cleavage of the allylic diphosphate bond of the substrate. 
     The putative cyclization mechanism of a farnesyl-diphosphate to a drimane sesquiterpene (such as albicanol or drimenol) starts with the protonation of the 10,11-double bond followed by the sequential rearrangements and carbon-bond formations. The carbocation intermediate of this first (class II) reaction can then undergo deprotonation at C15 or C4 (or eventually at C2) leading to an albicanyl-diphosphate or drimenyl-diphosphate intermediate. Finally the class I catalytic domain catalyzes the ionization of the allylic diphosphate bond and quenching of the carbocation intermediated by a water molecule leading to a drimane sesquiterpene containing a primary hydroxyl group ( FIG.  2   ). If necessary, any traces of residual phosphorylated intermediates of the albicanol or drimenol synthesis, like any albicanyl—or drimenyl-monophosphate and/or—diphosphate, may be chemically converted to the respective final product albicanol or drimenol. Certain corresponding methods are known and may comprise, for example, the hydrolytic cleavage of the phosphoric acid ester bond. Additionally, certain intermediates can also be converted enzymatically as shown in Examples 7 and 8. 
     Based on the above considerations, we searched the  C. volvatus  and  L. officinalis  genome and transcriptome data for sequences encoding for polypeptides containing together a class I and a class II terpene synthase motif. Recently, a drimanyl-diphosphate synthase (AstC) was identified in the fungus  Aspergillus oryzea  (Shinohara Y. et al., 2016, Sci Rep. 6, 32865). The enzyme contains a class II terpene synthase domain and catalyzes the protonation-initiation cyclization of farnesyl-diphosphate to drimanyl-diphosphate. However, this enzyme does not have a class I terpene synthase activity and thus does not catalyze the ionization and cleavage of the allylic diphosphate group. Using the sequence of AstC, we first search the amino acid sequences deduced from the genes predicted in the  C. volvatus  genome. Using a Blastp search against the amino acid sequences deduced from the predicted genes, 5 sequences were retrieved with an E value between 0.77 and 3e-089 (Altschul et al., 1990,  J. Mol. Biol.  215, 403-410). 
     Amongst these 5 sequences, CvTps1 was selected as the most relevant for a putative albicanol synthases. The amino acid sequence encoded by the CvTps1 gene shared 38% identity with the AstC amino acid sequence. Analysis of this sequence revealed the presence of a class II terpene synthase-like motif, DVDT, at position 275-279. This is a variant of the typical class II terpene synthase motif mentioned above, where the last Asp is replaced by a Thr. This DxDT class II motif is found in some class II diterpene synthases (Xu M. et al., 2014,  J. Nat. Prod.  77, 2144-2147; Morrone D. et al., 2009,  J. FEBS Lett.,  583, 475-480) and in AstC. Another interesting feature of the CvTps1 sequence is the presence of a typical class I motif in the N-terminal region (DDKLD at position 168-172). The presence of this class I motif, not present in AstC, suggests that CvTps1 can catalyze an ionization-initiated reaction in addition to the class II reaction. Another difference with AstC is the presence of a C-terminal extension, the CvTps1 peptide contains 46 additional amino acids at the C-terminal end. Thus CvTps1 was selected as putative candidate for a bi-functional albicanol synthase. 
     Protein family databases such as Pfam and Interpro (European Bioinformatic Institute (EMBL-EBI) are databases of protein families including functional annotation, protein domains and protein domain signatures. The amino acid sequence of CvTps1 was searched for the occurrence of motifs characteristic of protein domains using the HMMER algorithm available on the HMMER website (Finn R. D., 2015,  Nucleic Acids Research Web Server Issue  43:W30-W38; www.ebi.ac.uk/Tools/hmmer/). No domain associated with classical terpene synthases was found in the CvTps1 amino acid sequence. The query identified a domain characteristic of the Haloacid dehalogenase (HAD)-like hydrolase protein superfamily (PF13419.5) in the region between residues 115 and 187. A similar search using the Interpro protein family database (see the ebi.ac.uk/interpro/web site) and the Conserved Domain Database (NCBI web site at ncbi.nlm.nih.gov/Structure/cdd/wrpsb.cgi) provided the same results: only the prediction of a domain of the HAD-like hydrolase superfamily in the N-terminal region (IPR 023214 and CL21460, respectively). The HAD-like hydrolase superfamily contains a large number of proteins with various functions including enzymes with phosphatase activity (Koonin and Tatusov, 1994, J. Mol. Biol 244, 125-132; Kuznetsova et al, 2015, J Biol Chem. 290(30), 18678-18698). The class I terpene synthase-like motif identified above in the CvTps1 polypeptide contains one of the HAD-like hydrolase motif signatures containing a conserved aspartic acid residues involved in the catalytic (phosphatase) activity. This analysis thus confirms that the N-terminal region of CvTps1 is involved in hydrolysis of the diphosphate group (class I terpene synthase activity). 
     No significant domain prediction was obtained in the C-terminal portion the polypeptide. Given the presence of a class II terpene synthase-like motif, the C-terminal part is likely involved in the protonation-initiated cyclization. 
     The CvTps1 amino acid sequence was used to search for homologous sequences in the  L. officinalis  genome and transcriptome. For this search the tBlastn algorithm was used (Altschul et al 1990,  J. Mol. Biol.  215, 403-410). One transcript, LoTps1 showed sequence similarity with CvTps1: the length of the sequence (521 amino acid) was similar to the length of the CvTps1 amino acid sequence, the overall sequence identity between the two sequences was 71%, the N-terminal region contained a typical class I terpene synthase motif (DDKLD at position 162-166), a class II terpene synthase motif (DMDT) was found in position 267-270 and the N-terminal region contain a predicted HAD-like hydrolase domain. 
     Example 4 
     Heterologous Expression and Characterization of CvTps1 and LoTps1. 
     The CvTps1 and LoTps1 coding sequences were control and the intron-exon jonctions predictions were refined using mappings of the RNA sequencing reads against the genomic contigs. The coding sequences of the resulting cDNAs were codon optimized and cloned in the pJ401  E. coli  expression plasmid (pJ401, ATUM, Newark, Calif.). 
     The enzymes were functionally characterized in  E. coli  cells engineered to overproduce farnesyl-diphosphate (FPP). Competent  E. coli  cells were transformed with the plasmid pACYC-29258-4506 (described in WO2013064411 or in Schalk et al., 2013,  J. Am. Chem. Soc.  134, 18900-18903) and with the pJ401-CvTps1 or pJ401-LoTps1 expression plasmid. The pACYC-29258-4506 carries the cDNA encoding for a FPP synthase gene and the genes for a complete mevalonate pathway. The KRX  E. coli  cells (Promega) were used as a host. Transformed cells were selected on kanamycin (50 μg/ml) and chloramphenicol (34 μg/ml) LB-agarose plates. Single colonies were used to inoculate 5 mL liquid LB medium supplemented with the same antibiotics. The culture was incubated overnight at 37° C. The next day 2 mL of TB medium supplemented with the same antibiotics were inoculated with 0.2 mL of the overnight culture. After 6 hours incubation at 37° C., the culture was cooled down to 28° C. and 0.1 mM IPTG, 0.2% rhamnose and 10% in volume (0.2 ml) of dodecane were added to each tube. The cultures were incubated for 48 hours at 28° C. The cultures were then extracted twice with 2 volumes of tert-Butyl methyl ether (MTBE), the organic phase were concentrated to 500 μL and analyzed by GC-MS. 
     The GC-MS analysis were performed using an Agilent 6890 Series GC system connected to an Agilent 5975 mass detector. The GC was equipped with 0.25 mm inner diameter by 30 m DB-1MS capillary column (Agilent). The carrier gas was He at a constant flow of 1 mL/min. The inlet temperature was set at 250° C. The initial oven temperature was 80° C. followed by a gradient of 10° C./min to 220° C. and a second gradient of 30° C./min to 280° C. The identification of the products was based on the comparison of the mass spectra and retention indices with authentic standards and internal mass spectra databases. 
     In these conditions formation of a single product was observed with the recombinant CrVo07609 protein. The final concentration for this enzyme product was 200 mg/l of culture medium. The retention time in gas chromatography as well as the mass spectrum was in accordance with the GCMS data of an authentic (+)-albicanol standard. For structure confirmation, the recombinant cells were cultivated in a larger (500 ml) volume in the conditions described above. The MTBE was distilled form the extract and the resulting suspension in dodecane was subjected to flash chromatography. The product was eluted with a mixture 1:5 of MTBE and cyclohexane. The solvent was removed by distillation providing a product with 98% purity. The structure of albicanol was confirmed by 1H- and 13C-NMR analysis. The optical rotation was measured using a Bruker Avance 500 MHz spectrometer. The value of [α] D   20 =+3.8° (0.26%, CHCl3) confirmed the formation of (+)-albicanol (with the structure shown in  FIG.  1   ) by the recombinant CvTps1 protein. 
     The activity of LoTps1 was evaluated in the same conditions. The product profile was identical to the profile of CvTps1 with (+)-albicanol as the only detected product of the recombinant LoTps1 enzyme. 
     This experiments show that the CvTps1 and LoTps1 are enzyme with bifunctional class II cyclase activity and class I phosphatase activity. 
     Example 5 
     Search for Sequences Homologous to CvTps1 and LoTps1 in Other Organisms. 
     The amino acid sequences of CvTps1 and LoTps1 were used to search for homologous sequences from other organisms present in public databases. A blastp search approach (Altschul et al., 1990,  J. Mol. Biol.  215, 403-410) was first used to search in the protein database of the National Center for Biotechnology Information (NCBI, www.ncbi.nlm.nih.gov/) for sequences showing homology with CvTps1 and LoTps1. The retrieved amino acids were then analyzed for the presence of the CyTps1 and LoTps1 features described in Example 3. Fifteen sequences, all from fungi species, were selected for further analysis and enzymatic activity characterization: NCBI accession OCH93767.1 from  Obba rivulosa , NCBI accession EMD37666.1 from  Gelatoporia subvermispora , NCBI accession XP_001217376.1 from  Aspergillus terreus , NCBI accession OJJ98394.1 from  Aspergillus aculeatus , NCBI accession GAO87501.1 from  Aspergillus udagawae , NCBI accession XP_008034151.1 from  Trametes versicolor , NCBI accession XP_007369631.1 from  Dichomitus squalens , NCBI accession KIA75676.1 from  Aspergillus ustus , NCBI accession XP_001820867.2 from  Aspergillus oryzae , NCBI accession CEN60542.1 from  Aspergillus calidoustus , NCBI accession XP_009547469.1 from  Heterobasidion irregulare , NCBI accession KLO09124.1 from  Schizopora paradoxa , NCBI accession OJI95797.1 from  Aspergillus versicolor.    
     The sequence of EMD3766.1 was corrected by deleting the amino acids 261 to 266 present in the published sequence and probably resulting from incorrect splicing prediction (sequence EMD37666-B in table 1). Another sequence, ACg006372 was selected from the published annotated sequence of  Antrodia cinnamomea  (Lu et al., 2014,  Proc. Natl. Acad. Sci. USA.  111(44):E4743-52, (Dataset S1)). 
     The 15 putative terpene synthases amino acid sequences contain a class II terpene synthase-like motif with the consensus sequence D(V/M/L/F)D(T/S) as well as a class I terpene synthase-like motif with the consensus sequence DD(K/N/Q/R/S)xD (were x is a hydrophobic residue L, I, G, T or P). The class I and class II motifs are easily localized using an alignment of the amino acid sequences with the sequences of CvTps1 and LoTps1 ( FIG.  6   ). Such alignment can be made using for example the program Clustal W (Thompson J. D. et al., 1994,  Nucleic Acids Res.  22(22), 4673-80). In addition, the presence of a HAD-like hydrolase domain was identified in the N-terminal region of the 15 amino acid sequences (between positions 1 and 183 to 243 of the sequences) (Table 3). 
     The features of the above sequences thus suggest that the proteins contain a phosphatase or class I terpene synthase domain and a class II terpene synthase domain in the N-terminal and C-terminal region, respectively and thus have bifunctional protonation-initiated cyclization and ionization-initiated catalytic activities. Alignment of the sequences and pairwise comparisons (Table 2) of the above amino acid sequences showed a lowest sequence identity value of 37% and a highest value of 89% (without considering the two EMD37666.1 variants). Compared to CvTps1 and LoTps1, the closest sequences shared 85% identity and the most distant sequence only 42% identity. 
     
       
         
           
               
             
               
                 TABLE 1 
               
             
            
               
                   
               
               
                 List of selected sequences showing sequence homology with CyTps1 and LoTps1 
               
               
                 and containing a class I and a class II motifs. The source (species) of the 
               
               
                 sequences, SEQ ID NO, length of the sequence, sequence region containing the 
               
               
                 class I andclass II motifs, and positions of the class I and class II motifs 
               
               
                 are listed. The residues of class I and class II motifs are in bold. 
               
            
           
           
               
               
               
               
               
               
               
               
               
            
               
                   
                   
                   
                   
                 Putative 
                 Class 
                   
                 Class 
                   
               
               
                 Name or NCBI 
                   
                 Protein 
                 Length 
                 function 
                 I motif 
                 Class I 
                 II motif 
                 Class II 
               
               
                 accession 
                   
                 SEQ 
                 (amino 
                 (database 
                 region 
                 motif 
                 region 
                 motif 
               
               
                 number 
                 Source 
                 ID NO 
                 acids) 
                 annotation) 
                 sequence 
                 position 
                 sequence 
                 position 
               
               
                   
               
               
                 CvTps1 
                 
                   Cryptoporus 
                 
                  1 
                 525 
                   
                 VFV DDKLD   
                 168-172 
                 FPD DVDT T 
                 273-276 
               
               
                   
                 
                   volvatus 
                 
                   
                   
                   
                 NVA 
                   
                 S 
                   
               
               
                   
               
               
                 LoTps1 
                 
                   Laricifomes 
                 
                  5 
                 521 
                   
                 VFV DDKLD   
                 162-166 
                 FPD DMDT T 
                 267-270 
               
               
                   
                 
                   officinalis 
                 
                   
                   
                   
                 NVV 
                   
                 S 
                   
               
               
                   
               
               
                 OCH93767.1 
                 
                   Obba ribulosa 
                 
                  9 
                 527 
                 HAD-like 
                 VFV DDKID   
                 166-170 
                 FPD DLDT T 
                 271-274 
               
               
                   
                   
                   
                   
                 protein 
                 NVL 
                   
                 S 
                   
               
               
                   
               
               
                 EMD37666.1 
                 
                   Gelatoporia 
                 
                 12 
                 533 
                 hypothetical 
                 VFV DDKID   
                 166-170 
                 FPD DLDT T 
                 277-280 
               
               
                   
                 
                   subvermispora 
                 
                   
                   
                 protein 
                 NVL 
                   
                 S 
                   
               
               
                   
               
               
                 EMD37666-B 
                 
                   Gelatoporia 
                 
                 15 
                 528 
                 hypothetical 
                 VFV DDKID   
                 166-170 
                 FPD DLDT T 
                 271-274 
               
               
                   
                 
                   subvermispora 
                 
                   
                   
                 protein 
                 NVL 
                   
                 S 
                   
               
               
                   
               
               
                 XP_001217376.1 
                 
                   Aspergillus 
                 
                 17 
                 486 
                 Predicted 
                 MFID DKLE   
                 161-165 
                 FPD DMDT T 
                 267-270 
               
               
                   
                 
                   terreus 
                 
                   
                   
                 protein 
                 NVI 
                   
                 S 
                   
               
               
                   
               
               
                 OJJ98394.1 
                 
                   Aspergillus 
                 
                 20 
                 483 
                 Hypothetical 
                 VFV DDKTE   
                 162-166 
                 FPN DLDT T 
                 268-271 
               
               
                   
                 
                   aculeatus 
                 
                   
                   
                 protein 
                 NVL 
                   
                 S 
                   
               
               
                   
               
               
                 GAO87501.1 
                 
                   Aspergillus 
                 
                 23 
                 485 
                 alpha-D- 
                 IFI DDQLE   
                 167-171 
                 FPD DVDT T 
                 273-276 
               
               
                   
                 
                   udagawae 
                 
                   
                   
                 glucose-1- 
                 NVV 
                   
                 S 
                   
               
               
                   
                   
                   
                   
                 phosphate 
                   
                   
                   
                   
               
               
                   
                   
                   
                   
                 phosphatase 
                   
                   
                   
                   
               
               
                   
                   
                   
                   
                 YihX 
                   
                   
                   
                   
               
               
                   
               
               
                 XP_008034151.1 
                 
                   Trametes 
                 
                 26 
                 524 
                 HAD-like 
                 VFV DDKLD   
                 168-172 
                 FPD DVDT T 
                 273-276 
               
               
                   
                 
                   versicolor 
                 
                   
                   
                 protein 
                 NVV 
                   
                 S 
                   
               
               
                   
               
               
                 XP_007369631.1 
                 
                   Dichomitus 
                 
                 29 
                 527 
                 HAD-like 
                 VFV DDKLD   
                 168-172 
                 FPD DVDT T 
                 273-276 
               
               
                   
                 
                   squalens 
                 
                   
                   
                 protein 
                 NVA 
                   
                 S 
                   
               
               
                   
               
               
                 ACg006372 
                 
                   Antrodia 
                 
                 32 
                 496 
                 HAD-like 
                 VFVDDRIE 
                 179-183 
                 YPD DFDT T 
                 286-289 
               
               
                   
                 
                   cinnamomea 
                 
                   
                   
                 protein 
                 NVV 
                   
                 S 
                   
               
               
                   
               
               
                 KIA75676.1 
                 
                   Aspergillus 
                 
                 35 
                 543 
                 Hypothetical 
                 VFV DDNLE   
                 161-165 
                 FPD DMDT T 
                 267-270 
               
               
                   
                 
                   ustus 
                 
                   
                   
                 protein 
                 NVTS 
                   
                 S 
                   
               
               
                   
               
               
                 XP_001820867.2 
                 
                   Aspergillus 
                 
                 38 
                 477 
                 Hypothetical 
                 IFV DDQLE   
                 167-171 
                 FPD DVDT T 
                 273-276 
               
               
                   
                 
                   oryzae 
                 
                   
                   
                 protein 
                 NVIS 
                   
                 S 
                   
               
               
                   
               
               
                 CEN60542.1 
                 
                   Aspergillus 
                 
                 41 
                 528 
                 Hypothetical 
                 VFV DDNLD   
                 161-165 
                 FPD DLDT T 
                 267-270 
               
               
                   
                 
                   calidoustus 
                 
                   
                   
                 protein 
                 NVT 
                   
                 S 
                   
               
               
                   
               
               
                 XP_009547469.1 
                 
                   Heterobasidion 
                 
                 44 
                 531 
                 Hyopthetical 
                 VFV DDKGD   
                 166-170 
                 FPF DLDT T 
                 272-275 
               
               
                   
                 
                   irregulare 
                 
                   
                   
                 protein 
                 NVL 
                   
                 S 
                   
               
               
                   
               
               
                 KLO09124.1 
                 
                   Schizopora 
                 
                 47 
                 518 
                 HAD-like 
                 VFV DDKLD   
                 209-213 
                 FPC DLDS T 
                 315-318 
               
               
                   
                 
                   paradoxa 
                 
                   
                   
                 protein 
                 NVI 
                   
                 S 
                   
               
               
                   
               
               
                 OJI95797.1 
                 
                   Aspergillus 
                 
                 50 
                 507 
                 hypothetical 
                 VFI DDSPE   
                 163-167 
                 FPN DLDT T 
                 269-272 
               
               
                   
                 
                   versicolor 
                 
                   
                   
                 protein 
                 NIL 
                   
                 S 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 2 
               
               
                   
               
               
                 Pairwise sequence comparison of the selected putative bifunctional terpene synthases. 
               
               
                 The percentage of sequence identity is listed for each pairwise comparison. 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                 CvTps1 
                 LoTps1 
                 OCH93676.1 
                 EMD37666.1 
                 EMD37666-B 
                 XP_001217376.1 
               
               
                   
               
               
                 CvTps1 
                 100 
                 71 
                 60 
                 60 
                 60 
                 42 
               
               
                 LoTps1 
                 72 
                 100 
                 60 
                 58 
                 59 
                 43 
               
               
                 OCH93767.1 
                 61 
                 60 
                 100 
                 88 
                 89 
                 43 
               
               
                 EMD37666-B 
                 60 
                 59 
                 89 
                 99 
                 100 
                 43 
               
               
                 EMD37666.1 
                 60 
                 58 
                 88 
                 100 
                 99 
                 43 
               
               
                 XP_001217376.1 
                 42 
                 43 
                 43 
                 43 
                 43 
                 100 
               
               
                 OJJ98394.1 
                 47 
                 48 
                 47 
                 47 
                 47 
                 54 
               
               
                 GAO87501.1 
                 46 
                 45 
                 47 
                 47 
                 47 
                 42 
               
               
                 XP_008034151.1 
                 73 
                 85 
                 62 
                 60 
                 61 
                 43 
               
               
                 XP_007369631.1 
                 84 
                 74 
                 61 
                 60 
                 61 
                 44 
               
               
                 ACg006372 
                 45 
                 48 
                 47 
                 46 
                 47 
                 37 
               
               
                 KIA75676.1 
                 44 
                 43 
                 46 
                 45 
                 46 
                 45 
               
               
                 XP_001820867.2 
                 45 
                 44 
                 44 
                 43 
                 44 
                 41 
               
               
                 CEN60542.1 
                 44 
                 45 
                 45 
                 46 
                 46 
                 44 
               
               
                 XP_009547469.1 
                 54 
                 55 
                 54 
                 53 
                 54 
                 43 
               
               
                 KLO09124.1 
                 51 
                 53 
                 53 
                 51 
                 52 
                 39 
               
               
                 OJI95797.1 
                 45 
                 43 
                 45 
                 45 
                 46 
                 55 
               
               
                   
               
               
                   
                 OJJ98394.1 
                 GAO87501.1 
                 XP_008034151.1 
                 XP_007369631.1 
                 ACg006372 
                 KIA75676.1 
               
               
                   
               
               
                 CvTps1 
                 47 
                 46 
                 72 
                 84 
                 45 
                 44 
               
               
                 LoTps1 
                 48 
                 45 
                 85 
                 74 
                 48 
                 43 
               
               
                 OCH93767.1 
                 47 
                 47 
                 62 
                 62 
                 48 
                 46 
               
               
                 EMD37666-B 
                 47 
                 47 
                 61 
                 62 
                 47 
                 46 
               
               
                 EMD37666.1 
                 47 
                 47 
                 60 
                 61 
                 46 
                 45 
               
               
                 XP_001217376.1 
                 54 
                 42 
                 43 
                 44 
                 37 
                 45 
               
               
                 OJJ98394.1 
                 100 
                 44 
                 47 
                 48 
                 41 
                 48 
               
               
                 GAO87501.1 
                 44 
                 100 
                 46 
                 47 
                 45 
                 46 
               
               
                 XP_008034151.1 
                 47 
                 46 
                 100 
                 77 
                 49 
                 44 
               
               
                 XP_007369631.1 
                 48 
                 48 
                 77 
                 100 
                 48 
                 45 
               
               
                 ACg006372 
                 41 
                 45 
                 48 
                 48 
                 100 
                 42 
               
               
                 KIA75676.1 
                 48 
                 46 
                 44 
                 43 
                 42 
                 100 
               
               
                 XP_001820867.2 
                 44 
                 69 
                 45 
                 46 
                 44 
                 47 
               
               
                 CEN60542.1 
                 49 
                 43 
                 45 
                 45 
                 40 
                 72 
               
               
                 XP_009547469.1 
                 45 
                 47 
                 55 
                 55 
                 49 
                 44 
               
               
                 KLO09124.1 
                 44 
                 45 
                 51 
                 51 
                 55 
                 45 
               
               
                 OJI95797.1 
                 56 
                 43 
                 44 
                 46 
                 39 
                 45 
               
               
                   
               
               
                   
                   
                 XP_001820867.2 
                 CEN60542.1 
                 XP_009547469.1 
                 KLO09124.1 
                 OJI95797.1 
               
               
                   
               
               
                   
                 CvTps1 
                 45 
                 44 
                 55 
                 52 
                 45 
               
               
                   
                 LoTps1 
                 44 
                 45 
                 55 
                 53 
                 43 
               
               
                   
                 OCH93767.1 
                 44 
                 45 
                 54 
                 53 
                 45 
               
               
                   
                 EMD37666-B 
                 44 
                 46 
                 58 
                 52 
                 46 
               
               
                   
                 EMD37666.1 
                 43 
                 46 
                 57 
                 52 
                 45 
               
               
                   
                 XP_001217376.1 
                 41 
                 44 
                 43 
                 39 
                 55 
               
               
                   
                 OJJ98394.1 
                 44 
                 49 
                 45 
                 44 
                 56 
               
               
                   
                 GAO87501.1 
                 69 
                 43 
                 47 
                 45 
                 43 
               
               
                   
                 XP_008034151.1 
                 45 
                 45 
                 55 
                 52 
                 44 
               
               
                   
                 XP_007369631.1 
                 46 
                 46 
                 56 
                 52 
                 46 
               
               
                   
                 ACg006372 
                 44 
                 40 
                 49 
                 55 
                 39 
               
               
                   
                 KIA75676.1 
                 46 
                 72 
                 44 
                 45 
                 45 
               
               
                   
                 XP_001820867.2 
                 100 
                 47 
                 46 
                 42 
                 41 
               
               
                   
                 CEN60542.1 
                 47 
                 100 
                 48 
                 43 
                 45 
               
               
                   
                 XP_009547469.1 
                 46 
                 48 
                 100 
                 54 
                 47 
               
               
                   
                 KLO09124.1 
                 42 
                 44 
                 54 
                 100 
                 44 
               
               
                   
                 OJI95797.1 
                 41 
                 45 
                 47 
                 44 
                 100 
               
               
                   
               
            
           
         
       
     
     Example 6 
     Functional Characterisation of Other Fungal Hydrolase-Like Bifunctional Sesquiterpene Synthases. 
     The cDNAs encoding for the 15 new putative synthases described in Example 5 were codon optimized and cloned in the pJ401  E. coli  expression plasmid (pJ401, ATUM, Newark, California). The enzymes were functionally characterized in  E. coli  cells engineered to overproduce farnesyl-diphosphate (FPP) following the procedure described in example 4. Amongst the 15 new recombinant enzymes, 9 produced (+)-albicanol as major product: OCH93767.1, EMD37666.1, EMD37666-B, XP_001217376.1, OJJ98394.1, GAO87501.1 XP_008034151.1, XP_007369631.1 and ACg006372 ( FIGS.  7  and  8   ). These results confirm that these enzymes have bifunctional albicanol synthase enzymatic activities. 
     The 6 other new synthases, KIA75676.1, XP_001820867.2, CEN60542.1, XP_009547469.1 and KLO09124.1 and OJI95797.1, produced (−)-drimenol as major product ( FIG.  9   ). Drimenol is produced by a mechanism similar to the formation of albicanol and involving a class II followed by class I enzymatic activity. 
     For XP_001820867.2, the formation of a significant amount of trans-farnesol was detected ( FIG.  9   ). This was likely due to lower enzymatic activity of this synthase and thus a significant amount of the farnesyl-diphosphate produced in the bacterial cell was not converted to drimenol. This excess farnesyl-diphosphate was hydrolyzed by the endogenous alkaline phosphatase and the trans-farnesol produced was released in the growing medium. 
     The two Pfam domains identified in CvTps1, i.e. PF13419.5 and PF13242.5 as described in Example 3, are also found in these new putative synthases as shown in Table 3. 
     
       
         
           
               
             
               
                 TABLE 3 
               
             
            
               
                   
               
               
                 Locations of the haloacid dehalogenase-like hydrolase domain 
               
               
                 in each of the bifunctional synhtases described herein. 
               
            
           
           
               
               
               
               
               
            
               
                   
                   
                   
                 HAD-like 
                 HAD-like 
               
               
                   
                   
                   
                 hydrolase 
                 hydrolase 
               
               
                 Ezyme 
                 Length 
                 Product 
                 domain start 
                 domain end 
               
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 CvTps1 
                 525 
                 Albicanol 
                 115 
                 187 
               
               
                 LoTps1 
                 521 
                 Albicanol 
                 62 
                 181 
               
               
                 OCH93767.1 
                 527 
                 Albicanol 
                 51 
                 185 
               
               
                 EMD37666.1 
                 533 
                 Albicanol 
                 54 
                 185 
               
               
                 EMD37555-B 
                 528 
                 Albicanol 
                 54 
                 185 
               
               
                 XP_001217376.1 
                 486 
                 Albicanol 
                 25 
                 181 
               
               
                 OJJ98394.1 
                 483 
                 Albicanol 
                 25 
                 181 
               
               
                 GAO87501.1 
                 485 
                 Albicanol 
                 34 
                 186 
               
               
                 XP_008034151.1 
                 524 
                 Albicanol 
                 60 
                 187 
               
               
                 XP_007369631.1 
                 527 
                 Albicanol 
                 120 
                 187 
               
               
                 ACg006372 
                 496 
                 Albicanol 
                 60 
                 198 
               
               
                 KIA75676.1 
                 543 
                 Drimenol 
                 43 
                 180 
               
               
                 XP_001820867.2 
                 477 
                 Drimenol 
                 12 
                 186 
               
               
                 CEN60542.1 
                 528 
                 Drimenol 
                 20 
                 180 
               
               
                 XP_009547469.1 
                 531 
                 Drimenol 
                 77 
                 185 
               
               
                 KLO09124.1 
                 518 
                 Drimenol 
                 119 
                 228 
               
               
                 OJI95797 
                 507 
                 Drimenol 
                 48 
                 180 
               
               
                   
               
            
           
         
       
     
     Example 7 
     In-vitro assays. 
     Crude protein extracts containing the recombinant terpene synthases are prepared using KRX  E. coli  cells (Promega) or BL21 Star™ (DE3)  E. coli  (ThermoFisher). Single colonies of cells transformed with the expression plasmid are used to inoculate 5 ml LB medium. After 5 to 6 hours incubation at 37° C., the cultures are transferred to a 25° C. incubator and left 1 hour for equilibration. Expression of the protein is then induced by the addition of 1 mM IPTG and the cultures are incubated over-night at 25° C. The next day, the cells are collected by centrifugation, resuspended in 0.1 volume of 50 mM MOPSO pH 7 (3-Morpholino-2-hydroxypropanesulfonic acid (sigma-Aldrich), 10% glycerol and lyzed by sonication. The extracts are cleared by centrifugation (30 min at 20,000 g) and the supernatants containing the soluble proteins are used for further experiments. 
     These crude  E. coli  protein extracts containing the recombinant protein are used for the characterization of the enzymatic activities. The assays are performed in glass tubes in 2 mL of 50 mM MOPSO pH 7, 10% glycerol, 1 mM DTT, 15 mM MgCl2 in the presence of 80 μM of farnesyl-diphosphate (FPP, Sigma) and 0.1 to 0.5 mg of crude protein. The tubes are incubated 12 to 24 hours at 25° C. and extracted twice with one volume of pentane. After concentration under a nitrogen flux, the extracts are analyzed by GC-MS as described in Example 4 and compared to extracts from assays with control proteins. The aqueous phase is then treated by alkaline phosphatase (Sigma, 6 units/ml), followed by extraction with pentane and GC-MS analysis. 
     The assays without alkaline phosphatase treatment allow detecting and identifying the sesquiterpene compounds (hydrocarbons and oxygenated sesquiterpenes) present in the assay and produced by the recombinant enzymes. Albicanyl-diphosphate or drimenyl-diphosphate compounds are not soluble in the organic solvent and are thus not detected in the GC-MS analysis. Following the alkaline phosphatase treatment, allylic diphosphate bounds are cleaved and when albicanyl-diphosphate or drimenyl-diphosphate compounds are present, the sequiterpene moiety is released, extracted in the solvent phase and detected in the GC-MS analysis. This example allows to differentiate enzymes having only class II terpene synthase activity (such as AstC, NCBI accession XP_001822013.2, Shinohara Y. et al., 2016,  Sci Rep.  6, 32865) from enzyme having class II terpene synthase-like activity and class I (phosphatase) activity such as CvTps1 and LoTps1. 
     Example 8 
     Co-Expression of Terpene Synthases and Phosphatases. 
     In Shinohara Y. et al., 2016,  Sci Rep.  6, 32865 a drimane terpene synthase (AstC, NCBI accession XP_001822013.2) is described. This synthase produce a drimane sequiterpene bound to a diphosphate moiety. To produce a free drimane sesquiterpene the AstC enzyme must be combined with enzymes having phosphatase activity. The publication also describes two phosphatases AstI and AstK (XP_001822007.1 and XP_003189903.1) catalyzing the sequential cleavage of the phosphate moiety of the drimane-diphosphate produced by AstC. 
     Synthetic operons were designed to co-express the CvTps1 protein with the AstI and AstK proteins. The synthetic operon contains the optimized cDNA encoding for each of the 3 proteins separated by a ribosome binding sequence (RBS). A similar operon was designed to co-express AstC with AstI and AstK. The operons were synthesized and cloned in the pJ401 expression plasmid (ATUM, Newark, Calif.).  E coli  cells were co-transformed with these expression plasmids and with the pACYC-29258-4506 plasmid (Example 4) and the cells were cultivated under conditions to produce sesquiterpenes as described in Example 4. The sequiterpenes produced were analyzed by GCMS as described in Example 4 and compared to the sequiterpene profile of cells expression only CvTps1 or AstC. 
     As shown  FIG.  10   , with AstC a significant higher amount (78-fold increase) of sesquiterpene is produced when the enzyme is co-expressed with enzymes (AstI and AstK) having phosphatase activity. Typical concentrations of drimane sesquiterpene in the  E. coli  cultures were 2,600 mg/ml with cells expressing AstC, AstI and AstK and 34 mg/ml with cells expressing AstC alone. 
     In contrast, with CvTps1 no significant difference is observed for the amount of drimane sesquiterpene produced when the enzyme is expressed alone (1,000 mg/ml) or co-expressed with the phosphatases (1,200 mg/ml). This experiment confirms that the CvTps1 polypeptide, in contrast to the previously known AstC synthase, carries phosphatase activity in addition to the cyclase activity (i.e. class I and class II terpene synthase activity). 
     Example 9 
     Functional Characterisation of XP 006461126.1. 
     The NCBI accession No XP 006461126.1 from Agaricus bisporus was selected using the method described in Example 5. The XP006461126.1 amino acid (SEQ ID NO: 63) shared 48.9% and 48.1% identity with the CvTps1 and LoTps1 amino acid sequences, respectively. The XP_006461126.1 contains a class II terpene synthase-like motif (DLDT) (part of SEQ ID NO: 56) located between position 278 and 271 and a class I terpene synthase-like motif (DDKLE) (part of SEQ ID NO: 55) located at position 167 to 171. The amino acid contains also motifs characteristic of of the Haloacid dehalogenase-like hydrolase superfamily in the N-terminal region. 
     The cDNA encoding for XP 006461126.1 was codon optimized and cloned in the pJ401  E. coli  expression plasmid (pJ401, ATUM, Newark, Calif.). The enzyme was functionally characterized in  E. coli  cells engineered to overproduce farnesyl-diphosphate (FPP) following the procedure described in Example 4. The results show that XP 006461126.1 is a bifunctional drimenol synthase producing drimenol as major compound ( FIG.  11   ). 
     Example 10 
     In vivo drimane sesquiterpene production in  Saccharomyces cerevisiae  cells using fungal hydrolase-like bifunctional sesquiterpene synthases. 
     Different hydrolase-like bifunctional sesquiterpene synthases were evaluated for the production of drimane sesquiterpenes in  S. cerevisiae  cells. The selected synthases were:
         XP_007369631.1, NCBI accession No XP_007369631.1, from  Dichomitus squalens      XP_006461126, NCBI accession No XP_006461126, from  Agaricus bisporus      LoTps1, SEQ ID NO: 5, from  Laricifomes officinalis      EMD37666.1, NCBI accession No EMD37666.1, from  Gelatoporia subvermispora      XP_001217376.1, NCBI accession No XP_001217376.1, from  Aspergillus terreus          

     The codon usage of the cDNA encoding for the different synthases was modified for optimal expression in  S. cerevisiae  (SEQ ID NO: 66, SEQ ID NO: 67, SEQ ID NO: 68, SEQ ID NO: 69, SEQ ID NO: 70). 
     For expression of the different genes in  S. cerevisiae , a set of plasmids were constructed in vivo using yeast endogenous homologous recombination as previously described in Kuijpers et al., Microb Cell Fact., 2013, 12:47. Each plasmid is composed by five DNA fragments which were used for  S. cerevisiae  co-transformation. The fragments were:
         Fragment a: LEU2 yeast marker, constructed by PCR using the primers 5′-AGGTGCAGTTCGCGTGCAATTATAACGTCGTGGCAACTGTTATCAGTCGTACC GCGCCATTCGACTACGTCGTAAGGCC-3′ (SEQ ID NO: 71) and 5′-TCGTGGTCAAGGCGTGCAATTCTCAACACGAGAGTGATTCTTCGGCGTTGTTG CTGACCATCGACGGTCGAGGAGAACTT -3′ (SEQ ID NO: 72) with the plasmid pESC-LEU (Agilent Technologies, California, USA) as template;   Fragment b: AmpR  E. coli  marker, constructed by PCR using the primers 5′-TGGTCAGCAACAACGCCGAAGAATCACTCTCGTGTTGAGAATTGCACGCCTT GACCACGACACGTTAAGGGATTTTGGTCATGAG-3′ (SEQ ID NO: 73) and 5′-AACGCGTACCCTAAGTACGGCACCACAGTGACTATGCAGTCCGCACTTTGCC AATGCCAAAAATGTGCGCGGAACCCCTA-3′ (SEQ ID NO: 74) with the plasmid pESC-URA as template;   Fragment c: Yeast origin of replication, obtained by PCR using the primers 5′-TTGGCATTGGCAAAGTGCGGACTGCATAGTCACTGTGGTGCCGTACTTAGGG TACGCGTTCCTGAACGAAGCATCTGTGCTTCA-3′ (SEQ ID NO: 75) and 5′-CCGAGATGCCAAAGGATAGGTGCTATGTTGATGACTACGACACAGAACTGCG GGTGACATAATGATAGCATTGAAGGATGAGACT-3′ (SEQ ID NO: 76) with pESC-URA as template;   Fragment d:  E. coli  replication origin, obtained by PCR using the primers 5′-ATGTCACCCGCAGTTCTGTGTCGTAGTCATCAACATAGCACCTATCCTTTGGC ATCTCGGTGAGCAAAAGGCCAGCAAAAGG-3′ (SEQ ID NO: 77) and 5′-CTCAGATGTACGGTGATCGCCACCATGTGACGGAAGCTATCCTGACAGTGTA GCAAGTGCTGAGCGTCAGACCCCGTAGAA-3′ (SEQ ID NO: 78) with the plasmid pESC-URA as template and   Fragment e: A fragment composed by the last 60 nucleotides of the fragment “d”, 200 nucleotides downstream the stop codon of the yeast gene PGK1, one of the hydrolase-like bifunctional sesquiterpene synthase coding sequences tested, codon optimized for its expression in  S. cerevisiae , the promoter of GAL1 and 60 nucleotides corresponding to the beginning of the fragment “a”. These fragments were obtained by DNA synthesis (ATUM, Newark, Calif.).       

     To increase the level of endogenous farnesyl-diphosphate (FPP) pool in  S. cerevisiae  cells, an extra copy of all the yeast endogenous genes involved in the mevalonate pathway, from ERG10 coding for acetyl-CoA C-acetyltransferase to ERG20 coding for FPP synthetase, were integrated in the genome of the  S. cerevisiae  strain CEN.PK2-1C (Euroscarf, Frankfurt, Germany) under the control of galactose-inducible promoters, similarly as described in Paddon et al.,  Nature,  2013, 496:528-532. Briefly, three cassettes were integrated in the LEU2, TRP1 and URA3 loci respectively. A first cassette containing the genes ERG20 and a truncated HMG1 (tHMG1 as described in Donald et al.,  Proc Natl Acad Sci USA,  1997, 109:E111-8) under the control of the bidirectional promoter of GAL10/GAL1 and the genes ERG19 and ERG13 also under the control of GAL10/GAL1 promoter, the cassette was flanked by two 100 nucleotides regions corresponding to the up- and down-stream sections of LEU2. A second cassette where the genes IDI1 and tHMG1 were under the control of the GAL10/GAL1 promoter and the gene ERG13 under the control of the promoter region of GAL7, the cassette was flanked by two 100 nucleotides regions corresponding to the up- and down-stream sections of TRP1. A third cassette with the genes ERG10, ERG12, tHMG1 and ERG8, all under the control of GAL10/GAL1 promoters, the cassette was flanked by two 100 nucleotides regions corresponding to the up- and down-stream sections of URA3. All genes in the three cassettes included 200 nucleotides of their own terminator regions. Also, an extra copy of GAL4 under the control of a mutated version of its own promoter, as described in Griggs and Johnston,  Proc Natl Acad Sci USA,  1991, 88:8597-8601, was integrated upstream the ERG9 promoter region. In addition, the endogenous promoter of ERG9 was replaced by the yeast promoter region of CTR3 generating the strain YST035. Finally, YST035 was mated with the strain CEN.PK2-1D (Euroscarf, Frankfurt, Germany) obtaining a diploid strain termed YST045. 
     YST045 was transformed with the fragments required for in vivo plasmid assembly. Yeast transformations were performed with the lithium acetate protocol as described in Gietz and Woods,  Methods Enzymol.,  2002, 350:87-96. Transformation mixtures were plated on SmLeu-media containing 6.7 g/L of Yeast Nitrogen Base without amino acids (BD Difco, New Jersey, USA), 1.6 g/L Dropout supplement without leucine (Sigma Aldrich, Missouri, USA), 20 g/L glucose and 20 g/L agar. Plates were incubated for 3-4 days at 30° C. Individual colonies were used to produce drimane sesquiterpenes in tubes or shake flasks containing media as described in Westfall et al.,  Proc Natl Acad Sci USA,  2012, 109:E111-118 and mineral oil ((2705-01, J.T. Baker, Avantor Performance Materials, Inc. Center Valley, Pa., USA) as organic overlay. Under these culture conditions, albicanol or drimenol were produced with all hydrolase-like bifunctional sesquiterpene synthases tested. The production of drimane sesquiterpenes was identified using GC-MS analysis and quantified by GC-FID (see  FIG.  12   ) with an internal standard. The table below shows the quantities of drimane sesquiterpene produced relative to the quantity obtained by the synthase XP 007369631.1 (under these experimental conditions, the concentration of drimane sesquiterpene produced by cells expressing XP 007369631.1 was 805 to 854 mg/L, the highest quantity produced). 
     
       
         
           
               
               
               
               
             
               
                   
                   
               
               
                   
                   
                   
                 Relative quantity of drimane 
               
               
                   
                 Enzyme 
                 Product 
                 sesquiterpene produced 
               
               
                   
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 XP_007369631.1 
                 Albicanol 
                 100 
               
               
                   
                 XP_006461126 
                 Drimenol 
                 39 
               
               
                   
                 LoTps1 
                 Albicanol 
                 31 
               
               
                   
                 EMD37666.1 
                 Albicanol 
                 23 
               
               
                   
                 XP_001217376.1 
                 Albicanol 
                 3 
               
               
                   
                   
               
            
           
         
       
     
     
       
         
           
               
               
            
               
                 Sequence Listings 
                   
               
               
                 CvTps1 
               
               
                 - CvTps1 Protein 
               
               
                 SEQ ID NO: 1 
                   
               
               
                 MTTIHRRHTTLILDLGDVLFRWSPKTETAIPPRQLKEILTSVTWFEYERGQISQTECYERCAAEFKVDPLVIAEAFKQARES 
                   
               
               
                   
               
               
                 LRPNKAFIALIRELRHQMHGDLTVLALSNISLPDYEYIMSLSSDWATVFNRVFPSALVGERKPHLGCYRKVISEMSLEPQT 
               
               
                   
               
               
                 TVFVDDKLDNVASARSLGMHGIVFDNEANVFRQLRNIFGNPVSRGQGYLRKHAGKLESSTDNGLTFEENFTQLIIYEVT 
               
               
                   
               
               
                 QDRSLITLSECPRTWNFFRGQPLFSESFPDDVDTTSVALTVLQPDRALVDSILDQMLEYVDADGIMQTYFDSSRPRIDPF 
               
               
                   
               
               
                 VCVNVLSLFYANGRGRELPHTLEWVYEVLLHRAYHGGSRYYLSPDCFLFFMSRLLKRANDSALQARFRPLFMERVKERV 
               
               
                   
               
               
                 GAAGDSMDLAFRILAAATIGVHCPQDLERLAAAQCEDGGWDMCWFYAFGSTGIKAGNRGLTTALAVAAIRTALGRPP 
               
               
                   
               
               
                 SPSPSNISSSSKLDAPNSFLGIPRPTSPIRFGELFRSWRKNKPTAKSQ 
               
               
                   
               
               
                 - CvTps1 transcript (including non-coding sequences) 
               
               
                 SEQ ID NO: 2 
                   
               
               
                 CATCCCGCCTTTTGAGCATGGCACACAAACAGCCTTTAAGGAGCTCCTTGGTTGCCTAGTCATGCCTCCACCTGCCC 
                   
               
               
                   
               
               
                 CCTCCTCACTCATCCCCTCGCATCCTAAAACATGACCACGATTCACCGTCGGCACACCACTCTCATCTTGGACCTCG 
               
               
                   
               
               
                 GCGACGTCCTCTTCCGCTGGTCACCAAAGACCGAGACCGCCATCCCCCCTCGGCAGCTTAAGGAGATACTTACCTC 
               
               
                   
               
               
                 CGTCACCTGGTTCGAGTACGAACGAGGCCAGATATCCCAAACAGAATGTTACGAACGATGCGCTGCAGAATTCAA 
               
               
                   
               
               
                 AGTCGACCCCTTAGTGATCGCTGAAGCCTTCAAGCAAGCTCGCGAGTCATTACGGCCCAACAAAGCGTTCATCGCC 
               
               
                   
               
               
                 TTGATTCGCGAACTTCGCCATCAAATGCATGGAGACCTCACGGTCCTCGCCCTTTCCAACATTTCCCTCCCCGATTAC 
               
               
                   
               
               
                 GAATATATCATGTCTCTGAGCTCGGATTGGGCAACCGTCTTCAATCGCGTATTCCCTTCTGCACTTGTTGGCGAGCG 
               
               
                   
               
               
                 AAAACCCCATCTGGGGTGCTACCGCAAGGTCATTTCGGAGATGAGCTTGGAACCCCAGACAACCGTATTTGTCGAT 
               
               
                   
               
               
                 GATAAGCTAGACAACGTCGCCTCTGCTCGCTCACTTGGCATGCACGGCATCGTATTCGACAACGAAGCCAATGTCT 
               
               
                   
               
               
                 TCCGGCAACTGCGCAATATCTTCGGGAATCCGGTTAGCCGCGGTCAAGGCTATCTTCGCAAGCATGCCGGAAAGC 
               
               
                   
               
               
                 TTGAGTCTTCTACCGACAATGGCTTGACCTTTGAGGAGAACTTCACCCAGCTCATCATCTACGAGGTGACACAAGA 
               
               
                   
               
               
                 CAGGAGTCTCATCACGCTCTCAGAATGTCCCCGTACCTGGAATTTCTTTCGAGGTCAACCGCTCTTCTCGGAGTCTT 
               
               
                   
               
               
                 TCCCGGATGATGTGGACACAACATCCGTGGCATTGACAGTACTACAACCCGATAGAGCGCTCGTTGATTCTATTCT 
               
               
                   
               
               
                 AGACCAAATGCTTGAATATGTTGACGCCGACGGCATCATGCAGACATACTTCGACAGCTCGCGACCACGCATAGA 
               
               
                   
               
               
                 CCCTTTTGTTTGCGTCAATGTGCTTTCTCTGTTCTACGCAAACGGCCGGGGTCGGGAGCTCCCTCACACACTGGAGT 
               
               
                   
               
               
                 GGGTCTATGAAGTACTCCTGCATCGCGCCTACCATGGAGGCTCACGTTACTACCTATCACCGGACTGCTTTTTATTC 
               
               
                   
               
               
                 TTCATGAGCCGCTTGCTCAAGCGCGCCAACGACTCGGCCCTCCAGGCTCGGTTCCGCCCACTGTTCATGGAGAGAG 
               
               
                   
               
               
                 TGAAAGAACGAGTAGGGGCAGCCGGAGACTCAATGGACCTGGCCTTCCGCATCCTCGCCGCGGCTACCATTGGCG 
               
               
                   
               
               
                 TCCATTGCCCCCAAGATCTAGAAAGATTGGCCGCCGCGCAATGCGAGGACGGTGGATGGGACATGTGCTGGTTCT 
               
               
                   
               
               
                 ACGCGTTCGGGTCGACAGGTATCAAGGCGGGCAACCGCGGCCTCACCACGGCCCTTGCCGTCGCAGCTATACGAA 
               
               
                   
               
               
                 CCGCCCTCGGGCGCCCCCCCTCTCCCAGCCCCTCCAACATCTCGTCGTCGTCGAAGCTCGACGCTCCCAACAGCTTC 
               
               
                   
               
               
                 TTGGGCATCCCGCGCCCAACCAGCCCCATTCGCTTTGGCGAACTTTTCCGTTCCTGGCGAAAGAACAAACCGACCG 
               
               
                   
               
               
                 CAAAATCTCAATGAATCTCAGGTTCTCGTGCTCTCGTGCTATCTTCGTACTTATGCTACTCGACATTACCCGTCGCTG 
               
               
                   
               
               
                 TCTACAATGATACGGGTACTTTGATGAAACTGTAGATGTATTTGTATCATATTGACCTCCATCCATAGTCACCTAGC 
               
               
                   
               
               
                 TACTGTTCGTGTTATCACCTGTTGCTGTTATATGATACAAGATGCCCAAACGAGAATGTAGAAATGTTCCGTACACT 
               
               
                   
               
               
                 TGTGTACCTGTGATGAAGCTACATAGGCCTTCAATCGATCACTTGGTCC 
               
               
                   
               
               
                 - CvTps1 cDNA 
               
               
                 SEQ ID NO: 3 
                   
               
               
                 ATGACCACGATTCACCGTCGGCACACCACTCTCATCTTGGACCTCGGCGACGTCCTCTTCCGCTGGTCACCAAAGAC 
                   
               
               
                   
               
               
                 CGAGACCGCCATCCCCCCTCGGCAGCTTAAGGAGATACTTACCTCCGTCACCTGGTTCGAGTACGAACGAGGCCA 
               
               
                   
               
               
                 GATATCCCAAACAGAATGTTACGAACGATGCGCTGCAGAATTCAAAGTCGACCCCTTAGTGATCGCTGAAGCCTTC 
               
               
                   
               
               
                 AAGCAAGCTCGCGAGTCATTACGGCCCAACAAAGCGTTCATCGCCTTGATTCGCGAACTTCGCCATCAAATGCATG 
               
               
                   
               
               
                 GAGACCTCACGGTCCTCGCCCTTTCCAACATTTCCCTCCCCGATTACGAATATATCATGTCTCTGAGCTCGGATTGG 
               
               
                   
               
               
                 GCAACCGTCTTCAATCGCGTATTCCCTTCTGCACTTGTTGGCGAGCGAAAACCCCATCTGGGGTGCTACCGCAAGG 
               
               
                   
               
               
                 TCATTTCGGAGATGAGCTTGGAACCCCAGACAACCGTATTTGTCGATGATAAGCTAGACAACGTCGCCTCTGCTCG 
               
               
                   
               
               
                 CTCACTTGGCATGCACGGCATCGTATTCGACAACGAAGCCAATGTCTTCCGGCAACTGCGCAATATCTTCGGGAAT 
               
               
                   
               
               
                 CCGGTTAGCCGCGGTCAAGGCTATCTTCGCAAGCATGCCGGAAAGCTTGAGTCTTCTACCGACAATGGCTTGACCT 
               
               
                   
               
               
                 TTGAGGAGAACTTCACCCAGCTCATCATCTACGAGGTGACACAAGACAGGAGTCTCATCACGCTCTCAGAATGTCC 
               
               
                   
               
               
                 CCGTACCTGGAATTTCTTTCGAGGTCAACCGCTCTTCTCGGAGTCTTTCCCGGATGATGTGGACACAACATCCGTGG 
               
               
                   
               
               
                 CATTGACAGTACTACAACCCGATAGAGCGCTCGTTGATTCTATTCTAGACCAAATGCTTGAATATGTTGACGCCGA 
               
               
                   
               
               
                 CGGCATCATGCAGACATACTTCGACAGCTCGCGACCACGCATAGACCCTTTTGTTTGCGTCAATGTGCTTTCTCTGT 
               
               
                   
               
               
                 TCTACGCAAACGGCCGGGGTCGGGAGCTCCCTCACACACTGGAGTGGGTCTATGAAGTACTCCTGCATCGCGCCT 
               
               
                   
               
               
                 ACCATGGAGGCTCACGTTACTACCTATCACCGGACTGCTTTTTATTCTTCATGAGCCGCTTGCTCAAGCGCGCCAAC 
               
               
                   
               
               
                 GACTCGGCCCTCCAGGCTCGGTTCCGCCCACTGTTCATGGAGAGAGTGAAAGAACGAGTAGGGGCAGCCGGAGA 
               
               
                   
               
               
                 CTCAATGGACCTGGCCTTCCGCATCCTCGCCGCGGCTACCATTGGCGTCCATTGCCCCCAAGATCTAGAAAGATTG 
               
               
                   
               
               
                 GCCGCCGCGCAATGCGAGGACGGTGGATGGGACATGTGCTGGTTCTACGCGTTCGGGTCGACAGGTATCAAGGC 
               
               
                   
               
               
                 GGGCAACCGCGGCCTCACCACGGCCCTTGCCGTCGCAGCTATACGAACCGCCCTCGGGCGCCCCCCCTCTCCCAGC 
               
               
                   
               
               
                 CCCTCCAACATCTCGTCGTCGTCGAAGCTCGACGCTCCCAACAGCTTCTTGGGCATCCCGCGCCCAACCAGCCCCAT 
               
               
                   
               
               
                 TCGCTTTGGCGAACTTTTCCGTTCCTGGCGAAAGAACAAACCGACCGCAAAATCTCAATGA 
               
               
                   
               
               
                 - CvTps1 optimized cDNA 
               
               
                 SEQ ID NO: 4 
                   
               
               
                 ATGACTACGATCCACCGCCGCCATACTACGCTGATCCTGGACCTGGGTGATGTTCTGTTCCGCTGGTCCCCGAAAA 
                   
               
               
                   
               
               
                 CCGAAACCGCAATTCCGCCTCGTCAGCTGAAAGAAATCTTGACCAGCGTTACCTGGTTCGAGTATGAGCGTGGCCA 
               
               
                   
               
               
                 AATTAGCCAGACCGAATGCTACGAGCGTTGTGCTGCCGAGTTTAAAGTTGATCCGCTGGTTATTGCCGAAGCGTTT 
               
               
                   
               
               
                 AAACAAGCGCGTGAAAGCCTGCGTCCGAACAAAGCGTTTATCGCGTTGATCCGTGAGTTGCGCCACCAGATGCAT 
               
               
                   
               
               
                 GGTGACCTGACGGTCCTGGCACTGAGCAACATTAGCCTGCCTGATTATGAGTACATTATGTCGCTGAGCTCCGATT 
               
               
                   
               
               
                 GGGCGACGGTCTTTAATCGCGTGTTTCCGAGCGCACTGGTGGGTGAGCGTAAGCCACACCTGGGTTGCTACCGCA 
               
               
                   
               
               
                 AGGTCATCAGCGAGATGTCTCTGGAGCCGCAGACCACGGTTTTCGTCGATGACAAACTGGACAATGTCGCAAGCG 
               
               
                   
               
               
                 CTCGTAGCCTGGGCATGCATGGCATCGTGTTCGACAACGAAGCGAACGTTTTTCGTCAGCTGCGTAATATCTTCGG 
               
               
                   
               
               
                 TAACCCGGTTAGCCGCGGTCAAGGTTACTTGCGTAAACACGCCGGTAAACTGGAATCTAGCACGGATAATGGTCT 
               
               
                   
               
               
                 GACCTTCGAAGAGAACTTCACTCAATTAATTATTTACGAAGTCACGCAAGACCGCAGCCTGATCACCCTGAGCGAG 
               
               
                   
               
               
                 TGCCCGCGTACCTGGAACTTCTTCCGCGGTCAACCACTGTTTTCTGAGAGCTTTCCGGACGACGTGGACACCACCTC 
               
               
                   
               
               
                 TGTGGCGTTGACCGTTCTGCAGCCGGATCGTGCGTTGGTGGATAGCATCCTGGACCAGATGTTGGAATATGTTGA 
               
               
                   
               
               
                 CGCGGATGGTATTATGCAAACCTACTTTGATTCATCCCGTCCGCGCATTGACCCGTTCGTGTGCGTGAATGTCCTGA 
               
               
                   
               
               
                 GCCTGTTCTACGCCAATGGCAGAGGCCGCGAGCTGCCACACACGCTGGAATGGGTCTATGAAGTTCTGCTGCACC 
               
               
                   
               
               
                 GTGCGTACCACGGCGGTAGCCGTTATTACCTGAGCCCGGACTGTTTCCTGTTCTTTATGAGCCGTCTGCTGAAGCG 
               
               
                   
               
               
                 CGCGAATGACTCGGCGCTGCAGGCCCGTTTTCGCCCGCTTTTCATGGAACGTGTGAAAGAGCGTGTGGGCGCAGC 
               
               
                   
               
               
                 CGGCGATAGCATGGACCTGGCGTTCCGCATTCTGGCCGCTGCAACCATCGGCGTTCATTGCCCACAAGATCTGGA 
               
               
                   
               
               
                 GCGTCTGGCAGCAGCGCAGTGCGAAGATGGTGGCTGGGATATGTGTTGGTTTTATGCGTTTGGCAGCACGGGTAT 
               
               
                   
               
               
                 CAAGGCTGGCAACCGCGGTCTGACCACCGCGTTGGCTGTCGCCGCAATTCGTACCGCGCTGGGTCGTCCGCCTTCC 
               
               
                   
               
               
                 CCGAGCCCGAGCAATATTTCTAGCTCCAGCAAACTGGACGCGCCGAACTCCTTCCTGGGCATCCCGCGTCCGACCA 
               
               
                   
               
               
                 GCCCGATCCGTTTCGGTGAACTGTTTCGTAGCTGGCGTAAGAACAAGCCGACCGCGAAAAGCCAGTAA 
               
               
                   
               
               
                 LoTps1 
               
               
                 - LoTps1 protein 
               
               
                 SEQ ID NO: 5 
                   
               
               
                 MYTALILDLGDVLFSWSSTTNTTIPPRQLKEILSSPAWFEYERGRITQAECYERVSAEFSLDATAVAEAFRQARDSLRPND 
                   
               
               
                   
               
               
                 KFLTLIRELRQQSHGELTVLALSNISLPDYEFIMALDSKWTSVFDRVFPSALVGERKPHLGAFRQVLSEMNLDPHTTVFVD 
               
               
                   
               
               
                 DKLDNVVSARSLGMHGVVFDSQDNVFRMLRNIFGDPIHRGRDYLRQHAGRLETSTDAGVVFEENFTQLIIYELTNDKSL 
               
               
                   
               
               
                 ITTSNCARTWNFFRGKPLFSASFPDDMDTTSVALTVLRLDHALVNSVLDEMLKYVDADGIMQTYFDHTRPRMDPFVC 
               
               
                   
               
               
                 VNVLSLFHEQGRGHELPNTLEWVHEVLLHRAYIGGSRYYLSADCFLFFMSRLLQRITDPSVLGRFRPLFIERVRERVGATG 
               
               
                   
               
               
                 DSIDLAFRIIAASTVGIQCPRDLESLLAAQCEDGGWDLCWFYQYGSTGVKAGNRGLTTALAIKAIDSAIARPPSPALSVAS 
               
               
                   
               
               
                 SSKSEIPKPIQRSLRPLSPRRFGGFLMPWRRSQRNGVAVSS 
               
               
                   
               
               
                 - LoTps1 transcript (including non-coding sequence) 
               
               
                 SEQ ID NO: 6 
                   
               
               
                 GCGTCTGCTGCGGTCTCTCACCGCGCCGAGCGACGGGAAGCGGAGGCTTTTTGATGCAGCCAGCTCAGCGCCATC 
                   
               
               
                   
               
               
                 CTCTCACGCAGGGGGTTTGATCCAGATCTGATCGCCTCCGGGTTCTCATCTAGAACGCACGGCGGCTCCCAGGAA 
               
               
                   
               
               
                 GTTCTATCGACCCTCTGCGCGCTGGTCGGCGGCACGATGTGGCTACACCAGTCCCAATCATATCTCACACCCAGCA 
               
               
                   
               
               
                 CCATCATCTCGGGCCTCTTCGTCATGTAACCCTCCCAAGCCTATTTTTCAGGGCGTTCCCCCTCACCGGCGCGCTTCT 
               
               
                   
               
               
                 TAAAGAATCCCGAAATGTATACGGCTCTTATCCTTGACCTCGGCGACGTTCTGTTCTCTTGGTCGTCGACGACCAAC 
               
               
                   
               
               
                 ACGACTATTCCCCCTCGGCAGCTAAAGGAGATCCTCTCATCTCCTGCCTGGTTTGAGTACGAGCGTGGTCGCATAA 
               
               
                   
               
               
                 CGCAAGCCGAATGCTACGAGCGTGTCAGCGCCGAGTTCAGCCTAGACGCCACCGCCGTCGCGGAAGCATTCCGGC 
               
               
                   
               
               
                 AAGCTCGCGACTCCTTGCGCCCGAACGACAAGTTCCTCACGTTAATTCGCGAGCTTCGACAACAATCTCATGGGGA 
               
               
                   
               
               
                 GCTCACGGTGCTTGCGCTGTCCAACATATCCCTTCCCGACTATGAATTCATCATGGCCCTCGACTCGAAGTGGACTT 
               
               
                   
               
               
                 CTGTCTTTGACCGCGTCTTCCCTTCTGCCCTCGTGGGCGAACGGAAGCCACACCTTGGAGCGTTTCGCCAGGTTCT 
               
               
                   
               
               
                 GTCCGAGATGAATCTTGACCCGCACACAACTGTGTTCGTCGATGACAAGCTGGACAATGTCGTCTCCGCACGGTCC 
               
               
                   
               
               
                 CTCGGGATGCACGGCGTCGTGTTCGACTCCCAAGACAATGTCTTTCGGATGCTGAGAAACATCTTTGGCGATCCCA 
               
               
                   
               
               
                 TTCATCGGGGACGTGACTATCTCCGACAGCACGCCGGACGTCTGGAGACCTCCACGGATGCCGGTGTGGTCTTCG 
               
               
                   
               
               
                 AAGAGAATTTCACGCAACTCATCATCTACGAACTGACGAATGACAAGTCTCTCATCACGACATCAAACTGTGCTCG 
               
               
                   
               
               
                 TACTTGGAATTTCTTTCGTGGGAAGCCTTTGTTCTCAGCATCGTTCCCTGACGACATGGACACGACCTCGGTTGCCT 
               
               
                   
               
               
                 TGACTGTATTACGTTTAGACCACGCCCTCGTGAACTCGGTTTTGGACGAGATGCTAAAGTATGTCGACGCAGACGG 
               
               
                   
               
               
                 CATCATGCAGACCTACTTCGACCATACACGCCCACGCATGGATCCATTTGTCTGCGTCAATGTGCTCTCGTTGTTTC 
               
               
                   
               
               
                 ACGAACAAGGTCGTGGCCACGAGCTTCCGAACACCCTCGAATGGGTCCATGAGGTCCTCCTCCACCGCGCGTACA 
               
               
                   
               
               
                 TCGGGGGCTCGCGGTACTACCTCTCCGCGGACTGCTTCCTCTTTTTCATGAGCCGCCTCCTGCAGCGCATCACCGAC 
               
               
                   
               
               
                 CCGTCCGTCCTTGGCCGCTTCCGTCCACTATTCATAGAGCGCGTTCGGGAGCGTGTAGGTGCGACCGGGGACTCCA 
               
               
                   
               
               
                 TCGATCTCGCATTCCGCATCATCGCCGCGTCCACAGTAGGCATCCAGTGTCCACGCGACTTGGAAAGTCTCCTCGC 
               
               
                   
               
               
                 CGCACAGTGTGAAGACGGTGGCTGGGACCTGTGCTGGTTCTACCAGTACGGATCGACCGGTGTCAAGGCGGGCA 
               
               
                   
               
               
                 ACCGCGGGCTCACCACCGCTCTGGCGATCAAAGCTATTGACTCCGCCATTGCGAGGCCACCTTCGCCTGCCCTCTC 
               
               
                   
               
               
                 AGTCGCTTCGTCGTCCAAATCGGAGATACCGAAACCCATACAACGGTCCCTTAGGCCCCTTAGCCCCCGCCGGTTT 
               
               
                   
               
               
                 GGCGGTTTCCTGATGCCGTGGCGCAGGTCACAGCGCAATGGCGTGGCGGTCTCTAGTTGAACACTTGACCCTTGA 
               
               
                   
               
               
                 CACTTCGCTTTGCACTGCCTGCTCCCCTGCCAATCCTCCCCTACGATCGTATCATCCCTCTCTTGCCCTCGCCTCCCCC 
               
               
                   
               
               
                 TCGTACCCCCTCTCATGGGGTGCCATTTGTAGATATGTACGTAGCGTGATGTAGCGGTACTCGGATCGTTCTCGTA 
               
               
                   
               
               
                 CTCGTCTTGCTCTGCCGTCGCTTCCAGCCCGTGCTGTTCTCTCGTTCAGGCTATTCGTTGGTTACGCGTATATCGTAA 
               
               
                   
               
               
                 TAGACCGCCCCGGTTCCTCGCCTACAGACACTCGCCCGTCTCGCCACGGACTCGGCTACGGATTCAGACTACATGA 
               
               
                   
               
               
                 GTGGCAGTTATCACACGCAGATCCCTCCTTGGTCGTTCTGTAGTACCCACATATGTAATTGTACCAGTCCACTGTTG 
               
               
                   
               
               
                 CAGATC 
               
               
                   
               
               
                 - LoTps1 cDNA 
               
               
                 SEQ ID NO: 7 
                   
               
               
                 ATGTATACGGCTCTTATCCTTGACCTCGGCGACGTTCTGTTCTCTTGGTCGTCGACGACCAACACGACTATTCCCCCT 
                   
               
               
                   
               
               
                 CGGCAGCTAAAGGAGATCCTCTCATCTCCTGCCTGGTTTGAGTACGAGCGTGGTCGCATAACGCAAGCCGAATGC 
               
               
                   
               
               
                 TACGAGCGTGTCAGCGCCGAGTTCAGCCTAGACGCCACCGCCGTCGCGGAAGCATTCCGGCAAGCTCGCGACTCC 
               
               
                   
               
               
                 TTGCGCCCGAACGACAAGTTCCTCACGTTAATTCGCGAGCTTCGACAACAATCTCATGGGGAGCTCACGGTGCTTG 
               
               
                   
               
               
                 CGCTGTCCAACATATCCCTTCCCGACTATGAATTCATCATGGCCCTCGACTCGAAGTGGACTTCTGTCTTTGACCGC 
               
               
                   
               
               
                 GTCTTCCCTTCTGCCCTCGTGGGCGAACGGAAGCCACACCTTGGAGCGTTTCGCCAGGTTCTGTCCGAGATGAATC 
               
               
                   
               
               
                 TTGACCCGCACACAACTGTGTTCGTCGATGACAAGCTGGACAATGTCGTCTCCGCACGGTCCCTCGGGATGCACGG 
               
               
                   
               
               
                 CGTCGTGTTCGACTCCCAAGACAATGTCTTTCGGATGCTGAGAAACATCTTTGGCGATCCCATTCATCGGGGACGT 
               
               
                   
               
               
                 GACTATCTCCGACAGCACGCCGGACGTCTGGAGACCTCCACGGATGCCGGTGTGGTCTTCGAAGAGAATTTCACG 
               
               
                   
               
               
                 CAACTCATCATCTACGAACTGACGAATGACAAGTCTCTCATCACGACATCAAACTGTGCTCGTACTTGGAATTTCTT 
               
               
                   
               
               
                 TCGTGGGAAGCCTTTGTTCTCAGCATCGTTCCCTGACGACATGGACACGACCTCGGTTGCCTTGACTGTATTACGTT 
               
               
                   
               
               
                 TAGACCACGCCCTCGTGAACTCGGTTTTGGACGAGATGCTAAAGTATGTCGACGCAGACGGCATCATGCAGACCT 
               
               
                   
               
               
                 ACTTCGACCATACACGCCCACGCATGGATCCATTTGTCTGCGTCAATGTGCTCTCGTTGTTTCACGAACAAGGTCGT 
               
               
                   
               
               
                 GGCCACGAGCTTCCGAACACCCTCGAATGGGTCCATGAGGTCCTCCTCCACCGCGCGTACATCGGGGGCTCGCGG 
               
               
                   
               
               
                 TACTACCTCTCCGCGGACTGCTTCCTCTTTTTCATGAGCCGCCTCCTGCAGCGCATCACCGACCCGTCCGTCCTTGGC 
               
               
                   
               
               
                 CGCTTCCGTCCACTATTCATAGAGCGCGTTCGGGAGCGTGTAGGTGCGACCGGGGACTCCATCGATCTCGCATTCC 
               
               
                   
               
               
                 GCATCATCGCCGCGTCCACAGTAGGCATCCAGTGTCCACGCGACTTGGAAAGTCTCCTCGCCGCACAGTGTGAAG 
               
               
                   
               
               
                 ACGGTGGCTGGGACCTGTGCTGGTTCTACCAGTACGGATCGACCGGTGTCAAGGCGGGCAACCGCGGGCTCACC 
               
               
                   
               
               
                 ACCGCTCTGGCGATCAAAGCTATTGACTCCGCCATTGCGAGGCCACCTTCGCCTGCCCTCTCAGTCGCTTCGTCGTC 
               
               
                   
               
               
                 CAAATCGGAGATACCGAAACCCATACAACGGTCCCTTAGGCCCCTTAGCCCCCGCCGGTTTGGCGGTTTCCTGATG 
               
               
                   
               
               
                 CCGTGGCGCAGGTCACAGCGCAATGGCGTGGCGGTCTCTAGTTGA 
               
               
                   
               
               
                 - LoTps1 optimized cDNA 
               
               
                 SEQ ID NO: 8 
                   
               
               
                 ATGTACACGGCGCTGATTTTGGATTTGGGTGATGTTCTGTTTAGCTGGAGCTCAACGACTAACACCACCATTCCGC 
                   
               
               
                   
               
               
                 CGCGTCAGCTGAAAGAAATCTTGAGCTCCCCGGCGTGGTTCGAGTACGAGCGTGGCCGTATCACCCAGGCAGAGT 
               
               
                   
               
               
                 GTTATGAGCGTGTCAGCGCAGAGTTTAGCCTGGATGCGACGGCCGTGGCTGAGGCTTTTCGTCAGGCACGTGATA 
               
               
                   
               
               
                 GCCTGCGTCCGAACGACAAATTTCTGACCCTGATCCGTGAGCTGCGTCAACAGAGCCACGGTGAATTGACCGTTCT 
               
               
                   
               
               
                 GGCCTTGTCTAACATCAGCCTGCCGGATTACGAATTTATTATGGCACTGGACTCGAAGTGGACCAGCGTGTTTGAT 
               
               
                   
               
               
                 CGTGTGTTCCCGAGCGCCCTGGTGGGCGAACGCAAGCCGCACCTGGGCGCGTTCCGCCAAGTCCTGTCCGAGATG 
               
               
                   
               
               
                 AATTTGGACCCGCATACCACCGTTTTTGTGGACGACAAACTGGACAATGTTGTCAGCGCACGCAGCCTGGGTATGC 
               
               
                   
               
               
                 ACGGTGTCGTGTTCGACAGCCAAGACAATGTTTTTCGTATGCTGCGTAACATTTTCGGTGACCCAATTCACCGCGG 
               
               
                   
               
               
                 TCGTGACTATCTGCGCCAGCACGCTGGTCGTCTTGAAACGTCCACCGATGCGGGCGTTGTGTTCGAAGAGAACTTC 
               
               
                   
               
               
                 ACCCAACTGATCATTTACGAACTGACCAACGATAAGAGCCTGATCACCACCTCTAATTGCGCCCGCACCTGGAACTT 
               
               
                   
               
               
                 CTTCCGCGGCAAACCTCTGTTCTCCGCGAGCTTTCCGGACGATATGGACACTACGTCGGTAGCGCTGACCGTGCTG 
               
               
                   
               
               
                 CGTCTGGACCATGCGCTGGTGAATAGCGTTCTGGATGAAATGCTGAAATACGTCGATGCTGACGGTATTATGCAG 
               
               
                   
               
               
                 ACCTACTTTGATCATACGCGTCCTCGTATGGACCCGTTCGTTTGCGTCAATGTGCTGAGCCTGTTTCACGAGCAAGG 
               
               
                   
               
               
                 TCGCGGTCATGAACTGCCGAATACGCTGGAATGGGTGCATGAAGTCCTGCTGCACCGTGCGTATATCGGTGGCAG 
               
               
                   
               
               
                 CCGCTATTATCTGAGCGCGGATTGTTTCCTGTTCTTTATGAGCCGTCTGTTGCAACGTATTACCGACCCGAGCGTTT 
               
               
                   
               
               
                 TAGGTAGATTTCGCCCGCTGTTCATCGAGCGTGTTCGCGAGCGCGTTGGCGCGACTGGCGACAGCATCGACCTGG 
               
               
                   
               
               
                 CATTCCGTATCATCGCGGCCAGCACGGTCGGCATTCAATGCCCGCGTGACCTGGAGTCTCTGCTGGCAGCACAGTG 
               
               
                   
               
               
                 CGAAGATGGTGGCTGGGATCTGTGTTGGTTTTACCAGTACGGCAGCACGGGTGTTAAGGCCGGTAACCGTGGTCT 
               
               
                   
               
               
                 GACCACGGCGTTGGCGATCAAAGCGATTGACAGCGCCATCGCGCGTCCGCCAAGCCCGGCCCTGTCCGTTGCAAG 
               
               
                   
               
               
                 CTCCAGCAAGAGCGAGATTCCGAAGCCGATTCAGCGTAGCCTCCGCCCGTTGAGCCCGCGTCGCTTCGGTGGCTTC 
               
               
                   
               
               
                 CTGATGCCGTGGCGTCGTAGCCAACGCAATGGTGTCGCGGTGAGCTCTTAA 
               
               
                   
               
               
                 OCH93767.1 
               
               
                 - OCH93767.1 protein 
               
               
                 SEQ ID NO: 9 
                   
               
               
                 MSAAVRYTTLILDLGDVLFTWSPKTKTSISPRILKEILNSATWYEYERGSITQHECYERVGVEFGIAPSEIHNAFKQARDSM 
                   
               
               
                   
               
               
                 ESNDELIALVRELKEQSDGELLVFALSNISLPDYEYVLTKPADWSIFDKVFPSALVGERKPHLGIYKHVIAETGVDPRTTVFV 
               
               
                   
               
               
                 DDKIDNVLSARSLGMHGIVFDKHEDVMRALRNIFGDPVRRGREYLRRNARKLESITDHGVAFGENFTQLLILELTSDASL 
               
               
                   
               
               
                 VTLPDRPRTWNFFRGKPLFSEAFPDDLDTTSLALTVLKRDAATVSSVMDEMLKYRDADGIMQTYFDNGRQRLDPFVN 
               
               
                   
               
               
                 ANVLTLFYANGRGHELDQSLSWVREVLLYRAYLGGSRYYPSADCFLYFISRLFACTSDPVLHHQLKPLFVERVHERIGVQ 
               
               
                   
               
               
                 GDALELAFRLLVCASFNISNQPDMRKLLEMQCQDGGWDGGNLYRFGTTGLKVTNRGLTTAAAVQAIEATQLRPPSPA 
               
               
                   
               
               
                 FSVESPKSPVTPVTPMLEIPALGLSISRPSSPLLGYFKLPWKKSAEVH 
               
               
                   
               
               
                 - OCH93767.1 cDNA 
               
               
                 SEQ ID NO: 10 
                   
               
               
                 ATGTCCGCAGCAGTTCGGTACACGACCCTCATCCTCGACCTTGGCGACGTCTTGTTCACTTGGTCACCGAAGACGA 
                   
               
               
                   
               
               
                 AGACCAGCATCTCGCCTCGTATTCTGAAGGAGATCCTGAATTCCGCGACCTGGTATGAGTACGAGCGCGGTAGTA 
               
               
                   
               
               
                 TCACTCAGCACGAATGTTACGAACGCGTTGGCGTGGAGTTCGGTATTGCGCCGAGCGAGATCCACAACGCGTTCA 
               
               
                   
               
               
                 AGCAGGCTCGGGACTCTATGGAGTCGAATGACGAGCTGATCGCCCTTGTTCGGGAACTGAAGGAGCAGTCAGAT 
               
               
                   
               
               
                 GGAGAGCTTCTCGTCTTCGCATTATCGAACATCTCACTGCCGGACTACGAATACGTCCTGACGAAGCCCGCGGACT 
               
               
                   
               
               
                 GGTCCATCTTCGACAAAGTCTTTCCTTCCGCTCTCGTCGGCGAGCGCAAGCCCCATCTCGGCATCTACAAACACGTC 
               
               
                   
               
               
                 ATCGCAGAGACGGGCGTTGATCCGCGAACAACCGTCTTCGTGGACGACAAGATCGACAATGTGCTTTCGGCGCGG 
               
               
                   
               
               
                 TCGCTCGGTATGCACGGCATTGTCTTCGACAAACACGAAGACGTAATGCGCGCTCTGCGAAACATTTTCGGTGACC 
               
               
                   
               
               
                 CCGTGCGAAGAGGACGAGAATATTTGCGTCGAAATGCAAGGAAATTGGAATCCATCACAGATCACGGCGTCGCCT 
               
               
                   
               
               
                 TCGGGGAGAACTTCACCCAGCTTCTGATCCTCGAACTTACTAGTGATGCGTCCCTCGTTACTCTCCCTGATCGTCCT 
               
               
                   
               
               
                 CGGACATGGAATTTTTTCCGAGGGAAGCCGCTCTTTTCGGAGGCCTTCCCCGATGACCTTGATACTACTTCCTTGGC 
               
               
                   
               
               
                 ACTCACTGTCCTGAAAAGAGATGCCGCCACTGTATCGTCCGTGATGGACGAGATGCTGAAATACAGGGACGCGGA 
               
               
                   
               
               
                 CGGCATCATGCAGACATACTTCGACAACGGTCGGCAACGACTCGATCCGTTCGTCAACGCCAACGTTTTGACCCTC 
               
               
                   
               
               
                 TTCTACGCCAACGGTCGCGGACACGAGCTGGATCAGAGCCTCAGCTGGGTTCGCGAAGTCTTGCTCTACCGCGCTT 
               
               
                   
               
               
                 ACCTCGGCGGTTCCCGCTACTACCCCTCCGCCGACTGCTTCCTATATTTCATCAGCCGCCTCTTCGCCTGCACCAGCG 
               
               
                   
               
               
                 ACCCGGTCCTCCATCATCAACTTAAGCCCCTCTTTGTTGAGCGTGTGCACGAGCGGATAGGAGTGCAGGGCGACG 
               
               
                   
               
               
                 CGCTGGAGCTCGCCTTCCGCCTGCTTGTATGCGCGAGCTTCAACATCTCGAACCAGCCTGACATGCGCAAGCTGCT 
               
               
                   
               
               
                 CGAGATGCAGTGCCAGGACGGAGGCTGGGATGGCGGAAACCTGTATCGTTTCGGCACCACGGGCCTCAAGGTCA 
               
               
                   
               
               
                 CGAACCGGGGTCTGACCACCGCAGCAGCCGTGCAAGCCATCGAGGCGACGCAGCTGCGTCCACCATCACCGGCG 
               
               
                   
               
               
                 TTCTCTGTCGAGTCGCCTAAGAGCCCGGTGACGCCGGTGACGCCCATGCTGGAGATTCCAGCGCTGGGTCTCAGC 
               
               
                   
               
               
                 ATCTCGCGGCCCTCCAGTCCTCTGTTGGGGTATTTCAAGCTCCCGTGGAAGAAGTCAGCCGAGGTTCATTGA 
               
               
                   
               
               
                 - OCH93767 optimized cDNA 
               
               
                 SEQ ID NO: 11 
                   
               
               
                 ATGTCTGCAGCTGTTCGTTATACTACTCTGATCCTGGATTTGGGCGATGTTCTGTTCACCTGGTCCCCGAAAACCAA 
                   
               
               
                   
               
               
                 GACCTCTATCAGCCCACGTATCCTGAAAGAAATCCTGAACAGCGCGACCTGGTACGAGTATGAGCGTGGCAGCAT 
               
               
                   
               
               
                 CACCCAGCACGAGTGCTACGAGCGTGTTGGCGTCGAATTTGGTATTGCGCCGAGCGAGATTCACAACGCGTTCAA 
               
               
                   
               
               
                 ACAAGCCCGCGACAGCATGGAATCCAACGACGAACTGATTGCTCTGGTGCGTGAGCTGAAAGAACAGAGCGATG 
               
               
                   
               
               
                 GTGAGCTGCTGGTCTTTGCCCTGAGCAATATCTCTCTGCCGGATTACGAATACGTTCTGACCAAACCAGCGGACTG 
               
               
                   
               
               
                 GTCAATCTTCGATAAAGTCTTTCCGAGCGCTTTGGTCGGTGAGCGTAAACCGCATCTGGGTATTTACAAACACGTT 
               
               
                   
               
               
                 ATTGCGGAAACCGGTGTTGACCCGAGAACGACCGTTTTTGTTGACGATAAGATTGACAACGTCCTGAGCGCACGC 
               
               
                   
               
               
                 AGCCTGGGTATGCATGGTATTGTCTTTGATAAACACGAAGATGTGATGCGTGCTCTGCGCAATATCTTTGGCGACC 
               
               
                   
               
               
                 CGGTGCGTCGCGGTCGTGAGTATTTGCGCCGCAACGCGCGCAAATTGGAGTCCATTACCGATCATGGTGTCGCAT 
               
               
                   
               
               
                 TTGGTGAGAATTTCACCCAGCTCCTGATTCTGGAACTGACCAGCGACGCGTCCCTGGTGACGCTGCCGGATCGTCC 
               
               
                   
               
               
                 GCGTACGTGGAACTTCTTCCGCGGCAAGCCGCTGTTTAGCGAAGCGTTCCCGGATGACCTGGACACCACGAGCCT 
               
               
                   
               
               
                 GGCACTGACGGTGCTGAAACGCGATGCAGCAACTGTGAGCTCCGTCATGGACGAAATGCTGAAGTACCGCGACG 
               
               
                   
               
               
                 CGGATGGCATCATGCAGACGTATTTCGACAACGGTCGTCAGCGTCTGGACCCGTTTGTCAACGCCAATGTTCTGAC 
               
               
                   
               
               
                 GCTGTTTTACGCGAATGGCCGTGGTCATGAACTGGACCAGAGCTTATCATGGGTGCGTGAAGTGCTGCTGTATCG 
               
               
                   
               
               
                 CGCCTATCTGGGTGGCAGCCGCTACTATCCGAGCGCGGACTGTTTTCTGTACTTCATTAGCCGCTTGTTCGCCTGCA 
               
               
                   
               
               
                 CCAGCGATCCGGTTCTGCATCACCAACTGAAGCCATTGTTCGTCGAGCGTGTGCACGAGCGTATTGGTGTTCAGGG 
               
               
                   
               
               
                 CGACGCACTGGAACTGGCGTTCCGTCTGTTGGTGTGTGCGAGCTTCAACATTAGCAATCAGCCGGATATGCGTAA 
               
               
                   
               
               
                 GCTGCTGGAAATGCAATGCCAAGATGGCGGCTGGGACGGTGGTAATCTGTACCGTTTTGGCACCACCGGTTTAAA 
               
               
                   
               
               
                 AGTGACGAATCGTGGTTTGACCACCGCTGCGGCCGTTCAAGCAATTGAAGCAACGCAACTGCGTCCGCCGAGCCC 
               
               
                   
               
               
                 AGCATTTAGCGTAGAGTCGCCTAAGAGCCCGGTTACGCCGGTGACGCCGATGCTGGAAATCCCGGCGCTGGGTCT 
               
               
                   
               
               
                 GTCTATCAGCCGTCCGTCGAGCCCGCTGCTGGGCTATTTCAAGTTGCCGTGGAAGAAAAGCGCCGAAGTGCACTA 
               
               
                   
               
               
                 A 
               
               
                   
               
               
                 EMD37666.1 
               
               
                 - EMD37666.1 protein 
               
               
                 SEQ ID NO: 12 
                   
               
               
                 MSAAAQYTTLILDLGDVLFTWSPKTKTSIPPRTLKEILNSATWYEYERGRISQDECYERVGTEFGIAPSEIDNAFKQARDS 
                   
               
               
                   
               
               
                 MESNDELIALVRELKTQLDGELLVFALSNISLPDYEYVLTKPADWSIFDKVFPSALVGERKPHLGVYKHVIAETGIDPRTTV 
               
               
                   
               
               
                 FVDDKIDNVLSARSVGMHGIVFEKQEDVMRALRNIFGDPVRRGREYLRRNAMRLESVTDHGVAFGENFTQLLILELTN 
               
               
                   
               
               
                 DPSLVTLPDRPRTWNFFRGNGGRPSKPLFSEAFPDDLDTTSLALTVLQRDPGVISSVMDEMLNYRDPDGIMQTYFDDG 
               
               
                   
               
               
                 RQRLDPFVNVNVLTFFYTNGRGHELDQCLTWVREVLLYRAYLGGSRYYPSADCFLYFISRLFACTNDPVLHHQLKPLFVE 
               
               
                   
               
               
                 RVQEQIGVEGDALELAFRLLVCASLDVQNAIDMRRLLEMQCEDGGWEGGNLYRFGTTGLKVTNRGLTTAAAVQAIEA 
               
               
                   
               
               
                 SQRRPPSPSPSVESTKSPITPVTPMLEVPSLGLSISRPSSPLLGYFRLPWKKSAEVH 
               
               
                   
               
               
                 - EMD37666.1 cDNA 
               
               
                 SEQ ID NO: 13 
                   
               
               
                 ATGTCCGCGGCAGCTCAATACACGACCCTCATTCTCGACCTTGGCGACGTCCTGTTCACCTGGTCACCGAAAACCA 
                   
               
               
                   
               
               
                 AGACGAGCATCCCCCCTCGGACTCTGAAGGAGATTCTCAATTCCGCGACATGGTATGAGTATGAGCGCGGCCGCA 
               
               
                   
               
               
                 TCTCTCAGGACGAATGTTACGAACGCGTTGGCACGGAGTTCGGAATCGCGCCTAGCGAAATCGACAACGCGTTCA 
               
               
                   
               
               
                 AGCAAGCTCGGGATTCCATGGAATCCAACGACGAACTGATCGCCCTTGTTCGGGAACTCAAGACGCAGTTGGACG 
               
               
                   
               
               
                 GCGAACTCCTTGTCTTCGCACTCTCAAATATCTCGTTGCCTGACTACGAGTACGTCCTCACGAAACCGGCCGACTGG 
               
               
                   
               
               
                 TCCATCTTCGACAAGGTCTTCCCTTCCGCCCTCGTGGGCGAGCGCAAGCCGCACCTCGGCGTTTACAAGCACGTCA 
               
               
                   
               
               
                 TTGCAGAAACGGGCATTGATCCGCGAACCACCGTTTTCGTGGACGACAAGATCGACAACGTGCTCTCAGCGCGGT 
               
               
                   
               
               
                 CTGTAGGTATGCATGGGATCGTTTTCGAGAAGCAGGAAGACGTAATGCGCGCTCTCCGAAACATCTTCGGAGACC 
               
               
                   
               
               
                 CGGTTCGGCGAGGGCGCGAGTACTTGCGCCGTAATGCCATGAGGCTTGAATCGGTTACAGACCATGGTGTGGCGT 
               
               
                   
               
               
                 TTGGCGAGAACTTCACACAACTCCTTATCCTCGAACTAACGAACGATCCCTCCCTCGTTACGCTCCCTGATCGTCCTC 
               
               
                   
               
               
                 GAACATGGAATTTCTTCCGAGGTAACGGGGGACGACCAAGCAAACCATTATTCTCGGAGGCCTTCCCCGATGACTT 
               
               
                   
               
               
                 GGACACTACTTCACTAGCGTTGACTGTCCTCCAAAGAGATCCCGGCGTCATCTCTTCTGTGATGGACGAAATGTTG 
               
               
                   
               
               
                 AACTACAGGGATCCGGACGGCATTATGCAGACATACTTCGACGATGGTCGGCAAAGACTCGATCCATTTGTCAAT 
               
               
                   
               
               
                 GTCAATGTCTTAACGTTCTTCTACACCAACGGACGTGGTCATGAACTGGACCAATGCCTTACATGGGTCCGCGAAG 
               
               
                   
               
               
                 TTTTGCTCTATCGCGCCTATCTCGGCGGCTCACGTTATTACCCCTCCGCCGACTGCTTTCTCTACTTCATCAGCCGCC 
               
               
                   
               
               
                 TTTTCGCATGCACGAATGACCCCGTGCTACACCACCAACTCAAACCGCTCTTCGTCGAGCGCGTGCAGGAGCAAAT 
               
               
                   
               
               
                 CGGCGTGGAGGGCGATGCGCTCGAGTTGGCGTTCCGATTGCTCGTCTGTGCAAGCCTGGACGTCCAAAACGCGAT 
               
               
                   
               
               
                 CGACATGCGCAGGCTGCTCGAGATGCAATGCGAAGATGGCGGCTGGGAGGGCGGGAACCTTTATAGGTTTGGCA 
               
               
                   
               
               
                 CGACCGGGCTCAAGGTGACTAACCGGGGCCTGACGACTGCAGCGGCCGTACAGGCCATCGAGGCGTCCCAACGG 
               
               
                   
               
               
                 CGCCCACCATCACCGTCCCCCTCCGTCGAATCTACAAAGAGCCCAATAACCCCTGTGACGCCCATGCTGGAGGTCC 
               
               
                   
               
               
                 CCTCGCTCGGCCTGAGCATCTCGAGGCCGTCCAGCCCTTTACTCGGCTACTTCAGGCTCCCGTGGAAGAAGTCGGC 
               
               
                   
               
               
                 CGAAGTACACTGA 
               
               
                   
               
               
                 - EMD37666.1 optimized cDNA 
               
               
                 SEQ ID NO: 14 
                   
               
               
                 ATGTCTGCGGCGGCTCAATACACGACTTTGATTCTGGATCTGGGTGATGTTCTGTTCACTTGGTCCCCGAAAACCA 
                   
               
               
                   
               
               
                 AGACCAGCATCCCTCCGCGTACCCTGAAAGAAATCCTGAATAGCGCTACCTGGTATGAGTACGAGCGTGGTCGCA 
               
               
                   
               
               
                 TTTCCCAAGACGAGTGTTACGAACGTGTGGGCACCGAGTTCGGCATTGCGCCGAGCGAGATTGACAACGCGTTCA 
               
               
                   
               
               
                 AACAAGCGCGCGATTCGATGGAAAGCAATGATGAACTGATCGCACTGGTCCGTGAGCTGAAAACGCAGCTGGAC 
               
               
                   
               
               
                 GGTGAGCTGCTGGTTTTCGCACTGTCCAATATTAGCCTGCCGGATTACGAATACGTCTTGACCAAACCGGCGGACT 
               
               
                   
               
               
                 GGAGCATCTTTGACAAAGTGTTCCCTAGCGCCTTGGTGGGCGAGCGTAAGCCGCATCTGGGCGTTTATAAACACG 
               
               
                   
               
               
                 TTATTGCGGAAACGGGCATTGATCCGCGCACGACGGTTTTCGTGGACGACAAGATTGACAATGTGTTAAGCGCAC 
               
               
                   
               
               
                 GCAGCGTCGGTATGCATGGTATCGTGTTTGAGAAACAAGAAGATGTCATGCGTGCACTGCGTAACATCTTTGGTG 
               
               
                   
               
               
                 ATCCGGTCCGTCGTGGTCGTGAGTATCTGCGTAGAAACGCAATGCGTCTGGAGTCCGTGACCGACCACGGCGTGG 
               
               
                   
               
               
                 CGTTTGGTGAGAACTTTACCCAGTTGCTGATTCTGGAATTGACGAACGACCCGAGCCTGGTCACCCTGCCTGATCG 
               
               
                   
               
               
                 TCCGCGTACCTGGAACTTTTTTCGCGGCAATGGTGGCCGCCCGAGCAAGCCGCTGTTCAGCGAAGCGTTCCCGGAT 
               
               
                   
               
               
                 GATCTGGATACCACGAGCCTGGCGCTGACCGTGCTGCAGCGCGACCCGGGTGTTATCAGCAGCGTTATGGACGAA 
               
               
                   
               
               
                 ATGCTGAATTACCGTGACCCGGACGGTATCATGCAGACTTATTTCGATGACGGTCGCCAACGCTTGGACCCATTTG 
               
               
                   
               
               
                 TGAACGTCAATGTTCTGACCTTTTTCTATACGAACGGCCGTGGTCACGAACTGGACCAGTGTCTGACGTGGGTGCG 
               
               
                   
               
               
                 TGAAGTCCTCTTGTATCGTGCGTACCTTGGTGGCTCACGCTACTACCCATCGGCGGATTGCTTCCTGTACTTCATCT 
               
               
                   
               
               
                 CTCGTCTGTTTGCGTGTACCAATGACCCGGTGCTGCACCATCAGCTGAAGCCACTGTTTGTTGAGCGTGTCCAAGA 
               
               
                   
               
               
                 GCAAATTGGTGTCGAGGGTGATGCACTGGAACTGGCTTTTCGTCTGCTGGTCTGCGCCAGCCTGGATGTCCAGAA 
               
               
                   
               
               
                 TGCCATCGACATGCGCCGTCTGCTGGAAATGCAGTGCGAAGATGGCGGTTGGGAGGGTGGTAACCTCTACCGCTT 
               
               
                   
               
               
                 CGGCACCACGGGCCTGAAAGTTACCAACCGCGGTCTGACGACCGCAGCCGCCGTTCAAGCGATCGAAGCGAGCC 
               
               
                   
               
               
                 AACGCCGTCCGCCGAGCCCGAGCCCGTCTGTAGAGAGCACGAAAAGCCCGATTACCCCGGTGACCCCGATGCTGG 
               
               
                   
               
               
                 AAGTTCCAAGCCTGGGCTTATCTATCAGCCGTCCGTCCAGCCCGCTGCTGGGTTATTTCCGTTTGCCGTGGAAGAA 
               
               
                   
               
               
                 AAGCGCAGAAGTGCACTAA 
               
               
                   
               
               
                 EMD37666-B 
               
               
                 - EMD37666-B protein 
               
               
                 SEQ ID NO: 15 
                   
               
               
                 MSAAAQYTTLILDLGDVLFTWSPKTKTSIPPRTLKEILNSATWYEYERGRISQDECYERVGTEFGIAPSEIDNAFKQARDS 
                   
               
               
                   
               
               
                 MESNDELIALVRELKTQLDGELLVFALSNISLPDYEYVLTKPADWSIFDKVFPSALVGERKPHLGVYKHVIAETGIDPRTTV 
               
               
                   
               
               
                 FVDDKIDNVLSARSVGMHGIVFEKQEDVMRALRNIFGDPVRRGREYLRRNAMRLESVTDHGVAFGENFTQLLILELTN 
               
               
                   
               
               
                 DPSLVTLPDRPRTWNFFRGKPLFSEAFPDDLDTTSLALTVLQRDPGVISSVMDEMLNYRDPDGIMQTYFDDGRQRLDP 
               
               
                   
               
               
                 FVNVNVLTFFYTNGRGHELDQCLTWVREVLLYRAYLGGSRYYPSADCFLYFISRLFACTNDPVLHHQLKPLFVERVQEQI 
               
               
                   
               
               
                 GVEGDALELAFRLLVCASLDVQNAIDMRRLLEMQCEDGGWEGGNLYRFGTTGLKVTNRGLTTAAAVQAIEASQRRPP 
               
               
                   
               
               
                 SPSPSVESTKSPITPVTPMLEVPSLGLSISRPSSPLLGYFRLPWKKSAEVH 
               
               
                   
               
               
                 - EMD37666-B optimized cDNA 
               
               
                 SEQ ID NO: 16 
                   
               
               
                 ATGTCTGCGGCTGCTCAATATACTACTTTGATTCTGGATCTGGGCGACGTTCTGTTCACGTGGAGCCCGAAAACCA 
                   
               
               
                   
               
               
                 AGACCAGCATTCCACCGCGTACCCTGAAGGAGATCCTCAATAGCGCGACTTGGTACGAGTATGAGCGTGGCCGCA 
               
               
                   
               
               
                 TCAGCCAAGACGAGTGCTACGAACGCGTCGGTACGGAATTTGGCATTGCACCAAGCGAGATTGACAATGCGTTTA 
               
               
                   
               
               
                 AACAAGCGCGTGACAGCATGGAAAGCAATGACGAACTGATCGCGCTGGTCCGTGAGCTGAAAACCCAGCTGGAT 
               
               
                   
               
               
                 GGTGAGCTGTTGGTGTTTGCGCTGTCGAACATCTCTCTGCCGGACTACGAGTATGTTCTGACCAAACCGGCGGATT 
               
               
                   
               
               
                 GGAGCATTTTTGATAAAGTGTTTCCGAGCGCGCTGGTTGGTGAGCGCAAGCCGCACCTGGGTGTGTACAAACACG 
               
               
                   
               
               
                 TTATTGCAGAGACTGGCATCGACCCGCGTACGACGGTTTTCGTTGACGACAAGATCGATAACGTTCTGAGCGCAC 
               
               
                   
               
               
                 GTAGCGTCGGTATGCACGGTATTGTTTTCGAAAAACAAGAAGATGTTATGCGCGCACTGCGTAATATCTTCGGCGA 
               
               
                   
               
               
                 TCCGGTCAGACGTGGCCGTGAGTATCTGCGCCGCAATGCGATGCGTCTGGAATCGGTGACCGATCATGGTGTCGC 
               
               
                   
               
               
                 CTTTGGCGAGAATTTCACCCAGCTGCTGATTTTAGAGCTGACCAATGATCCTAGCCTGGTGACGCTGCCGGATCGT 
               
               
                   
               
               
                 CCGCGTACCTGGAACTTTTTCCGCGGCAAGCCGTTGTTCTCCGAAGCCTTCCCGGACGACCTGGACACGACCAGCC 
               
               
                   
               
               
                 TGGCGCTGACCGTGCTGCAACGTGATCCGGGTGTGATCTCTTCCGTAATGGACGAAATGCTGAACTACCGTGACCC 
               
               
                   
               
               
                 GGACGGTATCATGCAGACCTATTTTGACGACGGTCGTCAGCGTCTGGACCCGTTTGTGAACGTGAATGTCCTGACG 
               
               
                   
               
               
                 TTCTTTTACACCAATGGTCGCGGTCACGAACTGGATCAGTGTCTGACCTGGGTCCGCGAAGTGCTGCTGTATCGTG 
               
               
                   
               
               
                 CATACCTGGGTGGCAGCCGTTATTACCCGAGCGCCGATTGCTTTCTGTACTTTATCAGCCGTCTGTTCGCGTGCACG 
               
               
                   
               
               
                 AACGATCCGGTTCTGCATCACCAGCTGAAGCCGTTATTTGTTGAGCGCGTTCAGGAACAAATTGGTGTCGAGGGT 
               
               
                   
               
               
                 GATGCGCTGGAATTGGCATTCCGCCTGTTGGTCTGCGCCAGCCTTGATGTCCAGAACGCCATTGACATGCGTCGCT 
               
               
                   
               
               
                 TGCTCGAAATGCAGTGTGAGGACGGCGGTTGGGAGGGTGGCAACCTGTACCGTTTCGGTACGACCGGCCTGAAA 
               
               
                   
               
               
                 GTCACGAACCGTGGTCTGACGACGGCAGCTGCGGTGCAAGCAATTGAAGCCAGCCAACGTCGTCCGCCATCCCCG 
               
               
                   
               
               
                 TCACCGAGCGTTGAGTCCACCAAGAGCCCGATTACCCCTGTGACCCCGATGCTTGAAGTTCCGAGCCTGGGTCTGA 
               
               
                   
               
               
                 GCATCTCCCGTCCTAGCAGCCCGCTGTTGGGTTACTTCCGCCTGCCGTGGAAGAAAAGCGCTGAGGTGCATTAA 
               
               
                   
               
               
                 XP_001217376.1 
               
               
                 - XP_001217376.1 protein 
               
               
                 SEQ ID NO: 17 
                   
               
               
                 MAITKGPVKALILDFSNVLCSWKPPSNVAVPPQILKMIMSSDIWHDYECGRYSREDCYARVADRFHISAADMEDTLKQ 
                   
               
               
                   
               
               
                 ARKSLQVHHETLLFIQQVKKDAGGELMVCGMTNTPRPEQDVMHSINAEYPVFDRIYISGLMGMRKPSICFYQRVMEEI 
               
               
                   
               
               
                 GLSGDAIMFIDDKLENVIAAQSVGIRGVLFQSQQDLRRVVLNFLGDPVHRGLQFLAANAKKMDSVTNTGDTIQDNFA 
               
               
                   
               
               
                 QLLILELAQDRELVKLQAGKRTWNYFIGPPKLTTATFPDDMDTTSMALSVLPVAEDVVSSVLDEMLKFVTDDGIFMTYF 
               
               
                   
               
               
                 DSSRPRVDPVVCINVLGVFCRHNRERDVLPTFHWIRDILINRAYLSGTRYYPSPDLFLFFLARLCLAVRNQSLREQLVLPLV 
               
               
                   
               
               
                 DRLRERVGAPGEAVSLAARILACRSFGIDSARDMDSLRGKQCEDGGWPVEWVYRFASFGLNVGNRGLATAFAVRALE 
               
               
                   
               
               
                 SPYGESAVKVMRRIV 
               
               
                   
               
               
                 - XP_001217376.1 cDNA 
               
               
                 SEQ ID NO: 18 
                   
               
               
                 ATGGCTATCACCAAGGGTCCAGTTAAGGCGCTTATTCTTGACTTTTCCAATGTTCTCTGCTCGTGGAAGCCTCCCAG 
                   
               
               
                   
               
               
                 CAATGTTGCGGTGCCGCCCCAGATACTCAAAATGATCATGTCCTCTGACATATGGCATGACTACGAGTGCGGACG 
               
               
                   
               
               
                 GTACTCGAGAGAGGACTGCTATGCCAGAGTGGCAGACCGTTTTCATATCAGCGCCGCGGACATGGAAGACACGCT 
               
               
                   
               
               
                 GAAACAGGCGCGCAAGAGCCTGCAGGTTCACCATGAGACACTGTTGTTTATCCAGCAAGTCAAGAAGGATGCCGG 
               
               
                   
               
               
                 GGGCGAGTTGATGGTGTGTGGGATGACCAACACGCCCCGGCCAGAGCAAGACGTAATGCATTCAATCAACGCGG 
               
               
                   
               
               
                 AGTATCCTGTGTTTGATAGGATATATATATCCGGTCTCATGGGCATGAGGAAGCCGAGCATCTGCTTCTACCAGCG 
               
               
                   
               
               
                 GGTGATGGAGGAGATTGGCCTATCAGGCGATGCGATCATGTTTATAGATGACAAGTTGGAGAATGTCATCGCCGC 
               
               
                   
               
               
                 CCAGTCGGTAGGGATCCGAGGCGTTCTATTTCAGAGTCAGCAAGATCTCCGTCGGGTTGTATTAAATTTCTTGGGC 
               
               
                   
               
               
                 GATCCGGTCCATCGCGGCCTGCAGTTCCTAGCGGCCAATGCGAAAAAGATGGATAGTGTGACCAACACCGGCGAT 
               
               
                   
               
               
                 ACTATCCAAGATAATTTTGCTCAGCTCCTCATCTTGGAGCTGGCCCAGGACAGGGAATTGGTGAAGCTTCAGGCTG 
               
               
                   
               
               
                 GAAAAAGGACTTGGAATTACTTCATAGGGCCTCCCAAGCTCACAACAGCCACGTTCCCCGATGACATGGACACCAC 
               
               
                   
               
               
                 ATCTATGGCTCTCTCGGTCCTTCCTGTGGCCGAGGATGTGGTCTCTTCTGTCCTGGATGAGATGCTTAAATTCGTCA 
               
               
                   
               
               
                 CCGATGACGGTATCTTTATGACTTACTTCGATTCCTCGCGCCCTCGAGTCGACCCAGTCGTATGTATCAACGTCTTG 
               
               
                   
               
               
                 GGTGTTTTCTGCAGGCATAACCGAGAGCGAGACGTCCTTCCAACGTTCCATTGGATTCGAGACATCCTGATCAACC 
               
               
                   
               
               
                 GGGCATATCTCTCGGGCACCCGATACTACCCATCGCCCGATTTGTTTTTGTTTTTCCTTGCACGCCTCTGCCTGGCA 
               
               
                   
               
               
                 GTCCGGAATCAGAGCCTACGGGAACAACTTGTCTTGCCTCTGGTAGACCGACTGCGTGAGCGGGTGGGCGCACCT 
               
               
                   
               
               
                 GGAGAAGCGGTCTCATTGGCAGCGCGGATCCTTGCCTGCCGTAGCTTTGGTATCGACAGTGCGAGAGACATGGAC 
               
               
                   
               
               
                 AGCTTGAGGGGAAAACAATGCGAGGATGGCGGCTGGCCAGTGGAGTGGGTTTACCGGTTTGCCTCTTTCGGCCT 
               
               
                   
               
               
                 GAACGTAGGCAATCGGGGTCTTGCTACTGCCTTCGCGGTCAGGGCGCTCGAAAGCCCCTATGGTGAGTCGGCGGT 
               
               
                   
               
               
                 GAAGGTTATGAGACGCATCGTCTGA 
               
               
                   
               
               
                 - XP_001217376.1 optimized cDNA 
               
               
                 SEQ ID NO: 19 
                   
               
               
                 ATGGCAATCACTAAGGGCCCAGTTAAAGCGCTGATTCTTGATTTTTCTAACGTTCTGTGTAGCTGGAAGCCGCCGA 
                   
               
               
                   
               
               
                 GCAATGTTGCGGTCCCGCCTCAAATTCTGAAGATGATTATGTCGAGCGACATCTGGCATGATTATGAGTGTGGCCG 
               
               
                   
               
               
                 TTACAGCCGTGAGGACTGCTACGCCCGTGTTGCTGACCGTTTTCATATCAGCGCAGCGGACATGGAAGATACCCTG 
               
               
                   
               
               
                 AAACAGGCACGTAAGTCCCTGCAAGTGCACCACGAAACGCTGCTGTTCATCCAACAGGTGAAGAAAGACGCGGGT 
               
               
                   
               
               
                 GGTGAGCTGATGGTTTGCGGCATGACCAACACGCCGCGTCCGGAACAAGACGTGATGCATTCCATCAATGCTGAG 
               
               
                   
               
               
                 TATCCGGTGTTCGACCGTATTTACATTAGCGGCCTGATGGGCATGCGTAAACCGAGCATTTGTTTCTACCAACGCG 
               
               
                   
               
               
                 TAATGGAAGAGATTGGTCTGAGCGGTGACGCCATCATGTTCATTGACGATAAACTGGAAAATGTGATTGCCGCAC 
               
               
                   
               
               
                 AGAGCGTGGGTATCCGCGGTGTGCTGTTCCAAAGCCAGCAAGATCTGCGTCGTGTCGTGCTGAACTTTCTGGGCG 
               
               
                   
               
               
                 ATCCGGTCCACCGTGGTCTGCAGTTCTTGGCGGCGAACGCAAAGAAAATGGACAGCGTCACGAATACCGGCGACA 
               
               
                   
               
               
                 CTATCCAAGACAATTTCGCACAGCTGTTGATCTTAGAGCTGGCGCAGGATCGCGAATTGGTGAAATTGCAGGCCG 
               
               
                   
               
               
                 GTAAACGTACCTGGAACTACTTTATTGGTCCGCCGAAGCTGACCACGGCGACGTTTCCGGATGATATGGACACGA 
               
               
                   
               
               
                 CCAGCATGGCGCTGTCGGTGCTGCCTGTCGCGGAAGATGTCGTGAGCTCTGTTCTGGACGAGATGCTGAAGTTCG 
               
               
                   
               
               
                 TGACCGATGATGGTATCTTTATGACCTATTTCGACTCTAGCCGTCCGCGTGTCGATCCGGTTGTCTGCATTAATGTG 
               
               
                   
               
               
                 TTGGGTGTTTTCTGCCGCCACAATCGTGAGCGCGACGTGTTGCCGACCTTTCACTGGATTCGTGATATTCTGATCAA 
               
               
                   
               
               
                 CCGCGCATATCTGAGCGGCACGCGCTATTACCCGTCCCCGGATCTGTTTCTGTTTTTCCTGGCTCGTCTGTGCCTGG 
               
               
                   
               
               
                 CCGTTCGCAACCAGAGCCTGCGCGAACAACTGGTTCTCCCGCTGGTTGATCGTCTGCGCGAGCGTGTTGGTGCTCC 
               
               
                   
               
               
                 GGGTGAGGCTGTGAGCCTGGCGGCACGTATCCTGGCGTGCCGTAGCTTCGGTATCGACTCAGCCCGCGACATGGA 
               
               
                   
               
               
                 CTCCTTGCGTGGCAAACAGTGTGAAGATGGTGGTTGGCCGGTCGAATGGGTCTATCGCTTCGCGAGCTTTGGTCT 
               
               
                   
               
               
                 GAACGTTGGCAACCGTGGTTTGGCCACCGCGTTTGCGGTTAGAGCGCTGGAGTCCCCATACGGCGAGAGCGCAGT 
               
               
                   
               
               
                 TAAGGTTATGCGCCGTATCGTGTAA 
               
               
                   
               
               
                 OJJ98394.1 
               
               
                 - OJJ98394.1 protein 
               
               
                 SEQ ID NO: 20 
                   
               
               
                 MPSVKALVLDFAGVLCSWTPPAESPLSPAQLKQLMSSEIWFEYERGRYSEEECYAKLVERFSISAADMASTMEQARQSL 
                   
               
               
                   
               
               
                 ELNHAVLQLVSEIRKRNPGLKVYGMTNTPHAEQDCVNRIVNSYPVFDHVYLSGLVGMRKPDLGFYRFVLAETGLRPDE 
               
               
                   
               
               
                 VVFVDDKTENVLVAQSVGMHGVVFQNVTDFKQQIINVTGDPVSRGLRYLRSNAKSLLTVTSNNSVIHENFAQLLILELT 
               
               
                   
               
               
                 GDRDLIELEPWDRTWNYFIGVPQSPTSTFPNDLDTTSIALSVLPIHKDVVADVMDEIMLLLDNDGIVPTYFDPTRPRVDP 
               
               
                   
               
               
                 VVCVNVLSLFAQNGRESELLATFNWVLDVLRHRAYLQGTRYYISPDAFLYFLARLSVFLRMSPLRARLMPLLEERVYERIG 
               
               
                   
               
               
                 AHGDAISLAMRIYTCKLLGMSNMLDERALRDMQCEDGGFPTSWVYRFGSTGVKIGNRGLTTALAIKAIEMPLASLWKS 
               
               
                   
               
               
                 WGLTTDIR 
               
               
                   
               
               
                 - OJJ98394.1 cDNA 
               
               
                 SEQ ID NO: 21 
                   
               
               
                 ATGCCCTCCGTCAAAGCACTGGTCCTGGACTTCGCCGGAGTTCTATGCTCATGGACCCCGCCAGCCGAGAGCCCGC 
                   
               
               
                   
               
               
                 TCTCCCCAGCCCAGCTCAAACAACTCATGTCCTCCGAGATATGGTTCGAATACGAGCGCGGGAGATATTCCGAAGA 
               
               
                   
               
               
                 AGAATGTTATGCGAAGCTCGTCGAACGGTTCTCCATCAGCGCTGCGGACATGGCTTCCACCATGGAACAGGCCCG 
               
               
                   
               
               
                 TCAGAGCCTGGAACTGAACCACGCCGTACTTCAGCTTGTCAGCGAGATAAGGAAGCGGAACCCCGGGCTCAAAGT 
               
               
                   
               
               
                 TTATGGCATGACGAACACGCCCCATGCGGAACAGGATTGTGTGAATCGCATCGTGAACAGCTATCCTGTTTTCGAC 
               
               
                   
               
               
                 CATGTGTATCTCTCCGGGCTCGTTGGGATGCGCAAACCAGATCTTGGATTCTATCGGTTTGTTCTCGCAGAGACCG 
               
               
                   
               
               
                 GGTTGAGGCCTGACGAGGTCGTGTTCGTCGACGACAAAACGGAGAATGTGTTGGTCGCGCAGTCCGTGGGGATG 
               
               
                   
               
               
                 CACGGCGTGGTGTTCCAGAACGTTACGGATTTCAAGCAGCAGATCATAAACGTGACGGGAGACCCTGTCTCTCGG 
               
               
                   
               
               
                 GGCTTGAGGTATCTCCGCTCGAATGCAAAGAGCCTCCTCACTGTGACTAGCAATAACTCCGTGATCCACGAAAACT 
               
               
                   
               
               
                 TTGCGCAGTTGCTGATTCTGGAGCTGACGGGCGACCGAGACTTGATCGAACTCGAGCCTTGGGATCGAACATGGA 
               
               
                   
               
               
                 ACTACTTCATCGGGGTTCCTCAGTCGCCGACGAGCACCTTCCCCAACGACCTGGACACCACCTCTATCGCGCTCTCG 
               
               
                   
               
               
                 GTCCTTCCCATTCATAAGGACGTCGTTGCCGATGTGATGGACGAGATTATGCTTCTCCTAGACAACGACGGGATAG 
               
               
                   
               
               
                 TCCCAACATATTTTGATCCCACTCGCCCTCGAGTCGACCCAGTCGTGTGTGTGAATGTACTCAGCCTGTTTGCCCAA 
               
               
                   
               
               
                 AACGGCCGAGAATCCGAGTTACTCGCCACCTTCAACTGGGTGCTGGACGTGCTGCGACATAGAGCCTACCTGCAG 
               
               
                   
               
               
                 GGCACGAGATATTACATCAGTCCGGACGCCTTCTTGTACTTTCTAGCCAGACTCTCGGTCTTTCTGAGGATGAGTCC 
               
               
                   
               
               
                 ACTCCGCGCTCGGCTAATGCCTCTCCTGGAAGAAAGAGTGTATGAGCGAATTGGTGCCCATGGCGACGCCATTTC 
               
               
                   
               
               
                 GCTGGCTATGCGGATCTATACGTGTAAGCTGCTCGGGATGTCGAATATGCTCGATGAAAGAGCATTGCGGGACAT 
               
               
                   
               
               
                 GCAGTGTGAGGATGGCGGCTTCCCTACAAGTTGGGTCTATAGATTTGGATCGACCGGAGTGAAGATTGGGAACA 
               
               
                   
               
               
                 GGGGGTTGACTACTGCACTTGCAATAAAGGCCATTGAGATGCCTCTCGCTTCGCTTTGGAAGTCGTGGGGATTGA 
               
               
                   
               
               
                 CGACTGACATTCGATAA 
               
               
                   
               
               
                 - OJJ98394.1 optimized cDNA 
               
               
                 SEQ ID NO: 22 
                   
               
               
                 ATGCCGTCGGTTAAAGCGTTGGTTCTGGATTTTGCGGGTGTGTTGTGTTCTTGGACTCCACCGGCGGAAAGCCCGT 
                   
               
               
                   
               
               
                 TGTCCCCAGCGCAGCTGAAGCAGCTGATGAGCAGCGAGATCTGGTTTGAGTATGAGCGTGGCCGCTATAGCGAA 
               
               
                   
               
               
                 GAAGAGTGTTATGCAAAATTGGTGGAGCGTTTCTCTATCTCGGCCGCAGATATGGCGAGCACGATGGAACAGGCC 
               
               
                   
               
               
                 CGTCAATCGCTGGAGTTGAACCACGCCGTGCTGCAATTAGTTTCCGAGATTCGTAAACGTAATCCGGGCTTAAAGG 
               
               
                   
               
               
                 TTTACGGTATGACTAATACCCCGCATGCAGAGCAAGATTGTGTGAACCGTATTGTCAATAGCTATCCGGTTTTTGAT 
               
               
                   
               
               
                 CATGTCTACCTGAGCGGTCTGGTGGGTATGCGCAAACCGGATCTGGGCTTTTACCGTTTCGTTCTGGCAGAGACTG 
               
               
                   
               
               
                 GTCTGCGCCCGGATGAAGTCGTGTTCGTTGACGACAAGACCGAAAATGTCCTGGTGGCTCAATCCGTTGGCATGC 
               
               
                   
               
               
                 ATGGTGTGGTGTTCCAAAATGTAACCGACTTCAAACAACAGATTATCAATGTCACGGGTGATCCTGTCAGCCGTGG 
               
               
                   
               
               
                 TTTGCGCTACTTGCGTTCCAACGCGAAGTCTCTGCTCACTGTTACCAGCAATAACAGCGTTATCCATGAGAATTTCG 
               
               
                   
               
               
                 CGCAGCTGCTGATCCTGGAACTGACGGGCGACCGTGACCTGATTGAACTGGAACCGTGGGACCGTACGTGGAACT 
               
               
                   
               
               
                 ACTTTATCGGCGTGCCGCAAAGCCCGACCAGCACCTTTCCGAACGACCTGGATACGACCAGCATTGCCCTGAGCGT 
               
               
                   
               
               
                 TCTGCCGATTCACAAAGATGTGGTTGCGGACGTGATGGATGAGATTATGCTGCTGCTGGACAATGACGGTATTGT 
               
               
                   
               
               
                 CCCGACCTACTTCGATCCAACCCGTCCGCGTGTTGATCCTGTTGTGTGCGTCAACGTTCTGAGCCTGTTCGCACAGA 
               
               
                   
               
               
                 ACGGTCGCGAGTCCGAATTGCTGGCGACGTTCAACTGGGTTTTGGACGTTCTGAGACACCGTGCGTATTTGCAGG 
               
               
                   
               
               
                 GTACGCGCTATTATATCAGCCCGGATGCCTTTCTGTATTTTCTGGCGCGCCTGTCTGTGTTTCTGCGTATGTCTCCGT 
               
               
                   
               
               
                 TGCGCGCTCGTCTGATGCCGCTGCTGGAAGAACGCGTTTATGAGCGTATCGGCGCACACGGCGATGCTATTAGCC 
               
               
                   
               
               
                 TGGCGATGCGCATTTACACCTGTAAGCTGCTGGGCATGAGCAATATGCTGGACGAGCGTGCACTGCGTGACATGC 
               
               
                   
               
               
                 AGTGTGAAGATGGTGGTTTCCCAACCAGCTGGGTGTACCGTTTTGGTAGCACGGGCGTGAAAATTGGTAACCGTG 
               
               
                   
               
               
                 GCTTGACGACCGCACTGGCCATTAAGGCCATCGAAATGCCGCTGGCCAGCCTTTGGAAAAGCTGGGGCCTGACCA 
               
               
                   
               
               
                 CCGATATTCGCTAA 
               
               
                   
               
               
                 GAO87501.1 
               
               
                 - GAO87501.1 protein 
               
               
                 SEQ ID NO: 23 
                   
               
               
                 MTRQKSPQYKAIIFDLGDVFFTWDAPKDTAVLPNLFKKMLTSPTWSDYERGKLSEESCYERLAEQFDVDSSEIARSLRKA 
                   
               
               
                   
               
               
                 QQSLTTDAAIVSLISEIRALAGHIAIYAMSNISAPAYAAVLQTQPEMGIFDGVFPSGCYGTRKPELLFYKKVLQEIAVPPNQ 
               
               
                   
               
               
                 IIFIDDQLENVVSAQSTGMHGIVYTGAGELSRQLRNLVLDPVQRGREFLRRNAGALYSICETGQVIRENFSQLLILEATGD 
               
               
                   
               
               
                 RSLVNLEYQQRSWNFFQGGPPSTSETFPDDVDTTSIALMILPADDNTVNSVLGEISEVANDEGIVNTYFDQTRQRIDPA 
               
               
                   
               
               
                 VCVNVLRLFYTYGRGATLPLTLQWVSDVLEHRAHLHGTRYYPSPEVFLYFVSQLCRFSKREPTLQLLETLLTDRLKERIQVK 
               
               
                   
               
               
                 ADTLSLAMRILACLSVGISQVEVDVRELLALQCKDGSWEPGSFYRFGSSKMNVGNRGLTTALATRAVELYQGTRIRSKG 
               
               
                   
               
               
                 TE 
               
               
                   
               
               
                 - GAO87501.1 cDNA 
               
               
                 SEQ ID NO: 24 
                   
               
               
                 ATGACCCGACAGAAATCGCCTCAATACAAAGCAATCATCTTTGACCTAGGGGATGTCTTTTTCACCTGGGACGCCC 
                   
               
               
                   
               
               
                 CCAAAGACACTGCTGTCTTGCCCAACCTCTTCAAGAAAATGCTTACCTCGCCAACCTGGTCAGATTACGAGCGCGG 
               
               
                   
               
               
                 CAAGTTGAGCGAAGAAAGCTGCTACGAGAGACTGGCCGAACAGTTTGACGTTGACTCGTCGGAAATCGCGCGCA 
               
               
                   
               
               
                 GCTTAAGGAAAGCACAGCAGTCTCTTACCACAGACGCAGCAATCGTGAGCCTGATATCAGAGATCAGAGCGTTGG 
               
               
                   
               
               
                 CCGGACATATTGCCATCTACGCCATGTCCAACATTTCCGCCCCAGCTTATGCAGCTGTGCTCCAGACTCAGCCCGAA 
               
               
                   
               
               
                 ATGGGCATCTTTGACGGAGTGTTCCCGTCTGGATGCTATGGGACGAGGAAGCCGGAGCTGTTGTTCTATAAGAAA 
               
               
                   
               
               
                 GTCTTGCAGGAGATTGCAGTGCCGCCAAATCAGATCATCTTTATTGATGATCAGCTAGAGAATGTAGTTTCTGCGC 
               
               
                   
               
               
                 AGTCAACAGGTATGCACGGCATTGTCTACACCGGTGCGGGTGAGCTCAGTCGACAGCTCAGAAATCTGGTGTTGG 
               
               
                   
               
               
                 ACCCTGTACAAAGGGGTCGAGAGTTTCTACGGCGCAATGCTGGGGCATTGTATAGTATCTGCGAGACTGGTCAAG 
               
               
                   
               
               
                 TCATCCGGGAAAACTTCTCGCAGCTGCTCATCCTAGAGGCGACGGGTGATAGAAGCCTGGTCAACCTTGAATATCA 
               
               
                   
               
               
                 GCAGCGGAGCTGGAATTTCTTTCAAGGAGGTCCCCCTTCTACGTCGGAAACATTCCCAGATGATGTCGACACAACA 
               
               
                   
               
               
                 TCCATTGCCTTGATGATTCTCCCTGCCGATGATAACACAGTCAACTCGGTTCTCGGCGAGATTTCCGAGGTAGCTAA 
               
               
                   
               
               
                 TGACGAGGGCATTGTAAATACGTACTTTGACCAGACCCGACAGCGAATCGACCCAGCAGTCTGCGTCAATGTCCTC 
               
               
                   
               
               
                 CGTCTCTTTTATACCTACGGCCGGGGCGCCACTCTCCCATTGACCCTCCAGTGGGTGTCCGACGTTCTTGAGCATCG 
               
               
                   
               
               
                 TGCGCACTTACATGGTACGCGATACTACCCCAGCCCGGAGGTTTTCCTCTACTTTGTCAGTCAACTCTGCCGGTTCT 
               
               
                   
               
               
                 CCAAGAGGGAACCGACGCTGCAGCTGCTGGAGACGTTGCTCACGGATCGCCTCAAGGAGCGCATTCAGGTCAAG 
               
               
                   
               
               
                 GCAGACACTCTGTCACTGGCTATGCGGATCCTGGCATGCTTGTCTGTGGGTATATCACAAGTTGAAGTGGATGTCC 
               
               
                   
               
               
                 GAGAGCTGCTCGCCTTGCAATGCAAGGATGGATCGTGGGAACCCGGCTCGTTTTACCGGTTTGGGTCGTCCAAGA 
               
               
                   
               
               
                 TGAACGTTGGTAATCGAGGTCTTACGACTGCGTTGGCGACTAGGGCGGTTGAGTTGTACCAGGGGACTAGAATAC 
               
               
                   
               
               
                 GCTCTAAGGGCACCGAGTAG 
               
               
                   
               
               
                 - GAO87501.1 optimized cDNA 
               
               
                 SEQ ID NO: 25 
                   
               
               
                 ATGACTCGCCAAAAAAGCCCTCAATACAAAGCAATTATCTTCGATCTGGGTGACGTTTTCTTCACCTGGGATGCGC 
                   
               
               
                   
               
               
                 CGAAAGATACGGCCGTACTGCCGAACCTGTTCAAGAAAATGCTGACCTCGCCGACCTGGAGCGACTATGAGCGTG 
               
               
                   
               
               
                 GTAAGCTGTCTGAGGAAAGCTGTTACGAACGCTTGGCCGAGCAATTTGACGTGGACAGCAGCGAGATCGCGCGT 
               
               
                   
               
               
                 AGCCTCCGTAAAGCGCAGCAAAGCCTGACGACCGACGCAGCCATCGTGAGCCTGATCAGCGAGATCCGCGCATTG 
               
               
                   
               
               
                 GCGGGTCACATTGCTATCTATGCTATGTCTAACATTTCTGCGCCAGCATACGCAGCGGTGTTACAGACCCAGCCGG 
               
               
                   
               
               
                 AAATGGGTATCTTTGATGGTGTTTTTCCGAGCGGCTGCTATGGTACGCGTAAACCGGAACTGCTGTTTTACAAAAA 
               
               
                   
               
               
                 AGTGCTTCAAGAAATTGCGGTTCCGCCGAATCAGATTATCTTCATTGACGATCAGCTGGAAAACGTCGTCAGCGCA 
               
               
                   
               
               
                 CAGTCCACGGGCATGCATGGCATTGTTTACACCGGTGCCGGTGAGCTGAGCCGTCAACTGCGTAATCTGGTCCTG 
               
               
                   
               
               
                 GACCCGGTGCAGCGTGGTCGTGAGTTCCTGCGCCGTAATGCTGGCGCCCTGTACAGCATTTGTGAGACTGGCCAA 
               
               
                   
               
               
                 GTTATCCGTGAGAACTTCAGCCAGCTGCTGATTCTGGAAGCAACCGGCGATCGTTCGCTGGTGAACCTGGAGTATC 
               
               
                   
               
               
                 AACAACGTTCCTGGAACTTCTTTCAGGGTGGCCCTCCATCCACGAGCGAAACTTTTCCGGATGATGTTGACACGAC 
               
               
                   
               
               
                 CTCAATCGCGCTGATGATTTTACCGGCGGACGATAATACCGTCAATAGCGTCCTGGGTGAAATCAGCGAAGTCGC 
               
               
                   
               
               
                 GAATGACGAGGGCATTGTGAATACCTATTTCGATCAGACCCGCCAACGTATCGATCCGGCCGTGTGTGTCAACGT 
               
               
                   
               
               
                 GTTGCGCCTGTTTTACACCTATGGTCGTGGCGCTACGCTGCCGTTGACCCTGCAATGGGTTAGCGACGTGCTGGAG 
               
               
                   
               
               
                 CACCGTGCGCATCTGCACGGCACCCGCTACTATCCGTCCCCAGAGGTTTTCCTGTACTTTGTCTCTCAGCTGTGCCG 
               
               
                   
               
               
                 TTTTTCCAAGCGCGAACCGACCCTGCAGCTGCTGGAAACGCTGTTGACCGACAGACTGAAGGAACGCATCCAAGT 
               
               
                   
               
               
                 TAAGGCAGATACGCTGAGCTTGGCAATGCGTATTTTGGCGTGCCTGAGCGTGGGCATCAGCCAGGTTGAGGTTGA 
               
               
                   
               
               
                 CGTCCGCGAACTGCTGGCGCTGCAGTGCAAGGACGGTAGCTGGGAGCCGGGTAGCTTCTACCGTTTCGGTAGCA 
               
               
                   
               
               
                 GCAAGATGAATGTCGGTAACCGCGGTCTGACGACCGCTTTGGCGACCCGTGCGGTTGAGCTGTACCAGGGTACGC 
               
               
                   
               
               
                 GTATTCGTAGCAAGGGCACCGAGTAA 
               
               
                   
               
               
                 XP_008034151.1 
               
               
                 - XP_008034151.1 protein 
               
               
                 SEQ ID NO: 26 
                   
               
               
                 MASPHRRYTTLILDLGDVLFSWSSKTNTPIPPKKLKEILSSLTWFEYERGRISQAECYDRVSSEFSLDAATIAEAFQQARDS 
                   
               
               
                   
               
               
                 LRPNEEFLALIRELRQQTHGQLTVLALSNISLPDYEYIMALDSDWTSVFDRVFPSALVGERKPHLGAYRRVISEMHLDPET 
               
               
                   
               
               
                 TVFVDDKLDNVVSARSLGMHGVVFDSQENVFQTLRNIFGDPIHRGRDYLRRHAGRLETSTDAGVVFEENFTQLIIYELT 
               
               
                   
               
               
                 NDKSLITTSDCPRTWNFFRGKPLFSASFPDDVDTTSVALTVLRPPRTLVNSILDEMLEYVDADGIMQTYFDHSRPRMDP 
               
               
                   
               
               
                 FVCVNVLSLFYEYGRGQDLPKTLEWVYEVLLHRAYIGGSRYYMSADCFLFFMSRLLQRITDPAVLNRLRPLFVERMHERV 
               
               
                   
               
               
                 SAPGDSMELAFRILAGSSVGIQFPRDLEKLLAAQCADGGWDLCWFYQYGSTGVKAGNRGLTTALAIKAIESAIARPPSP 
               
               
                   
               
               
                 ALSAVSSSKLEVPKPILQRPLSPRRLGDFLMPWRRAQREVAVSS 
               
               
                   
               
               
                 - XP_008034151.1 - cDNA 
               
               
                 SEQ ID NO: 27 
                   
               
               
                 ATGGCTTCACCTCACCGCAGGTATACGACACTCATCCTAGACCTGGGCGACGTCCTCTTCTCTTGGTCATCCAAGAC 
                   
               
               
                   
               
               
                 CAACACACCTATCCCTCCCAAGAAGCTGAAGGAGATCCTCTCGTCCCTGACCTGGTTCGAGTACGAGCGCGGTCGG 
               
               
                   
               
               
                 ATATCACAGGCCGAGTGCTATGACCGGGTCAGCTCCGAGTTCAGTCTTGACGCTGCCACCATCGCAGAAGCGTTCC 
               
               
                   
               
               
                 AGCAGGCTCGCGACTCTCTGCGACCGAACGAAGAGTTCCTGGCGTTGATTCGCGAACTCCGCCAACAAACGCATG 
               
               
                   
               
               
                 GTCAGCTTACCGTCCTCGCGCTCTCGAACATCTCACTCCCCGACTATGAATACATCATGGCTCTCGACTCGGACTGG 
               
               
                   
               
               
                 ACGTCGGTCTTCGACCGCGTCTTCCCTTCTGCCCTCGTCGGCGAGCGCAAGCCACATCTGGGGGCGTACCGCCGTG 
               
               
                   
               
               
                 TCATCTCTGAGATGCACCTAGACCCAGAAACGACCGTCTTTGTGGACGACAAGCTGGACAACGTGGTGTCCGCGC 
               
               
                   
               
               
                 GATCGCTCGGGATGCACGGCGTGGTCTTCGACTCCCAGGAGAACGTCTTCCAGACGCTGAGGAATATCTTCGGCG 
               
               
                   
               
               
                 ACCCGATACATCGCGGACGTGACTATCTCCGCAGGCATGCCGGTCGTCTGGAGACATCTACGGACGCCGGCGTTG 
               
               
                   
               
               
                 TCTTCGAGGAAAACTTTACGCAGCTCATCATCTACGAACTAACAAATGACAAATCCCTCATCACGACATCAGACTGT 
               
               
                   
               
               
                 CCCCGCACTTGGAACTTCTTCCGCGGGAAGCCCTTGTTCTCGGCCTCGTTTCCCGACGATGTGGACACGACGTCGG 
               
               
                   
               
               
                 TTGCCCTGACAGTGTTGCGCCCACCCCGCACGCTTGTCAACTCGATCTTGGACGAGATGCTAGAGTATGTCGACGC 
               
               
                   
               
               
                 CGACGGCATCATGCAGACCTACTTCGACCACTCGCGCCCGCGGATGGATCCGTTCGTCTGTGTCAACGTCCTGTCG 
               
               
                   
               
               
                 CTGTTCTACGAGTACGGCCGGGGACAGGACCTCCCGAAGACCCTCGAATGGGTATACGAGGTTCTGCTGCACCGC 
               
               
                   
               
               
                 GCCTACATCGGCGGCTCGCGGTACTACATGTCCGCGGACTGCTTCCTCTTCTTCATGAGCCGCCTTCTCCAACGTAT 
               
               
                   
               
               
                 CACCGACCCAGCCGTCCTGAACCGCCTCCGCCCGTTGTTCGTCGAGCGCATGCACGAACGTGTCAGCGCACCGGG 
               
               
                   
               
               
                 CGACTCCATGGAGCTCGCGTTCCGCATCCTCGCTGGCTCGTCCGTCGGCATCCAGTTCCCACGTGACCTGGAGAAG 
               
               
                   
               
               
                 CTCCTCGCCGCGCAGTGCGCCGACGGCGGCTGGGACCTGTGCTGGTTCTACCAGTATGGGTCCACCGGCGTGAAG 
               
               
                   
               
               
                 GCAGGCAACCGCGGGCTCACCACCGCGCTCGCCATCAAGGCTATCGAGAGCGCTATCGCGCGCCCTCCGTCCCCC 
               
               
                   
               
               
                 GCTCTATCAGCTGTATCGTCGTCGAAACTGGAAGTGCCGAAACCAATTCTCCAGCGTCCCCTCAGCCCGCGCCGGC 
               
               
                   
               
               
                 TTGGCGACTTCCTGATGCCCTGGAGGAGAGCACAGCGCGAGGTCGCGGTTTCCAGCTAG 
               
               
                   
               
               
                 - XP_008034151 - optimized cDNA 
               
               
                 SEQ ID NO: 28 
                   
               
               
                 ATGGCTAGCCCGCACCGTCGCTATACTACTCTGATTCTGGATTTGGGTGATGTTTTGTTTAGCTGGAGCAGCAAAA 
                   
               
               
                   
               
               
                 CCAATACGCCTATTCCGCCGAAAAAGCTGAAAGAAATCCTGTCTAGCCTGACCTGGTTCGAGTACGAGCGCGGTC 
               
               
                   
               
               
                 GCATTTCTCAAGCCGAGTGCTATGACCGTGTGAGCTCTGAGTTTAGCCTGGACGCAGCGACCATTGCAGAGGCATT 
               
               
                   
               
               
                 CCAACAGGCTCGTGACTCGCTGCGCCCGAACGAAGAATTTCTGGCGTTGATTCGTGAGCTGCGCCAGCAGACCCA 
               
               
                   
               
               
                 CGGCCAACTCACCGTTCTGGCACTGAGCAACATCTCCCTGCCGGATTACGAGTACATCATGGCTCTGGATAGCGAT 
               
               
                   
               
               
                 TGGACCAGCGTCTTTGATAGAGTTTTCCCGAGCGCGCTGGTTGGTGAGCGTAAGCCGCATCTGGGTGCTTACCGTC 
               
               
                   
               
               
                 GTGTCATTAGCGAGATGCATCTGGACCCGGAGACTACGGTGTTTGTGGACGACAAACTGGACAACGTTGTCTCCG 
               
               
                   
               
               
                 CGCGCAGCCTGGGTATGCACGGCGTCGTTTTTGACTCACAAGAAAATGTTTTCCAGACGCTGCGTAACATTTTCGG 
               
               
                   
               
               
                 TGACCCTATCCACCGTGGCCGCGACTATTTGCGTCGTCATGCCGGTCGTTTGGAAACCAGCACCGACGCGGGCGTT 
               
               
                   
               
               
                 GTTTTTGAAGAAAACTTCACCCAGCTGATCATCTACGAACTGACGAATGACAAGAGCCTGATCACCACGAGCGATT 
               
               
                   
               
               
                 GTCCGCGCACCTGGAACTTCTTCCGTGGTAAGCCGCTGTTTAGCGCGTCCTTCCCAGACGATGTCGATACGACTTC 
               
               
                   
               
               
                 GGTGGCCCTGACCGTTCTGCGCCCACCGCGCACCCTGGTAAACAGCATCCTGGACGAAATGTTAGAATACGTCGA 
               
               
                   
               
               
                 TGCGGATGGTATTATGCAGACCTATTTCGACCACAGCCGTCCGCGCATGGACCCGTTTGTGTGTGTGAATGTGTTG 
               
               
                   
               
               
                 AGCCTGTTCTATGAGTACGGCCGTGGTCAAGATCTGCCAAAAACCCTGGAATGGGTCTACGAAGTCCTTCTGCATC 
               
               
                   
               
               
                 GTGCCTACATCGGTGGCTCCCGTTATTACATGAGCGCAGATTGCTTTTTGTTCTTTATGTCTCGTCTGCTGCAGCGC 
               
               
                   
               
               
                 ATCACGGACCCTGCCGTGCTGAATCGTCTGCGTCCGCTGTTCGTGGAGCGTATGCACGAGCGCGTGTCTGCCCCG 
               
               
                   
               
               
                 GGTGACAGCATGGAACTGGCGTTCCGTATCCTGGCGGGCAGCAGCGTGGGTATTCAATTTCCGCGTGATTTGGAG 
               
               
                   
               
               
                 AAACTGCTGGCTGCGCAGTGTGCGGACGGTGGCTGGGATCTGTGCTGGTTTTATCAATACGGTAGCACCGGCGTT 
               
               
                   
               
               
                 AAGGCCGGCAATCGTGGCCTGACGACGGCACTGGCAATTAAGGCCATTGAGTCCGCGATTGCGCGTCCGCCGAG 
               
               
                   
               
               
                 CCCGGCATTGAGCGCGGTCAGCAGCAGCAAACTGGAAGTGCCGAAGCCGATCTTGCAGCGTCCACTGAGCCCGC 
               
               
                   
               
               
                 GTCGTCTGGGTGACTTCCTGATGCCGTGGCGCCGTGCGCAACGCGAAGTCGCGGTTAGCTCCTAA 
               
               
                   
               
               
                 XP_007369631.1 
               
               
                 - XP_007369631.1 protein 
               
               
                 SEQ ID NO: 29 
                   
               
               
                 MASIHRRYTTLILDLGDVLFRWSPKTETAIPPQQLKDILSSVTWFEYERGRLSQEACYERCAEEFKIEASVIAEAFKQARGS 
                   
               
               
                   
               
               
                 LRPNEEFIALIRDLRREMHGDLTVLALSNISLPDYEYIMSLSSDWTTVFDRVFPSALVGERKPHLGCYRKVISEMNLEPQT 
               
               
                   
               
               
                 TVFVDDKLDNVASARSLGMHGIVFDNQANVFRQLRNIFGDPIRRGQEYLRGHAGKLESSTDNGLIFEENFTQLIIYELTQ 
               
               
                   
               
               
                 DRTLISLSECPRTWNFFRGEPLFSETFPDDVDTTSVALTVLQPDRALVNSVLDEMLEYVDADGIMQTYFDRSRPRMDPF 
               
               
                   
               
               
                 VCVNVLSLFYENGRGHELPRTLDWVYEVLLHRAYHGGSRYYLSPDCFLFFMSRLLKRADDPAVQARLRPLFVERVNERV 
               
               
                   
               
               
                 GAAGDSMDLAFRILAAASVGVQCPRDLERLTAGQCDDGGWDLCWFYVFGSTGVKAGNRGLTTALAVTAIQTAIGRPP 
               
               
                   
               
               
                 SPSPSAASSSFRPSSPYKFLGISRPASPIRFGDLLRPWRKMSRSNLKSQ 
               
               
                   
               
               
                 - XP_007369631.1 cDNA 
               
               
                 SEQ ID NO: 30 
                   
               
               
                 ATGGCCTCAATCCACCGTCGATACACTACTCTCATCCTCGACCTCGGCGACGTACTCTTTCGTTGGTCTCCAAAGAC 
                   
               
               
                   
               
               
                 TGAGACCGCCATTCCACCTCAACAACTCAAGGATATCCTCTCCTCTGTCACCTGGTTTGAGTACGAACGCGGCAGA 
               
               
                   
               
               
                 CTATCCCAGGAAGCATGCTACGAGCGCTGCGCCGAGGAGTTCAAGATAGAGGCCTCGGTCATTGCAGAAGCCTTT 
               
               
                   
               
               
                 AAGCAGGCTCGCGGGTCACTGCGGCCCAACGAGGAGTTCATCGCCTTGATCCGTGACCTCCGCCGTGAGATGCAC 
               
               
                   
               
               
                 GGTGACCTTACCGTTCTTGCCCTCTCCAACATCTCCCTCCCCGACTACGAATACATCATGTCGCTAAGCTCAGATTG 
               
               
                   
               
               
                 GACGACCGTCTTCGATCGCGTATTCCCCTCTGCACTCGTTGGCGAGCGCAAGCCTCATCTGGGATGCTATCGCAAG 
               
               
                   
               
               
                 GTCATCTCGGAGATGAACCTAGAACCTCAGACGACTGTGTTCGTGGATGACAAGCTTGACAACGTCGCGTCTGCTC 
               
               
                   
               
               
                 GCTCACTTGGTATGCACGGCATCGTGTTTGACAACCAAGCCAACGTCTTCCGCCAACTCCGCAATATCTTCGGAGA 
               
               
                   
               
               
                 CCCCATCCGCCGTGGCCAAGAGTATCTCCGTGGGCATGCTGGCAAACTCGAGTCTTCGACCGACAACGGGTTGAT 
               
               
                   
               
               
                 CTTCGAGGAGAACTTCACACAGCTGATCATCTACGAGTTGACGCAAGACAGGACTCTCATCTCGCTTTCAGAATGT 
               
               
                   
               
               
                 CCTCGTACTTGGAATTTCTTCCGAGGCGAACCGCTATTCTCGGAGACCTTCCCGGATGATGTCGACACAACATCTGT 
               
               
                   
               
               
                 GGCGTTGACGGTATTGCAACCGGACAGAGCACTGGTCAACTCCGTTCTAGACGAGATGCTGGAGTATGTCGACGC 
               
               
                   
               
               
                 CGATGGCATCATGCAGACATACTTCGATCGTTCACGACCACGCATGGACCCCTTCGTCTGCGTGAACGTACTCTCCC 
               
               
                   
               
               
                 TGTTCTACGAGAACGGTCGTGGTCACGAGCTCCCTCGCACATTGGACTGGGTCTACGAGGTGCTCCTCCATCGCGC 
               
               
                   
               
               
                 GTACCACGGCGGTTCGCGTTATTACCTGTCGCCCGACTGCTTTCTATTCTTCATGAGCCGCCTACTCAAGCGCGCAG 
               
               
                   
               
               
                 ACGATCCAGCAGTCCAGGCTCGGCTCCGCCCGCTCTTCGTCGAGCGGGTGAACGAGCGAGTAGGCGCCGCTGGC 
               
               
                   
               
               
                 GACTCGATGGACCTCGCCTTCCGCATCCTCGCCGCAGCGTCTGTTGGCGTCCAGTGCCCCCGCGATCTGGAAAGGT 
               
               
                   
               
               
                 TGACTGCCGGGCAATGCGACGACGGTGGATGGGACCTCTGCTGGTTCTACGTGTTCGGCTCGACGGGCGTGAAG 
               
               
                   
               
               
                 GCGGGCAACCGCGGCCTCACAACGGCCCTCGCTGTCACGGCCATACAGACGGCCATCGGACGCCCCCCTTCGCCC 
               
               
                   
               
               
                 AGTCCCTCCGCGGCCTCCTCGTCTTTCAGACCTAGTTCCCCTTACAAATTCCTAGGCATTTCGCGCCCAGCTAGCCCC 
               
               
                   
               
               
                 ATTCGCTTTGGCGACTTACTTCGCCCATGGCGGAAGATGAGCAGGTCGAACTTGAAGTCTCAATGA 
               
               
                   
               
               
                 - XP_007369631.1 optimized cDNA 
               
               
                 SEQ ID NO: 31 
                   
               
               
                 ATGGCAAGCATTCATCGTCGCTATACTACGCTGATTCTGGACCTGGGTGATGTTTTGTTCCGCTGGAGCCCGAAAA 
                   
               
               
                   
               
               
                 CCGAGACTGCGATTCCTCCGCAACAACTGAAAGACATCCTGAGCAGCGTCACCTGGTTCGAGTACGAGCGTGGCC 
               
               
                   
               
               
                 GTCTGAGCCAAGAGGCTTGCTACGAGCGTTGCGCCGAAGAGTTCAAGATTGAAGCCAGCGTGATTGCGGAAGCG 
               
               
                   
               
               
                 TTCAAACAAGCGCGTGGTAGCCTGCGTCCGAACGAAGAATTTATCGCACTGATCCGTGATCTGCGTCGCGAGATG 
               
               
                   
               
               
                 CATGGTGACCTGACCGTTCTGGCTCTGAGCAATATCTCGTTGCCGGATTACGAGTATATTATGTCTCTGAGCAGCG 
               
               
                   
               
               
                 ACTGGACGACGGTCTTTGATCGTGTGTTCCCGTCAGCTCTGGTGGGCGAGCGTAAACCGCACTTGGGTTGCTATCG 
               
               
                   
               
               
                 CAAGGTCATCAGCGAGATGAACCTGGAACCTCAGACCACGGTCTTTGTGGACGATAAACTGGATAATGTCGCAAG 
               
               
                   
               
               
                 CGCGCGTAGCCTGGGTATGCACGGTATCGTGTTTGATAATCAAGCGAATGTGTTTCGCCAGCTGCGTAATATTTTC 
               
               
                   
               
               
                 GGTGATCCAATCCGTCGCGGTCAAGAGTATCTGCGTGGCCATGCCGGTAAATTGGAGAGCAGCACGGACAATGG 
               
               
                   
               
               
                 TTTGATCTTTGAAGAGAACTTCACCCAGCTGATCATTTATGAACTGACCCAGGACCGCACGTTGATCAGCCTGTCG 
               
               
                   
               
               
                 GAGTGTCCGCGTACCTGGAACTTCTTCCGTGGCGAGCCGTTGTTTTCTGAAACCTTCCCGGACGACGTGGACACCA 
               
               
                   
               
               
                 CGTCCGTTGCACTGACGGTTCTGCAACCGGATCGCGCACTGGTTAACAGCGTGCTGGACGAAATGCTGGAATATG 
               
               
                   
               
               
                 TCGATGCGGATGGCATCATGCAGACGTATTTCGACCGCTCGCGTCCGCGTATGGACCCGTTTGTTTGCGTCAACGT 
               
               
                   
               
               
                 ACTGAGCCTGTTTTACGAGAACGGTCGTGGTCACGAACTGCCGCGCACTCTGGATTGGGTGTACGAAGTCCTGCTC 
               
               
                   
               
               
                 CACCGCGCCTACCACGGTGGTTCCCGTTACTACCTGAGCCCGGACTGTTTCTTGTTTTTTATGAGCCGTCTGCTGAA 
               
               
                   
               
               
                 ACGTGCAGACGACCCAGCGGTTCAGGCGAGATTGCGTCCGCTGTTTGTGGAACGCGTTAACGAACGTGTTGGCGC 
               
               
                   
               
               
                 GGCCGGTGATAGCATGGACCTGGCGTTTCGCATTCTGGCCGCAGCGAGCGTGGGTGTGCAGTGTCCGCGCGACCT 
               
               
                   
               
               
                 GGAGCGTCTGACCGCTGGTCAATGCGATGATGGCGGCTGGGATCTGTGTTGGTTCTACGTTTTCGGCAGCACCGG 
               
               
                   
               
               
                 CGTTAAGGCCGGTAATCGTGGTCTGACCACGGCGCTGGCAGTCACCGCGATCCAGACCGCCATCGGCCGTCCGCC 
               
               
                   
               
               
                 TAGCCCGAGCCCGTCCGCGGCAAGCTCCAGCTTCCGCCCGAGCAGCCCGTACAAGTTTCTGGGTATTAGCCGTCCG 
               
               
                   
               
               
                 GCGTCCCCAATTCGCTTCGGTGACCTTCTGCGTCCGTGGCGTAAAATGTCTCGCTCTAACCTGAAGTCCCAGTAA 
               
               
                   
               
               
                 ACg006372 
               
               
                 - ACg006372 protein 
               
               
                 SEQ ID NO: 32 
                   
               
               
                 MRRNVLNKATHSQSPLKPNITTLIFDLGDVLLTWSDSTPKSPLPPKIVKGILRSLTWFEYEKGNLTESQTYGQVAQEFGV 
                   
               
               
                   
               
               
                 DASEVKASFEAARDSLKSNPMLLQLIRSLKDSGHVIYAMSNISAPDWEFLKTRADLSDWALFDRVFPSAEAHDRKPNIG 
               
               
                   
               
               
                 FYQHVINETGLNPSNTVFVDDRIENVVSARSAGMHGIVFDDINNVIRQLKNLCEDPIHRARSFLYANKKCLNTVSTDGTI 
               
               
                   
               
               
                 VSENFSQLLILEAIGDESLVDFVRHEGRFNFFQGEAKLIMTNHYPDDFDTTSIGLTVVPYIDDKTRNRVMDEILAYQSEDG 
               
               
                   
               
               
                 IVLVYFDHKRPRIDPVVCVNVLTLFYRYGRGHQLQKTLDWVEQVLINRACASGTFYYATEEQFLFFLSRLIQSSPDVRQRL 
               
               
                   
               
               
                 EGVFKRRVVERFGADGDALAMAMRIHTAASVGLVDHVDLDKLFALQQNDGSWRDSAFYRFPSARQLASNDGLTTAIA 
               
               
                   
               
               
                 IQAIQAAERLREDGNVL 
               
               
                   
               
               
                 - ACg006372 cDNA 
               
               
                 SEQ ID NO: 33 
                   
               
               
                 ATGAGGCGAAACGTACTCAACAAAGCAACACATTCTCAGTCACCATTGAAGCCCAACATCACGACGCTCATATTTG 
                   
               
               
                   
               
               
                 ACTTGGGCGACGTACTTCTCACGTGGTCCGACTCAACACCTAAATCTCCACTGCCCCCAAAAATTGTCAAGGGAAT 
               
               
                   
               
               
                 ACTACGTTCACTGACCTGGTTTGAGTACGAGAAAGGGAACTTGACAGAGTCCCAGACCTACGGGCAAGTTGCTCA 
               
               
                   
               
               
                 GGAATTTGGAGTGGATGCTTCCGAAGTCAAAGCTTCCTTCGAAGCAGCTCGCGACTCGCTCAAGAGCAACCCAAT 
               
               
                   
               
               
                 GCTTCTCCAGTTGATCCGTAGCCTCAAAGACTCTGGCCACGTCATTTACGCAATGTCTAACATATCTGCTCCCGACT 
               
               
                   
               
               
                 GGGAATTTTTGAAGACGCGGGCAGACCTCTCAGATTGGGCTCTTTTTGACAGAGTCTTCCCTTCTGCCGAAGCGCA 
               
               
                   
               
               
                 TGACCGCAAGCCGAACATTGGTTTCTATCAGCACGTCATAAACGAGACTGGTCTGAACCCGTCCAACACTGTCTTT 
               
               
                   
               
               
                 GTCGATGACAGGATCGAGAATGTTGTATCCGCACGCTCAGCAGGAATGCACGGGATCGTGTTTGACGACATAAAT 
               
               
                   
               
               
                 AATGTGATCCGACAGTTGAAAAACCTCTGCGAGGATCCGATTCACCGCGCACGATCTTTTCTTTATGCAAATAAGA 
               
               
                   
               
               
                 AGTGTTTGAATACGGTTAGCACAGATGGCACAATTGTGAGCGAGAACTTCTCGCAATTGTTGATCCTTGAGGCCAT 
               
               
                   
               
               
                 TGGCGACGAAAGCCTAGTCGACTTTGTGAGGCATGAGGGCCGATTCAACTTCTTCCAGGGGGAGGCCAAACTCAT 
               
               
                   
               
               
                 CATGACGAATCACTACCCCGATGATTTCGATACTACATCCATAGGTTTAACCGTTGTTCCATATATTGACGACAAGA 
               
               
                   
               
               
                 CTAGAAATAGAGTTATGGATGAGATCCTGGCCTACCAAAGCGAAGACGGCATTGTGCTGGTATACTTTGACCACA 
               
               
                   
               
               
                 AGCGCCCCAGGATTGATCCTGTTGTCTGTGTCAATGTCCTCACCCTCTTCTATAGGTATGGCCGTGGGCACCAGCTT 
               
               
                   
               
               
                 CAAAAGACACTGGATTGGGTCGAACAGGTCCTGATCAACCGTGCGTGTGCGTCCGGCACGTTCTATTACGCAACA 
               
               
                   
               
               
                 GAGGAACAATTCCTCTTTTTCCTCTCCCGCCTGATCCAAAGCTCTCCGGACGTACGACAGCGGTTGGAAGGGGTCT 
               
               
                   
               
               
                 TTAAAAGAAGAGTAGTCGAGCGGTTTGGTGCAGACGGCGACGCTCTCGCTATGGCGATGCGCATTCACACCGCGG 
               
               
                   
               
               
                 CGAGCGTGGGCCTCGTTGACCATGTCGATCTTGACAAGCTGTTCGCATTGCAGCAAAATGACGGTTCTTGGAGAG 
               
               
                   
               
               
                 ACAGCGCTTTCTACAGATTTCCGTCGGCCAGGCAACTGGCTAGTAACGACGGCTTGACGACTGCAATCGCTATTCA 
               
               
                   
               
               
                 GGCCATTCAAGCTGCGGAGAGGCTCAGGGAGGATGGGAACGTGCTTTGA 
               
               
                   
               
               
                 - ACg006372 optimized cDNA 
               
               
                 SEQ ID NO: 34 
                   
               
               
                 ATGCGCCGTAATGTCCTGAACAAAGCAACCCATAGCCAGTCACCGTTGAAACCGAATATCACCACGCTGATTTTTG 
                   
               
               
                   
               
               
                 ACTTGGGCGATGTCCTGCTGACCTGGAGCGACAGCACTCCGAAATCTCCGTTGCCGCCGAAGATCGTCAAGGGCA 
               
               
                   
               
               
                 TCCTGCGTAGCCTGACTTGGTTCGAGTACGAAAAGGGCAATTTGACCGAAAGCCAAACGTATGGTCAGGTCGCGC 
               
               
                   
               
               
                 AAGAATTTGGTGTGGATGCCTCTGAAGTGAAGGCCAGCTTTGAGGCTGCGCGTGATAGCTTGAAATCGAATCCGA 
               
               
                   
               
               
                 TGCTGCTGCAGCTGATTCGCAGCCTGAAAGATTCCGGTCACGTGATCTACGCCATGAGCAACATCAGCGCGCCTGA 
               
               
                   
               
               
                 TTGGGAATTTCTGAAAACCCGCGCTGACCTGTCTGACTGGGCCCTGTTTGACCGCGTGTTCCCGTCTGCCGAGGCA 
               
               
                   
               
               
                 CATGACCGCAAACCGAACATTGGCTTTTACCAACACGTGATCAATGAAACGGGTCTGAATCCATCCAATACCGTGT 
               
               
                   
               
               
                 TCGTTGACGACCGTATTGAAAACGTTGTTAGCGCACGTAGCGCTGGTATGCACGGTATCGTTTTCGATGACATTAA 
               
               
                   
               
               
                 CAACGTCATTCGCCAGCTGAAGAATCTGTGCGAGGACCCAATTCACCGTGCACGTTCCTTTTTGTATGCGAACAAA 
               
               
                   
               
               
                 AAGTGCCTGAATACCGTGAGCACCGATGGTACGATCGTCAGCGAGAACTTTAGCCAGCTTCTGATTCTGGAAGCC 
               
               
                   
               
               
                 ATTGGTGACGAGTCCCTGGTAGACTTCGTCCGCCATGAGGGCCGTTTTAACTTCTTCCAGGGTGAGGCAAAGCTGA 
               
               
                   
               
               
                 TCATGACCAATCACTACCCGGACGATTTCGATACCACGAGCATTGGTCTGACCGTTGTCCCGTATATCGATGACAA 
               
               
                   
               
               
                 AACGCGTAATCGTGTGATGGATGAAATCCTGGCGTATCAGTCCGAGGATGGTATCGTTCTGGTGTACTTCGATCAC 
               
               
                   
               
               
                 AAGCGTCCGCGCATTGACCCGGTCGTTTGTGTGAACGTTCTGACGCTGTTCTACCGCTATGGTCGTGGCCATCAAC 
               
               
                   
               
               
                 TGCAGAAAACCCTGGACTGGGTTGAGCAAGTCCTGATTAATCGTGCGTGTGCGAGCGGCACGTTCTACTACGCGA 
               
               
                   
               
               
                 CCGAAGAACAGTTCCTGTTTTTCCTGAGCCGTCTGATTCAGTCGAGCCCTGACGTGCGCCAACGTCTGGAAGGCGT 
               
               
                   
               
               
                 GTTCAAGCGTCGTGTCGTTGAGCGCTTTGGTGCGGACGGTGATGCCCTGGCAATGGCGATGCGTATCCATACCGC 
               
               
                   
               
               
                 AGCGAGCGTTGGCCTGGTGGACCACGTGGATCTGGATAAGCTGTTCGCGCTGCAACAGAACGACGGTAGCTGGC 
               
               
                   
               
               
                 GCGATAGCGCGTTTTATCGTTTTCCGAGCGCGCGTCAACTCGCGAGCAACGACGGCTTGACCACGGCAATTGCTAT 
               
               
                   
               
               
                 TCAGGCCATCCAAGCGGCTGAGAGATTACGTGAGGATGGTAACGTTCTGTAA 
               
               
                   
               
               
                 KIA75676.1 
               
               
                 - KIA75676.1 protein 
               
               
                 SEQ ID NO: 35 
                   
               
               
                 MVRALILDLGDVLFNWDAPKSTPVSRKTLSQMLHSDIWGEYECGQLTEPESYKALASRYSCQAQDVADTFYLARESLRL 
                   
               
               
                   
               
               
                 DATFKTFLQDLKQRANGSLRVYGMSNISQPDYEVLLSKADDLSLFDKIFPSGHVGMRKPDLAFFRHVLREISTASEDIVFV 
               
               
                   
               
               
                 DDNLENVTSARSLGMQGIVFRDKEDVQRQLRNLFGSPAERGREYLSINKTKLQSVTTTNIPILDNFGQLLILEATRDPDLV 
               
               
                   
               
               
                 SMHPGQRTWNFFIGSPTLTTDAFPDDMDTTSLGLSIIPPSPEIAASVMDEIVTRLNKDGIVPTYFDSTRPRVDPIVCVNVL 
               
               
                   
               
               
                 TLFAKYGREDELSGTIAWVRDVLYHRAYLAGTRYYASPEAFLFFFTRFTRNLRPGPRKQELTALLSQRLQERNKTPVDALA 
               
               
                   
               
               
                 LSMRIIACLTLGIESPADDVATLTGMQCGDGGWPACVIYKYGAGGLGITNRGVSTAFAVKAITTTPLAVQPEVSVSAGA 
               
               
                   
               
               
                 GGSSRPVGADAAAVSLRPRWRAVVQSLHPLSRVGGLVAVIFAALHFNLAWLYNVSLASRIV 
               
               
                   
               
               
                 - KIA75676.1 cDNA 
               
               
                 SEQ ID NO: 36 
                   
               
               
                 ATGGTCCGCGCACTGATTCTCGATCTCGGCGACGTCCTCTTCAACTGGGACGCCCCAAAGTCAACCCCCGTTTCCCG 
                   
               
               
                   
               
               
                 CAAGACACTCAGCCAGATGCTGCATAGCGACATCTGGGGCGAATACGAATGTGGCCAACTGACAGAGCCGGAAA 
               
               
                   
               
               
                 GCTACAAGGCGCTTGCCAGCCGCTATTCTTGCCAGGCTCAAGATGTTGCAGATACCTTCTATCTAGCCCGCGAATC 
               
               
                   
               
               
                 GCTGAGGCTCGATGCGACCTTCAAGACCTTCCTGCAGGACTTGAAGCAGAGGGCCAACGGCTCACTTCGCGTATA 
               
               
                   
               
               
                 TGGGATGTCCAACATCTCCCAGCCCGATTATGAGGTCCTGCTGTCCAAGGCGGATGACTTGAGCCTGTTTGACAAG 
               
               
                   
               
               
                 ATCTTCCCATCCGGCCACGTCGGGATGCGTAAGCCTGACCTTGCGTTTTTTCGACATGTCCTGCGTGAGATCTCGAC 
               
               
                   
               
               
                 GGCCAGCGAGGATATTGTGTTTGTTGACGACAACCTGGAGAACGTGACATCTGCCCGGTCTCTGGGCATGCAGGG 
               
               
                   
               
               
                 GATTGTCTTTCGCGACAAGGAGGATGTACAGAGACAGCTGCGGAACCTCTTTGGCAGTCCTGCTGAACGTGGAAG 
               
               
                   
               
               
                 GGAGTATTTGTCCATCAACAAGACAAAGCTCCAGAGCGTCACGACGACCAATATCCCCATTCTCGACAACTTTGGC 
               
               
                   
               
               
                 CAGCTCCTTATCCTCGAAGCCACCAGAGACCCAGACCTGGTGTCCATGCATCCTGGACAGAGGACCTGGAACTTTT 
               
               
                   
               
               
                 TCATCGGATCTCCAACTCTGACAACGGACGCCTTCCCAGACGATATGGACACCACCTCACTTGGCCTTTCTATTATA 
               
               
                   
               
               
                 CCCCCAAGTCCCGAGATTGCAGCGTCCGTGATGGATGAGATTGTGACCCGCCTGAACAAGGACGGCATTGTCCCA 
               
               
                   
               
               
                 ACATATTTTGACAGCACCAGACCCCGCGTCGACCCGATCGTCTGCGTCAACGTTCTCACCCTCTTCGCTAAATACGG 
               
               
                   
               
               
                 CCGCGAAGACGAGCTGTCCGGGACCATAGCCTGGGTGCGCGATGTGCTGTATCACAGGGCCTACCTTGCAGGGA 
               
               
                   
               
               
                 CCAGATACTACGCATCCCCAGAAGCATTCCTTTTCTTCTTCACGCGCTTCACCCGAAACCTGCGCCCGGGCCCGCGC 
               
               
                   
               
               
                 AAGCAGGAGCTCACGGCGCTGCTGTCCCAGCGCCTGCAGGAGCGCAACAAGACGCCCGTTGACGCACTTGCGCTC 
               
               
                   
               
               
                 TCGATGCGGATTATTGCGTGCCTCACGCTGGGTATTGAATCCCCCGCTGACGACGTGGCTACCCTCACGGGCATGC 
               
               
                   
               
               
                 AGTGTGGGGATGGCGGGTGGCCGGCCTGTGTCATCTACAAGTACGGCGCCGGTGGGCTGGGGATCACGAACAG 
               
               
                   
               
               
                 GGGGGTCTCGACCGCGTTTGCTGTCAAGGCAATCACTACTACTCCTTTGGCGGTGCAGCCTGAAGTTAGTGTCAGC 
               
               
                   
               
               
                 GCAGGTGCAGGAGGCAGCAGTCGCCCTGTGGGTGCCGATGCTGCTGCAGTCTCGCTCCGCCCGAGATGGCGAGC 
               
               
                   
               
               
                 TGTTGTGCAGAGTCTCCATCCGCTCTCTCGGGTTGGTGGGTTGGTGGCCGTCATTTTTGCTGCACTGCATTTCAACT 
               
               
                   
               
               
                 TGGCCTGGCTTTATAATGTGTCCCTTGCTAGTAGGATCGTTTAG 
               
               
                   
               
               
                 - KIA75676.1 optimized cDNA 
               
               
                 SEQ ID NO: 37 
                   
               
               
                 ATGGTTCGTGCATTGATTTTGGATTTGGGTGATGTGTTGTTTAACTGGGATGCGCCTAAGAGCACCCCGGTTTCCC 
                   
               
               
                   
               
               
                 GCAAGACTCTGAGCCAAATGCTGCACTCGGATATTTGGGGCGAGTACGAGTGTGGTCAACTGACTGAGCCGGAGT 
               
               
                   
               
               
                 CCTATAAAGCCCTGGCGAGCCGCTATAGCTGCCAGGCGCAAGATGTCGCTGACACCTTTTACCTGGCGCGTGAGA 
               
               
                   
               
               
                 GCCTGCGTCTGGACGCAACGTTTAAGACCTTCCTGCAAGATCTGAAGCAACGCGCCAACGGTTCTCTGCGTGTCTA 
               
               
                   
               
               
                 TGGTATGAGCAATATCAGCCAGCCGGATTACGAAGTCCTGCTGAGCAAAGCTGACGATCTCAGCCTGTTTGACAA 
               
               
                   
               
               
                 AATCTTTCCGTCGGGTCACGTTGGTATGAGAAAGCCTGACCTGGCGTTTTTCCGTCACGTTCTGCGTGAGATCAGC 
               
               
                   
               
               
                 ACGGCTAGCGAAGATATTGTGTTTGTTGACGACAATTTGGAAAACGTCACGTCTGCACGCTCCCTGGGTATGCAAG 
               
               
                   
               
               
                 GCATCGTCTTTCGTGATAAGGAAGATGTCCAGCGCCAGCTGCGCAATCTGTTCGGTTCCCCGGCAGAGCGCGGTC 
               
               
                   
               
               
                 GTGAGTATCTGAGCATTAATAAGACCAAACTGCAGAGCGTGACCACCACCAATATCCCGATTCTGGACAACTTCGG 
               
               
                   
               
               
                 TCAGTTGCTGATCCTGGAAGCTACCCGTGACCCGGATTTAGTCAGCATGCATCCAGGCCAACGTACGTGGAACTTC 
               
               
                   
               
               
                 TTCATTGGCAGCCCGACCTTGACGACCGACGCGTTTCCGGACGATATGGACACGACTTCTCTGGGCCTGAGCATCA 
               
               
                   
               
               
                 TCCCGCCGAGCCCGGAAATTGCAGCAAGCGTTATGGACGAAATCGTCACCCGTCTGAATAAAGATGGTATTGTGC 
               
               
                   
               
               
                 CGACCTACTTCGACAGCACGCGTCCACGTGTGGACCCGATCGTCTGCGTTAACGTCCTGACCTTGTTTGCGAAATA 
               
               
                   
               
               
                 TGGTCGTGAAGATGAACTGAGCGGCACGATTGCGTGGGTCCGCGACGTTCTGTATCATCGCGCATACCTGGCGGG 
               
               
                   
               
               
                 CACGCGCTACTACGCGTCCCCAGAGGCCTTCCTGTTCTTCTTTACGCGTTTCACCCGCAATCTGCGTCCGGGTCCGC 
               
               
                   
               
               
                 GTAAACAAGAACTTACGGCGCTGCTGAGCCAGCGTCTGCAGGAACGCAACAAGACGCCGGTTGACGCTCTGGCCC 
               
               
                   
               
               
                 TGAGCATGCGTATCATCGCCTGTCTGACCCTGGGCATTGAGAGCCCGGCAGACGACGTGGCCACCCTGACCGGTA 
               
               
                   
               
               
                 TGCAGTGTGGTGATGGTGGCTGGCCGGCGTGCGTGATCTACAAATATGGTGCGGGTGGCTTGGGTATCACGAAT 
               
               
                   
               
               
                 CGTGGCGTTAGCACTGCCTTCGCGGTGAAAGCGATTACGACCACCCCGCTGGCAGTGCAGCCAGAAGTCAGCGTC 
               
               
                   
               
               
                 AGCGCTGGTGCCGGCGGCTCCAGCCGCCCGGTTGGTGCGGATGCGGCAGCGGTTAGCTTGCGTCCGCGTTGGCG 
               
               
                   
               
               
                 TGCGGTTGTGCAGAGCCTGCATCCGCTGAGCCGCGTGGGTGGCCTGGTTGCCGTGATCTTCGCGGCACTGCACTT 
               
               
                   
               
               
                 TAACCTGGCGTGGCTGTACAACGTAAGCCTGGCTAGCCGTATTGTGTAA 
               
               
                   
               
               
                 XP_001820867.2 
               
               
                 - XP_001820867.2 protein 
               
               
                 SEQ ID NO: 38 
                   
               
               
                 MTRWKSSQYQAIIFDLGGVILTWDLPEDTVISAQIFKRMLTSQTWSDYERGNLSENGCYQRLAEDFGIDSADIAHTVRQ 
                   
               
               
                   
               
               
                 ARESLVTDTAIMNIISEIRAGANHIAIFAMSNISQPDYAALLLDHRGMCSFDRVFPSGCYGTRKPELSFYNKVLREIDTPPE 
               
               
                   
               
               
                 NVIFVDDQLENVISAQSIGIHGIAYTNAAELGRQLRNLIFDPVERGREFLRRNAGEFHSITETDQIVRENFSQLLILEATGD 
               
               
                   
               
               
                 KSLVSLEYHQKSWNFFQGNPILTTETFPDDVDTTSLALMTLPTDTKTANLLLDQILGLVNADEIVTTYFDQTRERIDPVVC 
               
               
                   
               
               
                 VNVLRLFCTYGRGIALPLTLQWVYDVLAHRAYINGTRYYTSPESFLYFVGQLCRFSTGVLALRPLETLLIDRLKERLQVKAD 
               
               
                   
               
               
                 PLSLAMRILTCLSVGVSQVEVDLRELLSMQCEDGSWEHCPFTRYGLSKVSIGNRGLTTAFVVKAVEMCRGS 
               
               
                   
               
               
                 - XP_001820867.2 cDNA 
               
               
                 SEQ ID NO: 39 
                   
               
               
                 ATGACTCGATGGAAATCGTCCCAATACCAAGCAATTATCTTTGACCTAGGCGGTGTCATTTTAACATGGGACCTCCC 
                   
               
               
                   
               
               
                 GGAAGACACTGTGATATCGGCCCAGATCTTTAAGAGAATGCTCACATCGCAGACATGGTCAGATTATGAGCGCGG 
               
               
                   
               
               
                 AAATCTCAGCGAAAATGGTTGCTACCAGAGGTTGGCCGAGGATTTTGGCATTGACTCTGCCGACATTGCACATACC 
               
               
                   
               
               
                 GTTAGACAAGCACGGGAATCCCTTGTCACTGATACCGCTATCATGAACATTATATCTGAGATCAGAGCTGGGGCTA 
               
               
                   
               
               
                 ACCATATTGCTATCTTCGCTATGTCGAACATCTCCCAACCAGATTATGCGGCTCTGCTCCTTGATCATCGCGGGATG 
               
               
                   
               
               
                 TGCAGTTTTGACCGGGTGTTCCCATCTGGATGCTACGGGACAAGGAAACCAGAGCTCTCATTCTATAACAAAGTCT 
               
               
                   
               
               
                 TGCGGGAGATTGACACGCCACCGGAAAACGTCATCTTTGTCGATGATCAGCTGGAAAATGTGATCTCTGCGCAGT 
               
               
                   
               
               
                 CCATTGGCATACACGGGATTGCCTATACGAATGCTGCTGAACTCGGTCGACAGCTTAGGAACCTAATATTTGACCC 
               
               
                   
               
               
                 TGTAGAGAGGGGTAGGGAATTCTTACGGCGCAATGCTGGAGAGTTCCATAGCATCACTGAAACCGATCAAATTGT 
               
               
                   
               
               
                 TCGGGAAAATTTCTCACAGTTGCTCATTCTAGAAGCGACTGGTGATAAGAGTCTGGTATCTCTTGAATATCACCAG 
               
               
                   
               
               
                 AAGAGCTGGAATTTCTTCCAAGGAAACCCTATTCTCACGACAGAGACATTCCCAGATGATGTTGACACAACATCTC 
               
               
                   
               
               
                 TTGCCTTGATGACTCTACCTACAGACACAAAAACTGCAAATTTGTTACTCGACCAGATTTTGGGGCTAGTCAACGCT 
               
               
                   
               
               
                 GATGAAATCGTAACAACATACTTTGACCAGACCCGAGAACGGATCGATCCAGTAGTCTGCGTCAATGTCCTTCGTC 
               
               
                   
               
               
                 TCTTTTGCACCTACGGCCGGGGCATTGCGCTCCCTTTGACTCTTCAGTGGGTGTACGACGTCCTCGCTCATCGGGCA 
               
               
                   
               
               
                 TATATAAACGGTACACGTTACTACACAAGTCCCGAAAGCTTCCTATACTTCGTCGGTCAACTTTGTCGATTCTCAAC 
               
               
                   
               
               
                 AGGGGTACTGGCACTTCGGCCGCTGGAAACGTTGCTTATAGATCGTCTCAAGGAACGTCTTCAGGTCAAAGCAGA 
               
               
                   
               
               
                 TCCTCTATCACTCGCTATGCGGATCTTGACCTGTTTGTCCGTTGGTGTGTCTCAAGTTGAAGTCGATCTCCGAGAGT 
               
               
                   
               
               
                 TGCTCTCGATGCAGTGTGAAGATGGCTCGTGGGAACATTGTCCATTCACCCGGTATGGTTTGTCCAAAGTGAGCAT 
               
               
                   
               
               
                 TGGCAATCGGGGCCTTACAACTGCTTTTGTGGTCAAGGCGGTTGAAATGTGTCGAGGCAGTTAG 
               
               
                   
               
               
                 - XP_001820867.2 optimized cDNA 
               
               
                 SEQ ID NO: 40 
                   
               
               
                 ATGACTCGTTGGAAAAGCTCTCAATATCAGGCAATCATTTTCGATCTGGGCGGTGTTATTCTGACCTGGGACTTGC 
                   
               
               
                   
               
               
                 CGGAAGATACGGTTATCTCCGCGCAAATCTTTAAGCGTATGCTGACCAGCCAGACCTGGTCCGATTATGAGCGCG 
               
               
                   
               
               
                 GTAATCTGAGCGAGAACGGCTGCTATCAACGTTTGGCGGAAGATTTCGGCATCGATAGCGCCGATATTGCCCACA 
               
               
                   
               
               
                 CCGTCCGTCAGGCACGTGAGTCCCTGGTGACCGACACCGCCATCATGAATATCATCTCCGAGATCCGTGCAGGCGC 
               
               
                   
               
               
                 GAACCACATCGCAATTTTCGCGATGAGCAACATCTCACAGCCGGATTACGCTGCGCTGCTGCTGGACCATCGCGGT 
               
               
                   
               
               
                 ATGTGCAGCTTTGACCGCGTCTTTCCGAGCGGTTGTTACGGCACCCGTAAGCCTGAGCTGAGCTTCTACAATAAAG 
               
               
                   
               
               
                 TGCTGCGTGAAATTGACACCCCGCCGGAAAATGTTATTTTCGTTGACGATCAATTGGAAAATGTGATTAGCGCGCA 
               
               
                   
               
               
                 AAGCATTGGTATTCATGGCATTGCGTATACGAATGCCGCGGAACTGGGCCGCCAGCTGAGAAACCTGATCTTCGA 
               
               
                   
               
               
                 TCCGGTGGAGCGCGGTCGTGAGTTCCTGCGTCGTAACGCTGGTGAGTTTCACTCTATTACGGAAACGGACCAGAT 
               
               
                   
               
               
                 TGTGCGCGAGAACTTCAGCCAGCTGCTGATTCTGGAAGCGACCGGTGACAAAAGCCTGGTTAGCCTGGAATACCA 
               
               
                   
               
               
                 CCAAAAGTCGTGGAACTTCTTCCAAGGTAACCCAATCCTGACGACGGAAACCTTCCCGGACGATGTTGACACTACT 
               
               
                   
               
               
                 AGCCTGGCTCTGATGACGCTGCCGACGGACACCAAGACCGCGAATCTGTTGCTGGACCAGATTCTGGGTTTGGTT 
               
               
                   
               
               
                 AATGCCGATGAAATTGTGACTACGTACTTCGACCAGACCCGTGAGCGTATCGATCCAGTGGTCTGTGTGAATGTCC 
               
               
                   
               
               
                 TGCGCCTGTTCTGTACGTACGGCCGCGGCATCGCGCTGCCGCTGACCCTGCAATGGGTCTACGATGTGCTGGCGC 
               
               
                   
               
               
                 ACCGCGCATACATTAACGGTACGCGTTATTACACCAGCCCGGAGAGCTTTCTGTATTTTGTCGGTCAGCTCTGTCGT 
               
               
                   
               
               
                 TTTAGCACCGGTGTGCTGGCACTGCGTCCGCTGGAGACTCTGCTGATTGATCGTCTGAAAGAGCGCCTGCAAGTTA 
               
               
                   
               
               
                 AAGCTGACCCGCTGAGCCTGGCAATGCGCATCCTTACGTGCTTATCTGTCGGTGTCAGCCAGGTTGAAGTGGACTT 
               
               
                   
               
               
                 GCGTGAGTTGTTGAGCATGCAGTGCGAGGACGGTAGCTGGGAGCATTGCCCGTTCACCCGCTACGGCCTGAGCA 
               
               
                   
               
               
                 AGGTTTCCATCGGTAACCGTGGCCTGACCACGGCGTTTGTGGTTAAAGCCGTCGAGATGTGCCGTGGCAGCTAA 
               
               
                   
               
               
                 CEN60542.1 
               
               
                 - CEN60542.1 protein 
               
               
                 SEQ ID NO: 41 
                   
               
               
                 MVRALILDLGDVLFNWDAPASTPISRKTLGQMLHSEIWGEYERGHLTEDEAYNALAKRYSCEAKDVAHTFVLARESLRL 
                   
               
               
                   
               
               
                 DTKFKTFLQTLKQNANGSLRVYGMSNISKPDFEVLLGKADDWTLFDKIFPSGHVGMRKPDLAFFRYVLKDISTPVEDVV 
               
               
                   
               
               
                 FVDDNLDNVTSARSLGMRSVLFHKKDEVQRQLTNIFGSPAERGLEYLSANKTNLQSATTTDIPIQDNFGQLLILEATEDP 
               
               
                   
               
               
                 SLVRMEPGKRTWNFFIGSPSLTTDTFPDDLDTTSLALSIVPTSPDVVNSVIDEIISRRDKDGIVPTYFDNTRPRVDPIVCVN 
               
               
                   
               
               
                 VLSMFAKYGREHDLPATVAWVRDVLYHRAYLGGTRYYGSAEAFLFFFTRFVRNLRPGTLKQDLHALLSERVRERLNTPV 
               
               
                   
               
               
                 DALALSMRIQACHALGFDAPADIATLITMQDEDGGWPAAVIYKYGAGGLGITNRGVSTAFAVKAITGSPVKTETNIGGD 
               
               
                   
               
               
                 GARAVSAMSSLEARRLQPISSVGDWVRFIIASLHVHLAWLWNVLLLSKVV 
               
               
                   
               
               
                 - CEN60542.1 cDNA 
               
               
                 SEQ ID NO: 42 
                   
               
               
                 ATGGTCCGCGCACTCATCCTCGATCTCGGCGATGTCCTCTTCAACTGGGACGCGCCTGCGTCCACCCCCATTTCACG 
                   
               
               
                   
               
               
                 CAAGACCCTCGGCCAGATGCTGCATAGTGAGATCTGGGGTGAGTATGAACGTGGCCATTTGACAGAAGACGAGG 
               
               
                   
               
               
                 CATACAACGCACTCGCGAAGCGGTATTCCTGCGAGGCCAAGGATGTCGCACATACCTTTGTCCTGGCACGAGAAT 
               
               
                   
               
               
                 CGCTGCGGCTCGACACGAAATTCAAAACGTTTCTGCAGACTCTAAAGCAGAATGCCAACGGCTCCCTTCGTGTCTA 
               
               
                   
               
               
                 TGGCATGTCGAATATATCGAAACCGGATTTCGAAGTCCTGCTGGGCAAGGCCGATGACTGGACTCTGTTTGACAA 
               
               
                   
               
               
                 GATCTTCCCCTCTGGCCATGTCGGTATGCGCAAGCCAGATCTTGCCTTCTTCCGCTATGTGCTCAAGGACATTTCAA 
               
               
                   
               
               
                 CGCCTGTCGAGGATGTGGTGTTTGTTGACGATAACCTGGACAACGTGACGAGTGCTCGGTCTCTGGGCATGCGCA 
               
               
                   
               
               
                 GCGTCCTCTTTCATAAGAAAGACGAGGTCCAGCGACAGCTCACCAACATCTTTGGCAGCCCTGCTGAGCGGGGCTT 
               
               
                   
               
               
                 GGAGTATCTCTCCGCCAACAAGACGAATCTGCAGAGTGCTACCACGACAGATATCCCAATCCAGGATAACTTTGGC 
               
               
                   
               
               
                 CAACTTCTGATTCTCGAGGCCACTGAAGACCCATCGCTGGTCCGCATGGAGCCCGGTAAGCGAACCTGGAATTTCT 
               
               
                   
               
               
                 TCATCGGTTCTCCATCCCTCACAACCGACACCTTCCCCGACGATCTCGACACCACATCCCTTGCCCTCTCCATCGTAC 
               
               
                   
               
               
                 CCACAAGCCCCGACGTCGTCAACTCGGTCATCGACGAGATTATCAGCCGTCGCGACAAGGACGGTATCGTCCCGA 
               
               
                   
               
               
                 CTTACTTCGACAACACCCGCCCCCGCGTGGACCCAATCGTCTGCGTAAACGTCCTCTCCATGTTCGCAAAGTACGGC 
               
               
                   
               
               
                 CGCGAGCACGACCTCCCCGCAACAGTTGCGTGGGTCCGCGACGTCTTGTATCATCGAGCATACCTCGGCGGAACA 
               
               
                   
               
               
                 CGGTACTACGGGTCAGCTGAGGCCTTCCTCTTCTTCTTCACTCGCTTCGTTCGCAACCTCCGACCGGGAACTCTCAA 
               
               
                   
               
               
                 GCAGGATCTACACGCATTGCTATCAGAGCGCGTGCGCGAGCGACTCAATACCCCCGTCGACGCACTCGCCCTGTCA 
               
               
                   
               
               
                 ATGCGCATCCAGGCCTGTCATGCGCTGGGCTTTGACGCCCCCGCAGACATTGCGACGCTCATCACAATGCAGGAC 
               
               
                   
               
               
                 GAGGACGGCGGGTGGCCGGCAGCCGTCATCTACAAGTACGGGGCCGGGGGGTTGGGGATCACGAACCGGGGTG 
               
               
                   
               
               
                 TTTCGACTGCGTTTGCCGTAAAGGCGATTACAGGGTCGCCCGTGAAGACTGAAACCAACATAGGCGGCGATGGAG 
               
               
                   
               
               
                 CTCGCGCTGTCTCGGCCATGTCCTCCTTGGAGGCGAGGAGGCTACAGCCGATCTCGTCGGTTGGGGACTGGGTGC 
               
               
                   
               
               
                 GGTTTATCATTGCGTCGTTGCATGTCCATCTGGCTTGGCTTTGGAATGTTTTGCTTTTGAGCAAGGTTGTTTGA 
               
               
                   
               
               
                 - CEN60542.1 optimized cDNA 
               
               
                 SEQ ID NO: 43 
                   
               
               
                 ATGGTTCGTGCGTTGATTTTGGATTTGGGTGATGTGTTGTTTAATTGGGACGCCCCTGCAAGCACTCCGATCAGCC 
                   
               
               
                   
               
               
                 GTAAGACCCTGGGCCAGATGCTGCATTCCGAGATTTGGGGTGAGTATGAGCGTGGTCACCTGACCGAAGATGAA 
               
               
                   
               
               
                 GCGTACAACGCGCTGGCAAAGCGCTACAGCTGCGAGGCAAAAGACGTGGCGCATACTTTTGTTTTGGCGCGTGAA 
               
               
                   
               
               
                 AGCCTGCGCCTGGATACCAAGTTTAAGACTTTTCTGCAGACCCTGAAACAGAACGCGAACGGCTCGCTGCGTGTTT 
               
               
                   
               
               
                 ATGGTATGTCCAATATCAGCAAACCGGATTTTGAAGTGCTGCTGGGTAAAGCTGACGACTGGACCTTGTTCGACAA 
               
               
                   
               
               
                 GATCTTCCCGAGCGGTCATGTCGGTATGCGCAAACCGGACCTGGCTTTCTTTCGTTACGTGCTGAAAGACATCAGC 
               
               
                   
               
               
                 ACCCCGGTTGAGGATGTTGTGTTTGTTGACGATAACCTGGATAATGTGACGTCTGCCCGTTCCCTGGGTATGCGTA 
               
               
                   
               
               
                 GCGTCCTGTTCCACAAAAAAGACGAAGTCCAACGTCAGCTGACCAACATTTTCGGTAGCCCTGCTGAGCGCGGTCT 
               
               
                   
               
               
                 GGAGTATCTGTCCGCGAACAAGACCAATCTGCAAAGCGCAACCACCACCGACATCCCTATCCAAGACAACTTTGGT 
               
               
                   
               
               
                 CAATTACTGATTCTGGAAGCCACCGAAGATCCGAGCCTGGTACGCATGGAACCGGGCAAGCGTACCTGGAATTTC 
               
               
                   
               
               
                 TTCATTGGCTCTCCGAGCCTGACGACGGATACCTTCCCGGATGACCTGGACACGACGAGCCTCGCACTGTCCATCG 
               
               
                   
               
               
                 TGCCGACCAGCCCAGATGTTGTTAATAGCGTGATCGATGAGATCATCAGCCGTCGCGACAAGGACGGTATTGTGC 
               
               
                   
               
               
                 CGACGTACTTTGATAACACGCGCCCGCGTGTGGACCCGATTGTTTGTGTTAACGTTCTGTCTATGTTCGCGAAATAT 
               
               
                   
               
               
                 GGCCGTGAGCACGATCTGCCGGCGACGGTCGCGTGGGTCCGCGACGTCCTCTATCATCGCGCATACCTGGGTGGC 
               
               
                   
               
               
                 ACCAGATACTACGGTAGCGCGGAAGCCTTCCTTTTCTTCTTTACGCGCTTTGTGCGTAATCTGCGTCCGGGCACGCT 
               
               
                   
               
               
                 GAAACAAGATCTGCACGCGTTGCTGAGCGAGCGTGTCCGTGAGCGCCTGAATACCCCGGTGGATGCGCTGGCGCT 
               
               
                   
               
               
                 GAGCATGCGCATTCAGGCTTGCCACGCACTGGGCTTTGACGCCCCAGCTGACATCGCGACGCTGATTACCATGCAA 
               
               
                   
               
               
                 GATGAAGATGGTGGCTGGCCGGCGGCAGTTATCTACAAATATGGTGCGGGTGGCCTGGGCATTACGAACCGTGG 
               
               
                   
               
               
                 TGTGTCCACGGCATTCGCGGTGAAGGCAATCACGGGTAGCCCGGTTAAAACCGAAACCAACATCGGCGGCGACG 
               
               
                   
               
               
                 GTGCCCGTGCAGTGTCGGCCATGAGCAGCCTGGAAGCCCGTCGTTTGCAGCCGATTTCTAGCGTCGGCGACTGGG 
               
               
                   
               
               
                 TCCGTTTCATCATCGCATCACTGCACGTCCACCTGGCGTGGCTGTGGAATGTCCTGCTGCTGAGCAAAGTCGTTTAA 
               
               
                   
               
               
                 XP_009547469.1 
               
               
                 - XP_009547469.1 protein 
               
               
                 SEQ ID NO: 44 
                   
               
               
                 MSMIPRCSNLILDIGDVLFTWSPKTSTSISPRTMKSILSSTTWHQYETGHISQGDCYRLIGNQFSIDPQEVGLAFQQARD 
                   
               
               
                   
               
               
                 SLQPNVDFIHFIRALKAESHGTLRVFAMSNISQPDYAVLRTKDADWAVFDDIFTSADAGVRKPHLGFYKLVLGKIGADP 
               
               
                   
               
               
                 NDTVFVDDKGDNVLSARSLGLHGIVFDSMDNVKRALRYLISDPIRRGREFLQARAGHLESETNTGIEIGDNFAQLLILEAT 
               
               
                   
               
               
                 KDRTLVNYMDHPNKWNFFRDQPLLTTEEFPFDLDTTSIGTLATQRDDGTANLVMDEMLQYRDEDGIIQTYFDHERPRI 
               
               
                   
               
               
                 DPIVCVNVLSLFYSRGRGSELAPTLEWVRGVLKHRAYLDGTRYYETGECFLFFLSRLLQSTKDAALHASLKSLFAERVKERI 
               
               
                   
               
               
                 GAPGDALALAMRILACAAVGVRDEIDLRSLLPLQCEDGGWEAGWVYKYGSSGVKIGNRGLTTALALNAIEAVEGRRTR 
               
               
                   
               
               
                 PKSGKISRVSRHSEVAAAPRSSTSSHRSNRSISRTFQAYFKASWTSMKQVAVA 
               
               
                   
               
               
                 - XP_009547469.1 cDNA 
               
               
                 SEQ ID NO: 45 
                   
               
               
                 ATGTCCATGATACCCAGATGCTCGAATCTCATCCTCGACATCGGGGATGTTCTCTTCACATGGTCTCCGAAGACGTC 
                   
               
               
                   
               
               
                 CACTTCGATCTCCCCCCGCACCATGAAGAGCATACTGTCATCGACGACCTGGCACCAATACGAGACCGGGCACATT 
               
               
                   
               
               
                 TCACAGGGCGACTGCTACCGCCTCATAGGCAACCAGTTCTCCATCGATCCTCAGGAAGTCGGACTTGCATTCCAAC 
               
               
                   
               
               
                 AAGCTCGGGACTCATTGCAGCCTAATGTTGACTTCATTCACTTCATCCGCGCCCTCAAGGCGGAATCACACGGGAC 
               
               
                   
               
               
                 GCTGCGCGTCTTCGCTATGTCCAACATCTCTCAGCCCGATTACGCAGTTCTTCGGACTAAGGACGCCGACTGGGCC 
               
               
                   
               
               
                 GTTTTTGACGATATATTCACGTCTGCAGATGCTGGGGTTCGAAAGCCACACCTTGGGTTCTACAAGTTGGTACTCG 
               
               
                   
               
               
                 GAAAGATCGGCGCCGATCCAAACGATACCGTCTTCGTCGATGACAAGGGGGACAATGTCCTCTCTGCACGGTCTC 
               
               
                   
               
               
                 TCGGCCTTCATGGAATCGTCTTTGACAGTATGGACAACGTCAAGCGAGCCCTGCGCTACTTGATCAGCGACCCCAT 
               
               
                   
               
               
                 ACGGCGAGGACGAGAGTTTCTCCAAGCGCGAGCCGGCCATTTGGAGTCGGAGACCAATACGGGCATCGAAATCG 
               
               
                   
               
               
                 GTGATAATTTTGCCCAGCTCCTTATTCTCGAGGCCACGAAGGATAGGACACTCGTCAATTATATGGACCATCCGAA 
               
               
                   
               
               
                 CAAATGGAATTTCTTCCGAGATCAACCGCTCCTCACAACGGAGGAGTTCCCTTTCGATCTCGATACGACATCTATTG 
               
               
                   
               
               
                 GAACGCTTGCGACGCAGCGCGATGATGGGACTGCCAATCTAGTAATGGATGAGATGCTTCAGTACCGTGATGAG 
               
               
                   
               
               
                 GATGGCATAATACAAACATATTTCGATCATGAACGACCGAGGATAGATCCCATCGTCTGTGTCAACGTCTTGAGCC 
               
               
                   
               
               
                 TTTTCTACTCCCGGGGTCGTGGTTCGGAGCTAGCACCGACACTAGAGTGGGTGCGTGGTGTCCTCAAGCACCGCG 
               
               
                   
               
               
                 CGTATCTCGATGGAACGCGATACTACGAGACAGGCGAATGCTTCCTTTTCTTCCTCAGCCGGCTCTTGCAATCAACC 
               
               
                   
               
               
                 AAGGACGCCGCCTTGCACGCATCGTTGAAATCTTTGTTCGCCGAACGGGTCAAGGAGCGCATAGGGGCACCAGG 
               
               
                   
               
               
                 GGACGCGCTGGCGCTGGCGATGCGTATACTGGCATGCGCAGCAGTGGGCGTGCGGGACGAGATCGATCTTCGAT 
               
               
                   
               
               
                 CACTATTACCTCTGCAGTGCGAGGATGGGGGGTGGGAGGCAGGCTGGGTGTACAAGTATGGGTCTTCGGGAGTC 
               
               
                   
               
               
                 AAGATCGGCAATCGTGGCCTCACGACTGCGCTTGCGCTCAATGCCATCGAGGCTGTGGAGGGACGTCGCACGAG 
               
               
                   
               
               
                 GCCGAAGTCGGGTAAGATCAGCCGAGTCAGCCGTCATTCTGAGGTCGCAGCAGCGCCACGGTCTTCCACCAGCAG 
               
               
                   
               
               
                 TCATCGTTCTAATCGCTCGATCTCAAGGACATTCCAGGCGTACTTCAAGGCGTCGTGGACATCGATGAAACAGGTG 
               
               
                   
               
               
                 GCCGTGGCGTGA 
               
               
                   
               
               
                 - XP_009547469.1 optimized cDNA 
               
               
                 SEQ ID NO: 46 
                   
               
               
                 ATGAGCATGATTCCACGTTGTAGCAATCTGATTCTCGACATCGGTGATGTGTTGTTTACGTGGAGCCCGAAAACCA 
                   
               
               
                   
               
               
                 GCACCAGCATTAGCCCGCGTACCATGAAATCTATCCTGAGCTCTACCACCTGGCATCAATATGAGACTGGCCACAT 
               
               
                   
               
               
                 CAGCCAGGGTGATTGCTACCGCCTGATCGGTAATCAGTTCTCCATCGACCCGCAAGAGGTCGGTTTGGCCTTCCAG 
               
               
                   
               
               
                 CAAGCCAGAGACAGCCTGCAACCGAATGTTGATTTCATCCATTTCATTCGTGCCCTGAAAGCTGAGTCGCACGGCA 
               
               
                   
               
               
                 CCCTGCGCGTTTTTGCGATGAGCAATATCAGCCAACCTGACTATGCAGTCCTGCGTACGAAAGACGCGGACTGGG 
               
               
                   
               
               
                 CTGTTTTTGATGATATCTTCACGAGCGCGGATGCTGGTGTTCGTAAACCGCACCTGGGTTTTTATAAACTGGTCTTA 
               
               
                   
               
               
                 GGCAAGATTGGCGCGGACCCTAACGACACCGTTTTTGTGGATGATAAGGGTGACAACGTCCTCTCTGCACGTTCCC 
               
               
                   
               
               
                 TGGGTCTGCACGGTATCGTTTTTGATTCAATGGACAACGTGAAGCGCGCACTGCGCTACCTGATTAGCGACCCGAT 
               
               
                   
               
               
                 CCGCCGCGGCCGTGAATTTCTGCAGGCCCGTGCGGGTCACCTGGAGTCCGAAACGAACACGGGTATTGAGATTGG 
               
               
                   
               
               
                 TGATAATTTCGCGCAATTGCTGATCCTGGAAGCGACCAAAGATCGTACTCTGGTGAACTACATGGACCACCCGAAC 
               
               
                   
               
               
                 AAGTGGAACTTCTTCCGTGACCAGCCGCTGCTGACCACCGAAGAATTTCCGTTCGACCTGGACACGACCAGCATTG 
               
               
                   
               
               
                 GCACGCTGGCCACCCAACGTGACGATGGTACGGCGAATCTGGTAATGGACGAAATGTTGCAGTATCGTGACGAA 
               
               
                   
               
               
                 GATGGCATCATTCAGACCTATTTCGATCATGAGCGCCCGCGTATTGATCCGATTGTTTGTGTGAATGTGCTGTCTCT 
               
               
                   
               
               
                 GTTCTACAGCCGTGGCCGTGGCTCTGAGTTGGCGCCGACGCTGGAATGGGTGCGCGGTGTGTTGAAACATCGTGC 
               
               
                   
               
               
                 GTACCTGGATGGTACGCGTTATTACGAGACTGGTGAGTGTTTCCTGTTTTTCCTGAGCCGTCTGCTGCAGAGCACC 
               
               
                   
               
               
                 AAAGACGCAGCCCTGCACGCGAGCCTGAAGTCCCTGTTTGCAGAGCGTGTTAAAGAGCGCATCGGTGCGCCGGG 
               
               
                   
               
               
                 CGATGCTCTGGCGCTGGCTATGCGCATCCTGGCGTGCGCCGCTGTTGGTGTGCGCGATGAAATTGATTTGCGTAG 
               
               
                   
               
               
                 CCTGCTGCCGCTGCAATGCGAAGATGGCGGCTGGGAAGCGGGCTGGGTCTACAAATACGGCAGCAGCGGTGTGA 
               
               
                   
               
               
                 AGATTGGCAATCGCGGTCTTACCACGGCGCTGGCATTGAATGCTATCGAAGCCGTTGAGGGCCGTCGCACCCGCC 
               
               
                   
               
               
                 CAAAGTCCGGTAAGATCAGCCGTGTTAGCCGTCATAGCGAAGTCGCAGCGGCACCGCGTTCCTCGACGAGCAGCC 
               
               
                   
               
               
                 ACCGTAGCAACCGTAGCATTAGCCGCACCTTCCAGGCATATTTTAAAGCGAGCTGGACCAGCATGAAACAAGTCG 
               
               
                   
               
               
                 CAGTGGCGTAA 
               
               
                   
               
               
                 KLO09124.1 
               
               
                 - KLO09124.1 protein 
               
               
                 SEQ ID NO: 47 
                   
               
               
                 MSIHGSSMSSYSSTVPSMTSSPASTSTPSSPASSIHEIGPVPEARRKGQCNALIFDLGDVLFTWSAETKTTISPKLLKKILNS 
                   
               
               
                   
               
               
                 LTWFEYEKGNIGEQEAYDAVAKEFGVPSSEVGAAFQCARDSLQSNPRLVSLIRELKSQYDLKVYAMSNISAPDWEVLRT 
               
               
                   
               
               
                 KATPEEWAMFDRVFTSAAARERKPNLGFYRQVVEATGVDPARSVFVDDKLDNVISARSVGLNAIIFDSFENVARQLKN 
               
               
                   
               
               
                 YVADPIGRAEAWLRDNAKKMLSITDAGVVVYENFGQMLILEATGDRSLVDYVEYPRLFNFFQGNGVFTTESFPCDLDST 
               
               
                   
               
               
                 SIGLTVTNHVDEKTRHSVMDEMLTYKNEDGIIATYFDATRPRIDPVVCANVLTFFYKNGRGEELNETLDWVYDILLHRAY 
               
               
                   
               
               
                 LDGTRYYFGSDTFLFFLSRLLSESPSVYARFAPVFQERVKERMGATGDAMSLAMRIIAAATVKIQDRVDCDALLQTQED 
               
               
                   
               
               
                 DGGFPIGWMYKYGATGMLLGNKGLSTALAIQAIKAVESFP 
               
               
                   
               
               
                 - KLO09124.1 cDNA 
               
               
                 SEQ ID NO: 48 
                   
               
               
                 ATGTCGATTCACGGTTCTTCTATGTCCTCCTATTCCTCGACTGTGCCGTCAATGACTTCCTCTCCCGCGTCCACTTCTA 
                   
               
               
                   
               
               
                 CTCCGTCGTCTCCTGCATCGTCGATCCATGAGATTGGTCCTGTCCCAGAAGCTCGACGAAAGGGACAGTGCAACGC 
               
               
                   
               
               
                 GCTGATCTTCGACCTCGGAGACGTCCTCTTCACCTGGTCGGCAGAGACTAAGACCACCATTTCCCCGAAACTCCTG 
               
               
                   
               
               
                 AAAAAGATCCTTAACTCCTTAACATGGTTCGAATACGAGAAGGGAAACATCGGGGAGCAGGAGGCGTATGACGC 
               
               
                   
               
               
                 AGTCGCAAAGGAGTTTGGCGTCCCGTCGTCCGAGGTCGGGGCCGCTTTCCAGTGCGCGCGCGATTCGCTACAGAG 
               
               
                   
               
               
                 CAATCCCCGCCTCGTCTCGCTCATCCGTGAGCTGAAGTCGCAATATGATCTCAAGGTGTACGCCATGTCCAACATCT 
               
               
                   
               
               
                 CTGCGCCGGACTGGGAAGTCCTAAGGACGAAGGCGACCCCTGAGGAGTGGGCAATGTTTGACCGCGTCTTCACG 
               
               
                   
               
               
                 AGCGCGGCCGCGCGCGAGCGTAAGCCAAACCTCGGATTCTACAGACAGGTTGTTGAGGCGACCGGCGTCGACCC 
               
               
                   
               
               
                 CGCTCGCTCCGTGTTCGTCGACGATAAACTCGACAATGTCATCTCTGCGCGTTCAGTCGGATTAAATGCGATCATCT 
               
               
                   
               
               
                 TCGACTCATTTGAGAACGTCGCCCGGCAGCTCAAAAACTATGTCGCTGATCCTATCGGACGGGCGGAGGCGTGGT 
               
               
                   
               
               
                 TGCGCGATAACGCAAAGAAGATGTTGTCAATTACGGATGCCGGGGTGGTCGTATACGAGAATTTCGGCCAGATGC 
               
               
                   
               
               
                 TGATCTTGGAGGCAACAGGCGATAGGTCGCTTGTGGACTACGTCGAGTACCCTCGTCTCTTCAACTTCTTCCAAGG 
               
               
                   
               
               
                 CAATGGCGTCTTTACGACCGAGTCATTCCCTTGCGACCTTGATTCGACTTCCATCGGCTTAACCGTCACGAACCACG 
               
               
                   
               
               
                 TCGATGAGAAAACAAGGCACAGCGTCATGGATGAGATGCTGACCTACAAAAATGAGGATGGTATCATTGCGACTT 
               
               
                   
               
               
                 ACTTTGATGCCACGCGTCCCCGAATTGACCCCGTCGTCTGCGCCAATGTCTTGACGTTCTTCTACAAGAACGGCCGA 
               
               
                   
               
               
                 GGGGAGGAGCTCAATGAAACACTTGACTGGGTCTACGACATCCTCCTTCATCGCGCGTACCTCGATGGCACACGCT 
               
               
                   
               
               
                 ATTATTTCGGCTCAGACACCTTCCTCTTCTTCCTTTCTCGACTTCTCTCCGAATCGCCATCCGTTTACGCCCGTTTCGC 
               
               
                   
               
               
                 TCCGGTGTTCCAGGAGAGAGTCAAGGAGCGCATGGGGGCGACGGGAGATGCGATGTCCCTTGCGATGCGCATCA 
               
               
                   
               
               
                 TCGCGGCCGCAACTGTCAAGATCCAAGACCGAGTCGACTGCGACGCTCTGCTGCAGACGCAGGAAGACGACGGT 
               
               
                   
               
               
                 GGATTCCCGATAGGTTGGATGTACAAGTACGGGGCGACCGGGATGCTTCTGGGTAACAAGGGCTTGTCGACAGC 
               
               
                   
               
               
                 TCTGGCAATCCAAGCTATCAAAGCGGTCGAATCTTTCCCTTGA 
               
               
                   
               
               
                 - KLO09124.1 optimized cDNA 
               
               
                 SEQ ID NO: 49 
                   
               
               
                 GGATCCAAGCTTAAGGAGGTAAAAAATGTCGATTCACGGTAGCAGCATGTCGTCTTATAGCAGCACGGTTCCATCT 
                   
               
               
                   
               
               
                 ATGACTAGCAGCCCGGCTTCCACGAGCACGCCGTCCAGCCCGGCCAGCAGCATCCACGAAATCGGCCCGGTCCCT 
               
               
                   
               
               
                 GAGGCGCGTCGCAAGGGCCAATGCAATGCACTGATCTTCGACCTGGGTGATGTTCTGTTTACCTGGAGCGCAGAA 
               
               
                   
               
               
                 ACCAAGACCACGATCAGCCCGAAGCTGCTGAAAAAGATTCTGAACAGCTTGACCTGGTTTGAGTATGAGAAAGGC 
               
               
                   
               
               
                 AACATCGGTGAACAAGAAGCCTATGACGCCGTTGCGAAAGAGTTCGGTGTGCCGAGCTCTGAGGTTGGCGCTGC 
               
               
                   
               
               
                 GTTTCAATGTGCGCGTGACTCCCTGCAAAGCAATCCGCGTTTGGTTAGCCTGATTCGTGAGCTGAAGTCCCAGTAC 
               
               
                   
               
               
                 GACCTGAAAGTGTACGCTATGAGCAATATTAGCGCGCCAGACTGGGAAGTGCTGCGTACTAAAGCGACCCCGGAA 
               
               
                   
               
               
                 GAGTGGGCAATGTTCGATCGTGTCTTTACTTCTGCGGCGGCGCGTGAGCGTAAGCCGAACTTGGGCTTTTACCGCC 
               
               
                   
               
               
                 AAGTCGTGGAAGCAACCGGTGTCGATCCGGCGCGTAGCGTTTTCGTCGATGATAAACTGGACAATGTGATCAGCG 
               
               
                   
               
               
                 CGCGCTCTGTCGGTCTGAACGCTATTATCTTCGACTCCTTCGAAAACGTCGCCCGTCAGCTGAAGAATTACGTCGCA 
               
               
                   
               
               
                 GACCCGATTGGTCGCGCTGAGGCGTGGCTGCGCGACAACGCAAAGAAAATGCTGAGCATCACCGATGCGGGTGT 
               
               
                   
               
               
                 TGTGGTTTACGAGAATTTTGGCCAGATGCTGATCCTGGAAGCTACCGGTGACCGTAGCCTGGTGGACTATGTGGA 
               
               
                   
               
               
                 GTATCCGCGCCTCTTTAACTTCTTCCAGGGTAACGGCGTTTTTACGACCGAGAGCTTTCCATGCGATCTGGACAGCA 
               
               
                   
               
               
                 CCAGCATCGGTCTGACTGTGACCAATCATGTGGACGAAAAGACTCGCCACAGCGTCATGGACGAAATGCTGACCT 
               
               
                   
               
               
                 ACAAAAATGAAGATGGTATTATTGCGACGTACTTTGACGCGACGCGCCCGCGCATTGACCCTGTTGTCTGTGCCAA 
               
               
                   
               
               
                 TGTTCTGACCTTCTTCTACAAAAACGGTCGTGGTGAAGAATTGAACGAAACCCTGGATTGGGTGTACGACATTCTG 
               
               
                   
               
               
                 CTGCATCGCGCGTATCTGGACGGTACGCGTTATTATTTCGGCTCCGATACGTTCCTGTTTTTCCTGAGCCGTCTGCT 
               
               
                   
               
               
                 GAGCGAGTCTCCGAGCGTTTACGCGCGTTTTGCCCCGGTGTTTCAAGAGCGCGTGAAAGAGCGTATGGGCGCGAC 
               
               
                   
               
               
                 CGGTGATGCGATGAGCCTGGCCATGCGTATCATTGCAGCAGCAACCGTAAAGATCCAGGATCGTGTGGATTGCGA 
               
               
                   
               
               
                 CGCACTGTTGCAGACCCAAGAAGATGATGGCGGTTTCCCGATTGGTTGGATGTACAAATATGGTGCGACCGGTAT 
               
               
                   
               
               
                 GTTGCTGGGCAACAAAGGCCTGAGCACGGCCCTGGCGATCCAGGCAATTAAAGCCGTCGAGTCGTTCCCGTAAGG 
               
               
                   
               
               
                 TACCATATATGAATTCATTAATCTCGAG 
               
               
                   
               
               
                 OJI95797.1 
               
               
                 - 0JI95797.1 protein 
               
               
                 SEQ ID NO: 50 
                   
               
               
                 MGSTKALVVDFGNVLCTWTPPRELSIPPKKLKQIMSSDIWLDYERGIYKSEDECYLAVATRFGVSPSDLSSVMKKARESL 
                   
               
               
                   
               
               
                 QPNTATLNHLSHLKKTQPGLRIYGLTNTPLPEQSSVRSIAQEWPIFDHIYISGILGMRKPDIGCYRLVLRKIGLPAESVVFID 
               
               
                   
               
               
                 DSPENILAAQSLGVHSILFQSHDQLSRQLGNVLGDPIQRGHNFLLSNAKQMNSTTDKGVIIRDNFAQLLIIELTQNPDLV 
               
               
                   
               
               
                 ALETWDRTWNFFIGPPQLTTESFPNDLDTTSIALSVLPVDKEVVWSVMDEMLTFTNADGIFMTYFDRSRPRVDPVVCT 
               
               
                   
               
               
                 NVLNLFCMHGRESEVAATFDWVLDVLRNSAYLSGSRYYSSPDCFLYFLSRLSCVVRDGTRRRELKSLLKQQVSQRIGAD 
               
               
                   
               
               
                 GDSVSLATRLLASNILGITNGRDRSRLLALQETDGGWPAGWVYKFGSSGVQIGNRGLSTALALKSIERQKGPVEAISSEP 
               
               
                   
               
               
                 EAWWPSLRLDRLLNVWPFIDWKGYSPS 
               
               
                   
               
               
                 - 0JI95797.1 cDNA 
               
               
                 SEQ ID NO: 51 
                   
               
               
                 ATGGGTTCCACCAAGGCTCTTGTTGTTGACTTTGGGAATGTTTTGTGTACCTGGACACCACCCAGGGAGTTATCCAT 
                   
               
               
                   
               
               
                 CCCGCCCAAGAAGCTGAAACAAATCATGTCTTCTGACATTTGGCTCGACTATGAACGGGGTATCTATAAGTCGGAG 
               
               
                   
               
               
                 GACGAGTGCTACTTGGCGGTTGCAACTCGCTTCGGCGTCTCTCCCAGCGACCTCTCCTCGGTGATGAAAAAGGCCC 
               
               
                   
               
               
                 GCGAGAGCCTGCAACCAAACACCGCAACCCTGAATCATCTGTCTCATCTCAAAAAGACCCAGCCTGGCCTCAGGAT 
               
               
                   
               
               
                 ATACGGTTTGACCAACACCCCTCTCCCAGAACAAAGCAGTGTACGATCCATCGCCCAGGAATGGCCTATCTTCGAC 
               
               
                   
               
               
                 CATATCTACATATCAGGCATCCTCGGAATGCGCAAGCCGGACATTGGCTGCTACAGGCTGGTGCTGCGAAAGATT 
               
               
                   
               
               
                 GGGCTTCCAGCGGAGTCCGTGGTCTTCATTGATGATTCACCCGAGAACATCCTGGCCGCGCAGTCACTGGGAGTA 
               
               
                   
               
               
                 CACAGCATACTGTTCCAAAGCCACGACCAGCTCTCTCGTCAGCTTGGCAATGTGCTGGGTGATCCAATCCAGCGGG 
               
               
                   
               
               
                 GCCATAACTTCCTACTCTCGAACGCAAAGCAAATGAATAGTACGACCGACAAGGGAGTTATTATCCGGGACAACTT 
               
               
                   
               
               
                 TGCGCAACTGCTGATCATCGAGCTGACGCAGAACCCAGACCTTGTGGCGTTAGAAACATGGGACCGTACCTGGAA 
               
               
                   
               
               
                 TTTTTTTATTGGACCTCCACAATTGACAACTGAAAGCTTTCCCAATGATCTTGACACTACCTCCATCGCTCTCTCGGT 
               
               
                   
               
               
                 TCTTCCGGTTGACAAAGAAGTGGTATGGTCTGTGATGGACGAGATGCTAACGTTTACCAATGCGGATGGGATTTTT 
               
               
                   
               
               
                 ATGACCTATTTCGACCGATCACGCCCTCGAGTTGATCCGGTAGTTTGCACCAATGTCCTGAATCTTTTCTGCATGCA 
               
               
                   
               
               
                 TGGACGGGAAAGCGAAGTTGCAGCCACATTTGACTGGGTGCTGGACGTTCTTCGAAATTCGGCCTATTTATCAGG 
               
               
                   
               
               
                 ATCCAGATACTATTCTTCGCCTGATTGCTTTCTATACTTTCTTTCACGGCTGAGCTGTGTGGTCCGAGACGGCACGC 
               
               
                   
               
               
                 GACGCAGGGAGCTCAAGTCACTGTTGAAACAACAAGTGAGCCAGCGTATTGGCGCTGATGGTGATTCCGTCTCTC 
               
               
                   
               
               
                 TCGCCACTAGGCTACTTGCATCGAACATTTTAGGAATCACAAATGGCCGTGATCGCTCCAGGCTTCTTGCTCTGCAG 
               
               
                   
               
               
                 GAAACTGACGGTGGATGGCCTGCTGGGTGGGTTTATAAATTCGGAAGCTCGGGGGTACAGATTGGCAATCGGGG 
               
               
                   
               
               
                 GCTCAGTACAGCCTTGGCGTTAAAATCAATTGAGCGTCAGAAGGGGCCTGTTGAGGCGATATCCAGTGAGCCAGA 
               
               
                   
               
               
                 AGCGTGGTGGCCATCCCTCAGGCTTGACCGACTTCTCAACGTTTGGCCTTTCATCGACTGGAAGGGATATTCGCCG 
               
               
                   
               
               
                 AGTTGA 
               
               
                   
               
               
                 - 0JI95797.1 optimized cDNA 
               
               
                 SEQ ID NO: 52 
                   
               
               
                 ATGGGTTCTACGAAAGCGTTGGTTGTTGATTTTGGTAATGTTCTGTGCACTTGGACGCCACCACGTGAATTGTCCA 
                   
               
               
                   
               
               
                 TCCCGCCGAAGAAACTGAAGCAAATCATGAGCAGCGACATTTGGCTGGACTATGAGCGTGGTATCTACAAATCGG 
               
               
                   
               
               
                 AAGATGAGTGCTACCTGGCAGTTGCGACGCGCTTTGGTGTCAGCCCGTCCGACCTGAGCTCCGTTATGAAAAAAG 
               
               
                   
               
               
                 CCCGTGAGAGCCTGCAGCCGAATACCGCAACGCTGAACCACTTGAGCCATCTGAAGAAAACCCAGCCTGGCCTTC 
               
               
                   
               
               
                 GTATCTACGGCCTGACGAACACCCCGTTGCCGGAACAGAGCTCAGTCCGTAGCATTGCGCAGGAATGGCCGATTT 
               
               
                   
               
               
                 TTGACCACATCTACATTAGCGGCATCTTGGGTATGCGCAAACCGGATATTGGTTGTTACCGTCTGGTTCTGCGTAA 
               
               
                   
               
               
                 GATCGGTCTGCCAGCGGAGTCCGTCGTATTCATCGACGACAGCCCGGAGAACATTCTGGCAGCTCAATCGTTGGG 
               
               
                   
               
               
                 TGTCCATAGCATCCTGTTCCAGTCCCACGATCAGCTGAGCCGTCAGCTGGGCAATGTGCTGGGTGATCCGATTCAG 
               
               
                   
               
               
                 CGCGGTCACAACTTCCTCCTGTCCAACGCGAAGCAAATGAACAGCACCACCGATAAGGGTGTGATTATCCGCGAC 
               
               
                   
               
               
                 AACTTCGCCCAGCTGCTGATTATTGAGCTGACCCAAAATCCGGATCTGGTTGCGCTGGAGACTTGGGACCGTACGT 
               
               
                   
               
               
                 GGAATTTCTTTATTGGTCCGCCGCAACTGACCACCGAGAGCTTTCCGAACGACCTGGACACCACGAGCATTGCCCT 
               
               
                   
               
               
                 GAGCGTGTTGCCGGTGGATAAAGAAGTCGTTTGGTCTGTGATGGATGAGATGCTGACCTTCACCAACGCAGACGG 
               
               
                   
               
               
                 CATCTTCATGACCTATTTCGATCGTAGCCGTCCGCGTGTTGACCCGGTCGTTTGTACCAATGTCCTGAATCTGTTTTG 
               
               
                   
               
               
                 CATGCATGGTCGCGAGAGCGAAGTGGCCGCGACGTTCGACTGGGTGCTGGACGTGCTGCGCAACAGCGCGTACC 
               
               
                   
               
               
                 TGAGCGGTTCCCGTTATTACAGCAGCCCGGATTGTTTTCTGTATTTCCTGTCTCGTCTGAGCTGCGTCGTCCGTGAT 
               
               
                   
               
               
                 GGCACGCGTCGTCGTGAACTGAAAAGCCTGCTGAAGCAACAAGTTTCTCAACGTATCGGCGCTGACGGTGATTCC 
               
               
                   
               
               
                 GTCAGCCTGGCCACCCGTTTGCTGGCGAGCAACATCCTGGGCATTACTAACGGTCGTGACCGCAGCCGTCTGCTG 
               
               
                   
               
               
                 GCATTGCAAGAAACCGATGGTGGCTGGCCTGCAGGCTGGGTCTATAAGTTTGGTAGCAGCGGCGTGCAAATTGG 
               
               
                   
               
               
                 CAATCGCGGTCTGAGCACCGCGCTGGCTCTGAAGTCTATCGAGCGCCAGAAAGGTCCGGTGGAAGCAATCAGCA 
               
               
                   
               
               
                 GCGAGCCGGAAGCGTGGTGGCCTAGCTTACGCTTGGACCGCTTGCTGAATGTTTGGCCATTTATCGACTGGAAGG 
               
               
                   
               
               
                 GCTACTCCCCGAGCTAA 
               
               
                   
               
               
                 Class I terpene synthase-like motif 
               
               
                 SEQ ID NO: 53 
                   
               
               
                 DDxx(D/E), where x at position 3 is K, N, R, S, or Q and x at position 4 is 
                   
               
               
                 L, I, G, P, or T 
               
               
                   
               
               
                 Class I terpene synthase-like motif 
               
               
                 SEQ ID NO: 54 
                   
               
               
                 DD(K/Q/R)(L/I/T)(D/E)NV 
                   
               
               
                   
               
               
                 Class I terpene synthase-like motif 
               
               
                 SEQ ID NO: 55 
                   
               
               
                 DD(N/K/S/Q)(L/G/P)(D/E)N(V/I) 
                   
               
               
                   
               
               
                 Class II terpene synthase-like motif 
               
               
                 SEQ ID NO: 56 
                   
               
               
                 DxD(T/S)T, where x at position 2 is V, M, F or L 
                   
               
               
                   
               
               
                 Class II terpene synthase-like motif 
               
               
                 SEQ ID NO: 57 
                   
               
               
                 D(V/M/L/F)DTTS 
                   
               
               
                   
               
               
                 Class II terpene synthase-like motif 
               
               
                 SEQ ID NO: 58 
                   
               
               
                 D(V/M/L)D(T/S)TS 
                   
               
               
                   
               
               
                 Conserved motif A 
               
               
                 SEQ ID NO: 59 
                   
               
               
                 SxxWxxYExG, where x is any amino acid 
                   
               
               
                   
               
               
                 Conserved motif B 
               
               
                 SEQ ID NO: 60 
                   
               
               
                 NFxQx(I/L)IxE, where x is any amino acid 
                   
               
               
                   
               
               
                 Conserved motif C 
               
               
                 SEQ ID NO: 61 
                   
               
               
                 (D/E)(G/E)Ixx(T/V)YFDxxRxRxDPxVxxNVL 
                   
               
               
                   
               
               
                 Conserved motif D 
               
               
                 SEQ ID NO: 62 
                   
               
               
                 QxxDGx(W/F) 
                   
               
               
                   
               
               
                 XP_006461126.1 
               
               
                 - XP_006461126.1 protein 
               
               
                 SEQ ID NO: 63 
                   
               
               
                 MAPPQRPFTAIVFDIGDVLFQWSATTKTSISPKTLRSILNCPTWFDYERGRLAENACYAAISQEFNVNPDEVRDAFSQAR 
                   
               
               
                   
               
               
                 DSLQANHDFISLIRELKAQANGRLRVYAMSNISLPDWEVLRMKPADWDIFDHVFTSGAVGERKPNLAFYRHVIAATDL 
               
               
                   
               
               
                 QPHQTIFVDDKLENVLSARSLGFTGIVFDEPSEVKRALRNLIGDPVQRGGEFLVRNAGKLGSITRTTAKHESIPLDENFAQ 
               
               
                   
               
               
                 LLILEITGNRALVNLVEHPQTWNFFQGKGQLTTEEFPFDLDTTSLGLTILKRSREIADSVMDEMLEYVDPDGIIQTYFDHR 
               
               
                   
               
               
                 RPRFDPVVCVNALSLFYAYGRGEQLRSTLTWVHEVLLNRAYLDGTRYYETAECFLYFMSRLLATSGDPDLHSLLKPLLKER 
               
               
                   
               
               
                 VQERIGADGDSLALAMRILACDFVGIRDEVDLRTLLTLQCEDGGWEVGWMYKYGSSGISIGNRGLATALAIKAVDTMF 
               
               
                   
               
               
                 QPQIRFSESPTDTLVENAIHKRRPSFSEKFLGKRPRSGSFRKPLQWILQGSKLRKSVEIGS 
               
               
                   
               
               
                 - XP_006461126.1 cDNA 
               
               
                 SEQ ID NO: 64 
                   
               
               
                 ATGGCTCCGCCTCAGCGACCCTTTACTGCGATTGTCTTTGACATCGGGGATGTTCTATTCCAATGGTCTGCAACCAC 
                   
               
               
                   
               
               
                 CAAAACCTCTATCTCACCAAAGACACTCCGCTCTATTCTCAACTGTCCGACATGGTTTGACTATGAACGTGGACGCC 
               
               
                   
               
               
                 TGGCAGAAAACGCTTGTTATGCCGCTATCTCACAAGAATTCAACGTCAACCCAGACGAAGTTCGCGACGCTTTCAG 
               
               
                   
               
               
                 CCAAGCGCGCGACTCTCTCCAAGCAAACCACGACTTCATCAGTCTCATCCGTGAGCTGAAGGCACAAGCAAATGGT 
               
               
                   
               
               
                 CGTTTACGTGTGTACGCCATGTCGAACATATCTCTTCCTGATTGGGAAGTGCTGCGGATGAAACCTGCTGATTGGG 
               
               
                   
               
               
                 ATATTTTCGACCACGTCTTCACATCCGGTGCGGTTGGGGAACGCAAGCCCAATCTCGCCTTTTATCGCCATGTTATC 
               
               
                   
               
               
                 GCGGCCACCGATCTGCAGCCTCATCAGACAATATTTGTTGACGATAAGCTGGAGAATGTTCTCTCAGCACGTTCCC 
               
               
                   
               
               
                 TCGGGTTCACAGGCATCGTGTTTGACGAGCCCTCCGAGGTCAAACGTGCGCTTCGTAACCTCATTGGGGATCCTGT 
               
               
                   
               
               
                 TCAACGAGGAGGTGAATTCTTGGTTCGGAATGCCGGAAAGCTTGGCTCTATCACAAGGACTACTGCAAAGCACGA 
               
               
                   
               
               
                 GTCAATCCCCCTCGACGAGAATTTTGCTCAGCTTCTTATTCTCGAGATAACGGGGAACAGGTGCGTTAGCTTCTTGT 
               
               
                   
               
               
                 AGGGTCTTCTGTCGTAATACTAAATTTTTTCTGGTGTTTAGGGCTTTGGTCAACCTCGTTGAGCATCCTCAAACGTG 
               
               
                   
               
               
                 GAATTTCTTCCAAGGTGCGCTGCTAAAATAAACATCCAGTTGCGTTTCGAAGCTCATTGTGGGCGTCCCGTCACAG 
               
               
                   
               
               
                 GCAAGGGCCAGCTGACAACAGAAGAATTTCCATTCGATCTCGATACAACTTCTCTTGGTCTCACGATCCTCAAGCG 
               
               
                   
               
               
                 AAGCAGGGAAATCGCCGATTCAGTCATGGATGAAATGCTGGAGTATGTCGATCCTGATGGTATCATTCAGGCAAG 
               
               
                   
               
               
                 TTTCATTTATCGGCTTGAGAAAATAAAGACAAAAACGTTCTGATGGGGGGATGTTTCTAGACGTATTTCGATCATC 
               
               
                   
               
               
                 GGAGACCACGTTTTGATCCAGTCGTGTGTGTCAATGCATTAAGCCTCTTCTATGCTTACGGCCGCGGGGAGCAACT 
               
               
                   
               
               
                 GCGGTCGACTTTGACATGGGTACATGAAGTCCTTCTCAATCGAGCCTACTTGGATGGCACACGGTACTACGAAACA 
               
               
                   
               
               
                 GCCGAATGCTTCCTCTATTTCATGAGCCGACTTCTCGCCACTTCAGGCGACCCTGACCTTCACTCCCTTCTTAAACCT 
               
               
                   
               
               
                 CTTCTCAAAGAACGGGTGCAAGAACGCATTGGAGCTGATGGAGACTCTCTTGCACTCGCAATGCGTATTCTCGCCT 
               
               
                   
               
               
                 GTGATTTCGTCGGAATCAGAGATGAAGTGGATTTACGCACACTTCTGACTTTGCAATGTGAAGATGGAGGTTGGG 
               
               
                   
               
               
                 AAGTGGGTTGGATGTACAAGTATGGATCTTCCGGTATCAGTATCGGAAATCGTGGACTGGCCACCGCGCTCGCTA 
               
               
                   
               
               
                 TCAAGGCCGTCGACACGATGTTTCAACCCCAAATTCGGTTCTCTGAATCACCCACAGATACTTTGGTTGAAAACGCT 
               
               
                   
               
               
                 ATCCACAAACGCCGTCCCTCATTTTCCGAAAAATTCCTCGGCAAACGTCCTCGCAGCGGATCGTTCAGGAAACCTTT 
               
               
                   
               
               
                 ACAGTGGATACTGCAAGGTTCCAAGCTTCGCAAATCTGTCGAAATAGGAAGCTAA 
               
               
                   
               
               
                 - XP_006461126.1 optimized cDNA 
               
               
                 SEQ ID NO: 65 
                   
               
               
                 ATGGCACCACCGCAACGTCCGTTCACTGCAATTGTTTTCGATATTGGCGATGTTTTGTTCCAATGGTCTGCGACCAC 
                   
               
               
                   
               
               
                 GAAAACCAGCATTAGCCCGAAAACCCTGCGCAGCATTCTGAATTGTCCGACCTGGTTTGATTATGAGCGCGGCCGT 
               
               
                   
               
               
                 CTGGCGGAAAATGCGTGTTACGCTGCGATCAGCCAAGAATTTAACGTCAACCCGGACGAAGTTCGCGACGCCTTC 
               
               
                   
               
               
                 AGCCAAGCGCGCGACAGCCTGCAGGCGAATCACGACTTCATCAGCCTGATTCGTGAGCTGAAAGCTCAGGCGAAC 
               
               
                   
               
               
                 GGTCGTCTGCGTGTCTACGCCATGTCTAATATCAGCCTGCCGGATTGGGAAGTCCTGCGTATGAAGCCAGCCGATT 
               
               
                   
               
               
                 GGGACATCTTTGACCATGTATTTACCAGCGGTGCGGTGGGTGAGCGCAAGCCGAACCTGGCCTTTTATCGTCACGT 
               
               
                   
               
               
                 CATCGCGGCCACGGATCTGCAGCCGCACCAGACGATCTTCGTGGATGACAAACTGGAAAACGTGCTGTCTGCGCG 
               
               
                   
               
               
                 CTCGCTGGGCTTCACGGGTATCGTGTTCGACGAGCCAAGCGAAGTCAAACGTGCGCTGCGTAATCTGATCGGCGA 
               
               
                   
               
               
                 CCCGGTGCAGCGTGGTGGCGAGTTCCTGGTTCGTAATGCTGGCAAACTGGGTTCTATCACCCGTACGACCGCAAA 
               
               
                   
               
               
                 ACATGAGAGCATCCCGCTGGATGAGAATTTTGCACAACTGTTGATTCTGGAAATTACTGGTAACCGCGCACTGGTC 
               
               
                   
               
               
                 AATCTGGTTGAGCACCCGCAGACGTGGAACTTCTTCCAGGGTAAGGGCCAGCTGACGACCGAAGAATTTCCTTTT 
               
               
                   
               
               
                 GACCTGGATACGACGAGCCTGGGTCTGACGATCCTGAAGCGTAGCCGCGAGATTGCCGACTCCGTCATGGACGAA 
               
               
                   
               
               
                 ATGTTGGAATACGTGGACCCTGACGGCATCATTCAGACCTACTTCGATCATCGTCGCCCGCGCTTTGACCCGGTTG 
               
               
                   
               
               
                 TTTGCGTTAATGCCCTGAGCCTGTTCTATGCATACGGCCGTGGTGAGCAACTGCGTTCCACCTTGACCTGGGTGCA 
               
               
                   
               
               
                 CGAAGTTCTGTTGAACCGTGCGTATTTGGATGGTACGCGTTACTATGAAACGGCCGAGTGCTTTCTGTATTTCATG 
               
               
                   
               
               
                 TCCCGTCTGCTGGCAACCAGCGGTGACCCGGATCTGCATTCCCTGCTGAAGCCGTTGCTGAAGGAACGCGTGCAA 
               
               
                   
               
               
                 GAGCGCATCGGCGCTGACGGTGACAGCCTGGCGCTGGCGATGCGCATTTTGGCATGTGATTTTGTTGGCATCCGT 
               
               
                   
               
               
                 GATGAAGTGGATCTGCGTACCCTGCTGACCTTACAGTGCGAGGATGGCGGTTGGGAAGTGGGCTGGATGTACAA 
               
               
                   
               
               
                 ATACGGTAGCAGCGGTATTAGCATTGGTAACCGTGGTCTGGCAACCGCATTGGCGATCAAAGCTGTTGACACCAT 
               
               
                   
               
               
                 GTTTCAACCGCAAATCCGTTTCAGCGAGAGCCCGACCGACACTCTGGTGGAGAACGCGATTCACAAGCGCCGCCC 
               
               
                   
               
               
                 GAGCTTTTCAGAGAAATTTTTAGGTAAGCGTCCGCGTTCCGGTTCGTTCCGTAAACCGCTGCAATGGATTCTGCAG 
               
               
                   
               
               
                 GGCAGCAAGCTGCGCAAGAGCGTCGAGATCGGTAGCTAA 
               
               
                   
               
               
                 XP_007369631.1 
               
               
                 - XP_007369631.1 Optimized cDNA for  S .  cerevisiae  expression 
               
               
                 SEQ ID NO: 66 
                   
               
               
                 ATGGCTTCTATCCACAGAAGATACACTACTTTGATCTTGGACTTGGGTGACGTTTTGTTCAGATGGTCTCCAAAGAC 
                   
               
               
                   
               
               
                 TGAAACTGCTATCCCACCACAACAATTGAAGGACATCTTGTCTTCTGTTACTTGGTTCGAATACGAAAGAGGTAGA 
               
               
                   
               
               
                 TTGTCTCAAGAAGCTTGTTACGAAAGATGTGCTGAAGAATTCAAGATCGAAGCTTCTGTTATCGCTGAAGCTTTCA 
               
               
                   
               
               
                 AGCAAGCTAGAGGTTCTTTGAGACCAAACGAAGAATTCATCGCTTTGATCAGAGACTTGAGAAGAGAAATGCACG 
               
               
                   
               
               
                 GTGACTTGACTGTTTTGGCTTTGTCTAACATCTCTTTGCCAGACTACGAATACATCATGTCTTTGTCTTCTGACTGGA 
               
               
                   
               
               
                 CTACTGTTTTCGACAGAGTTTTCCCATCTGCTTTGGTTGGTGAAAGAAAGCCACACTTGGGTTGTTACAGAAAGGTT 
               
               
                   
               
               
                 ATCTCTGAAATGAACTTGGAACCACAAACTACTGTTTTCGTTGACGACAAGTTGGACAACGTTGCTTCTGCTAGATC 
               
               
                   
               
               
                 TTTGGGTATGCACGGTATCGTTTTCGACAACCAAGCTAACGTTTTCAGACAATTGAGAAACATCTTCGGTGACCCA 
               
               
                   
               
               
                 ATCAGAAGAGGTCAAGAATACTTGAGAGGTCACGCTGGTAAGTTGGAATCTTCTACTGACAACGGTTTGATCTTCG 
               
               
                   
               
               
                 AAGAAAACTTCACTCAATTGATCATCTACGAATTGACTCAAGACAGAACTTTGATCTCTTTGTCTGAATGTCCAAGA 
               
               
                   
               
               
                 ACTTGGAACTTCTTCAGAGGTGAACCATTGTTCTCTGAAACTTTCCCAGACGACGTTGACACTACTTCTGTTGCTTT 
               
               
                   
               
               
                 GACTGTTTTGCAACCAGACAGAGCTTTGGTTAACTCTGTTTTGGACGAAATGTTGGAATACGTTGACGCTGACGGT 
               
               
                   
               
               
                 ATCATGCAAACTTACTTCGACAGATCTAGACCAAGAATGGACCCATTCGTTTGTGTTAACGTTTTGTCTTTGTTCTAC 
               
               
                   
               
               
                 GAAAACGGTAGAGGTCACGAATTGCCAAGAACTTTGGACTGGGTTTACGAAGTTTTGTTGCACAGAGCTTACCAC 
               
               
                   
               
               
                 GGTGGTTCTAGATACTACTTGTCTCCAGACTGTTTCTTGTTCTTCATGTCTAGATTGTTGAAGAGAGCTGACGACCC 
               
               
                   
               
               
                 AGCTGTTCAAGCTAGATTGAGACCATTGTTCGTTGAAAGAGTTAACGAAAGAGTTGGTGCTGCTGGTGACTCTATG 
               
               
                   
               
               
                 GACTTGGCTTTCAGAATCTTGGCTGCTGCTTCTGTTGGTGTTCAATGTCCAAGAGACTTGGAAAGATTGACTGCTG 
               
               
                   
               
               
                 GTCAATGTGACGACGGTGGTTGGGACTTGTGTTGGTTCTACGTTTTCGGTTCTACTGGTGTTAAGGCTGGTAACAG 
               
               
                   
               
               
                 AGGTTTGACTACTGCTTTGGCTGTTACTGCTATCCAAACTGCTATCGGTAGACCACCATCTCCATCTCCATCTGCTGC 
               
               
                   
               
               
                 TTCTTCTTCTTTCAGACCATCTTCTCCATACAAGTTCTTGGGTATCTCTAGACCAGCTTCTCCAATCAGATTCGGTGA 
               
               
                   
               
               
                 CTTGTTGAGACCATGGAGAAAGATGTCTAGATCTAACTTGAAGTCTCAATAA 
               
               
                   
               
               
                 XP_006461126 
               
               
                 - XP_006461126 Optimized cDNA for  S .  cerevisiae  expression 
               
               
                 SEQ ID NO: 67 
                   
               
               
                 ATGGCTCCACCACAAAGACCATTCACTGCTATCGTTTTCGACATCGGTGACGTTTTGTTCCAATGGTCTGCTACTAC 
                   
               
               
                   
               
               
                 TAAGACTTCTATCTCTCCAAAGACTTTGAGATCTATCTTGAACTGTCCAACTTGGTTCGACTACGAAAGAGGTAGAT 
               
               
                   
               
               
                 TGGCTGAAAACGCTTGTTACGCTGCTATCTCTCAAGAATTCAACGTTAACCCAGACGAAGTTAGAGACGCTTTCTCT 
               
               
                   
               
               
                 CAAGCTAGAGACTCTTTGCAAGCTAACCACGACTTCATCTCTTTGATCAGAGAATTGAAGGCTCAAGCTAACGGTA 
               
               
                   
               
               
                 GATTGAGAGTTTACGCTATGTCTAACATCTCTTTGCCAGACTGGGAAGTTTTGAGAATGAAGCCAGCTGACTGGGA 
               
               
                   
               
               
                 CATCTTCGACCACGTTTTCACTTCTGGTGCTGTTGGTGAAAGAAAGCCAAACTTGGCTTTCTACAGACACGTTATCG 
               
               
                   
               
               
                 CTGCTACTGACTTGCAACCACACCAAACTATCTTCGTTGACGACAAGTTGGAAAACGTTTTGTCTGCTAGATCTTTG 
               
               
                   
               
               
                 GGTTTCACTGGTATCGTTTTCGACGAACCATCTGAAGTTAAGAGAGCTTTGAGAAACTTGATCGGTGACCCAGTTC 
               
               
                   
               
               
                 AAAGAGGTGGTGAATTCTTGGTTAGAAACGCTGGTAAGTTGGGTTCTATCACTAGAACTACTGCTAAGCACGAAT 
               
               
                   
               
               
                 CTATCCCATTGGACGAAAACTTCGCTCAATTGTTGATCTTGGAAATCACTGGTAACAGAGCTTTGGTTAACTTGGTT 
               
               
                   
               
               
                 GAACACCCACAAACTTGGAACTTCTTCCAAGGTAAGGGTCAATTGACTACTGAAGAATTCCCATTCGACTTGGACA 
               
               
                   
               
               
                 CTACTTCTTTGGGTTTGACTATCTTGAAGAGATCTAGAGAAATCGCTGACTCTGTTATGGACGAAATGTTGGAATA 
               
               
                   
               
               
                 CGTTGACCCAGACGGTATCATCCAAACTTACTTCGACCACAGAAGACCAAGATTCGACCCAGTTGTTTGTGTTAAC 
               
               
                   
               
               
                 GCTTTGTCTTTGTTCTACGCTTACGGTAGAGGTGAACAATTGAGATCTACTTTGACTTGGGTTCACGAAGTTTTGTT 
               
               
                   
               
               
                 GAACAGAGCTTACTTGGACGGTACTAGATACTACGAAACTGCTGAATGTTTCTTGTACTTCATGTCTAGATTGTTGG 
               
               
                   
               
               
                 CTACTTCTGGTGACCCAGACTTGCACTCTTTGTTGAAGCCATTGTTGAAGGAAAGAGTTCAAGAAAGAATCGGTGC 
               
               
                   
               
               
                 TGACGGTGACTCTTTGGCTTTGGCTATGAGAATCTTGGCTTGTGACTTCGTTGGTATCAGAGACGAAGTTGACTTG 
               
               
                   
               
               
                 AGAACTTTGTTGACTTTGCAATGTGAAGACGGTGGTTGGGAAGTTGGTTGGATGTACAAGTACGGTTCTTCTGGTA 
               
               
                   
               
               
                 TCTCTATCGGTAACAGAGGTTTGGCTACTGCTTTGGCTATCAAGGCTGTTGACACTATGTTCCAACCACAAATCAGA 
               
               
                   
               
               
                 TTCTCTGAATCTCCAACTGACACTTTGGTTGAAAACGCTATCCACAAGAGAAGACCATCTTTCTCTGAAAAGTTCTT 
               
               
                   
               
               
                 GGGTAAGAGACCAAGATCTGGTTCTTTCAGAAAGCCATTGCAATGGATCTTGCAAGGTTCTAAGTTGAGAAAGTC 
               
               
                   
               
               
                 TGTTGAAATCGGTTCTTAA 
               
               
                   
               
               
                 LoTps1 
               
               
                 - LoTps1 Optimized cDNA for  S .  cerevisiae  expression 
               
               
                 SEQ ID NO: 68 
                   
               
               
                 ATGTACACTGCTTTGATCTTGGACTTGGGTGACGTTTTGTTCTCTTGGTCTTCTACTACTAACACTACTATCCCACCA 
                   
               
               
                   
               
               
                 AGACAATTGAAGGAAATCTTGTCTTCTCCAGCTTGGTTCGAATACGAAAGAGGTAGAATCACTCAAGCTGAATGTT 
               
               
                   
               
               
                 ACGAAAGAGTTTCTGCTGAATTCTCTTTGGACGCTACTGCTGTTGCTGAAGCTTTCAGACAAGCTAGAGACTCTTTG 
               
               
                   
               
               
                 AGACCAAACGACAAGTTCTTGACTTTGATCAGAGAATTGAGACAACAATCTCACGGTGAATTGACTGTTTTGGCTT 
               
               
                   
               
               
                 TGTCTAACATCTCTTTGCCAGACTACGAATTCATCATGGCTTTGGACTCTAAGTGGACTTCTGTTTTCGACAGAGTTT 
               
               
                   
               
               
                 TCCCATCTGCTTTGGTTGGTGAAAGAAAGCCACACTTGGGTGCTTTCAGACAAGTTTTGTCTGAAATGAACTTGGA 
               
               
                   
               
               
                 CCCACACACTACTGTTTTCGTTGACGACAAGTTGGACAACGTTGTTTCTGCTAGATCTTTGGGTATGCACGGTGTTG 
               
               
                   
               
               
                 TTTTCGACTCTCAAGACAACGTTTTCAGAATGTTGAGAAACATCTTCGGTGACCCAATCCACAGAGGTAGAGACTA 
               
               
                   
               
               
                 CTTGAGACAACACGCTGGTAGATTGGAAACTTCTACTGACGCTGGTGTTGTTTTCGAAGAAAACTTCACTCAATTG 
               
               
                   
               
               
                 ATCATCTACGAATTGACTAACGACAAGTCTTTGATCACTACTTCTAACTGTGCTAGAACTTGGAACTTCTTCAGAGG 
               
               
                   
               
               
                 TAAGCCATTGTTCTCTGCTTCTTTCCCAGACGACATGGACACTACTTCTGTTGCTTTGACTGTTTTGAGATTGGACCA 
               
               
                   
               
               
                 CGCTTTGGTTAACTCTGTTTTGGACGAAATGTTGAAGTACGTTGACGCTGACGGTATCATGCAAACTTACTTCGACC 
               
               
                   
               
               
                 ACACTAGACCAAGAATGGACCCATTCGTTTGTGTTAACGTTTTGTCTTTGTTCCACGAACAAGGTAGAGGTCACGA 
               
               
                   
               
               
                 ATTGCCAAACACTTTGGAATGGGTTCACGAAGTTTTGTTGCACAGAGCTTACATCGGTGGTTCTAGATACTACTTGT 
               
               
                   
               
               
                 CTGCTGACTGTTTCTTGTTCTTCATGTCTAGATTGTTGCAAAGAATCACTGACCCATCTGTTTTGGGTAGATTCAGAC 
               
               
                   
               
               
                 CATTGTTCATCGAAAGAGTTAGAGAAAGAGTTGGTGCTACTGGTGACTCTATCGACTTGGCTTTCAGAATCATCGC 
               
               
                   
               
               
                 TGCTTCTACTGTTGGTATCCAATGTCCAAGAGACTTGGAATCTTTGTTGGCTGCTCAATGTGAAGACGGTGGTTGG 
               
               
                   
               
               
                 GACTTGTGTTGGTTCTACCAATACGGTTCTACTGGTGTTAAGGCTGGTAACAGAGGTTTGACTACTGCTTTGGCTAT 
               
               
                   
               
               
                 CAAGGCTATCGACTCTGCTATCGCTAGACCACCATCTCCAGCTTTGTCTGTTGCTTCTTCTTCTAAGTCTGAAATCCC 
               
               
                   
               
               
                 AAAGCCAATCCAAAGATCTTTGAGACCATTGTCTCCAAGAAGATTCGGTGGTTTCTTGATGCCATGGAGAAGATCT 
               
               
                   
               
               
                 CAAAGAAACGGTGTTGCTGTTTCTTCTTAA 
               
               
                   
               
               
                 EMD37666.1 
               
               
                 - EMD37666.1 Optimized cDNA for  S .  cerevisiae  expression 
               
               
                 SEQ ID NO: 69 
                   
               
               
                 ATGTCTGCTGCTGCTCAATACACTACTTTGATCTTGGACTTGGGTGACGTTTTGTTCACTTGGTCTCCAAAGACTAA 
                   
               
               
                   
               
               
                 GACTTCTATCCCACCAAGAACTTTGAAGGAAATCTTGAACTCTGCTACTTGGTACGAATACGAAAGAGGTAGAATC 
               
               
                   
               
               
                 TCTCAAGACGAATGTTACGAAAGAGTTGGTACTGAATTCGGTATCGCTCCATCTGAAATCGACAACGCTTTCAAGC 
               
               
                   
               
               
                 AAGCTAGAGACTCTATGGAATCTAACGACGAATTGATCGCTTTGGTTAGAGAATTGAAGACTCAATTGGACGGTG 
               
               
                   
               
               
                 AATTGTTGGTTTTCGCTTTGTCTAACATCTCTTTGCCAGACTACGAATACGTTTTGACTAAGCCAGCTGACTGGTCTA 
               
               
                   
               
               
                 TCTTCGACAAGGTTTTCCCATCTGCTTTGGTTGGTGAAAGAAAGCCACACTTGGGTGTTTACAAGCACGTTATCGCT 
               
               
                   
               
               
                 GAAACTGGTATCGACCCAAGAACTACTGTTTTCGTTGACGACAAGATCGACAACGTTTTGTCTGCTAGATCTGTTG 
               
               
                   
               
               
                 GTATGCACGGTATCGTTTTCGAAAAGCAAGAAGACGTTATGAGAGCTTTGAGAAACATCTTCGGTGACCCAGTTA 
               
               
                   
               
               
                 GAAGAGGTAGAGAATACTTGAGAAGAAACGCTATGAGATTGGAATCTGTTACTGACCACGGTGTTGCTTTCGGTG 
               
               
                   
               
               
                 AAAACTTCACTCAATTGTTGATCTTGGAATTGACTAACGACCCATCTTTGGTTACTTTGCCAGACAGACCAAGAACT 
               
               
                   
               
               
                 TGGAACTTCTTCAGAGGTAACGGTGGTAGACCATCTAAGCCATTGTTCTCTGAAGCTTTCCCAGACGACTTGGACA 
               
               
                   
               
               
                 CTACTTCTTTGGCTTTGACTGTTTTGCAAAGAGACCCAGGTGTTATCTCTTCTGTTATGGACGAAATGTTGAACTAC 
               
               
                   
               
               
                 AGAGACCCAGACGGTATCATGCAAACTTACTTCGACGACGGTAGACAAAGATTGGACCCATTCGTTAACGTTAAC 
               
               
                   
               
               
                 GTTTTGACTTTCTTCTACACTAACGGTAGAGGTCACGAATTGGACCAATGTTTGACTTGGGTTAGAGAAGTTTTGTT 
               
               
                   
               
               
                 GTACAGAGCTTACTTGGGTGGTTCTAGATACTACCCATCTGCTGACTGTTTCTTGTACTTCATCTCTAGATTGTTCGC 
               
               
                   
               
               
                 TTGTACTAACGACCCAGTTTTGCACCACCAATTGAAGCCATTGTTCGTTGAAAGAGTTCAAGAACAAATCGGTGTT 
               
               
                   
               
               
                 GAAGGTGACGCTTTGGAATTGGCTTTCAGATTGTTGGTTTGTGCTTCTTTGGACGTTCAAAACGCTATCGACATGA 
               
               
                   
               
               
                 GAAGATTGTTGGAAATGCAATGTGAAGACGGTGGTTGGGAAGGTGGTAACTTGTACAGATTCGGTACTACTGGTT 
               
               
                   
               
               
                 TGAAGGTTACTAACAGAGGTTTGACTACTGCTGCTGCTGTTCAAGCTATCGAAGCTTCTCAAAGAAGACCACCATC 
               
               
                   
               
               
                 TCCATCTCCATCTGTTGAATCTACTAAGTCTCCAATCACTCCAGTTACTCCAATGTTGGAAGTTCCATCTTTGGGTTT 
               
               
                   
               
               
                 GTCTATCTCTAGACCATCTTCTCCATTGTTGGGTTACTTCAGATTGCCATGGAAGAAGTCTGCTGAAGTTCACTAA 
               
               
                   
               
               
                 XP_001217376.1 
               
               
                 - XP_001217376.1 Optimized cDNA for  S .  cerevisiae  expression 
               
               
                 SEQ ID NO: 70 
                   
               
               
                 ATGGCTATCACTAAGGGTCCAGTTAAGGCTTTGATCTTGGACTTCTCTAACGTTTTGTGTTCTTGGAAGCCACCATC 
                   
               
               
                   
               
               
                 TAACGTTGCTGTTCCACCACAAATCTTGAAGATGATCATGTCTTCTGACATCTGGCACGACTACGAATGTGGTAGAT 
               
               
                   
               
               
                 ACTCTAGAGAAGACTGTTACGCTAGAGTTGCTGACAGATTCCACATCTCTGCTGCTGACATGGAAGACACTTTGAA 
               
               
                   
               
               
                 GCAAGCTAGAAAGTCTTTGCAAGTTCACCACGAAACTTTGTTGTTCATCCAACAAGTTAAGAAGGACGCTGGTGGT 
               
               
                   
               
               
                 GAATTGATGGTTTGTGGTATGACTAACACTCCAAGACCAGAACAAGACGTTATGCACTCTATCAACGCTGAATACC 
               
               
                   
               
               
                 CAGTTTTCGACAGAATCTACATCTCTGGTTTGATGGGTATGAGAAAGCCATCTATCTGTTTCTACCAAAGAGTTATG 
               
               
                   
               
               
                 GAAGAAATCGGTTTGTCTGGTGACGCTATCATGTTCATCGACGACAAGTTGGAAAACGTTATCGCTGCTCAATCTG 
               
               
                   
               
               
                 TTGGTATCAGAGGTGTTTTGTTCCAATCTCAACAAGACTTGAGAAGAGTTGTTTTGAACTTCTTGGGTGACCCAGTT 
               
               
                   
               
               
                 CACAGAGGTTTGCAATTCTTGGCTGCTAACGCTAAGAAGATGGACTCTGTTACTAACACTGGTGACACTATCCAAG 
               
               
                   
               
               
                 ACAACTTCGCTCAATTGTTGATCTTGGAATTGGCTCAAGACAGAGAATTGGTTAAGTTGCAAGCTGGTAAGAGAAC 
               
               
                   
               
               
                 TTGGAACTACTTCATCGGTCCACCAAAGTTGACTACTGCTACTTTCCCAGACGACATGGACACTACTTCTATGGCTT 
               
               
                   
               
               
                 TGTCTGTTTTGCCAGTTGCTGAAGACGTTGTTTCTTCTGTTTTGGACGAAATGTTGAAGTTCGTTACTGACGACGGT 
               
               
                   
               
               
                 ATCTTCATGACTTACTTCGACTCTTCTAGACCAAGAGTTGACCCAGTTGTTTGTATCAACGTTTTGGGTGTTTTCTGT 
               
               
                   
               
               
                 AGACACAACAGAGAAAGAGACGTTTTGCCAACTTTCCACTGGATCAGAGACATCTTGATCAACAGAGCTTACTTGT 
               
               
                   
               
               
                 CTGGTACTAGATACTACCCATCTCCAGACTTGTTCTTGTTCTTCTTGGCTAGATTGTGTTTGGCTGTTAGAAACCAAT 
               
               
                   
               
               
                 CTTTGAGAGAACAATTGGTTTTGCCATTGGTTGACAGATTGAGAGAAAGAGTTGGTGCTCCAGGTGAAGCTGTTTC 
               
               
                   
               
               
                 TTTGGCTGCTAGAATCTTGGCTTGTAGATCTTTCGGTATCGACTCTGCTAGAGACATGGACTCTTTGAGAGGTAAG 
               
               
                   
               
               
                 CAATGTGAAGACGGTGGTTGGCCAGTTGAATGGGTTTACAGATTCGCTTCTTTCGGTTTGAACGTTGGTAACAGAG 
               
               
                   
               
               
                 GTTTGGCTACTGCTTTCGCTGTTAGAGCTTTGGAATCTCCATACGGTGAATCTGCTGTTAAGGTTATGAGAAGAATC 
               
               
                   
               
               
                 GTTTAA 
               
               
                   
               
               
                 Primers 
               
               
                 - Primer for construction of fragment “a” (LEU2 yeast marker) 
               
               
                 SEQ ID NO: 71 
                   
               
               
                 AGGTGCAGTTCGCGTGCAATTATAACGTCGTGGCAACTGTTATCAGTCGTACCGCGCCATTCGACTACGTCGTAAG 
                   
               
               
                   
               
               
                 GCC 
               
               
                   
               
               
                 - Primer for construction of fragment “a” (LEU2 yeast marker) 
               
               
                 SEQ ID NO: 72 
                   
               
               
                 TCGTGGTCAAGGCGTGCAATTCTCAACACGAGAGTGATTCTTCGGCGTTGTTGCTGACCATCGACGGTCGAGGAG 
                   
               
               
                   
               
               
                 AACTT 
               
               
                   
               
               
                 - Primer for construction of fragment “b” (AmpR  E .  coli  marker) 
               
               
                 SEQ ID NO: 73 
                   
               
               
                 TGGTCAGCAACAACGCCGAAGAATCACTCTCGTGTTGAGAATTGCACGCCTTGACCACGACACGTTAAGGGATTTT 
                   
               
               
                   
               
               
                 GGTCATGAG 
               
               
                   
               
               
                 - Primer for construction of fragment “b” (AmpR  E .  coli  marker) 
               
               
                 SEQ ID NO: 74 
                   
               
               
                 AACGCGTACCCTAAGTACGGCACCACAGTGACTATGCAGTCCGCACTTTGCCAATGCCAAAAATGTGCGCGGAAC 
                   
               
               
                   
               
               
                 CCCTA 
               
               
                   
               
               
                 - Primer for construction of fragment “c” (Yeast origin of replication) 
               
               
                 SEQ ID NO: 75 
                   
               
               
                 TTGGCATTGGCAAAGTGCGGACTGCATAGTCACTGTGGTGCCGTACTTAGGGTACGCGTTCCTGAACGAAGCATC 
                   
               
               
                   
               
               
                 TGTGCTTCA 
               
               
                   
               
               
                 - Primer for construction of fragment “c” (Yeast origin of replication) 
               
               
                 SEQ ID NO: 76 
                   
               
               
                 CCGAGATGCCAAAGGATAGGTGCTATGTTGATGACTACGACACAGAACTGCGGGTGACATAATGATAGCATTGAA 
                   
               
               
                   
               
               
                 GGATGAGACT 
               
               
                   
               
               
                 - Primer for construction of fragment “d” ( E .  coli  origin of replication) 
               
               
                 SEQ ID NO: 77 
                   
               
               
                 ATGTCACCCGCAGTTCTGTGTCGTAGTCATCAACATAGCACCTATCCTTTGGCATCTCGGTGAGCAAAAGGCCAGC 
                   
               
               
                   
               
               
                 AAAAGG 
               
               
                   
               
               
                 - Primer for construction of fragment “d” ( E .  coli  origin of replication) 
               
               
                 SEQ ID NO: 78 
                   
               
               
                 CTCAGATGTACGGTGATCGCCACCATGTGACGGAAGCTATCCTGACAGTGTAGCAAGTGCTGAGCGTCAGACCCC 
                   
               
               
                   
               
               
                 GTAGAA