Patent Publication Number: US-2017362616-A1

Title: Biosynthetic production of caffeine

Description:
The present application claims priority to U.S. Prov. Pat. Appln. Ser. No. 62/084,797, filed Nov. 26, 2014, hereby incorporated by reference in its entirety, for all purposes. 
    
    
     REFERENCE TO SEQUENCE LISTING, TABLE OR COMPUTER PROGRAM 
     The official copy of the Sequence Listing is submitted concurrently with the specification as an ASCII formatted text file via EFS-Web, with a file name of “CX8-146WO1_ST25.txt”, a creation date of Nov. 23, 2015, and a size of 196 kilobytes. The Sequence Listing filed via EFS-Web is part of the specification and is incorporated in its entirety by reference herein. 
     FIELD OF THE INVENTION 
     The present invention provides an enzymatic means for the biosynthetic production of caffeine. 
     BACKGROUND OF THE INVENTION 
     Caffeine is a purine alkaloid that is contained within Theaceae plants (e.g.,  Camellia sinensis ) and Rubiaceae plants (e.g.,  Coffea arabica ). It is commonly used in beverages and food, as well as a raw material for some medicaments. Typically, caffeine is produced by extraction from caffeine-producing plants or by organic synthesis. The chemical pathway used to synthesize caffeine involves the methylation of xanthosine to produce 7-methylxanthine, which is then methylated to produce theobromine, which is then methylated to produce caffeine as an end-product. While use of this pathway successfully results in the production of commercially useful caffeine, there remains a need in the art for a synthetic pathway that is economical and environmentally friendly. 
     SUMMARY OF THE INVENTION 
     The present invention provides enzymatic means for the biosynthetic production of caffeine. 
     The present invention provides biosynthetic methods for production of caffeine comprising: providing guanine, a guanine deaminase, at least one methyl transferase, and a methyl donor; contacting the guanine with the gtheuanine deaminase to produce xanthine; contacting the xanthine with the methyl transferase and a methyl donor, under conditions wherein the xanthine is methylated, to produce a monomethylxanthine; contacting the monomethylxanthine with the methyl transferase and a methyl donor, under conditions wherein the monomethylxanthine is methylated, to produce a dimethylxanthine; and contacting the dimethylxanthine with the methyl transferase and a methyl donor, under conditions wherein the dimethylxanthine is methylated, to produce caffeine (i.e., 1,3,7-trimethylxanthine). 
     The present invention provides biosynthetic methods for production of caffeine comprising: providing guanine, a guanine deaminase, at least one methyl transferase, and a methyl donor; contacting the guanine with the guanine deaminase to produce xanthine; contacting the xanthine with the methyl transferase and a methyl donor, under conditions wherein the xanthine is methylated, to produce 7-methylxanthine; contacting the 7-methylxanthine with the methyl transferase and a methyl donor, under conditions wherein the 7-methylxanthine is methylated, to produce theobromine; and contacting the theobromine with the methyl transferase and a methyl donor, under conditions wherein the theobromine is methylated, to produce caffeine. In some embodiments, the methyl transferase is selected from XMT, MXMT, and DXMT. In some further embodiments, the methods comprise at least two methyl transferases selected from XMT, MXMT, and/or DXMT. In some alternative embodiments, the methods comprise the methyl transferases XMT, MXMT, and DXMT. 
     The present invention also provides biosynthetic methods for production of caffeine, wherein the method comprises: providing guanine, a guanine deaminase, at least two methyl transferases selected from XMT, MXMT, and/or DXMT, and a methyl donor; contacting the guanine with the guanine deaminase to produce xanthine; contacting the xanthine with the XMT and a methyl donor, under conditions wherein the xanthine is methylated, to produce 7-methylxanthine; contacting the 7-methylxanthine with the MXMT and a methyl donor, under conditions wherein the 7-methylxanthine is methylated, to produce theobromine; and contacting the theobromine with the DXMT and a methyl donor, under conditions wherein the theobromine is methylated, to produce caffeine. 
     The present invention further provides biosynthetic methods for the production of caffeine comprising: providing guanine, a guanine deaminase, XMT, DXMT, and a methyl donor; contacting the guanine with the guanine deaminase to produce xanthine; contacting the xanthine with the DXMT and a methyl donor, under conditions wherein the xanthine is methylated, to produce caffeine. 
     In some embodiments of these biosynthetic methods for the production of caffeine, the guanine deaminase comprises a polypeptide selected from SEQ ID NOS:2, 4, 6, 8, 10, 12, 14, 16, 18, 20, and 22. In some embodiments, the guanine deaminase is encoded by a polynucleotide selected from SEQ ID NOS:1, 3, 5, 7, 9, 11, 13, 15, 17, 19, and 21. 
     In some embodiments of these biosynthetic methods for the production of caffeine, the methyl transferase comprises a polypeptide selected from SEQ ID NOS: 24, 26, 28, 30, 32, 34, 46, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60, 62, 64, 66, 68, 70, 72, 74, 76, 78, 80, 82, or 84. In some embodiments, the methyl transferase is encoded by a polynucleotide selected from SEQ ID NOS:3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77, 79, 81, and/or 83. 
     In some embodiments of these biosynthetic methods for the production of caffeine, the methyl donor is SAM. In some other embodiments, the methyl donor is an alternative methyl donor. 
     The present invention also provides non-naturally occurring polynucleotide sequences encoding a guanine deaminase, wherein the polynucleotide is codon-optimized and selected from SEQ ID NOS:2, 4, 6, 8, 10, 12, 14, 16, and 18. 
     The present invention also provides non-naturally occurring polynucleotide sequences encoding a methyl transferase, wherein the polynucleotide is codon-optimized and selected from SEQ ID NOS:24, 26, 28, 30, 32, 34, 46, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60, 62, 64, 66, 68, 70, 72, 74, 76, 78, 80, and 82. 
     The present invention also provides expression vectors comprising at least one polynucleotide sequence selected from SEQ ID NOS:2, 4, 6, 8, 10, 12, 14, 16, and 18. 
     The present invention also provides expression vectors comprising at least one polynucleotide sequence selected from SEQ ID NOS:24, 26, 28, 30, 32, 34, 46, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60, 62, 64, 66, 68, 70, 72, 74, 76, 78, 80, and 82. 
     The present invention also provides expression vectors comprising at least one polynucleotide sequence selected from SEQ ID NOS:2, 4, 6, 8, 10, 12, 14, 16, 18, and at least one polynucleotide sequence selected from SEQ ID NOS:24, 26, 28, 30, 32, 34, 46, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60, 62, 64, 66, 68, 70, 72, 74, 76, 78, 80, and 82. 
     The present invention further provides host cells comprising at least one expression vector, wherein the expression vector comprises at least one polynucleotide sequence selected from SEQ ID NOS:2, 4, 6, 8, 10, 12, 14, 16, and 18. 
     In some further embodiments, the present invention further provides host cells comprising at least one expression vector, wherein the expression vector comprises at least one polynucleotide sequence selected from SEQ ID NOS:24, 26, 28, 30, 32, 34, 46, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60, 62, 64, 66, 68, 70, 72, 74, 76, 78, 80, and 82. 
     In some further embodiments, the present invention further provides host cells comprising at least one expression vector, wherein the provides expression vector comprises at least one polynucleotide sequence selected from SEQ ID NOS:2, 4, 6, 8, 10, 12, 14, 16, 18, and at least one polynucleotide sequence selected from SEQ ID NOS:24, 26, 28, 30, 32, 34, 46, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60, 62, 64, 66, 68, 70, 72, 74, 76, 78, 80, and 82. 
     The present invention also provides methods of expressing at least one non-naturally occurring polynucleotide selected from SEQ ID NOS:24, 26, 28, 30, 32, 34, 46, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60, 62, 64, 66, 68, 70, 72, 74, 76, 78, 80, and 8; comprising placing the host cell comprising at least one polynucleotide sequence selected from SEQ ID NOS:24, 26, 28, 30, 32, 34, 46, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60, 62, 64, 66, 68, 70, 72, 74, 76, 78, 80, and 82, in conditions suitable for the expression of the polynucleotide. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1  provides schematics of the native and engineered pathways for production of caffeine. 
     
    
    
     DESCRIPTION OF THE INVENTION 
     The present invention provides an enzymatic means for the biosynthetic production of caffeine. 
     Abbreviations and Definitions 
     Unless defined otherwise, all technical and scientific terms used herein generally have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. Generally, the nomenclature used herein and the laboratory procedures of cell culture, molecular genetics, microbiology, organic chemistry, analytical chemistry and nucleic acid chemistry described below are those well-known and commonly employed in the art. Such techniques are well-known and described in numerous texts and reference works well known to those of skill in the art. Standard techniques, or modifications thereof, are used for chemical syntheses and chemical analyses. All patents, patent applications, articles and publications mentioned herein, both supra and infra, are hereby expressly incorporated herein by reference. 
     Although any suitable methods and materials similar or equivalent to those described herein find use in the practice of the present invention, some methods and materials are described herein. It is to be understood that this invention is not limited to the particular methodology, protocols, and reagents described, as these may vary, depending upon the context they are used by those of skill in the art. Accordingly, the terms defined immediately below are more fully described by reference to the application as a whole. All patents, patent applications, articles and publications mentioned herein, both supra and infra, are hereby expressly incorporated herein by reference. 
     Also, as used herein, the singular “a”, “an,” and “the” include the plural references, unless the context clearly indicates otherwise. 
     Numeric ranges are inclusive of the numbers defining the range. Thus, every numerical range disclosed herein is intended to encompass every narrower numerical range that falls within such broader numerical range, as if such narrower numerical ranges were all expressly written herein. It is also intended that every maximum (or minimum) numerical limitation disclosed herein includes every lower (or higher) numerical limitation, as if such lower (or higher) numerical limitations were expressly written herein. 
     The term “about” means an acceptable error for a particular value. In some instances “about” means within 0.05%, 0.5%, 1.0%, or 2.0%, of a given value range. In some instances, “about” means within 1, 2, 3, or 4 standard deviations of a given value. 
     Furthermore, the headings provided herein are not limitations of the various aspects or embodiments of the invention which can be had by reference to the application as a whole. Accordingly, the terms defined immediately below are more fully defined by reference to the application as a whole. Nonetheless, in order to facilitate understanding of the invention, a number of terms are defined below. 
     Unless otherwise indicated, nucleic acids are written left to right in 5′ to 3′ orientation; amino acid sequences are written left to right in amino to carboxy orientation, respectively. 
     As used herein, the term “comprising” and its cognates are used in their inclusive sense (i.e., equivalent to the term “including” and its corresponding cognates). 
     “EC” number refers to the Enzyme Nomenclature of the Nomenclature Committee of the International Union of Biochemistry and Molecular Biology (NC-IUBMB). The IUBMB biochemical classification is a numerical classification system for enzymes based on the chemical reactions they catalyze. 
     “ATCC” refers to the American Type Culture Collection whose biorepository collection includes genes and strains. 
     “NCBI” refers to National Center for Biological Information and the sequence databases provided therein. 
     “Protein,” “polypeptide,” and “peptide” are used interchangeably herein to denote a polymer of at least two amino acids covalently linked by an amide bond, regardless of length or post-translational modification (e.g., glycosylation or phosphorylation). 
     “Amino acids” are referred to herein by either their commonly known three-letter symbols or by the one-letter symbols recommended by IUPAC-IUB Biochemical Nomenclature Commission. Nucleotides, likewise, may be referred to by their commonly accepted single letter codes. 
     The term “engineered,” “recombinant,” “non-naturally occurring,” and “variant,” when used with reference to a cell, a polynucleotide or a polypeptide refers to a material or a material corresponding to the natural or native form of the material that has been modified in a manner that would not otherwise exist in nature or is identical thereto but produced or derived from synthetic materials and/or by manipulation using recombinant techniques. 
     As used herein, “wild-type” and “naturally-occurring” refer to the form found in nature. For example a wild-type polypeptide or polynucleotide sequence is a sequence present in an organism that can be isolated from a source in nature and which has not been intentionally modified by human manipulation. 
     “Coding sequence” refers to that part of a nucleic acid (e.g., a gene) that encodes an amino acid sequence of a protein. 
     The term “percent (%) sequence identity” is used herein to refer to comparisons among polynucleotides and polypeptides, and are determined by comparing two optimally aligned sequences over a comparison window, wherein the portion of the polynucleotide or polypeptide sequence in the comparison window may comprise additions or deletions (i.e., gaps) as compared to the reference sequence for optimal alignment of the two sequences. The percentage may be calculated by determining the number of positions at which the identical nucleic acid base or amino acid residue occurs in both sequences to yield the number of matched positions, dividing the number of matched positions by the total number of positions in the window of comparison and multiplying the result by 100 to yield the percentage of sequence identity. Alternatively, the percentage may be calculated by determining the number of positions at which either the identical nucleic acid base or amino acid residue occurs in both sequences or a nucleic acid base or amino acid residue is aligned with a gap to yield the number of matched positions, dividing the number of matched positions by the total number of positions in the window of comparison and multiplying the result by 100 to yield the percentage of sequence identity. Those of skill in the art appreciate that there are many established algorithms available to align two sequences. Optimal alignment of sequences for comparison can be conducted, e.g., by the local homology algorithm of Smith and Waterman (Smith and Waterman, Adv. Appl. Math., 2:482 [1981]), by the homology alignment algorithm of Needleman and Wunsch (Needleman and Wunsch, J. Mol. Biol., 48:443 [1970), by the search for similarity method of Pearson and Lipman (Pearson and Lipman, Proc. Natl. Acad. Sci. USA 85:2444 [1988]), by computerized implementations of these algorithms (e.g., GAP, BESTFIT, FASTA, and TFASTA in the GCG Wisconsin Software Package), or by visual inspection, as known in the art. Examples of algorithms that are suitable for determining percent sequence identity and sequence similarity include, but are not limited to the BLAST and BLAST 2.0 algorithms, which are described by Altschul et al. (See, Altschul et al., J. Mol. Biol., 215: 403-410 [1990]; and Altschul et al., 1977, Nucleic Acids Res., 3389-3402 [1977], respectively). Software for performing BLAST analyses is publicly available through the National Center for Biotechnology Information website. This algorithm involves first identifying high scoring sequence pairs (HSPs) by identifying short words of length W in the query sequence, which either match or satisfy some positive-valued threshold score T when aligned with a word of the same length in a database sequence. T is referred to as, the neighborhood word score threshold (See, Altschul et al, supra). These initial neighborhood word hits act as seeds for initiating searches to find longer HSPs containing them. The word hits are then extended in both directions along each sequence for as far as the cumulative alignment score can be increased. Cumulative scores are calculated using, for nucleotide sequences, the parameters M (reward score for a pair of matching residues; always &gt;0) and N (penalty score for mismatching residues; always &lt;0). For amino acid sequences, a scoring matrix is used to calculate the cumulative score. Extension of the word hits in each direction are halted when: the cumulative alignment score falls off by the quantity X from its maximum achieved value; the cumulative score goes to zero or below, due to the accumulation of one or more negative-scoring residue alignments; or the end of either sequence is reached. The BLAST algorithm parameters W, T, and X determine the sensitivity and speed of the alignment. The BLASTN program (for nucleotide sequences) uses as defaults a wordlength (W) of 11, an expectation (E) of 10, M=5, N=−4, and a comparison of both strands. For amino acid sequences, the BLASTP program uses as defaults a wordlength (W) of 3, an expectation (E) of 10, and the BLOSUM62 scoring matrix (See, Henikoff and Henikoff, Proc. Natl. Acad. Sci. USA 89:10915 [1989]). Exemplary determination of sequence alignment and % sequence identity can employ the BESTFIT or GAP programs in the GCG Wisconsin Software package (Accelrys, Madison Wis.), using default parameters provided. 
     “Reference sequence” refers to a defined sequence used as a basis for a sequence comparison. A reference sequence may be a subset of a larger sequence, for example, a segment of a full-length gene or polypeptide sequence. Generally, a reference sequence is at least 20 nucleotide or amino acid residues in length, at least 25 residues in length, at least 50 residues in length, at least 100 residues in length or the full length of the nucleic acid or polypeptide. Since two polynucleotides or polypeptides may each (1) comprise a sequence (i.e., a portion of the complete sequence) that is similar between the two sequences, and (2) may further comprise a sequence that is divergent between the two sequences, sequence comparisons between two (or more) polynucleotides or polypeptide are typically performed by comparing sequences of the two polynucleotides or polypeptides over a “comparison window” to identify and compare local regions of sequence similarity. In some embodiments, a “reference sequence” can be based on a primary amino acid sequence, where the reference sequence is a sequence that can have one or more changes in the primary sequence. “Comparison window” refers to a conceptual segment of at least about 20 contiguous nucleotide positions or amino acids residues wherein a sequence may be compared to a reference sequence of at least 20 contiguous nucleotides or amino acids and wherein the portion of the sequence in the comparison window may comprise additions or deletions (i.e., gaps) of 20 percent or less as compared to the reference sequence (which does not comprise additions or deletions) for optimal alignment of the two sequences. The comparison window can be longer than 20 contiguous residues, and includes, optionally 30, 40, 50, 100, or longer windows. 
     “Amino acid difference” or “residue difference” refers to a difference in the amino acid residue at a position of a polypeptide sequence relative to the amino acid residue at a corresponding position in a reference sequence. The positions of amino acid differences generally are referred to herein as “Xn,” where n refers to the corresponding position in the reference sequence upon which the residue difference is based. For example, a “residue difference at position X3 as compared to SEQ ID NO:1” refers to a difference of the amino acid residue at the polypeptide position corresponding to position 3 of SEQ ID NO:1. Thus, if the reference polypeptide of SEQ ID NO:1 has a serine at position 3, then a “residue difference at position X3 as compared to SEQ ID NO:1” an amino acid substitution of any residue other than serine at the position of the polypeptide corresponding to position 3 of SEQ ID NO:1. In most instances herein, the specific amino acid residue difference at a position is indicated as “XnY” where “Xn” specified the corresponding position as described above, and “Y” is the single letter identifier of the amino acid found in the engineered polypeptide (i.e., the different residue than in the reference polypeptide). In some instances (e.g., in Table 4.1), the present disclosure also provides specific amino acid differences denoted by the conventional notation “AnB”, where A is the single letter identifier of the residue in the reference sequence, “n” is the number of the residue position in the reference sequence, and B is the single letter identifier of the residue substitution in the sequence of the engineered polypeptide. In some instances, a polypeptide of the present disclosure can include one or more amino acid residue differences relative to a reference sequence, which is indicated by a list of the specified positions where residue differences are present relative to the reference sequence. In some embodiments, where more than one amino acid can be used in a specific residue position of a polypeptide, the various amino acid residues that can be used are separated by a “/” (e.g., X307H/X307P or X307H/P). The present application includes engineered polypeptide sequences comprising one or more amino acid differences that include either/or both conservative and non-conservative amino acid substitutions. 
     “Conservative amino acid substitution” refers to a substitution of a residue with a different residue having a similar side chain, and thus typically involves substitution of the amino acid in the polypeptide with amino acids within the same or similar defined class of amino acids. By way of example and not limitation, an amino acid with an aliphatic side chain may be substituted with another aliphatic amino acid (e.g., alanine, valine, leucine, and isoleucine); an amino acid with hydroxyl side chain is substituted with another amino acid with a hydroxyl side chain (e.g., serine and threonine); an amino acids having aromatic side chains is substituted with another amino acid having an aromatic side chain (e.g., phenylalanine, tyrosine, tryptophan, and histidine); an amino acid with a basic side chain is substituted with another amino acid with a basis side chain (e.g., lysine and arginine); an amino acid with an acidic side chain is substituted with another amino acid with an acidic side chain (e.g., aspartic acid or glutamic acid); and/or a hydrophobic or hydrophilic amino acid is replaced with another hydrophobic or hydrophilic amino acid, respectively. 
     “Non-conservative substitution” refers to substitution of an amino acid in the polypeptide with an amino acid with significantly differing side chain properties. Non-conservative substitutions may use amino acids between, rather than within, the defined groups and affects (a) the structure of the peptide backbone in the area of the substitution (e.g, proline for glycine) (b) the charge or hydrophobicity, or (c) the bulk of the side chain. By way of example and not limitation, an exemplary non-conservative substitution can be an acidic amino acid substituted with a basic or aliphatic amino acid; an aromatic amino acid substituted with a small amino acid; and a hydrophilic amino acid substituted with a hydrophobic amino acid. 
     “Deletion” refers to modification to the polypeptide by removal of one or more amino acids from the reference polypeptide. Deletions can comprise removal of 1 or more amino acids, 2 or more amino acids, 5 or more amino acids, 10 or more amino acids, 15 or more amino acids, or 20 or more amino acids, up to 10% of the total number of amino acids, or up to 20% of the total number of amino acids making up the reference enzyme while retaining enzymatic activity and/or retaining the improved properties of an engineered transaminase enzyme. Deletions can be directed to the internal portions and/or terminal portions of the polypeptide. In various embodiments, the deletion can comprise a continuous segment or can be discontinuous. 
     “Insertion” refers to modification to the polypeptide by addition of one or more amino acids from the reference polypeptide. Insertions can be in the internal portions of the polypeptide, or to the carboxy or amino terminus. Insertions as used herein include fusion proteins as is known in the art. The insertion can be a contiguous segment of amino acids or separated by one or more of the amino acids in the naturally occurring polypeptide. 
     A “functional fragment” or a “biologically active fragment” used interchangeably herein refers to a polypeptide that has an amino-terminal and/or carboxy-terminal deletion(s) and/or internal deletions, but where the remaining amino acid sequence is identical to the corresponding positions in the sequence to which it is being compared (e.g., a full-length methyltransferase or guanine deaminase of the present invention) and that retains substantially all of the activity of the full-length polypeptide. 
     “Isolated polypeptide” refers to a polypeptide which is substantially separated from other contaminants that naturally accompany it, e.g., protein, lipids, and polynucleotides. The term embraces polypeptides which have been removed or purified from their naturally-occurring environment or expression system (e.g., host cell or in vitro synthesis). The recombinant methyltransferase or guanine deaminase polypeptides may be present within a cell, present in the cellular medium, or prepared in various forms, such as lysates or isolated preparations. As such, in some embodiments, the recombinant methyltransferase or guanine deaminase polypeptides can be an isolated polypeptide. 
     “Substantially pure polypeptide” refers to a composition in which the polypeptide species is the predominant species present (i.e., on a molar or weight basis it is more abundant than any other individual macromolecular species in the composition), and is generally a substantially purified composition when the object species comprises at least about 50 percent of the macromolecular species present by mole or % weight. Generally, a substantially pure methyltransferase or guanine deaminase composition comprises about 60% or more, about 70% or more, about 80% or more, about 90% or more, about 95% or more, and about 98% or more of all macromolecular species by mole or % weight present in the composition. In some embodiments, the object species is purified to essential homogeneity (i.e., contaminant species cannot be detected in the composition by conventional detection methods) wherein the composition consists essentially of a single macromolecular species. Solvent species, small molecules (&lt;500 Daltons), and elemental ion species are not considered macromolecular species. In some embodiments, the isolated recombinant methyltransferase or guanine deaminase polypeptides are substantially pure polypeptide compositions. 
     “Improved enzyme property” refers to a polypeptide that exhibits an improvement in any enzyme property as compared to a reference polypeptide and/or as a wild-type polypeptide or another engineered polypeptide. Improved properties include but are not limited to such properties as increased protein expression, increased thermoactivity, increased thermostability, increased pH activity, increased stability, increased enzymatic activity, increased substrate specificity or affinity, increased specific activity, increased resistance to substrate or end-product inhibition, increased chemical stability, improved chemoselectivity, improved solvent stability, increased tolerance to acidic pH, increased tolerance to proteolytic activity (i.e., reduced sensitivity to proteolysis), and/or altered temperature profile. 
     “Increased enzymatic activity” or “enhanced catalytic activity” refers to an improved property of the engineered polypeptides, which can be represented by an increase in specific activity (e.g., product produced/time/weight protein) or an increase in percent conversion of the substrate to the product (e.g., percent conversion of starting amount of substrate to product in a specified time period using a specified amount of enzyme) as compared to the reference enzyme. Exemplary methods to determine enzyme activity are provided in the Examples. Any property relating to enzyme activity may be affected, including the classical enzyme properties of K m , V max  or k cat , changes of which can lead to increased enzymatic activity. 
     “Conversion” refers to the enzymatic conversion (or biotransformation) of a substrate(s) to the corresponding product(s). “Percent conversion” refers to the percent of the substrate that is converted to the product within a period of time under specified conditions. Thus, the “enzymatic activity” or “activity” of a polypeptide can be expressed as “percent conversion” of the substrate to the product in a specific period of time. 
     “Hybridization stringency” relates to hybridization conditions, such as washing conditions, in the hybridization of nucleic acids. Generally, hybridization reactions are performed under conditions of lower stringency, followed by washes of varying but higher stringency. The term “moderately stringent hybridization” refers to conditions that permit target-DNA to bind a complementary nucleic acid that has about 60% identity, preferably about 75% identity, about 85% identity to the target DNA, with greater than about 90% identity to target-polynucleotide. Exemplary moderately stringent conditions are conditions equivalent to hybridization in 50% formamide, 5×Denhart&#39;s solution, 5×SSPE, 0.2% SDS at 42° C., followed by washing in 0.2×SSPE, 0.2% SDS, at 42° C. “High stringency hybridization” refers generally to conditions that are about 10° C. or less from the thermal melting temperature T m  as determined under the solution condition for a defined polynucleotide sequence. In some embodiments, a high stringency condition refers to conditions that permit hybridization of only those nucleic acid sequences that form stable hybrids in 0.018M NaCl at 65° C. (i.e., if a hybrid is not stable in 0.018M NaCl at 65° C., it will not be stable under high stringency conditions, as contemplated herein). High stringency conditions can be provided, for example, by hybridization in conditions equivalent to 50% formamide, 5×Denhart&#39;s solution, 5×SSPE, 0.2% SDS at 42° C., followed by washing in 0.1×SSPE, and 0.1% SDS at 65° C. Another high stringency condition is hybridizing in conditions equivalent to hybridizing in 5×SSC containing 0.1% (w:v) SDS at 65° C. and washing in 0.1×SSC containing 0.1% SDS at 65° C. Other high stringency hybridization conditions, as well as moderately stringent conditions, are described in the references cited above. 
     “Codon optimized” refers to changes in the codons of the polynucleotide encoding a protein to those preferentially used in a particular organism such that the encoded protein is more efficiently expressed in the organism of interest (i.e., the chosen host cell). Although the genetic code is degenerate in that most amino acids are represented by several codons, called “synonyms” or “synonymous” codons, it is well known that codon usage by particular organisms is nonrandom and biased towards particular codon triplets. This codon usage bias may be higher in reference to a given gene, genes of common function or ancestral origin, highly expressed proteins versus low copy number proteins, and the aggregate protein coding regions of an organism&#39;s genome. In some embodiments, the polynucleotides encoding the methyltransferase or guanine deaminase enzymes may be codon optimized for optimal production from the host organism selected for expression. 
     “Control sequence” refers herein to include all components, which are necessary or advantageous for the expression of a polynucleotide and/or polypeptide of the present application. Each control sequence may be native or foreign to the nucleic acid sequence encoding the polypeptide. Such control sequences include, but are not limited to, a leader, polyadenylation sequence, propeptide sequence, promoter sequence, signal peptide sequence, initiation sequence and transcription terminator. At a minimum, the control sequences include a promoter, and transcriptional and translational stop signals. The control sequences may be provided with linkers for the purpose of introducing specific restriction sites facilitating ligation of the control sequences with the coding region of the nucleic acid sequence encoding a polypeptide. 
     “Operably linked” is defined herein as a configuration in which a control sequence is appropriately placed (i.e., in a functional relationship) at a position relative to a polynucleotide of interest such that the control sequence directs or regulates the expression of the polynucleotide and/or polypeptide of interest. 
     “Promoter sequence” refers to a nucleic acid sequence that is recognized by a host cell for expression of a polynucleotide of interest, such as a coding sequence. The promoter sequence contains transcriptional control sequences, which mediate the expression of a polynucleotide of interest. The promoter may be any nucleic acid sequence which shows transcriptional activity in the host cell of choice including mutant, truncated, and hybrid promoters, and may be obtained from genes encoding extracellular or intracellular polypeptides either homologous or heterologous to the host cell. 
     “Suitable reaction conditions” refers to those conditions in the enzymatic conversion reaction solution (e.g., ranges of enzyme loading, substrate loading, temperature, pH, buffers, co-solvents, etc.) under which a polypeptide of the present application is capable of converting a substrate to the desired product compound, Exemplary “suitable reaction conditions” are provided in the present application and illustrated by the Examples. “Loading”, such as in “compound loading” or “enzyme loading” refers to the concentration or amount of a component in a reaction mixture at the start of the reaction. “Substrate” in the context of an enzymatic conversion reaction process refers to the compound or molecule acted on by the polypeptide. “Product” in the context of an enzymatic conversion process refers to the compound or molecule resulting from the action of the polypeptide on a substrate. 
     As used herein the term “culturing” refers to the growing of a population of microbial cells under any suitable conditions (e.g., using a liquid, gel or solid medium). 
     Recombinant polypeptides can be produced using any suitable methods known the art. Genes encoding the wild-type polypeptide of interest can be cloned in vectors, such as plasmids, and expressed in desired hosts, such as  E. coli , etc. Variants of recombinant polypeptides can be generated by various methods known in the art. Indeed, there is a wide variety of different mutagenesis techniques well known to those skilled in the art. In addition, mutagenesis kits are also available from many commercial molecular biology suppliers. Methods are available to make specific substitutions at defined amino acids (site-directed), specific or random mutations in a localized region of the gene (regio-specific), or random mutagenesis over the entire gene (e.g., saturation mutagenesis). Numerous suitable methods are known to those in the art to generate enzyme variants, including but not limited to site-directed mutagenesis of single-stranded DNA or double-stranded DNA using PCR, cassette mutagenesis, gene synthesis, error-prone PCR, shuffling, and chemical saturation mutagenesis, or any other suitable method known in the art. Non-limiting examples of methods used for DNA and protein engineering are provided in the following patents: U.S. Pat. No. 6,117,679; U.S. Pat. No. 6,420,175; U.S. Pat. No. 6,376,246; U.S. Pat. No. 6,586,182; U.S. Pat. No. 7,747,391; U.S. Pat. No. 7,747,393; U.S. Pat. No. 7,783,428; and U.S. Pat. No. 8,383,346. After the variants are produced, they can be screened for any desired property (e.g., high or increased activity, or low or reduced activity, increased thermal activity, increased thermal stability, and/or acidic pH stability, etc.). 
     As used herein, a “vector” is a DNA construct for introducing a DNA sequence into a cell. In some embodiments, the vector is an expression vector that is operably linked to a suitable control sequence capable of effecting the expression in a suitable host of the polypeptide encoded in the DNA sequence. In some embodiments, an “expression vector” has a promoter sequence operably linked to the DNA sequence (e.g., transgene) to drive expression in a host cell, and in some embodiments, also comprises a transcription terminator sequence. 
     As used herein, the term “expression” includes any step involved in the production of the polypeptide including, but not limited to, transcription, post-transcriptional modification, translation, and post-translational modification. In some embodiments, the term also encompasses secretion of the polypeptide from a cell. 
     As used herein, the term “produces” refers to the production of proteins and/or other compounds by cells. It is intended that the term encompass any step involved in the production of polypeptides including, but not limited to, transcription, post-transcriptional modification, translation, and post-translational modification. In some embodiments, the term also encompasses secretion of the polypeptide from a cell. 
     As used herein, an amino acid or nucleotide sequence (e.g., a promoter sequence, signal peptide, terminator sequence, etc.) is “heterologous” to another sequence with which it is operably linked if the two sequences are not associated in nature. 
     As used herein, the terms “host cell” and “host strain” refer to suitable hosts for expression vectors comprising DNA provided herein (e.g., the polynucleotides encoding methyltransferase or guanine deaminase). In some embodiments, the host cells are prokaryotic or eukaryotic cells that have been transformed or transfected with vectors constructed using recombinant DNA techniques as known in the art. 
     The term “analogue” means a polypeptide having more than 70% sequence identity but less than 100% sequence identity (e.g., more than 75%, 78%, 80%, 83%, 85%, 88%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% sequence identity) with a reference polypeptide. In some embodiments, analogues means polypeptides that contain one or more non-naturally occurring amino acid residues including, but not limited, to homoarginine, ornithine and norvaline, as well as naturally occurring amino acids. In some embodiments, analogues also include one or more D-amino acid residues and non-peptide linkages between two or more amino acid residues. 
     The term “effective amount” means an amount sufficient to produce the desired result. One of general skill in the art may determine what the effective amount by using routine experimentation. 
     The terms “isolated” and “purified” are used to refer to a molecule (e.g., an isolated nucleic acid, polypeptide, etc.) or other component that is removed from at least one other component with which it is naturally associated. The term “purified” does not require absolute purity, rather it is intended as a relative definition. 
     As used herein, “composition” and “formulation” encompass products comprising at least one enzyme of the present invention, intended for any suitable use (e.g., production of caffeine). 
     As used herein, “caffeine” refers to the xanthine alkaloid 1,3,7-trimethylxanthine. 
     As used herein, “xanthosine” refers to the nucleoside derived from xanthine and ribose 9-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-3H-purine-2,6-dione. 
     As used herein, “xanthine” refers to the purine base 3,7-dihydropurine-2,6-dione. 
     As used herein, “7-methylxanthine” refers to the purine base 7-methyl-3H-purine-2,6-dione (also referred to as heteroxanthine, heteroxanthin, 7-methylxanthin, and 2,6-dihydroxy-7-methylpurine). 
     As used herein, “theobromine” refers to the purine base 3,7-dimethylpurine-2,6-dione (also referred to as 3,7-dimethylxanthine, diurobromine, teobromine, 83-67-0, theosalvose, and santheose). 
     As used herein, “guanine” refers to the purine base 2-amino-1H-purin-6(9H)-one. 
     As used herein, “trimethylglycine” and “betaine” refer to 2-trimethylammonioacetate. 
     As used herein, “butyrobetaine” refers to gamma-butyrobetaine or 3-carboxy-N,N,N-trimethyl-1-propanaminium. 
     As used herein, “guanine deaminase” and “GDA” refer to an enzyme that converts guanine to xanthine. 
     As used herein, “methyl group” refers to an alkyl functional group containing one carbon atom bonded to three hydrogen atoms. 
     As used herein, “methyltransferase” refers to an enzyme capable of catalyzing the transfer of a methyl group from a donor molecule to a specific substrate or group of substrates. 
     As used herein, “alternative methyl donor” refers to any methyl donor other than the preferred natural methyl donor for a specific enzyme. For example, for enzymes with the preferred natural methyl donor S-adenosylmethionine (SAM), an alternate methyl donor is any suitable methyl donor other than SAM. 
     As used herein, “XMT” refers to an enzyme that is capable of, but is not necessarily limited to, catalyzing the transfer of a methyl group to xanthosine to form 7-methylxanthosine. The designation can be based on measured activity or putative activity based on homology to proteins with measured activity. 
     As used herein, “MXMT” refers to an enzyme that is capable of, but is not necessarily limited to, catalyzing the transfer of a methyl group to 7-methylxanthine to form 3,7-dimethylxanthine (theobromine). The designation can be based on measured activity or putative activity based on homology to proteins with measured activity. 
     As used herein, “DXMT” refers to an enzyme that is capable of, but is not necessarily limited to, catalyzing the transfer of a methyl group to 3,7-dimethylxanthine (theobromine) to form 1,3,7-trimethylxanthine (caffeine). The designation can be based on measured activity or putative activity based on homology to proteins with measured activity. 
     A New Biosynthetic Pathway for Caffeine Production: 
     The present invention provides a new biosynthetic pathway for the production of caffeine. In this pathway, guanine is used the starting material. Guanine deaminase (GDA) is used to convert guanine to xanthine. The xanthine is them converted to 7-methylxanthine by the enzyme XMT. Then, 7-methylxanthine is then methylated by MXMT to produce theobromine, which is then methylated by DXMT to produce caffeine. In some embodiments, native MXMT, DXMT and/or XMT enzymes are utilized, while in some other embodiments, recombinant enzymes find use. In some embodiments, caffeine is produced in a one-pot reaction, while in some other embodiments, the methods involve two-pot reactions. 
     Polynucleotides Encoding Engineered Polypeptides, Expression Vectors and Host Cells: 
     The present invention provides polynucleotides encoding the polypeptides described herein. In some embodiments, the polynucleotides are codon-optimized for expression in the chosen host cells. In some embodiments, the polynucleotides are operatively linked to one or more heterologous regulatory sequences that control gene expression to create a recombinant polynucleotide capable of expressing the polypeptide. Expression constructs containing a heterologous polynucleotide encoding the polypeptides can be introduced into appropriate host cells to express the corresponding polypeptide. 
     As will be apparent to the skilled artisan, availability of a protein sequence and the knowledge of the codons corresponding to the various amino acids provide a description of all the polynucleotides capable of encoding the subject polypeptides. The degeneracy of the genetic code, where the same amino acids are encoded by alternative or synonymous codons, allows an extremely large number of nucleic acids to be made, all of which encode the polypeptide. Thus, having knowledge of a particular amino acid sequence, those skilled in the art could make any number of different nucleic acids by simply modifying the sequence of one or more codons in a way which does not change the amino acid sequence of the protein. In this regard, the present invention specifically contemplates each and every possible variation of polynucleotides that could be made encoding the polypeptides described herein by selecting combinations based on the possible codon choices, and all such variations are to be considered specifically disclosed for any polypeptide described herein. 
     In various embodiments, the codons are preferably selected to fit the host cell in which the protein is being produced. For example, preferred codons used in bacteria are used for expression in bacteria. Consequently, codon optimized polynucleotides encoding the polypeptides contain preferred codons at about 40%, 50%, 60%, 70%, 80%, or greater than 90% of codon positions of the full length coding region. 
     In some embodiments, as described above, the polynucleotide encodes an engineered polypeptide having methyltransferase or guanine deaminase activity with the properties disclosed herein, wherein the polypeptide comprises an amino acid sequence having at least 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identity to a reference sequence selected from the even-numbered sequences of SEQ ID NOS:1-84, or the amino acid sequence of any enzyme as disclosed in the Tables provided in the Examples. 
     In some embodiments, the polynucleotide encodes a polypeptide having guanine deaminase activity with the properties disclosed herein, wherein the polypeptide comprises an amino acid sequence having at least 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more sequence identity to reference sequence SEQ ID NOS:2, 4, 6, 8, 10, 12, 14, 16, 18, 20, or 22. 
     In some embodiments, the polynucleotide encodes a polypeptide having methyltransferase activity with the properties disclosed herein, wherein the polypeptide comprises an amino acid sequence having at least 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more sequence identity to reference sequence SEQ ID NOS:24, 26, 28, 30, 32, 34, 46, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60, 62, 64, 66, 68, 70, 72, 74, 76, 78, 80, 82, or 84. 
     In some embodiments, an isolated polynucleotide encoding any of the methyltransferase or guanine deaminase polypeptides provided herein is manipulated in a variety of ways to provide for expression of the polypeptide. In some embodiments, the polynucleotides encoding the polypeptides are provided as expression vectors where one or more control sequences is present to regulate the expression of the polynucleotides and/or polypeptides. Manipulation of the isolated polynucleotide prior to its insertion into a vector may be desirable or necessary depending on the expression vector. The techniques for modifying polynucleotides and nucleic acid sequences utilizing recombinant DNA methods are well known in the art. 
     In some embodiments, the control sequences include among other sequences, promoters, leader sequences, polyadenylation sequences, propeptide sequences, signal peptide sequences, and transcription terminators. As known in the art, suitable promoters can be selected based on the host cells used. For bacterial host cells, suitable promoters for directing transcription of the nucleic acid constructs of the present application, include, but are not limited to the promoters obtained from the  E. coli  lac operon,  Streptomyces coelicolor  agarase gene (dagA),  Bacillus subtilis  levansucrase gene (sacB),  Bacillus licheniformis  alpha-amylase gene (amyL),  Bacillus stearothermophilus  maltogenic amylase gene (amyM),  Bacillus amyloliquefaciens  alpha-amylase gene (amyQ),  Bacillus licheniformis  penicillinase gene (penP),  Bacillus subtilis  xylA and xylB genes, and prokaryotic beta-lactamase gene (See e.g., Villa-Kamaroff et al., Proc. Natl Acad. Sci. USA 75: 3727-3731 [1978]), as well as the tac promoter (See e.g., DeBoer et al., Proc. Natl Acad. Sci. USA 80: 21-25 [1983]). Exemplary promoters for filamentous fungal host cells, include promoters obtained from the genes for  Aspergillus oryzae  TAKA amylase,  Rhizomucor miehei  aspartic proteinase,  Aspergillus niger  neutral alpha-amylase,  Aspergillus niger  acid stable alpha-amylase,  Aspergillus niger  or  Aspergillus awamori  glucoamylase (glaA),  Rhizomucor miehei  lipase,  Aspergillus oryzae  alkaline protease,  Aspergillus oryzae  triose phosphate isomerase,  Aspergillus nidulans  acetamidase, and  Fusarium oxysporum  trypsin-like protease (See e.g., WO 96/00787), as well as the NA2-tpi promoter (a hybrid of the promoters from the genes for  Aspergillus niger  neutral alpha-amylase and  Aspergillus oryzae  triose phosphate isomerase), and mutant, truncated, and hybrid promoters thereof. Exemplary yeast cell promoters can be from the genes can be from the genes for  Saccharomyces cerevisiae  enolase (ENO-1),  Saccharomyces cerevisiae  galactokinase (GAL1),  Saccharomyces cerevisiae  alcohol dehydrogenase/glyceraldehyde-3-phosphate dehydrogenase (ADH2/GAP), and  Saccharomyces cerevisiae  3-phosphoglycerate kinase. Other useful promoters for yeast host cells are known in the art (See e.g., Romanos et al., Yeast 8:423-488 [1992]). 
     In some embodiments, the control sequence is a suitable transcription terminator sequence, a sequence recognized by a host cell to terminate transcription. The terminator sequence is operably linked to the 3′ terminus of the nucleic acid sequence encoding the polypeptide. Any terminator which is functional in the host cell of choice finds use in the present invention. For example, exemplary transcription terminators for filamentous fungal host cells can be obtained from the genes for  Aspergillus oryzae  TAKA amylase,  Aspergillus niger  glucoamylase,  Aspergillus nidulans  anthranilate synthase,  Aspergillus niger  alpha-glucosidase, and  Fusarium oxysporum  trypsin-like protease. Exemplary terminators for yeast host cells can be obtained from the genes for  Saccharomyces cerevisiae  enolase,  Saccharomyces cerevisiae  cytochrome C (CYC1), and  Saccharomyces cerevisiae  glyceraldehyde-3-phosphate dehydrogenase. Other useful terminators for yeast host cells are known in the art (See e.g., Romanos et al., supra). 
     In some embodiments, the control sequence is a suitable leader sequence, a non-translated region of an mRNA that is important for translation by the host cell. The leader sequence is operably linked to the 5′ terminus of the nucleic acid sequence encoding the polypeptide. Any leader sequence that is functional in the host cell of choice may be used. Exemplary leaders for filamentous fungal host cells are obtained from the genes for  Aspergillus oryzae  TAKA amylase and  Aspergillus nidulans  triose phosphate isomerase. Suitable leaders for yeast host cells include, but are not limited to those obtained from the genes for  Saccharomyces cerevisiae  enolase (ENO-1),  Saccharomyces cerevisiae  3-phosphoglycerate kinase,  Saccharomyces cerevisiae  alpha-factor, and  Saccharomyces cerevisiae  alcohol dehydrogenase/glyceraldehyde-3-phosphate dehydrogenase (ADH2/GAP). 
     The control sequence may also be a polyadenylation sequence, a sequence operably linked to the 3′ terminus of the nucleic acid sequence and which, when transcribed, is recognized by the host cell as a signal to add polyadenosine residues to transcribed mRNA. Any polyadenylation sequence which is functional in the host cell of choice may be used in the present invention. Exemplary polyadenylation sequences for filamentous fungal host cells include, but are not limited to those from the genes for  Aspergillus oryzae  TAKA amylase,  Aspergillus niger  glucoamylase,  Aspergillus nidulans  anthranilate synthase,  Fusarium oxysporum  trypsin-like protease, and  Aspergillus niger  alpha-glucosidase. Useful polyadenylation sequences for yeast host cells are also known in the art (See e.g., Guo and Sherman, Mol. Cell. Bio., 15:5983-5990 [1995]). 
     In some embodiments, the control sequence is a signal peptide coding region that codes for an amino acid sequence linked to the amino terminus of a polypeptide and directs the encoded polypeptide into the cell&#39;s secretory pathway. The 5′ end of the coding sequence of the nucleic acid sequence may inherently contain a signal peptide coding region naturally linked in translation reading frame with the segment of the coding region that encodes the secreted polypeptide. Alternatively, the 5′ end of the coding sequence may contain a signal peptide coding region that is foreign to the coding sequence. Any signal peptide coding region that directs the expressed polypeptide into the secretory pathway of a host cell of choice finds use for expression of the methyltransferase or guanine deaminase polypeptides provided herein. Effective signal peptide coding regions for bacterial host cells include, but are not limited to the signal peptide coding regions obtained from the genes for  Bacillus  NC1B 11837 maltogenic amylase,  Bacillus stearothermophilus  alpha-amylase,  Bacillus licheniformis  subtilisin,  Bacillus licheniformis  beta-lactamase,  Bacillus stearothermophilus  neutral proteases (nprT, nprS, nprM), and  Bacillus subtilis  prsA. Further signal peptides are known in the art (See e.g., Simonen and Palva, Microbiol. Rev., 57:109-137 [1993]). Effective signal peptide coding regions for filamentous fungal host cells include, but are not limited to the signal peptide coding regions obtained from the genes for  Aspergillus oryzae  TAKA amylase,  Aspergillus niger  neutral amylase,  Aspergillus niger  glucoamylase,  Rhizomucor miehei  aspartic proteinase,  Humicola insolens  cellulase, and  Humicola lanuginosa  lipase. Useful signal peptides for yeast host cells include, but are not limited to those from the genes for  Saccharomyces cerevisiae  alpha-factor and  Saccharomyces cerevisiae  invertase. 
     In some embodiments, the control sequence is a propeptide coding region that codes for an amino acid sequence positioned at the amino terminus of a polypeptide. The resultant polypeptide is referred to as a “proenzyme,” “propolypeptide,” or “zymogen,” in some cases). A propolypeptide can be converted to a mature active polypeptide by catalytic or autocatalytic cleavage of the propeptide from the propolypeptide. The propeptide coding region includes, but is not limited to the genes for  Bacillus subtilis  alkaline protease (aprE),  Bacillus subtilis  neutral protease (nprT),  Saccharomyces cerevisiae  alpha-factor,  Rhizomucor miehei  aspartic proteinase, and  Myceliophthora thermophila  lactase (See e.g., WO 95/33836). Where both signal peptide and propeptide regions are present at the amino terminus of a polypeptide, the propeptide region is positioned next to the amino terminus of a polypeptide and the signal peptide region is positioned next to the amino terminus of the propeptide region. 
     In some embodiments, regulatory sequences are also utilized. These sequences facilitate the regulation of the expression of the polypeptide relative to the growth of the host cell. Examples of regulatory systems are those which cause the expression of the gene to be turned on or off in response to a chemical or physical stimulus, including the presence of a regulatory compound. In prokaryotic host cells, suitable regulatory sequences include, but are not limited to the lac, tac, and trp operator systems. In yeast host cells, suitable regulatory systems include, but are not limited to the ADH2 system or GAL1 system. In filamentous fungi, suitable regulatory sequences include, but are not limited to the TAKA alpha-amylase promoter,  Aspergillus niger  glucoamylase promoter, and  Aspergillus oryzae  glucoamylase promoter. 
     In another aspect, the present invention also provides a recombinant expression vector comprising a polynucleotide encoding a methyltransferase or guanine deaminase polypeptide, and one or more expression regulating regions such as a promoter and a terminator, a replication origin, etc., depending on the type of hosts into which they are to be introduced. in some embodiments, the various nucleic acid and control sequences described above are joined together to produce a recombinant expression vector which includes one or more convenient restriction sites to allow for insertion or substitution of the nucleic acid sequence encoding the polypeptide at such sites. Alternatively, the polynucleotide sequence(s) of the present invention are expressed by inserting the polynucleotide sequence or a nucleic acid construct comprising the polynucleotide sequence into an appropriate vector for expression. In creating the expression vector, the coding sequence is located in the vector so that the coding sequence is operably linked with the appropriate control sequences for expression. 
     The recombinant expression vector may be any vector (e.g., a plasmid or virus), that can be conveniently subjected to recombinant DNA procedures and can result in the expression of the methyltransferase or guanine deaminase polynucleotide sequence. The choice of the vector will typically depend on the compatibility of the vector with the host cell into which the vector is to be introduced. The vectors may be linear or closed circular plasmids. 
     In some embodiments, the expression vector is an autonomously replicating vector (i.e., a vector that exists as an extra-chromosomal entity, the replication of which is independent of chromosomal replication, such as a plasmid, an extra-chromosomal element, a minichromosome, or an artificial chromosome). The vector may contain any means for assuring self-replication. In some alternative embodiments, the vector may be one which, when introduced into the host cell, is integrated into the genome and replicated together with the chromosome(s) into which it has been integrated. Furthermore, a single vector or plasmid or two or more vectors or plasmids which together contain the total DNA to be introduced into the genome of the host cell, or a transposon may be used. 
     In some embodiments, the expression vector preferably contains one or more selectable markers, which permit easy selection of transformed cells. A “selectable marker” is a gene the product of which provides for biocide or viral resistance, resistance to heavy metals, prototrophy to auxotrophs, and the like. Examples of bacterial selectable markers include, but are not limited to the dal genes from  Bacillus subtilis  or  Bacillus licheniformis , or markers, which confer antibiotic resistance such as ampicillin, kanamycin, chloramphenicol or tetracycline resistance. Suitable markers for yeast host cells include, but are not limited to ADE2, HIS3, LEU2, LYS2, MET3, TRP1, and URA3. Selectable markers for use in a filamentous fungal host cell include, but are not limited to, amdS (acetamidase), argB (ornithine carbamoyltransferases), bar (phosphinothricin acetyltransferase), hph (hygromycin phosphotransferase), niaD (nitrate reductase), pyrG (orotidine-5′-phosphate decarboxylase), sC (sulfate adenyltransferase), and trpC (anthranilate synthase), as well as equivalents thereof. In another aspect, the present invention provides a host cell comprising a polynucleotide encoding at least one methyltransferase or guanine deaminase polypeptide of the present application, the polynucleotide being operatively linked to one or more control sequences for expression of the methyltransferase or guanine deaminase enzyme(s) in the host cell. Host cells for use in expressing the polypeptides encoded by the expression vectors of the present invention are well known in the art and include but are not limited to, bacterial cells, such as  E. coli, Vibrio fluvialis, Streptomyces  and  Salmonella typhimurium  cells; fungal cells, such as yeast cells (e.g.,  Saccharomyces cerevisiae  and  Pichia pastoris  (ATCC Accession No. 201178)); insect cells such as  Drosophila  S2 and  Spodoptera  Sf9 cells; animal cells such as CHO, COS, BHK, 293, and Bowes melanoma cells; and plant cells. Exemplary host cells are  Escherichia coli  strains (such as W3110 (AfhuA) and BL21). 
     Accordingly, in another aspect, the present invention provides methods for producing the methyltransferase or guanine deaminase polypeptides, where the methods comprise culturing a host cell capable of expressing a polynucleotide encoding the methyltransferase or guanine deaminase polypeptide under conditions suitable for expression of the polypeptide. In some embodiments, the methods further comprise the steps of isolating and/or purifying the methyltransferase or guanine deaminase polypeptides, as described herein. 
     Appropriate culture media and growth conditions for the above-described host cells are well known in the art. Polynucleotides for expression of the methyltransferase or guanine deaminase polypeptides may be introduced into cells by various methods known in the art. Techniques include, among others, electroporation, biolistic particle bombardment, liposome mediated transfection, calcium chloride transfection, and protoplast fusion. 
     The methyltransferase or guanine deaminase enzymes with the properties disclosed herein can be obtained by subjecting the polynucleotide encoding the naturally occurring or engineered methyltransferase or guanine deaminase polypeptide to mutagenesis and/or directed evolution methods known in the art, and as described herein. An exemplary directed evolution technique is mutagenesis and/or DNA shuffling (See e.g., Stemmer, Proc. Natl. Acad. Sci. USA 91:10747-10751 [1994]; WO 95/22625; WO 97/0078; WO 97/35966; WO 98/27230; WO 00/42651; WO 01/75767 and U.S. Pat. No. 6,537,746). Other directed evolution procedures that can be used include, among others, staggered extension process (StEP), in vitro recombination (See e.g., Zhao et al., Nat. Biotechnol., 16:258-261 [1998]), mutagenic PCR (See e.g., Caldwell et al., PCR Methods Appl., 3:S136-S140 [1994]), and cassette mutagenesis (See e.g., Black et al., Proc. Natl. Acad. Sci. USA 93:3525-3529 [1996]). 
     For example, mutagenesis and directed evolution methods can be readily applied to polynucleotides to generate variant libraries that can be expressed, screened, and assayed. Mutagenesis and directed evolution methods are well known in the art (See e.g., U.S. Pat. Nos. 5,605,793, 5,830,721, 6,132,970, 6,420,175, 6,277,638, 6,365,408, 6,602,986, 7,288,375, 6,287,861, 6,297,053, 6,576,467, 6,444,468, 5,811238, 6,117,679, 6,165,793, 6,180,406, 6,291,242, 6,995,017, 6,395,547, 6,506,602, 6,519,065, 6,506,603, 6,413,774, 6,573,098, 6,323,030, 6,344,356, 6,372,497, 7,868,138, 5,834,252, 5,928,905, 6,489,146, 6,096,548, 6,387,702, 6,391,552, 6,358,742, 6,482,647, 6,335,160, 6,653,072, 6,355,484, 6,03,344, 6,319,713, 6,613,514, 6,455,253, 6,579,678, 6,586,182, 6,406,855, 6,946,296, 7,534,564, 7,776,598, 5,837,458, 6,391,640, 6,309,883, 7,105,297, 7,795,030, 6,326,204, 6,251,674, 6,716,631, 6,528,311, 6,287,862, 6,335,198, 6,352,859, 6,379,964, 7,148,054, 7,629,170, 7,620,500, 6,365,377, 6,358,740, 6,406,910, 6,413,745, 6,436,675, 6,961,664, 7,430,477, 7,873,499, 7,702,464, 7,783,428, 7,747,391, 7,747,393, 7,751,986, 6,376,246, 6,426,224, 6,423,542, 6,479,652, 6,319,714, 6,521,453, 6,368,861, 7,421,347, 7,058,515, 7,024,312, 7,620,502, 7,853,410, 7,957,912, 7,904,249, and all related non-US counterparts; Ling et al., Anal. Biochem., 254:157-78 [1997]; Dale et al., Meth. Mol. Biol., 57:369-74 [1996]; Smith, Ann. Rev. Genet., 19:423-462 [1985]; Botstein et al., Science, 229:1193-1201 [1985]; Carter, Biochem. J., 237:1-7 [1986]; Kramer et al., Cell, 38:879-887 [1984]; Wells et al., Gene, 34:315-323 [1985]; Minshull et al., Curr. Op. Chem. Biol., 3:284-290 [1999]; Christians et al., Nat. Biotechnol., 17:259-264 [1999]; Crameri et al., Nature, 391:288-291 [1998]; Crameri, et al., Nat. Biotechnol., 15:436-438 [1997]; Zhang et al., Proc. Nat. Acad. Sci. U.S.A., 94:4504-4509 [1997]; Crameri et al., Nat. Biotechnol., 14:315-319 [1996]; Stemmer, Nature, 370:389-391 [1994]; Stemmer, Proc. Nat. Acad. Sci. USA, 91:10747-10751 [1994]; WO 95/22625; WO 97/0078; WO 97/35966; WO 98/27230; WO 00/42651; WO 01/75767; WO 2009/152336, and U.S. Pat. No. 6,537,746. all of which are incorporated herein by reference). 
     In some embodiments, the enzyme clones obtained following mutagenesis treatment are screened by subjecting the enzymes to a defined temperature (or other assay conditions) and measuring the amount of enzyme activity remaining after heat treatments or other assay conditions. Clones containing a polynucleotide encoding a methyltransferase or guanine deaminase polypeptide are then isolated from the gene, sequenced to identify the nucleotide sequence changes (if any), and used to express the enzyme in a host cell. Measuring enzyme activity from the expression libraries can be performed using any suitable method known in the art (e.g., standard biochemistry techniques, such as HPLC analysis). 
     For engineered polypeptides of known sequence, the polynucleotides encoding the enzyme can be prepared by standard solid-phase methods, according to known synthetic methods. In some embodiments, fragments of up to about 100 bases can be individually synthesized, then joined (e.g., by enzymatic or chemical litigation methods, or polymerase mediated methods) to form any desired continuous sequence. For example, polynucleotides and oligonucleotides disclosed herein can be prepared by chemical synthesis using the classical phosphoramidite method (See e.g., Beaucage et al., Tetra. Lett., 22:1859-69 [1981]; and Matthes et al., EMBO J., 3:801-05 [1984]), as it is typically practiced in automated synthetic methods. According to the phosphoramidite method, oligonucleotides are synthesized (e.g., in an automatic DNA synthesizer), purified, annealed, ligated and cloned in appropriate vectors. 
     Accordingly, in some embodiments, a method for preparing the methyltransferase or guanine deaminase polypeptide can comprise: (a) synthesizing a polynucleotide encoding a polypeptide comprising an amino acid sequence selected from the amino acid sequence of any variant provided in the Tables in the Examples; and (b) expressing the methyltransferase or guanine deaminase polypeptide encoded by the polynucleotide. In some embodiments of the method, the amino acid sequence encoded by the polynucleotide can optionally have one or several (e.g., up to 3, 4, 5, or up to 10) amino acid residue deletions, insertions and/or substitutions. In some embodiments, the amino acid sequence has optionally 1-2, 1-3, 1-4, 1-5, 1-6, 1-7, 1-8, 1-9, 1-10, 1-15, 1-20, 1-21, 1-22, 1-23, 1-24, 1-25, 1-30, 1-35, 1-40, 1-45, or 1-50 amino acid residue deletions, insertions and/or substitutions. In some embodiments, the amino acid sequence has optionally 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 30, 30, 35, 40, 45, or 50 amino acid residue deletions, insertions and/or substitutions. In some embodiments, the amino acid sequence has optionally 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 18, 20, 21, 22, 23, 24, or 25 amino acid residue deletions, insertions and/or substitutions. In some embodiments, the substitutions can be conservative or non-conservative substitutions. 
     The expressed methyltransferase or guanine deaminase polypeptide can be measured for any desired improved property (e.g., activity, selectivity, stability, etc.), using any suitable assay known in the art, including but not limited to the assays and conditions described herein. 
     In some embodiments, any of the methyltransferase or guanine deaminase polypeptides expressed in a host cell are recovered from the cells and/or the culture medium using any one or more of the well-known techniques for protein purification, including, among others, lysozyme treatment, sonication, filtration, salting-out, ultra-centrifugation, and chromatography. 
     Chromatographic techniques for isolation of the methyltransferase or guanine deaminase polypeptides include, among others, reverse phase chromatography high performance liquid chromatography, ion exchange chromatography, hydrophobic interaction chromatography, gel electrophoresis, and affinity chromatography. Conditions for purifying a particular enzyme depends, in part, on factors such as net charge, hydrophobicity, hydrophilicity, molecular weight, molecular shape, etc., and will be apparent to those having skill in the art. In some embodiments, affinity techniques may be used to isolate the methyltransferase or guanine deaminase enzymes. In some embodiments utilizing affinity chromatography purification, any antibody which specifically binds the methyltransferase or guanine deaminase polypeptide finds use. For the production of antibodies, various host animals, including but not limited to rabbits, mice, rats, etc., are immunized by injection with a methyltransferase or guanine deaminase polypeptide or a fragment thereof. In some embodiments, the methyltransferase or guanine deaminase polypeptide or fragment is attached to a suitable carrier, such as BSA, by means of a side chain functional group or linkers attached to a side chain functional group. 
     In some embodiments, the methyltransferase or guanine deaminase polypeptide is produced in a host cell by a method comprising culturing a host cell (e.g., an  E. coli  strain) comprising a polynucleotide sequence encoding a methyltransferase or guanine deaminase polypeptide as described herein under conditions conducive to the production of the methyltransferase or guanine deaminase polypeptide and recovering the polypeptide from the cells and/or culture medium. 
     In some embodiments, the invention encompasses a method of producing an methyltransferase or guanine deaminase polypeptide comprising culturing a recombinant bacterial cell comprising a polynucleotide sequence encoding a methyltransferase or guanine deaminase polypeptide wherein the polynucleotide sequence has at least 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to at least one reference sequence selected from SEQ ID NOS:1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77, 79, 81, and/or 83, under suitable culture conditions to allow the production of the methyltransferase or guanine deaminase polypeptide and optionally recovering the methyltransferase or guanine deaminase polypeptide from the culture and/or cultured cells (e.g., bacterial or fungal host cells). 
     In some embodiments, the invention encompasses a method of producing an methyltransferase or guanine deaminase polypeptide comprising culturing a recombinant bacterial cell comprising a polynucleotide sequence encoding a methyltransferase or guanine deaminase polypeptide having at least 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to at least one reference sequence selected from SEQ ID NOS:2, 4, 6, 7, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60, 62, 64, 66, 68, 70, 72, 74, 75, 78, 80, 82, and/or 84, under suitable culture conditions to allow the production of the methyltransferase or guanine deaminase polypeptide and optionally recovering the methyltransferase or guanine deaminase polypeptide from the culture and/or cultured cells (e.g., bacterial or fungal host cells). 
     In some embodiments, once the methyltransferase or guanine deaminase polypeptides are recovered from the recombinant host cells or cell culture and they are further purified by any suitable method(s) known in the art. In some additional embodiments, the purified methyltransferase or guanine deaminase polypeptides are combined with other ingredients and compounds to provide compositions and formulations comprising the methyltransferase or guanine deaminase polypeptide as appropriate for different applications and uses (e.g., pharmaceutical compositions). 
     Compositions: 
     The present invention provides compositions comprising the enzymes provided herein, as well as compositions comprising the end-product, caffeine. In some embodiments, the compositions comprise food, while in other embodiments, the compositions comprise beverages. 
     The foregoing and other aspects of the invention may be better understood in connection with the following non-limiting examples. The examples are provided for illustrative purposes only and are not intended to limit the scope of the present invention in any way. 
     EXPERIMENTAL 
     The following Examples, including experiments and results achieved, are provided for illustrative purposes only and are not to be construed as limiting the present invention. 
     In the experimental disclosure below, the following abbreviations apply: ppm (parts per million); M (molar); mM (millimolar), uM and μM (micromolar); nM (nanomolar); mol (moles); gm and g (gram); mg (milligrams); ug and μg (micrograms); L and l (liter); ml and mL (milliliter); cm (centimeters); mm (millimeters); um and μm (micrometers); sec. (seconds); min(s) (minute(s)); h(s) and hr(s) (hour(s)); U (units); MW (molecular weight); rpm (rotations per minute); ° C. (degrees Centigrade); CDS (coding sequence); DNA (deoxyribonucleic acid); RNA (ribonucleic acid);  E. coli  W3110 (commonly used laboratory  E. coli  strain, available from the  Coli  Genetic Stock Center [CGSC], New Haven, Conn.); HPLC (high pressure liquid chromatography); LC (liquid chromatography); SDS-PAGE (sodium dodecyl sulfate polyacrylamide gel electrophoresis); FIOPC (fold improvements over positive control); LB (Luria broth); TB (Terrific broth); MeOH (methanol); (IPTG) isopropyl-β-D-thiogalactoside; Athens Research (Athens Research Technology, Athens, Ga.); ProSpec (ProSpec Tany Technogene, East Brunswick, N.J.); Sigma-Aldrich (Sigma-Aldrich, St. Louis, Mo.); Ram Scientific (Ram Scientific, Inc., Yonkers, N.Y.); Pall Corp. (Pall, Corp., Pt. Washington, N.Y.); Millipore (Millipore, Corp., Billerica Mass.); Difco (Difco Laboratories, BD Diagnostic Systems, Detroit, Mich.); Molecular Devices (Molecular Devices, LLC, Sunnyvale, Calif.); Kuhner (Adolf Kuhner, AG, Basel, Switzerland); Cambridge Isotope Laboratories, (Cambridge Isotope Laboratories, Inc., Tewksbury, Mass.); Applied Biosystems (Applied Biosystems, part of Life Technologies, Corp., Grand Island, N.Y.), Agilent (Agilent Technologies, Inc., Santa Clara, Calif.); Thermo Scientific (part of Thermo Fisher Scientific, Waltham, Mass.); Corning (Corning, Inc., Palo Alto, Calif.); Megazyme (Megazyme International, Wicklow, Ireland); Enzo (Enzo Life Sciences, Inc., Farmingdale, N.Y.); GE Healthcare (GE Healthcare Bio-Sciences, Piscataway, N.J.); Pierce (Pierce Biotechnology (now part of Thermo Fisher Scientific), Rockford, Ill.); Phenomenex (Phenomenex, Inc., Torrance, Calif.); Optimal (Optimal Biotech Group, Belmont, Calif.); and Bio-Rad (Bio-Rad Laboratories, Hercules, Calif.). 
     The following polynucleotide and polypeptide sequences find use in the present invention. In some cases (as shown below), the polynucleotide sequence is followed by the encoded polypeptide. 
     
       
         
           
               
               
            
               
                 GDA_01:  
                   
               
               
                 (SEQ ID NO: 1) 
                   
               
               
                 ATGATGTCCGGCGAACATACTCTGAAGGCAGTACGCGGGTCATTCATCGATGTTACCCGT  
                   
               
               
                   
               
               
                 ACTATTGATAATCCAGAAGAAATAGCCTCAGCTCTGCGGTTCATCGAGGATGGATTGTTA  
               
               
                   
               
               
                 TTAATAAAGCAGGGTAAAGTTGAGTGGTTCGGCGAGTGGGAAAACGGTAAGCACCAGAT  
               
               
                   
               
               
                 TCCGGATACTATTCGTGTTCGTGACTATCGGGGGAAACTTATAGTTCCCGGGTTCGTGGA  
               
               
                   
               
               
                 TACGCACATCCATTACCCCCAGTCCGAAATGGTAGGAGCGTATGGCGAACAATTATTGG  
               
               
                   
               
               
                 AATGGCTCAACAAGCATACATTCCCGACTGAGCGTAGATATGAAGATCTGGAATATGCC  
               
               
                   
               
               
                 CGCGAAATGAGTGCGTTTTTCATAAAGCAGCTTTTGCGGAATGGCACTACAACCGCTCTT  
               
               
                   
               
               
                 GTCTTTGGTACCGTGCATCCTCAGTCTGTCGATGCTCTGTTTGAGGCCGCTTCACACATCA  
               
               
                   
               
               
                 ATATGCGGATGATAGCAGGAAAGGTAATGATGGATAGAAACGCGCCCGATTACCTCCTC  
               
               
                   
               
               
                 GATACTGCCGAATCAAGCTATCATCAAAGCAAGGAGCTGATCGAGCGTTGGCATAAAAA  
               
               
                   
               
               
                 TGGACGCCTTCTTTATGCGATTACCCCTAGATTCGCACCAACGAGCTCACCTGAACAGAT  
               
               
                   
               
               
                 GGCCATGGCACAGCGCTTAAAGGAAGAGTATCCTGATACATGGGTCCACACGCACCTTT  
               
               
                   
               
               
                 GTGAGAATAAGGATGAAATTGCATGGGTCAAATCACTGTACCCAGATCATGATGGCTAC  
               
               
                   
               
               
                 TTAGATGTGTATCACCAATATGGGTTAACTGGTAAGAATTGCGTATTCGCTCACTGTGTG  
               
               
                   
               
               
                 CATCTTGAAGAAAAGGAATGGGATCGTCTGTCAGAGACTAAATCGTCAATTGCATTCTGT  
               
               
                   
               
               
                 CCCACATCCAATCTGTATCTCGGTAGCGGCCTGTTTAATCTGAAAAAGGCGTGGCAAAAG  
               
               
                   
               
               
                 AAGGTCAAAGTCGGGATGGGTACAGACATAGGCGCAGGTACAACGTTTAATATGTTGCA  
               
               
                   
               
               
                 GACGTTGAACGAGGCCTACAAGGTCTTGCAATTGCAAGGCTATCGGCTTTCAGCTTACGA  
               
               
                   
               
               
                 AGCTTTTTATCTGGCGACTTTGGGCGGAGCAAAATCCCTGGGTTTAGATGATCTGATAGG  
               
               
                   
               
               
                 GAACTTCCTGCCTGGTAAAGAGGCTGACTTCGTAGTTATGGAACCCACTGCCACTCCACT  
               
               
                   
               
               
                 TCAACAACTTCGTTATGACAATTCGGTTAGTTTGGTAGACAAACTTTTCGTTATGATGAC  
               
               
                   
               
               
                 GTTAGGGGACGACCGCAGTATCTATAGAACCTACGTTGATGGTAGACTGGTATATGAGC  
               
               
                   
               
               
                 GGAATTAA  
               
               
                   
               
               
                 Polypeptide sequence encoded by the polynucleotide of SEQ ID NO: 1:  
               
               
                 (SEQ ID NO: 2) 
                   
               
               
                 MMSGEHTLKAVRGSFIDVTRTIDNPEEIASALRFIEDGLLLIKQGKVEWFGEWENGKHQIPDTI 
                   
               
               
                   
               
               
                 RVRDYRGKLIVPGFVDTHIHYPQSEMVGAYGEQLLEWLNKHTFPTERRYEDLEYAREMSAF 
               
               
                   
               
               
                 FIKQLLRNGTTTALVFGTVHPQSVDALFEAASHINMRMIAGKVMMDRNAPDYLLDTAESSY 
               
               
                   
               
               
                 HQSKELIERWHKNGRLLYAITPRFAPTSSPEQMAMAQRLKEEYPDTWVHTHLCENKDEIAW 
               
               
                   
               
               
                 VKSLYPDHDGYLDVYHQYGLTGKNCVFAHCVHLEEKEWDRLSETKSSIAFCPTSNLYLGSG 
               
               
                   
               
               
                 LFNLKKAWQKKVKVGMGTDIGAGTTFNMLQTLNEAYKVLQLQGYRLSAYEAFYLATLGGA 
               
               
                   
               
               
                 KSLGLDDLIGNFLPGKEADFVVMEPTATPLQQLRYDNSVSLVDKLFVMMTLGDDRSIYRTYV 
               
               
                   
               
               
                 DGRLVYERN 
               
               
                   
               
               
                 GDA_02:  
               
               
                 (SEQ ID NO: 3)  
                   
               
               
                 ATGAATCACGAAACATTCCTCAAAAGAGCCGTCACGCTTGCTTGCGAGGGTGTTAATGCC 
                   
               
               
                   
               
               
                 GGCATTGGGGGACCATTTGGCGCAGTCATCGTTAAAGATGGGGCGATCATAGCTGAGGG 
               
               
                   
               
               
                 CCAGAACAACGTGACTACCTCTAATGACCCAACAGCACACGCGGAGGTGACAGCTATAC 
               
               
                   
               
               
                 GGAAGGCTTGCAAAGTACTCGGTGCGTACCAACTGGACGACTGTATTTTATATACTTCCT 
               
               
                   
               
               
                 GTGAGCCATGCCCAATGTGCCTCGGTGCGATATACTGGGCTAGACCAAAAGCTGTCTTTT 
               
               
                   
               
               
                 ACGCCGCCGAACATACCGATGCAGCGGAAGCGGGGTTCGATGACTCCTTCATATACAAG 
               
               
                   
               
               
                 GAAATCGACAAACCGGCCGAGGAGCGCACAATTCCCTTCTACCAGGTCACGCTGACCGA 
               
               
                   
               
               
                 GCACCTTTCTCCTTTCCAAGCCTGGAGAAACTTCGCTAACAAGAAAGAGTATTAA 
               
               
                   
               
               
                 Polypeptide sequence encoded by the polynucleotide of SEQ ID NO: 3:  
               
               
                 (SEQ ID NO: 4) 
                   
               
               
                 MNHETFLKRAVTLACEGVNAGIGGPFGAVIVKDGAIIAEGQNNVTTSNDPTAHAEVTAIRKA 
                   
               
               
                 CKVLGAYQLDDCILYTSCEPCPMCLGAIYWARPKAVFYAAEHTDAAEAGFDDSFIYKEIDKP 
               
               
                 AEERTIPFYQVTLTEHLSPFQAWRNFANKKEY 
               
               
                   
               
               
                 GDA_03:  
               
               
                 (SEQ ID NO: 5) 
                   
               
               
                 ATGATGGACTACCAGACCGCGGTGCGCGGTGCGTTTTTCGATATTGCCGGCGTAGCAGAA 
                   
               
               
                   
               
               
                 ACCCCCGATGAAGTGGCAGCACAGGCCCGTTACCTCGATGATGGGTTACTTTTTCTGCGC 
               
               
                   
               
               
                 GATGGAAAGATAATTGCGTTGCTGCCGTGGCAAGAAGGGGAAGCATTCTTACATCCGCT 
               
               
                   
               
               
                 GAAGGGCTATGTAGATCAGCGCGGCAAGCTGTTACTGCCTGGATTTGTCGATACACATAT 
               
               
                   
               
               
                 CCACTACCCTCAGACCGAAATGATAGGTGCCTTTGGTGAGCAGCTCCTTGAATGGCTTAC 
               
               
                   
               
               
                 AACATATACGTTTCCTGTCGAATCACAGTTTGCCGATGCCGATTATGCACAGGAAATCGC 
               
               
                   
               
               
                 GCAGTTCTTTGTCAACCAGTTAATTTCACACGGCACTACAACCGCACTGGTCTTTTGCAC 
               
               
                   
               
               
                 ACTGCACCCGGCCTCTGCCGAGGCCTTATTCTCGGAAGCATTACGGTTGAACATGAGACT 
               
               
                   
               
               
                 GATAGCCGGTAAGGTCATGATGGATCGCCATGTCCCAGATTACTTGTGCGAAACGGCCG 
               
               
                   
               
               
                 GTGAATCATACGAACAAACAAGAGAGTTGATACTTCGGTGGCATCAGCGTGGACGGTTA 
               
               
                   
               
               
                 GGTTACGCCATCACACCTCGCTTTGCGCCAACTTCAACTCCTGCCCTTTTAGAAGCGGTCC 
               
               
                   
               
               
                 AGAGACTTCGTACCGAATTTCCTGATACCTGGTTGCAGACCCACTTATCAGAAAACCGCG 
               
               
                   
               
               
                 AAGAAATTGCTTGGGTGAAACAGCTGTGGCCAGAGCATGAGCATTATTTGGACGTCTATC 
               
               
                   
               
               
                 ACCATTATCAGCTGACAGGGGAGCGGTCAGTCTTCGCGCACGGCATTCATTTGGATGATG 
               
               
                   
               
               
                 CGGAGTGGCAGTGTCTGCACGACACTGGGTCTGCCGTCGCATTTTGTCCGACATCAAATC 
               
               
                   
               
               
                 TGTTCCTGGGATCTGGTCTGTTTCGCTTACCCGCGTGTTGGCAGCATCAGGTAAGAATGG 
               
               
                   
               
               
                 GAATAGGTAGTGACGTTGGTGCTGGAACTACATTCTCTATGCTCCGTACACTGGGTGAAG 
               
               
                   
               
               
                 CGTATAAAGTCGGACAGCTGCAGTCCTACCGGTTGCGTGCATCGGAAGCCTTCTACCATG 
               
               
                   
               
               
                 CTACGTTGGGAGGGGCTAGAGCATTAAGATTGGAGGATAAAATTGGTAACTTCCAGCCG 
               
               
                   
               
               
                 GGTAAAGAGGCGGATTTTGTCGTAATTGATCCCGCTGTTACACCTCTTCAACGTCTGCGT 
               
               
                   
               
               
                 ACCGGACGCTGCCATGACATCTATGAACAGCTTTTCGTTTTAATGACACTGGGGGACGAG 
               
               
                   
               
               
                 AGAAACATCAGTGAAACATGGGTCAACGGGGAGCGCGTTTGGTGCCAGGATTAA 
               
               
                   
               
               
                 Polypeptide sequence encoded by the polynucleotide of SEQ ID NO: 5:  
               
               
                 (SEQ ID NO: 6) 
                   
               
               
                 MMDYQTAVRGAFFDIAGVAETPDEVAAQARYLDDGLLFLRDGKIIALLPWQEGEAFLHPLK 
                   
               
               
                   
               
               
                 GYVDQRGKLLLPGFVDTHIHYPQTEMIGAFGEQLLEWLTTYTFPVESQFADADYAQEIAQFF 
               
               
                   
               
               
                 VNQLISHGTTTALVFCTLHPASAEALFSEALRLNMRLIAGKVMMDRHVPDYLCETAGESYEQ 
               
               
                   
               
               
                 TRELILRWHQRGRLGYAITPRFAPTSTPALLEAVQRLRTEFPDTWLQTHLSENREEIAWVKQL 
               
               
                   
               
               
                 WPEHEHYLDVYHHYQLTGERSVFAHGIHLDDAEWQCLHDTGSAVAFCPTSNLFLGSGLFRL 
               
               
                   
               
               
                 PACWQHQVRMGIGSDVGAGTTFSMLRTLGEAYKVGQLQSYRLRASEAFYHATLGGARALR 
               
               
                   
               
               
                 LEDKIGNFQPGKEADFVVIDPAVTPLQRLRTGRCHDIYEQLFVLMTLGDERNISETWVNGER 
               
               
                   
               
               
                 VWCQD  
               
               
                   
               
               
                 GDA_04:  
               
               
                 (SEQ ID NO: 7) 
                   
               
               
                 ATGACTGTCACTCGCAAGGCTTATCGCGCGGCAATACTTCACTCAATCGCTGATCCCGCA 
                   
               
               
                   
               
               
                 GAGGTCGGATTAGACGCGTCACATGAGTACTTCGAGGACGGCCTTCTTGTGATCGACGG 
               
               
                   
               
               
                 AGGTCGTATTCAAGCGGTTGGCCATGCGAGTGACCTGCTGCCCACCCTGGATGCTGATAT 
               
               
                   
               
               
                 CCCGGTTGAACATTATCAGGATGCTCTCATTACGCCTGGCTTTATAGATACTCATATCCAC 
               
               
                   
               
               
                 TTCCCCCAAACGGGTATGATAGGCAGTTATGGGGAACAGTTGCTGGATTGGCTGAACAC 
               
               
                   
               
               
                 CTACACATTTCCGTGCGAGAAACAGTTTGCGGATAAAGATCATGCAGATCAAGTGGCCC 
               
               
                   
               
               
                 ATGTGTTCTTAAAAGAGCTGTTACGCAACGGCACCACGACCGCGCTGGTATTTGGTTCGG 
               
               
                   
               
               
                 TACATCCCGAAAGCGTAAATGCGCTGTTTGAGGCAGCTGAGCGTCTTGATCTTCGGCTCA 
               
               
                   
               
               
                 TAGCTGGTAAAGTTATGATGGATCGCAACGCACCCGATTATCTGACCGACACTGCTGAGA 
               
               
                   
               
               
                 GCAGCTACGCCCAGTCCAAAGCTCTCATCGAGCGGTGGCACGGTAAAGGCAGATTACAC 
               
               
                   
               
               
                 TACGCCGTGACGCCGAGATTTGCGCCAACATCTACGCCAGAACAGCTCGCACGTGCAGG 
               
               
                   
               
               
                 TCAACTGCTGAAAGAGCACCCTGGAGTGTATTTGCATACCCATCTCAGCGAGAACCTCCA 
               
               
                   
               
               
                 AGAAATCGACTGGGTTAAGTCTTTATTCCCTGAACAAAAGGGCTACCTTGATGTCTATGA 
               
               
                   
               
               
                 CCACTTCGAACTGTTAGGGGAACGCAGCGTATTTGCTCACGGGGTTCATCTCTGCGATGA 
               
               
                   
               
               
                 AGAATGTCAGCGTTTGGCGGAAACAGGTTCGGCTGTGGCATTCTGCCCTACGTCCAATTT 
               
               
                   
               
               
                 ATTTCTCGGAAGTGGACTGTTTAATCTTCCCCAGGCCGAGAGATTCAAAGTGAACGTGGG 
               
               
                   
               
               
                 GCTGGGGACAGATGTGGGTGCTGGTACTAGTTTCTCCCTGCTGAATACCCTGAACGAAGC 
               
               
                   
               
               
                 TTATAAGGTTATGCAGCTGCAAGGTGCGCGGCTCCACCCGTACAAATCTCTTTACCTCGC 
               
               
                   
               
               
                 TACACTTGGTGGTGCAAGAGCGTTAAGACTTGATGACCGCATTGGGAGCCTGCGCCCTGG 
               
               
                   
               
               
                 TAATGATGCAGACTTTGTGGTGCTCGATTATAAAGCTACTCCCTTACTGGACTATCGGTT 
               
               
                   
               
               
                 ACAGCAATCTAGATCCATCGAGGAAACATTATTTGTGCTGACAACTCTCGGGGATGATAG 
               
               
                   
               
               
                 AACTGTTCGCGAAACGTATGCGGCAGGTCGGTGTGTCCATCAAAGAGAAGGATAA 
               
               
                   
               
               
                 Polypeptide sequence encoded by the polynucleotide of SEQ ID NO: 7:  
               
               
                 (SEQ ID NO: 8) 
                   
               
               
                 MTVTRKAYRAAILHSIADPAEVGLDASHEYFEDGLLVIDGGRIQAVGHASDLLPTLDADIPVE 
                   
               
               
                   
               
               
                 HYQDALITPGFIDTHIHFPQTGMIGSYGEQLLDWLNTYTFPCEKQFADKDHADQVAHVFLKE 
               
               
                   
               
               
                 LLRNGTTTALVFGSVHPESVNALFEAAERLDLRLIAGKVMMDRNAPDYLTDTAESSYAQSK 
               
               
                   
               
               
                 ALIERWHGKGRLHYAVTPRFAPTSTPEQLARAGQLLKEHPGVYLHTHLSENLQEIDWVKSLF 
               
               
                   
               
               
                 PEQKGYLDVYDHFELLGERSVFAHGVHLCDEECQRLAETGSAVAFCPTSNLFLGSGLFNLPQ 
               
               
                   
               
               
                 AERFKVNVGLGTDVGAGTSFSLLNTLNEAYKVMQLQGARLHPYKSLYLATLGGARALRLD 
               
               
                   
               
               
                 DRIGSLRPGNDADFVVLDYKATPLLDYRLQQSRSIEETLFVLTTLGDDRTVRETYAAGRCVH 
               
               
                   
               
               
                 QREG  
               
               
                   
               
               
                 GDA_05:  
               
               
                 (SEQ ID NO: 9) 
                   
               
               
                 ATGACCAAATCGGATTTATTGTTCGATAAATTTAACGATAAACACGGAAAATTTTTGGTA 
                   
               
               
                   
               
               
                 TTCTTTGGAACATTCGTGGACACGCCGAAGCTGGGAGAACTCCGGATTCGCGAAAAGAC 
               
               
                   
               
               
                 GTCAGTGGGAGTTTTAAACGGAATTATACGGTTCGTTAACCGGAACTCGTTAGATCCGGT 
               
               
                   
               
               
                 TAAGGATTGCCTGGATCATGATTCTTCGTTGTCTCCGGAGGACGTCACCGTCGTCGATAT 
               
               
                   
               
               
                 AATCGGTAAAGATAAGACTCGGAACAACTCCTTCTACTTTCCCGGATTTGTCGACACTCA 
               
               
                   
               
               
                 TAATCATGTTTCACAGTACCCAAATGTGGGGGTTTTTGGTAATTCAACACTGTTGGATTG 
               
               
                   
               
               
                 GCTGGAGAAATATACTTTCCCGATCGAGGCTGCTTTGGCCAACGAAAACATTGCCCGTGA 
               
               
                   
               
               
                 GGTCTACAACAAGGTTATCTCCAAAACTCTGAGTCATGGTACAACTACTGTGGCGTATTA 
               
               
                   
               
               
                 CAACACCATAGATCTGAAGTCTACAAAGCTTCTGGCCCAGTTATCATCCCTTCTCGGTCA 
               
               
                   
               
               
                 GCGTGTACTTGTTGGCAAAGTCTGTATGGATACCAATGGACCGGAATATTATATTGAAGA 
               
               
                   
               
               
                 TACGAAAACGAGCTTCGAATCTACGGTCAAAGTTGTCAAATACATACGCGAAACGATTT 
               
               
                   
               
               
                 GCGATCCTCTGGTAAACCCAATAGTGACTCCTAGATTCGCTCCATCGTGCAGCCGTGAGT 
               
               
                   
               
               
                 TAATGCAGCAGTTAAGCAAGCTTGTTAAGGACGAAAATATCCATGTTCAGACGCACCTGT 
               
               
                   
               
               
                 CAGAGAACAAAGAAGAAATCCAATGGGTGCAGGATCTGTTCCCCGAGTGCGAATCTTAT 
               
               
                   
               
               
                 ACAGACGTCTATGATAAGTATGGCCTGCTCACTGAGAAAACGGTTTTAGCACATTGCATT 
               
               
                   
               
               
                 CATCTGACAGATGCAGAAGCACGTGTTATAAAGCAGCGGCGCTGTGGCATCAGTCACTG 
               
               
                   
               
               
                 CCCGATAAGTAACTCCTCATTGACATCGGGAGAATGTCGGGTTCGCTGGCTGCTGGATCA 
               
               
                   
               
               
                 AGGTATTAAAGTTGGTCTGGGAACGGATGTCTCGGCAGGGCATTCATGTTCAATTTTGAC 
               
               
                   
               
               
                 AACTGGACGGCAGGCGTTCGCGGTTAGCCGCCATTTAGCCATGCGTGAGACTGATCACG 
               
               
                   
               
               
                 CAAAATTATCGGTTTCAGAGTGCTTGTTTCTTGCAACTATGGGCGGTGCGCAGGTTTTAA 
               
               
                   
               
               
                 GAATGGATGAGACGTTGGGAACATTTGATGTCGGTAAACAATTCGATGCGCAAATGATA 
               
               
                   
               
               
                 GATACGAATGCTCCGGGCTCCAACGTAGATATGTTTCACTGGCAGTTGAAGGAAAAAGA 
               
               
                   
               
               
                 TCAAATGCAGGAGCAAGAGCAGGAACAAGGACAGGACCCTTACAAAAATCCGCCGTTAC 
               
               
                   
               
               
                 TGACAAACGAAGATATCATTGCGAAGTGGTTCTTTAATGGTGACGATCGTAACACCACA 
               
               
                   
               
               
                 AAAGTGTGGGTGGCAGGTCAGCAAGTTTATCAGATCTAA 
               
               
                   
               
               
                 Polypeptide sequence encoded by the polynucleotide of SEQ ID NO: 9:  
               
               
                 (SEQ ID NO: 10)  
                   
               
               
                 MTKSDLLFDKFNDKHGKFLVFFGTFVDTPKLGELRIREKTSVGVLNGIIRFVNRNSLDPVKDC 
                   
               
               
                   
               
               
                 LDHDSSLSPEDVTVVDIIGKDKTRNNSFYFPGFVDTHNHVSQYPNVGVFGNSTLLDWLEKYT 
               
               
                   
               
               
                 FPIEAALANENIAREVYNKVISKTLSHGTTTVAYYNTIDLKSTKLLAQLSSLLGQRVLVGKVC 
               
               
                   
               
               
                 MDTNGPEYYIEDTKTSFESTVKVVKYIRETICDPLVNPIVTPRFAPSCSRELMQQLSKLVKDEN 
               
               
                   
               
               
                 IHVQTHLSENKEEIQWVQDLFPECESYTDVYDKYGLLTEKTVLAHCIHLTDAEARVIKQRRC 
               
               
                   
               
               
                 GISHCPISNSSLTSGECRVRWLLDQGIKVGLGTDVSAGHSCSILTTGRQAFAVSRHLAMRETD 
               
               
                   
               
               
                 HAKLSVSECLFLATMGGAQVLRMDETLGTFDVGKQFDAQMIDTNAPGSNVDMFHWQLKEK 
               
               
                   
               
               
                 DQMQEQEQEQGQDPYKNPPLLTNEDIIAKWFFNGDDRNTTKVWVAGQQVYQI 
               
               
                   
               
               
                 GDA_06:  
               
               
                 (SEQ ID NO: 11) 
                   
               
               
                 ATGCGGGATTTGGAGAAGAACATAAAAATTCTGAAGGGCAACATCATCTACACCGAAAA 
                   
               
               
                   
               
               
                 CTCTGATTCATTTAACGTTGTGGAAAAGGGGTTTATCATTGTAAAGGATGGCATTATCGA 
               
               
                   
               
               
                 TGGCACGTACGAGAAATTACCTGAAGAATTTAAAGATGTTCAAGTCGAGGATTACGGTG 
               
               
                   
               
               
                 ATAAACTGATTATACCTGGGTTTATCGACCTTCACACCCATGCATCTCAGTTCGCTATCAA 
               
               
                   
               
               
                 GGGTATTGGATATGATAAAGAGCTTTTGCCATGGTTGGAAACTTACACATTTCCTGAGGA 
               
               
                   
               
               
                 GGCGAAGTTTATCGACAAGGTGTATGCCGAAAAAGTATATAAGGAGTTTGTGGACGAAT 
               
               
                   
               
               
                 TGTATGAGGAGGGCACTACCCGTGCAGTAATTTTTGCTACAATACATAGCGAATCTACAG 
               
               
                   
               
               
                 AGATCCTGATGAAATTACTGGAAGAAAAAGGCATTGAGGCTTATGTTGGGAAAGTCAAT 
               
               
                   
               
               
                 ATGGATCGCAATTGCCCTGAATCCCTCAAAGAAAATTCAGACGAGTCTGTGGAGGCGAC 
               
               
                   
               
               
                 CATCAAGTGGATTGAGAACTCAAGCAAGAAATATAAGTATGTTAAACCAATCATCACCC 
               
               
                   
               
               
                 CAAGATTCGTACCTTCATGTACAGGCCACTTAATGAAAGAACTGGGCAGCATCGCAGTTT 
               
               
                   
               
               
                 CGAAATCGATGCCGGTCCAGAGCCATTTGTCCGAGAACCTTAGTGAAATAGAGTGGGTT 
               
               
                   
               
               
                 AAAGAATTGCACCCCGAATGTAAGAACTACGGCGAAGTGTATGACAAGTTCAACTTGTT 
               
               
                   
               
               
                 TGGCCAAACCAAAACAATTATGGCGCACTGCGTGTATTTAACAGAGGATGAGATCAACG 
               
               
                   
               
               
                 CTATAGAAGATAATAACGTGACTATTGCTCACTGCCCAACCAGCAACGTTAATATCTCGT 
               
               
                   
               
               
                 CGGGAATTGCTCCGATCAATACGTTGCTGAGAAAGAAGAAAGTGAAAATTGGACTCGGC 
               
               
                   
               
               
                 TCCGATATTGCCGGAGGGGAAAGTCTGAGTCTTCTTTCTGTGATGAAAAGTGCGGTTTCT 
               
               
                   
               
               
                 TTATCGAAAATGCGCGCGGTGTGTTTCAAAGAAGAAGAAAAGGCGCTGACGCTCCCCGA 
               
               
                   
               
               
                 AGTGTTTTACTTAGCGACTAAAGGTGGCGGTTCCTTCTTTGGTAATGTAGGCTCGTTTGAG 
               
               
                   
               
               
                 AAATCTTACGAGTTTGATGCCCTGATTATCGACGACGACTCTTTATGGAAAGTTAATAAA 
               
               
                   
               
               
                 GGAAATATTGAGGAACGTCTGGAGAAACTGGTGTACTTAGGAGACAAACGCAATATTAT 
               
               
                   
               
               
                 AAAACGCTATGTCTGTGGACGCGAAATCTAA 
               
               
                   
               
               
                 Polypeptide sequence encoded by the polynucleotide of SEQ ID NO: 11:  
               
               
                 (SEQ ID NO: 12) 
                   
               
               
                 MRDLEKNIKILKGNIIYTENSDSFNVVEKGFIIVKDGIIDGTYEKLPEEFKDVQVEDYGDKLIIP 
                   
               
               
                   
               
               
                 GFIDLHTHASQFAIKGIGYDKELLPWLETYTFPEEAKFIDKVYAEKVYKEFVDELYEEGTTRA 
               
               
                   
               
               
                 VIFATIHSESTEILMKLLEEKGIEAYVGKVNMDRNCPESLKENSDESVEATIKWIENSSKKYKY 
               
               
                   
               
               
                 VKPIITPRFVPSCTGHLMKELGSIAVSKSMPVQSHLSENLSEIEWVKELHPECKNYGEVYDKF 
               
               
                   
               
               
                 NLFGQTKTIMAHCVYLTEDEINAIEDNNVTIAHCPTSNVNISSGIAPINTLLRKKKVKIGLGSDI 
               
               
                   
               
               
                 AGGESLSLLSVMKSAVSLSKMRAVCFKEEEKALTLPEVFYLATKGGGSFFGNVGSFEKSYEF 
               
               
                   
               
               
                 DALIIDDDSLWKVNKGNIEERLEKLVYLGDKRNIIKRYVCGREI 
               
               
                   
               
               
                 GDA_07:  
               
               
                 (SEQ ID NO: 13) 
                   
               
               
                 ATGTCAGCTCACAGTGCACAACAGCGGGATGAGTATCTTAACCTTGCCATACAGCTGGCG 
                   
               
               
                   
               
               
                 GTGCACAATGTCAGCGACGGCGGTGGACCTTTTGGGGCAGTAGTAGTGACTGCTGACGG 
               
               
                   
               
               
                 AACAGTGCATGAGGGAGTCAACCGGGTGACACGCGATCATGACCCAACGGCACATGCTG 
               
               
                   
               
               
                 AAGTGGTCGCCATACGTCGCGCAGCTGCAGCGTCGAAACGGTTCGACCTGACTGGGTCT 
               
               
                   
               
               
                 GTCTTATATGCGTCGTGCGAACCGTGTCCCCTGTGCCTGTCTGCTACGTTGTGGGCTCGCA 
               
               
                   
               
               
                 TTGGGCATGTCTACTTCGCAGCGGATAGACATGGAGCAGCAAAGGCCGGGTTCGACGAT 
               
               
                   
               
               
                 GCGGTGTTTTATGAATATTTCGCAGGCACACGGCCCGAGTTACTTCCCGTTGAACATGCA 
               
               
                   
               
               
                 GAGCTTGCTGCCAGTAACGAACCATTTGACGCATGGAGAAACCACGCTCGCCGTACAGC 
               
               
                   
               
               
                 CTATTAA  
               
               
                   
               
               
                 Polypeptide sequence encoded by the polynucleotide of SEQ ID NO: 13:  
               
               
                 (SEQ ID NO: 14) 
                   
               
               
                 MSAHSAQQRDEYLNLAIQLAVHNVSDGGGPFGAVVVTADGTVHEGVNRVTRDHDPTAHAE 
                   
               
               
                 VVAIRRAAAASKRFDLTGSVLYASCEPCPLCLSATLWARIGHVYFAADRHGAAKAGFDDAV 
               
               
                 FYEYFAGTRPELLPVEHAELAASNEPFDAWRNHARRTAY 
               
               
                   
               
               
                 GDA_08:  
               
               
                 (SEQ ID NO: 15) 
                   
               
               
                 ATGACGACTGTAGGCATCCGGGGCACTTTCTTTGACTTTGTGGATGATCCATGGAAGCAC 
                   
               
               
                   
               
               
                 ATAGGTAACGAGCAAGCGGCAGCGAGATTCCACCAGGACGGGCTCATGGTAGTCACAGG 
               
               
                   
               
               
                 TGGCGTGATAAAAGCTTTTGGGCCACACGACAAAATCGCTGCGGCGCATCCCGGGGTTG 
               
               
                   
               
               
                 AGATTACACACATCAAGGACCGGATAATCGTTCCGGGTTTTATTGATGGTCACATTCATC 
               
               
                   
               
               
                 TGCCGCAAACTCGTGTCCTTGGTGCGTATGGTGAGCAGTTGCTTCCGTGGCTGCAGAAAA 
               
               
                   
               
               
                 GTATCTACCCCGAAGAGATCAAATACAAAGATCGTAACTACGCTCGCGAGGGCGTGAAA 
               
               
                   
               
               
                 CGTTTCTTAGATGCGCTGCTGGCAGCTGGTACTACGACTTGTCAGGCTTTTACGAGCTCCT 
               
               
                   
               
               
                 CTCCTGTTGCGACTGAAGAGCTTTTTGAAGAAGCAGCACGGCGGAATATGCGTGTTATCG 
               
               
                   
               
               
                 CGGGTCTGACGGGCATCGATCGCAATGCTCCTGCTGAATTCATAGATACTCCAGAAAACT 
               
               
                   
               
               
                 TCTACCGCGATAGTAAACGGCTCATTGCGCAGTATCATAACAAAGGGAGAAACTTATAC 
               
               
                   
               
               
                 GCGATCACACCCCGTTTCGCATTTGGAGCGAGCCCCGAACTGCTCAAAGCATGCCAACGT 
               
               
                   
               
               
                 TTAAAACACGAGCATCCTGATTGCTGGGTCAATACCCATATTTCTGAGAATCCCGCTGAG 
               
               
                   
               
               
                 TGCTCAGGGGTTCTGGTTGAGCATCCGGATTGTCAGGACTACCTGGGTGTTTACGAGAAG 
               
               
                   
               
               
                 TTTGATCTCGTAGGACCAAAATTTAGCGGAGGACACGGGGTATATCTGTCGAATAACGA 
               
               
                   
               
               
                 GTTCCATAGAATGTCTAAGAAGGGTGCGGCTGTGGTATTTTGCCCTTGCTCCAATTTGTTT 
               
               
                   
               
               
                 CTTGGAAGCGGTTTGTTTCGGCTCGGTAGAGCCACCGATCCAGAACATCGGGTCAAAATG 
               
               
                   
               
               
                 AGTTTCGGGACCGATGTGGGCGGCGGTAATCGCTTTTCTATGATTTCCGTTTTGGACGAC 
               
               
                   
               
               
                 GCCTATAAAGTAGGTATGTGCAACAACACTATGCTGGATGGTTCGATAGATCCCGCACG 
               
               
                   
               
               
                 GAAAGATCTGGCTGAGGCAGAGCGTAATAAATTATCCCCATACCGCGGTTTTTGGTCAGT 
               
               
                   
               
               
                 TACCTTAGGGGGTGCAGAAGGCCTTTACATTGACGATAAATTAGGCAATTTTGAACCAGG 
               
               
                   
               
               
                 TAAAGAAGCAGATTTTGTAGCGTTAGATCCGAACGGTGGACAGCTTGCTCAGCCATGGC 
               
               
                   
               
               
                 ACCAAAGTCTTATAGCTGACGGAGCGGGACCGCGTACCGTAGATGACGCAGCCAACATG 
               
               
                   
               
               
                 CTGTTCTCCGTAATGATGGTTGGGGATGATCGTTGTGTGGACGAGACGTGGGTCATGGGA 
               
               
                   
               
               
                 AAACGGCTGTACAAACAGTCATAA 
               
               
                   
               
               
                 Polypeptide sequence encoded by the polynucleotide of SEQ ID NO: 15:  
               
               
                 (SEQ ID NO: 16) 
                   
               
               
                 MTTVGIRGTFFDFVDDPWKHIGNEQAAARFHQDGLMVVTGGVIKAFGPHDKIAAAHPGVEI 
                   
               
               
                   
               
               
                 THIKDRIIVPGFIDGHIHLPQTRVLGAYGEQLLPWLQKSIYPEEIKYKDRNYAREGVKRFLDAL 
               
               
                   
               
               
                 LAAGTTTCQAFTSSSPVATEELFEEAARRNMRVIAGLTGIDRNAPAEFIDTPENFYRDSKRLIA 
               
               
                   
               
               
                 QYHNKGRNLYAITPRFAFGASPELLKACQRLKHEHPDCWVNTHISENPAECSGVLVEHPDCQ 
               
               
                   
               
               
                 DYLGVYEKFDLVGPKFSGGHGVYLSNNEFHRMSKKGAAVVFCPCSNLFLGSGLFRLGRATD 
               
               
                   
               
               
                 PEHRVKMSFGTDVGGGNRFSMISVLDDAYKVGMCNNTMLDGSIDPARKDLAEAERNKLSPY 
               
               
                   
               
               
                 RGFWSVTLGGAEGLYIDDKLGNFEPGKEADFVALDPNGGQLAQPWHQSLIADGAGPRTVDD 
               
               
                   
               
               
                 AANMLFSVMMVGDDRCVDETWVMGKRLYKQS 
               
               
                   
               
               
                 GDA_09:  
               
               
                 (SEQ ID NO: 17)  
                   
               
               
                 ATGAAGATTTACCGCAGTACCCTTCTGCATACACCAGCCAGCCCGTTTGCGGTGCCGGAT 
                   
               
               
                   
               
               
                 GCGCTGCAGACTTTCAGCGACGGTGCTCTGGCCGTAGGTGATACGGGTACCATTGCACAC 
               
               
                   
               
               
                 CTTGGTACATTCACCGAAGTACTTGCAGAAGTGCGTGCCGCATGCCCAGATGCGGAAGT 
               
               
                   
               
               
                 ACACGATCTGCGTGGTGGCGTTCTGCTGCCTGGCTTTATCGATACTCACGTTCACTATCCG 
               
               
                   
               
               
                 CAGGTACGCGTTTTGGGAGGGCTGGGGATGGCCTTATTAGAGTGGCTTGATCGTAATACA 
               
               
                   
               
               
                 CTGCCCGAAGAAGCTCGCTTAGCTGATGCGGCTTATGCTCGCACAATAGCCGGCGAGTTC 
               
               
                   
               
               
                 CTTCACGGTCTTGCAAGTCATGGAACTACTACCGCCCTGGTGTTTGGTAGTCACTTTGCG 
               
               
                   
               
               
                 GGAGCTATGGATGAGTTCTTTGCGGAAGCTGCGGCAAGAGGTTTACGGGTGGTTGCGGG 
               
               
                   
               
               
                 CCAAGTGGTCAGTGATCGTCTGCTGCGCCCCGAATTACACACTACTCCGGAGCGGGCTTA 
               
               
                   
               
               
                 TGCCGAGGGCAAAGCGCTGATTGAACGTTGGCATGGACAAGGAAGATCTCTGTATGCCG 
               
               
                   
               
               
                 TGACTCCGCGCTTTTCGCTCTCGGCCAGTGAGGGCATCCTCGATGCGTGTGCGGCATTGC 
               
               
                   
               
               
                 TGACTGAATTTCCAGACGTGCGGTTTACGAGTCACATAAACGAGAATAATCAGGAGATC 
               
               
                   
               
               
                 GAAGTGGTGCGGGGGCTGTTCCCAGGTGCACGTGACTACCTCGATACTTATGAAAGAGC 
               
               
                   
               
               
                 TGGCTTGGTGACGCCGCGCTCTGTTTTTGCCCATAACGTGCACCCCAACGAGCGGGAACT 
               
               
                   
               
               
                 CGGTGTCTTGGCGGCACAACGGTGCTCTGTCGCGCATTGCCCATGTAGTAATTCAGCCTT 
               
               
                   
               
               
                 AGGGTCTGGACTTTTCCCACTGCGTCGGCACCTGGCAGCAGGCGTGCATGTAGCGCTGGG 
               
               
                   
               
               
                 GACGGACGTGGGTGGAGGAACGGGATTCAGCTTACTCAAAGAAGGTTTGCAAGCGTATT 
               
               
                   
               
               
                 TCATGCAGCAACTGTTGGGTGAAGAAGGTGCGGCACTGTCTCCTGCCCATCTCTTATACT 
               
               
                   
               
               
                 TAGCAACACTGGCGGGCGCGCAGGCACTTGGTCTGGATGGACAAGTTGGAGATTTCACG 
               
               
                   
               
               
                 CCTGGAAAACAGTTCGACGCTGTCTGGTTGCGTCCAAGAGCAGGGTCAACCCTGGCAAC 
               
               
                   
               
               
                 CGTCCTCGCTCATGCTGAGTCTGAAGAACGTACGCTCGCCGCGTTGTTCGCACTCGGTAC 
               
               
                   
               
               
                 AGGGGATGATGTCGAACGTGTGTGGGTTGGCGGAGGCGTGGTCTTTGCCCGTGAAGCAG 
               
               
                   
               
               
                 AAGCGTAA 
               
               
                   
               
               
                 Polypeptide sequence encoded by the polynucleotide of SEQ ID NO: 17:  
               
               
                 (SEQ ID NO: 18) 
                   
               
               
                 MKIYRSTLLHTPASPFAVPDALQTFSDGALAVGDTGTIAHLGTFTEVLAEVRAACPDAEVHD 
                   
               
               
                   
               
               
                 LRGGVLLPGFIDTHVHYPQVRVLGGLGMALLEWLDRNTLPEEARLADAAYARTIAGEFLHG 
               
               
                   
               
               
                 LASHGTTTALVFGSHFAGAMDEFFAEAAARGLRVVAGQVVSDRLLRPELHTTPERAYAEGK 
               
               
                   
               
               
                 ALIERWHGQGRSLYAVTPRFSLSASEGILDACAALLTEFPDVRFTSHINENNQEIEVVRGLFPG 
               
               
                   
               
               
                 ARDYLDTYERAGLVTPRSVFAHNVHPNERELGVLAAQRCSVAHCPCSNSALGSGLFPLRRHL 
               
               
                   
               
               
                 AAGVHVALGTDVGGGTGFSLLKEGLQAYFMQQLLGEEGAALSPAHLLYLATLAGAQALGL 
               
               
                   
               
               
                 DGQVGDFTPGKQFDAVWLRPRAGSTLATVLAHAESEERTLAALFALGTGDDVERVWVGGG 
               
               
                   
               
               
                 VVFAREAEA  
               
               
                   
               
               
                 GDA_10:  
               
               
                 (SEQ ID NO: 19) 
                   
               
               
                 ATGATGTCAGGAGAACACACGTTAAAAGCGGTACGAGGCAGTTTTATTGATGTCACCCG 
                   
               
               
                   
               
               
                 TACGATCGATAACCCGGAAGAGATTGCCTCTGCGCTGCGGTTTATTGAGGATGGTTTATT 
               
               
                   
               
               
                 ACTCATTAAACAGGGAAAAGTGGAATGGTTTGGCGAATGGGAAAACGGAAAGCATCAA 
               
               
                   
               
               
                 ATTCCTGACACCATTCGCGTGCGCGACTATCGCGGCAAACTGATAGTACCGGGCTTTGTC 
               
               
                   
               
               
                 GATACACATATCCATTATCCGCAAAGTGAAATGGTGGGGGCCTATGGTGAGCAATTGCT 
               
               
                   
               
               
                 GGAGTGGTTGAATAAACACACCTTCCCTACTGAACGTCGTTATGAGGATTTAGAGTACGC 
               
               
                   
               
               
                 CCGCGAAATGTCGGCGTTCTTCATCAAGCAGCTTTTACGTAACGGAACCACCACGGCGCT 
               
               
                   
               
               
                 GGTGTTTGGCACTGTTCATCCGCAATCTGTTGATGCGCTGTTTGAAGCCGCCAGTCATATC 
               
               
                   
               
               
                 AATATGCGTATGATTGCCGGTAAGGTGATGATGGACCGCAACGCACCGGATTATCTGCTC 
               
               
                   
               
               
                 GACACTGCCGAAAGCAGCTATCACCAAAGCAAAGAACTGATCGAACGCTGGCACAAAA 
               
               
                   
               
               
                 ATGGTCGTCTGCTATATGCGATTACGCCACGCTTCGCCCCGACCTCATCTCCTGAACAGA 
               
               
                   
               
               
                 TGGCGATGGCGCAACGCCTGAAAGAAGAATATCCGGATACGTGGGTACATACCCATCTC 
               
               
                   
               
               
                 TGTGAAAACAAAGATGAAATTGCCTGGGTGAAATCGCTTTATCCTGACCATGATGGTTAT 
               
               
                   
               
               
                 CTGGATGTTTACCATCAGTACGGCCTGACCGGTAAAAACTGTGTCTTTGCTCACTGCGTC 
               
               
                   
               
               
                 CATCTCGAAGAAAAAGAGTGGGATCGTCTCAGCGAAACCAAATCCAGCATTGCTTTCTGT 
               
               
                   
               
               
                 CCGACCTCCAACCTTTACCTCGGCAGCGGCTTATTCAACTTGAAAAAAGCATGGCAGAAG 
               
               
                   
               
               
                 AAAGTTAAAGTGGGCATGGGAACGGATATCGGTGCCGGAACCACTTTCAACATGCTGCA 
               
               
                   
               
               
                 AACGCTGAACGAAGCCTACAAAGTATTGCAATTACAAGGCTATCGCCTCTCGGCATATG 
               
               
                   
               
               
                 AAGCGTTTTACCTGGCCACGCTCGGCGGAGCGAAATCTCTGGGCCTTGACGATTTGATTG 
               
               
                   
               
               
                 GCAACTTTTTACCTGGCAAAGAGGCTGATTTCGTGGTGATGGAACCCACCGCCACTCCGC 
               
               
                   
               
               
                 TACAGCAGCTGCGCTATGACAACTCTGTTTCTTTAGTCGACAAATTGTTCGTGATGATGA 
               
               
                   
               
               
                 CGTTGGGCGATGACCGTTCGATCTACCGCACCTACGTTGATGGTCGTCTGGTGTACGAAC 
               
               
                   
               
               
                 GCAACTAA 
               
               
                   
               
               
                 Polypeptide sequence encoded by the polynucleotide of SEQ ID NO: 19:  
               
               
                 (SEQ ID NO: 20) 
                   
               
               
                 MMSGEHTLKAVRGSFIDVTRTIDNPEEIASALRFIEDGLLLIKQGKVEWFGEWENGKHQIPDTI 
                   
               
               
                   
               
               
                 RVRDYRGKLIVPGFVDTHIHYPQSEMVGAYGEQLLEWLNKHTFPTERRYEDLEYAREMSAF 
               
               
                   
               
               
                 FIKQLLRNGTTTALVFGTVHPQSVDALFEAASHINMRMIAGKVMMDRNAPDYLLDTAESSY 
               
               
                   
               
               
                 HQSKELIERWHKNGRLLYAITPRFAPTSSPEQMAMAQRLKEEYPDTWVHTHLCENKDEIAW 
               
               
                   
               
               
                 VKSLYPDHDGYLDVYHQYGLTGKNCVFAHCVHLEEKEWDRLSETKSSIAFCPTSNLYLGSG 
               
               
                   
               
               
                 LFNLKKAWQKKVKVGMGTDIGAGTTFNMLQTLNEAYKVLQLQGYRLSAYEAFYLATLGGA 
               
               
                   
               
               
                 KSLGLDDLIGNFLPGKEADFVVMEPTATPLQQLRYDNSVSLVDKLFVMMTLGDDRSIYRTYV 
               
               
                   
               
               
                 DGRLVYERN 
               
               
                   
               
               
                 GDA_11:  
               
               
                 (SEQ ID NO: 21) 
                   
               
               
                 ATGATGTCAGGAGAACACACGTTAAAAGCGGTACGAGGCAGTTTTATTGATGTCACCCG  
                   
               
               
                   
               
               
                 TACGGTCGATAACCCGGAAGAGATTGCCTCTGCGCTGCGGTTTATTGAGGATGGTTTATT  
               
               
                   
               
               
                 ACTCATTAAACAGGGAAAAGTGGAATGGTTTGGCGAATGGGAAAACGGAAAGCATCAA  
               
               
                   
               
               
                 ATTCCTGACACCATTCGCGTGCGCGACTATCGCGGCAAACTGATAGTACCGGGCTTTGTC  
               
               
                   
               
               
                 GATACACATATCCATTATCCGCAAAGTGAAATGGTGGGGGCCTATGGTGAGCAATTGCT  
               
               
                   
               
               
                 GGAGTGGTTGAATAAACACACCTTCCCTACTGAACGGCGTTATGAGGATTTAGAGTACGC  
               
               
                   
               
               
                 CCGCGAAATGTCGGCGTTCTTCATCAAGCAGCTTTTACGTAACGGAACCACCACGGCGCT  
               
               
                   
               
               
                 GGTGTTTGGCACTGTTCATCCGCAATCCGTTGATGCGCTGTTTGAAGCCGCCAGTCATAT  
               
               
                   
               
               
                 CAATATGCGTATGATTGCCGGTAAGGTGATGATGGACCGTAACGCACCGGATTATCTGCT  
               
               
                   
               
               
                 CGACACTGCCGAAAGCAGCTATCACCAAAGCAAAGAACTGATTGAACGCTGGCACAAAA  
               
               
                   
               
               
                 ATGGTCGTCTGCTATATGCGATTACGCCACGCTTCGCCCCGACCTCATCTCCTGAACAGA  
               
               
                   
               
               
                 TGGCGATGGCGCAACGCCTGAAAGAAGAATATCCGGATACGTGGGTACATACCCATCTC  
               
               
                   
               
               
                 AGTGAAAACAAAGATGAAATTGCCTGGGTGAAATCGCTTTATCCTGACCATGATGGTTAT  
               
               
                   
               
               
                 CTGGATGTTTACCATCAGTACGGCCTGACCGGTAAAAACTGTGTCTTTGCTCACTGCGTC  
               
               
                   
               
               
                 CATCTCGAAGAAAAAGAGTGGGATCGTCTCAGCGAAACCAAATCCAGCATTGCTTTCTGT  
               
               
                   
               
               
                 CCGACCTCCAACCTTTACCTCGGCAGCGGCTTATTCAACTTGAAAAAAGCATGGCAGAAG  
               
               
                   
               
               
                 AAAGTTAAAGTGGGCATGGGAACGGATATCGGTGCCGGAACCACTTTCAACATGCTGCA  
               
               
                   
               
               
                 AACGCTGAACGAAGCCTACAAAGTATTGCAATTACAAGGCTATCGCCTCTCGGCATATG  
               
               
                   
               
               
                 AAGCGTTTTACTTGGCCACGCTCGGCGGAGCGAAATCTCTGGGCCTTGACGATTTGATTG  
               
               
                   
               
               
                 GCAACTTTTTACCTGGCAAAGAGGCTGATTTCGTGGTGATGGAACCCACCGCCACTCCGC  
               
               
                   
               
               
                 TACAGCAGCTGCGCTATGACAACTCTGTTTCTTTAGTCGACAAATTGTTCGTGATGATGA  
               
               
                   
               
               
                 CGTTGGGCGATGACCGTTCGATCTACCGCACCTACGTTGATGGTCGTCTGGTGTACGAAC  
               
               
                   
               
               
                 GCAACTAA  
               
               
                   
               
               
                 Polypeptide sequence encoded by the polynucleotide of SEQ ID NO: 21:  
               
               
                 (SEQ ID NO: 22) 
                   
               
               
                 MMSGEHTLKAVRGSFIDVTRTVDNPEEIASALRFIEDGLLLIKQGKVEWFGEWENGKHQIPD  
                   
               
               
                   
               
               
                 TIRVRDYRGKLIVPGFVDTHIHYPQSEMVGAYGEQLLEWLNKHTFPTERRYEDLEYAREMSA  
               
               
                   
               
               
                 FFIKQLLRNGTTTALVFGTVHPQSVDALFEAASHINMRMIAGKVMMDRNAPDYLLDTAESSY  
               
               
                   
               
               
                 HQSKELIERWHKNGRLLYAITPRFAPTSSPEQMAMAQRLKEEYPDTWVHTHLSENKDEIAW  
               
               
                   
               
               
                 VKSLYPDHDGYLDVYHQYGLTGKNCVFAHCVHLEEKEWDRLSETKSSIAFCPTSNLYLGSG  
               
               
                   
               
               
                 LFNLKKAWQKKVKVGMGTDIGAGTTFNMLQTLNEAYKVLQLQGYRLSAYEAFYLATLGGA  
               
               
                   
               
               
                 KSLGLDDLIGNFLPGKEADFVVMEPTATPLQQLRYDNSVSLVDKLFVMMTLGDDRSIYRTYV  
               
               
                   
               
               
                 DGRLVYERN  
               
               
                   
               
               
                 MXMT_10:  
               
               
                 (SEQ ID NO: 23) 
                   
               
               
                 ATGGAGCTTCAAGAGGTACTGCACATGAACGAGGGCGAAGGAGATACGAGCTACGCGA 
                   
               
               
                   
               
               
                 AAAATGCGAGTTATAACCTGGCGCTCGCAAAAGTGAAACCTTTCCTGGAACAGTGTATA 
               
               
                   
               
               
                 CGCGAGTTGCTTCGCGCAAACCTGCCAAACATAAATAAATGCATTAAGGTAGCGGATTT 
               
               
                   
               
               
                 AGGCTGTGCCTCAGGCCCAAATACGCTGCTCACTGTTCGTGACATAGTACAGTCGATAGA 
               
               
                   
               
               
                 CAAAGTTGGCCAGGAGGAGAAAAACGAATTAGAACGGCCAACGATACAAATTTTTCTGA 
               
               
                   
               
               
                 ACGACCTGTTCCAAAACGATTTTAATTCCGTCTTTAAGCTGCTTCCGTCTTTCTATCGGAA 
               
               
                   
               
               
                 ACTCGAGAAGGAAAATGGTCGTAAAATCGGTAGTTGTCTGATTAGTGCGATGCCCGGCT 
               
               
                   
               
               
                 CGTTCTATGGTAGACTTTTTCCGGAAGAGTCCATGCATTTTCTGCATTCTTGTTACAGTGT 
               
               
                   
               
               
                 GCACTGGCTGAGTCAGGTTCCTTCGGGGTTAGTGATCGAACTTGGTATCGGCGCGAACAA 
               
               
                   
               
               
                 AGGAAGTATCTACAGCTCCAAAGGATGCCGTCCACCGGTCCAGAAGGCCTATTTGGACC 
               
               
                   
               
               
                 AGTTTACAAAGGACTTCACCACCTTCCTGCGCATACATAGTAAAGAACTGTTTTCTCGTG 
               
               
                   
               
               
                 GCCGCATGCTCTTAACTTGTATTTGCAAGGTTGATGAGTTTGATGAACCTAACCCTCTGG 
               
               
                   
               
               
                 ACCTTCTTGACATGGCAATCAATGACCTTATTGTCGAAGGCTTGCTTGAGGAGGAGAAAT 
               
               
                   
               
               
                 TAGACTCATTCAATATTCCGTTTTTCACGCCATCCGCCGAAGAAGTAAAGTGTATCGTAG 
               
               
                   
               
               
                 AAGAAGAAGGGAGCTGTGAGATCCTCTATCTCGAGACATTCAAGGCCCACTATGATGCA 
               
               
                   
               
               
                 GCGTTCTCCATAGACGACGATTACCCTGTTCGGTCACACGAACAAATCAAAGCCGAATAT 
               
               
                   
               
               
                 GTGGCCAGTCTGATCAGATCTGTCTATGAACCTATCCTCGCCTCCCACTTTGGCGAAGCA 
               
               
                   
               
               
                 ATAATGCCCGACCTGTTTCACCGCCTTGCTAAGCACGCTGCCAAAGTTTTGCACATGGGG 
               
               
                   
               
               
                 AAGGGGTGTTACAACAACTTGATCATTTCACTTGCCAAGAAACCGGAGAAGTCTGATGT 
               
               
                   
               
               
                 GTAA 
               
               
                   
               
               
                 Polypeptide sequence encoded by the polynucleotide of SEQ ID NO: 23:  
               
               
                 (SEQ ID NO: 24) 
                   
               
               
                 MELQEVLHMNEGEGDTSYAKNASYNLALAKVKPFLEQCIRELLRANLPNINKCIKVADLGC 
                   
               
               
                   
               
               
                 ASGPNTLLTVRDIVQSIDKVGQEEKNELERPTIQIFLNDLFQNDFNSVFKLLPSFYRKLEKENG 
               
               
                   
               
               
                 RKIGSCLISAMPGSFYGRLFPEESMHFLHSCYSVHWLSQVPSGLVIELGIGANKGSIYSSKGCR 
               
               
                   
               
               
                 PPVQKAYLDQFTKDFTTFLRIHSKELFSRGRMLLTCICKVDEFDEPNPLDLLDMAINDLIVEGL 
               
               
                   
               
               
                 LEEEKLDSFNIPFFTPSAEEVKCIVEEEGSCEILYLETFKAHYDAAFSIDDDYPVRSHEQIKAEY 
               
               
                   
               
               
                 VASLIRSVYEPILASHFGEAIMPDLFHRLAKHAAKVLHMGKGCYNNLIISLAKKPEKSDV 
               
               
                   
               
               
                 MXMT_11:  
               
               
                 (SEQ ID NO: 25) 
                   
               
               
                 ATGGAACTGCAGGCCGTTTTACACATGAATGGAGGGGAAGGAGACACGAGCTATGCTAA 
                   
               
               
                   
               
               
                 AAATTCTTCATATAACCTGGCGTTGGCGAAAGTAAAACCAGTGTTAGAACAATGCATTCG 
               
               
                   
               
               
                 TGAACTGTTACGGGCGAATCTTCCAAATATTAACAATTGTATAAAAGTAGCGGACCTTGG 
               
               
                   
               
               
                 CTGCGCAAGTGGACCGAACACGTTATTAACTGTTAGAGATATCGTACAAAGTATTGACA 
               
               
                   
               
               
                 AGGTTGGCCAGGAGGAGAAAAATGAACTGGAGCGGCCGACTATACAGATATTCCTGAAT 
               
               
                   
               
               
                 GATTTATTTCAGAACGATTTCAATAGCGTTTTCAAGCTGCTTCCTTCGTTTTACCGTAAAC 
               
               
                   
               
               
                 TTGAGAAAGAAAATGGACGGAAAATTGGGTCATGTTTAATTTCCGCAATGCCCGGCAGT 
               
               
                   
               
               
                 TTCTATGGGCGCTTGTTTCCGGAAGAAAGCATGCATTTTATTCACTCATGCTATTCGTTCC 
               
               
                   
               
               
                 ACTGGCTGTCACAAGTGCCAAGTGGACTCGTTATTGAACTGGGGATCTCAGCCAACAAA 
               
               
                   
               
               
                 GGCAGTATATATTCCTCAAAGGCCTCAAGACCGCCTGTGCAAAAAGCTTACTTAGACCAG 
               
               
                   
               
               
                 TTCACAAAGGATTTTACAACGTTCCTTCGCATTCACAGCAAGGAATTGTTCTCACGCGGA 
               
               
                   
               
               
                 CGGATGCTTCTTACATGTATCTGCAAAGTGGATGAGTATGACGAACCAAACCCTCTTGAC 
               
               
                   
               
               
                 TTGTTAGACATGGCGATAAACGATCTCATTGTGGAAGGTCATCTCGAGGAAGAAAAGTT 
               
               
                   
               
               
                 AGCTTCTTTTAACCTGCCATTTTTCACACCATCGGCCGAGGAGGTTAAGTGCATCGTTGA 
               
               
                   
               
               
                 GGAAGAGGGTTCTTTCGAGATCCTCTATCTCGAGACATTTAAAGCGCATTATGATGCGGG 
               
               
                   
               
               
                 GTTTAGCATAGATGATGATTACCCAGTCCGGTCCCATTTTCAAGTATATGGCGATGAACA 
               
               
                   
               
               
                 TATTAAAGCAGAGTATGTCGCATCTCTGATCCGCTCCGTTTATGAGCCGATTCTTGCAAG 
               
               
                   
               
               
                 TCATTTTGGTGAGGCTATCATGCCAGACTTGTTTCACCGGTTAGCCAAACACGCTGCTAA 
               
               
                   
               
               
                 GGTACTCCATCTGGGTAAGGGTTGTTATAACAATCTCATAATTTCTCTTGCGAAGAAGCC 
               
               
                   
               
               
                 AGAAAAATCAGACATGTAA 
               
               
                   
               
               
                 Polypeptide sequence encoded by the polynucleotide of SEQ ID NO: 25:  
               
               
                 (SEQ ID NO: 26) 
                   
               
               
                 MELQAVLHMNGGEGDTSYAKNSSYNLALAKVKPVLEQCIRELLRANLPNINNCIKVADLGC 
                   
               
               
                   
               
               
                 ASGPNTLLTVRDIVQSIDKVGQEEKNELERPTIQIFLNDLFQNDFNSVFKLLPSFYRKLEKENG 
               
               
                   
               
               
                 RKIGSCLISAMPGSFYGRLFPEESMHFIHSCYSFHWLSQVPSGLVIELGISANKGSIYSSKASRP 
               
               
                   
               
               
                 PVQKAYLDQFTKDFTTFLRIHSKELFSRGRMLLTCICKVDEYDEPNPLDLLDMAINDLIVEGH 
               
               
                   
               
               
                 LEEEKLASFNLPFFTPSAEEVKCIVEEEGSFEILYLETFKAHYDAGFSIDDDYPVRSHFQVYGD 
               
               
                   
               
               
                 EHIKAEYVASLIRSVYEPILASHFGEAIMPDLFHRLAKHAAKVLHLGKGCYNNLIISLAKKPEK 
               
               
                   
               
               
                 SDM 
               
               
                   
               
               
                 XMT_12:  
               
               
                 (SEQ ID NO: 27) 
                   
               
               
                 ATGGAATTGCAAGAAGTTCTGCGTATGAACGGTGGCGAAGGTGACACTAGCTACGCTAA 
                   
               
               
                   
               
               
                 AAATAGTGCTTATAACCAACTGGTACTCGCAAAAGTTAAACCGGTTTTGGAGCAGTGTGT 
               
               
                   
               
               
                 TCGTGAACTGCTGAGAGCAAACTTACCGAACATAAATAAATGCATCAAAGTTGCCGATTT 
               
               
                   
               
               
                 GGGCTGTGCAAGCGGCCCTAATACCCTTTTAACCGTTCGGGATATCGTGCAGTCAATCGA 
               
               
                   
               
               
                 TAAAGTAGGTCAAGAGAAAAAGAATGAATTAGAGCGCCCAACTATCCAGATCTTTCTTA 
               
               
                   
               
               
                 ACGACCTGTTTCCCAACGACTTCAATAGCGTTTTTAAACTCTTGCCTTCTTTTTATCGGAA 
               
               
                   
               
               
                 ATTAGAGAAGGAAAATGGGCGTAAGATCGGTTCCTGCCTTATCGGTGCGATGCCAGGTT 
               
               
                   
               
               
                 CATTTTACTCCCGTTTATTTCCGGAAGAAAGTATGCATTTTCTCCACTCTTGCTATTGTCTT 
               
               
                   
               
               
                 CAGTGGTTATCTCAGGTCCCTAGTGGATTGGTAACAGAATTAGGGATTAGCACTAACAAG 
               
               
                   
               
               
                 GGCTCCATTTATAGTTCGAAAGCCTCACGTCTGCCTGTACAAAAGGCATATCTTGATCAG 
               
               
                   
               
               
                 TTTACGAAAGACTTTACTACCTTCCTGAGAATCCATTCAGAGGAGTTGTTTTCGCATGGG 
               
               
                   
               
               
                 CGGATGCTTCTTACATGTATATGCAAAGGAGTTGAATTAGACGCAAGAAATGCTATCGAT 
               
               
                   
               
               
                 CTGTTAGAGATGGCAATTAACGACTTAGTAGTCGAGGGTCATCTTGAAGAGGAAAAACT 
               
               
                   
               
               
                 TGACTCTTTTAACCTGCCGGTCTATATTCCTTCAGCCGAGGAAGTTAAATGCATTGTAGA 
               
               
                   
               
               
                 AGAAGAGGGGTCCTTTGAGATACTCTATCTTGAGACTTTTAAGGTCTTATACGACGCGGG 
               
               
                   
               
               
                 GTTCTCAATCGACGATGAGCACATCAAAGCAGAATATGTTGCCTCTTCGGTGCGGGCGGT 
               
               
                   
               
               
                 ATATGAACCGATATTAGCCAGTCATTTCGGAGAAGCGATTATACCGGATATCTTTCATCG 
               
               
                   
               
               
                 TTTTGCTAAGCATGCCGCTAAAGTACTCCCTTTGGGGAAAGGATTTTATAACAATCTGAT 
               
               
                   
               
               
                 CATTTCACTTGCCAAGAAACCCGAGAAATCTGATGTGTAA 
               
               
                   
               
               
                 Polypeptide sequence encoded by the polynucleotide of SEQ ID NO: 27:  
               
               
                 (SEQ ID NO: 28) 
                   
               
               
                 MELQEVLRMNGGEGDTSYAKNSAYNQLVLAKVKPVLEQCVRELLRANLPNINKCIKVADLG 
                   
               
               
                   
               
               
                 CASGPNTLLTVRDIVQSIDKVGQEKKNELERPTIQIFLNDLFPNDFNSVFKLLPSFYRKLEKEN 
               
               
                   
               
               
                 GRKIGSCLIGAMPGSFYSRLFPEESMHFLHSCYCLQWLSQVPSGLVTELGISTNKGSIYSSKAS 
               
               
                   
               
               
                 RLPVQKAYLDQFTKDFTTFLRIHSEELFSHGRMLLTCICKGVELDARNAIDLLEMAINDLVVE 
               
               
                   
               
               
                 GHLEEEKLDSFNLPVYIPSAEEVKCIVEEEGSFEILYLETFKVLYDAGFSIDDEHIKAEYVASSV 
               
               
                   
               
               
                 RAVYEPILASHFGEAIIPDIFHRFAKHAAKVLPLGKGFYNNLIISLAKKPEKSDV 
               
               
                   
               
               
                 XMT_13:  
               
               
                 (SEQ ID NO: 29) 
                   
               
               
                 ATGGAATTGCAAGAGGTGTTGCGCATGAACGGAGGGGAAGGGGATACTAGTTATGCAAA 
                   
               
               
                   
               
               
                 GAATTCCGCCTATAATCAGTTGGTACTGGCCAAGGTCAAACCCGTATTAGAGCAATGCGT 
               
               
                   
               
               
                 GCGGGAGTTATTACGTGCGAATCTGCCAAACATCAATAAATGTATAAAAGTTGCAGACTT 
               
               
                   
               
               
                 GGGTTGTGCCAGTGGGCCTAACACACTTCTGACGGTAAGAGACATCGTTCAGTCCATCGA 
               
               
                   
               
               
                 TAAAGTCGGACAAGAGAAGAAAAACGAATTAGAGCGCCCGACGATCCAAATTTTCCTTA 
               
               
                   
               
               
                 ATGATCTGTTCCCCAACGACTTCAACTCGGTCTTCAAACTTCTGCCCTCGTTTTATCGCAA 
               
               
                   
               
               
                 GTTGGAAAAGGAGAATGGTCGCAAAATTGGTTCGTGTTTAATCGGCGCGATGCCGGGTA 
               
               
                   
               
               
                 GTTTTTATTCGCGCTTGTTTCCAGAAGAATCAATGCATTTCTTACACTCGTGTTACTGCTT 
               
               
                   
               
               
                 ACAGTGGTTGTCACAGGTCCCTTCAGGATTGGTAACTGAACTGGGGATTAGCACAAACA 
               
               
                   
               
               
                 AAGGGTCAATATATTCAAGTAAAGCTAGTAGACTGCCCGTGCAAAAGGCATATCTGGAT 
               
               
                   
               
               
                 CAGTTCACAAAAGATTTTACTACCTTTCTGCGTATCCATAGTGAAGAGCTGTTCTCGCAT 
               
               
                   
               
               
                 GGTCGGATGTTATTAACCTGTATATGTAAGGGTGTTGAACTCGATGCACGGAATGCCATC 
               
               
                   
               
               
                 GACCTGCTTGAAATGGCGATTAATGATCTGGTGGTGGAGGGACACCTCGAAGAAGAAAA 
               
               
                   
               
               
                 GCTGGACTCGTTCAACCTCCCAGTTTATATACCGAGTGCTGAAGAAGTTAAGTGCATCGT 
               
               
                   
               
               
                 GGAAGAAGAGGGTAGCTTTGAAATCCTGTACCTTGAAACGTTCAAAGTGCTGTACGACG 
               
               
                   
               
               
                 CAGGATTTTCAATTGATGATGACTATCCCGTGCGCTCACATTTTCAAGTATATGGAGATG 
               
               
                   
               
               
                 AACACATCAAAGCAGAATATGTAGCGAGTTTAATCCGTAGTGTCTATGAGCCAATCTTAG 
               
               
                   
               
               
                 CAAGTCATTTCGGTGAGGCGATTATGCCAGACTTGTTTCATCGCCTGGCTAAACACGCCG 
               
               
                   
               
               
                 CTAAAGTTCTCCACCTTGGAAAAGGGTTCTATAATAATCTGATAATCTCTCTTGCCAAAA 
               
               
                   
               
               
                 AGCCCGAAAAATCCGATGTCTAA 
               
               
                   
               
               
                 Polypeptide sequence encoded by the polynucleotide of SEQ ID NO: 29:  
               
               
                 (SEQ ID NO: 30) 
                   
               
               
                 MELQEVLRMNGGEGDTSYAKNSAYNQLVLAKVKPVLEQCVRELLRANLPNINKCIKVADLG 
                   
               
               
                   
               
               
                 CASGPNTLLTVRDIVQSIDKVGQEKKNELERPTIQIFLNDLFPNDFNSVFKLLPSFYRKLEKEN 
               
               
                   
               
               
                 GRKIGSCLIGAMPGSFYSRLFPEESMHFLHSCYCLQWLSQVPSGLVTELGISTNKGSIYSSKAS 
               
               
                   
               
               
                 RLPVQKAYLDQFTKDFTTFLRIHSEELFSHGRMLLTCICKGVELDARNAIDLLEMAINDLVVE 
               
               
                   
               
               
                 GHLEEEKLDSFNLPVYIPSAEEVKCIVEEEGSFEILYLETFKVLYDAGFSIDDDYPVRSHFQVY 
               
               
                   
               
               
                 GDEHIKAEYVASLIRSVYEPILASHFGEAIMPDLFHRLAKHAAKVLHLGKGFYNNLIISLAKKP 
               
               
                   
               
               
                 EKSDV  
               
               
                   
               
               
                 MXMT_14:  
               
               
                 (SEQ ID NO: 31) 
                   
               
               
                 ATGGAACTCCAGGAAGTTCTTCGGATGAATGGTGGCGAAGGCGACACAAGCTATGCCAA 
                   
               
               
                   
               
               
                 AAATTCGTCATATAATCTTGCCCTGGCGAAAGTAAAACCCGTTTTGGAACAGTGTATCCG 
               
               
                   
               
               
                 GGAATTATTACGTGCTAACCTGCCCAACATTAATAATTGCATTAAAGTAGCTGATCTCGG 
               
               
                   
               
               
                 TTGCGCATCGGGACCGAATACGTTACTTACTGTCAGAGACATCGTTCAGTCGATTGACAA 
               
               
                   
               
               
                 ACTTGGGCTGGAGGAAAAGAATGAGCTGGAACGCCCGACAATACAGATATTTCTGAACG 
               
               
                   
               
               
                 ATCTGTTTCAGAACGACTTTAACTCTGTCTTTAAGCTGTTACCCAGTTTCTACCGCAAATT 
               
               
                   
               
               
                 GGAAAAAGAAAACGGCCGTAAGATTGGCTCCTGCCTCATTTCCGCTATGCCGGGTTCATT 
               
               
                   
               
               
                 CTATGGTAGATTGTTCCCCGAGGAATCAATGCACTTCCTGCATTCATGTTACTGCCTGCAC 
               
               
                   
               
               
                 TGGTTGTCCCAGGTTCCCTCGGGCCTTGTCACGGAACTGGGTATCTCAGCAAATAAGGGA 
               
               
                   
               
               
                 AGTATATACTCTTCAAAGGCCAGTCGCCTGCCGGTTAGAAAAGCGTATCTTGACCAATTC 
               
               
                   
               
               
                 ACTAAGGATTTCACCACTTTCTTGCGCATCCACTCAGAGGAGCTGTTTTCTCATGGAAGA 
               
               
                   
               
               
                 ATGCTGCTCACTTGCATTTGCAAAGGGGTAGAATTTGATGCCCGGAATGCCATAGATTTA 
               
               
                   
               
               
                 TTAGAAATGGCTATTAATGACCTGGTGGTGGAGGGTCACTTGGAAGAGGAAAAATTGGA 
               
               
                   
               
               
                 TAGCTTTAACCTGCCGGTGTATATTCCGTCAACAGAGGAGGTGAAGTGCATCGTAGAAG 
               
               
                   
               
               
                 AAGAAGGCAGTTTCGAGATTCTGTACCTGGAAACTTTCAAAGTTCTGTACGATGCAGGTT 
               
               
                   
               
               
                 TCTCAATTGACGATGATTATCCGCTCCGTAGTCATGTCCAGGTGTATTCAGATGAGCATA 
               
               
                   
               
               
                 TTAAGGCGGAATACGTTGCGTCATCGGTACGGGCAGTATATGAGCCTATCCTTGCATCAC 
               
               
                   
               
               
                 ACTTTGGTGAAGCTATCATTCCTGATATCTTTCATCGGTTCGCTAAACATGCGGCGAAAG 
               
               
                   
               
               
                 TGCTGCCTTTAGGTAAAGGCTTTTATAACAACCTTATCATCTCTCTGGCTAAAAAGCCTG 
               
               
                   
               
               
                 AAAAGTCCGACGTGAACCACTAA 
               
               
                   
               
               
                 Polypeptide sequence encoded by the polynucleotide of SEQ ID NO: 31:  
               
               
                 (SEQ ID NO: 32) 
                   
               
               
                 MELQEVLRMNGGEGDTSYAKNSSYNLALAKVKPVLEQCIRELLRANLPNINNCIKVADLGC 
                   
               
               
                   
               
               
                 ASGPNTLLTVRDIVQSIDKLGLEEKNELERPTIQIFLNDLFQNDFNSVFKLLPSFYRKLEKENG 
               
               
                   
               
               
                 RKIGSCLISAMPGSFYGRLFPEESMHFLHSCYCLHWLSQVPSGLVTELGISANKGSIYSSKASR 
               
               
                   
               
               
                 LPVRKAYLDQFTKDFTTFLRIHSEELFSHGRMLLTCICKGVEFDARNAIDLLEMAINDLVVEG 
               
               
                   
               
               
                 HLEEEKLDSFNLPVYIPSTEEVKCIVEEEGSFEILYLETFKVLYDAGFSIDDDYPLRSHVQVYSD 
               
               
                   
               
               
                 EHIKAEYVASSVRAVYEPILASHFGEAIIPDIFHRFAKHAAKVLPLGKGFYNNLIISLAKKPEKS 
               
               
                   
               
               
                 DVNH  
               
               
                   
               
               
                 DXMT_15:  
               
               
                 (SEQ ID NO: 33) 
                   
               
               
                 ATGGAACTTCAGGAAGTCCTTCACATGAATGAGGGAGAGGGAGATACCTCTTACGCCAA 
                   
               
               
                   
               
               
                 GAACGCTTCTTATAACCTGGCGTTGGCCAAAGTGAAGCCTTTCCTTGAACAGTGCATTAG 
               
               
                   
               
               
                 AGAATTACTGCGGGCCAATTTACCAAACATTAATAAGTACATCAAAGTGGCTGACTTAG 
               
               
                   
               
               
                 GTTGCGCGAGCGGTCCAAACACGCTCCTGACCGTGCGTGATATCGTACAATCAATAGATA 
               
               
                   
               
               
                 AAGTTGGACAGGAGGAGAAGAATGAACTGGAGCGGCCGACGATACAAATCTTTCTGAAT 
               
               
                   
               
               
                 GATCTCTTTCAAAACGATTTCAACTCGGTGTTTAAGCTGCTGCCAAGTTTCTATCGGAAA 
               
               
                   
               
               
                 CTTGAAAAGGAAAACGGGCGTAAAATTGGAAGTTGCCTGATTTCAGCCATGCCAGGTTC 
               
               
                   
               
               
                 TTTTTATGGCCGTTTATTCCCCGAGGAATCAATGCACTTTCTTCACAGTTGCTACTCAGTC 
               
               
                   
               
               
                 CATTGGCTGTCGCAGGTTCCTTCCGGCCTTGTAATCGAACTGGGTATTGGTGCAAATAAA 
               
               
                   
               
               
                 GGGAGCATCTACTCTTCAAAAGGGTGCCGTCCGCCTGTGCAAAAAGCTTATTTGGATCAA 
               
               
                   
               
               
                 TTTACGAAAGACTTCACTACGTTTTTGCGGATACATTCCGAAGAGCTGTTTTCTCACGGA 
               
               
                   
               
               
                 CGCATGCTCCTGACATGCATCTGCAAAGGTGTTGAGTTGGATGCCCGCAATGCCATCGAT 
               
               
                   
               
               
                 TTGCTTGAAATGGCAATTAATGACCTCGTAGTGGAAGGCCATCTGGAAGAGGAGAAGCT 
               
               
                   
               
               
                 TGACTCTTTCAACTTGCCTGTATACATACCATCTGCCGAAGAAGTAAAATGCATCGTGGA 
               
               
                   
               
               
                 GGAAGAAGGTTCTTTCGAGATCTTGTATCTTGAAACATTTAAGGTCTTGTATGATGCTGG 
               
               
                   
               
               
                 CTTTAGTATAGATGATGAGCACATCAAGGCGGAGTATGTCGCCTCTTCAGTTAGAGCCGT 
               
               
                   
               
               
                 TTATGAACCTATATTGGCGAGCCATTTCGGAGAGGCCATTATACCCGATATCTTCCATCG 
               
               
                   
               
               
                 GTTTGCCAAACATGCCGCAAAAGTTTTACCCCTTGGCAAAGGTTTCTACAACAACCTGAT 
               
               
                   
               
               
                 TATTTCGCTCGCGAAGAAACCCGAAAAATCTGATGTTTAA 
               
               
                   
               
               
                 Polypeptide sequence encoded by the polynucleotide of SEQ ID NO: 33:  
               
               
                 (SEQ ID NO: 34) 
                   
               
               
                 MELQEVLHMNEGEGDTSYAKNASYNLALAKVKPFLEQCIRELLRANLPNINKYIKVADLGC 
                   
               
               
                   
               
               
                 ASGPNTLLTVRDIVQSIDKVGQEEKNELERPTIQIFLNDLFQNDFNSVFKLLPSFYRKLEKENG 
               
               
                   
               
               
                 RKIGSCLISAMPGSFYGRLFPEESMHFLHSCYSVHWLSQVPSGLVIELGIGANKGSIYSSKGCR 
               
               
                   
               
               
                 PPVQKAYLDQFTKDFTTFLRIHSEELFSHGRMLLTCICKGVELDARNAIDLLEMAINDLVVEG 
               
               
                   
               
               
                 HLEEEKLDSFNLPVYIPSAEEVKCIVEEEGSFEILYLETFKVLYDAGFSIDDEHIKAEYVASSVR 
               
               
                   
               
               
                 AVYEPILASHFGEAIIPDIFHRFAKHAAKVLPLGKGFYNNLIISLAKKPEKSDV 
               
               
                   
               
               
                 DXMT_16:  
               
               
                 (SEQ ID NO: 35) 
                   
               
               
                 ATGGAACTCCAGGAGGTGCTGCAGATGAATGGCGGTGAAGGGGATACATCCTATGCCAA 
                   
               
               
                   
               
               
                 GAATTCGGCTTATAATCAGTTGGTGCTTGCTAAGGTGAAACCTGTCCTTGAGCAGTGCGT 
               
               
                   
               
               
                 CAGAGAACTCCTTCGCGCTAACCTTCCGAACATTAATAAATGCATTAAAGTCGCTGACTT 
               
               
                   
               
               
                 GGGCTGCGCGAGTGGACCCAATACCTTATTAACTGTTCGCGACATAGTCCAGTCCATAGA 
               
               
                   
               
               
                 CAAAGTGGGCCAGGAGAAGAAGAACGAACTGGAACGCCCGACTATTCAAATTTTTCTGA 
               
               
                   
               
               
                 ATGACCTTTTCCCGAACGATTTCAATAGCGTGTTTAAACTCTTGCCTTCGTTTTACAGAAA 
               
               
                   
               
               
                 ACTGGAAAAGGAAAATGGGCGTAAAATTGGGTCGTGCTTGATCGGAGCCATGCCTGGCT 
               
               
                   
               
               
                 CTTTTTATTCACGGCTGTTTCCGGAAGAATCTATGCATTTCTTACACAGCTGTTATTCAGT 
               
               
                   
               
               
                 GCATTGGCTGTCACAGGTCCCGAGTGGATTAGTGACAGAACTGGGCATCTCTGCAAACA 
               
               
                   
               
               
                 AGGGGTGTATCTATTCATCTAAAGCAAGCCGGCCCCCAGTACAGAAGACGTACCTTGAC 
               
               
                   
               
               
                 CAATTCACCAAAGACTTTACGACTTTCCTGCGTATTCACTCGGAAGAGCTGATTTCGCGC 
               
               
                   
               
               
                 GGAAGAATGTTGTTGACTTTTATCTGTAAGGAAGACGAATTCGGAAACCCTAATAGTATG 
               
               
                   
               
               
                 GACCTGTTAGAGATGTCAATAAATGACTTGGTGATCGAGGGTCATCTCGAAGAGGAAAA 
               
               
                   
               
               
                 GCTTGATTCCTTTAATGTCCCAGTTTATGCCGCCAGTGCAGAAGAAGTGAAGCGTATAGT 
               
               
                   
               
               
                 AGAGGAGGAAGGTTCCTTCGAGATTCTGTATTTGGAGACGTTTAAGGCCCCGTACGACGC 
               
               
                   
               
               
                 TGGCTTCTCTATCGATGACGACTATCAAGGTCGGAGTCACAGTCCGGTGTCATGTGATGA 
               
               
                   
               
               
                 GCATGCGAGAGCGGCTCATGTTGCGAGTGTTGTACGGAGCGTGTACGAGCCTATCCTGGC 
               
               
                   
               
               
                 AGGACACTTTGGTGAGGCAATCTTACCGGACCTCTCTCACAGAATCGAGAAAAATGCTG 
               
               
                   
               
               
                 CGAAAGTATTACGTTCTGGCAAAGGATTCTATGACTCGCTGATCATAAGTTTGGCTAAGA 
               
               
                   
               
               
                 AGCCGGAAAAATCTGACGTGTAA 
               
               
                   
               
               
                 Polypeptide sequence encoded by the polynucleotide of SEQ ID NO: 35:  
               
               
                 (SEQ ID NO: 36) 
                   
               
               
                 MELQEVLQMNGGEGDTSYAKNSAYNQLVLAKVKPVLEQCVRELLRANLPNINKCIKVADL 
                   
               
               
                   
               
               
                 GCASGPNTLLTVRDIVQSIDKVGQEKKNELERPTIQIFLNDLFPNDFNSVFKLLPSFYRKLEKE 
               
               
                   
               
               
                 NGRKIGSCLIGAMPGSFYSRLFPEESMHFLHSCYSVHWLSQVPSGLVTELGISANKGCIYSSKA 
               
               
                   
               
               
                 SRPPVQKTYLDQFTKDFTTFLRIHSEELISRGRMLLTFICKEDEFGNPNSMDLLEMSINDLVIEG 
               
               
                   
               
               
                 HLEEEKLDSFNVPVYAASAEEVKRIVEEEGSFEILYLETFKAPYDAGFSIDDDYQGRSHSPVSC 
               
               
                   
               
               
                 DEHARAAHVASVVRSVYEPILAGHFGEAILPDLSHRIEKNAAKVLRSGKGFYDSLIISLAKKPE 
               
               
                   
               
               
                 KSDV  
               
               
                   
               
               
                 DXMT_17:  
               
               
                 (SEQ ID NO: 37) 
                   
               
               
                 ATGGAACTGCAGGAAGTGTTGCACATGAACGGCGGCGAGGGCGATACCTCCTATGCTAA 
                   
               
               
                   
               
               
                 GAATTCAAGTTATAATCTGTTTCTGATTCGGGTTAAACCGGTACTGGAACAGTGCATACA 
               
               
                   
               
               
                 AGAATTGCTGCGTGCGAATTTACCTAACATAAATAAGTGTTTTAAAGTGGGTGATCTTGG 
               
               
                   
               
               
                 GTGTGCGTCAGGACCGAACACTTTTTCTACCGTTCGGGACATCGTGCAGTCAATCGATAA 
               
               
                   
               
               
                 AGTCGGTCAGGAGAAAAAGAACGAGTTGGAACGTCCAACGATACAAATCTTCCTCAATG 
               
               
                   
               
               
                 ACCTTTTCCAGAACGACTTTAACTCGGTTTTTAAGTTACTGCCCTCCTTCTATCGTAATCT 
               
               
                   
               
               
                 GGAAAAAGAGAATGGCCGGAAAATTGGTTCATGTCTGATTGGTGCGATGCCGGGCTCAT 
               
               
                   
               
               
                 TTTATTCACGTTTGTTTCCAGAGGAAAGCATGCATTTTCTCCATTCCTGTTACTGCCTCCA 
               
               
                   
               
               
                 TTGGTTGAGCCAGGTTCCTTCTGGCCTTGTCACAGAACTCGGTATTTCTGTGAATAAAGG 
               
               
                   
               
               
                 CTGTATTTATTCCTCGAAGGCCTCCAGACCACCTATCCAGAAAGCGTATTTAGATCAGTT 
               
               
                   
               
               
                 TACAAAGGATTTTACCACGTTTCTGAGAATTCACTCTGAAGAGCTCATATCACGCGGTAG 
               
               
                   
               
               
                 AATGCTGTTAACGTTCATTTGTAAAGAAGATGAGTTCGACCACCCAAATTCAATGGATCT 
               
               
                   
               
               
                 GCTGGAGATGTCTATAAATGATCTGGTTGTCGAGGGTCATTTAGAAGAGGAAAAACTGG 
               
               
                   
               
               
                 ATTCCTTTAACGTCCCCATTTATGCTCCCAGCACGGAAGAGGTGAAACGCATCGTTGAAG 
               
               
                   
               
               
                 AAGAAGGGTCATTTGAAATCTTATATTTAGAAACGTTTTATGCACCTTATGATGCGGGCT 
               
               
                   
               
               
                 TTTCCATCGATGACGACTATCAAGGTCGCTCCCACAGTCCAGTCAGTTGCGATGAGCATG 
               
               
                   
               
               
                 CTCGGGCTGCACATGTTGCTTCAGTTGTGCGCTCTATTTACGAACCAATTCTTGCATCACA 
               
               
                   
               
               
                 TTTCGGAGAGGCTATTCTTCCGGACCTTTCTCACCGCATTGCGAAAAACGCAGCAAAAGT 
               
               
                   
               
               
                 CTTACGCTCGGGTAAGGGGTTTTATGATTCCGTTATAATCAGTCTCGCAAAGAAGCCTGA 
               
               
                   
               
               
                 AAAAGCTGATATGTAA 
               
               
                   
               
               
                 Polypeptide sequence encoded by the polynucleotide of SEQ ID NO: 37:  
               
               
                 (SEQ ID NO: 38) 
                   
               
               
                 MELQEVLHMNGGEGDTSYAKNSSYNLFLIRVKPVLEQCIQELLRANLPNINKCFKVGDLGCA 
                   
               
               
                   
               
               
                 SGPNTFSTVRDIVQSIDKVGQEKKNELERPTIQIFLNDLFQNDFNSVFKLLPSFYRNLEKENGR 
               
               
                   
               
               
                 KIGSCLIGAMPGSFYSRLFPEESMHFLHSCYCLHWLSQVPSGLVTELGISVNKGCIYSSKASRP 
               
               
                   
               
               
                 PIQKAYLDQFTKDFTTFLRIHSEELISRGRMLLTFICKEDEFDHPNSMDLLEMSINDLVVEGHL 
               
               
                   
               
               
                 EEEKLDSFNVPIYAPSTEEVKRIVEEEGSFEILYLETFYAPYDAGFSIDDDYQGRSHSPVSCDEH 
               
               
                   
               
               
                 ARAAHVASVVRSIYEPILASHFGEAILPDLSHRIAKNAAKVLRSGKGFYDSVIISLAKKPEKADM 
               
               
                   
               
               
                 DXMT_18:  
               
               
                 (SEQ ID NO: 39) 
                   
               
               
                 ATGGAACTGCAGGAGGTCCTGCACATGAATGGTGGTGAGGGTGATACCTCGTACGCCAA 
                   
               
               
                   
               
               
                 AAATAGTTTTTATAACCTTTTTCTGATTCGTGTCAAACCCATACTCGAGCAGTGTATACAA 
               
               
                   
               
               
                 GAATTACTGCGCGCTAACTTGCCGAATATCAACAAGTGCATAAAAGTTGCCGACCTGGGT 
               
               
                   
               
               
                 TGCGCTTCAGGGCCTAATACGTTGTTGACAGTGCGTGATATTGTTCAGTCTATTGATAAG 
               
               
                   
               
               
                 GTCGGACAAGAGAAGAAAAATGAACTGGAACGCCCTACAATCCAGATATTTCTGAATGA 
               
               
                   
               
               
                 TCTGTTTCAGAACGACTTTAATAGTGTGTTTAAAAGCCTTCCGTCATTCTACCGCAAGCTG 
               
               
                   
               
               
                 GAGAAAGAAAATGGGTGTAAGATTGGCAGTTGTTTGATAGGTGCGATGCCAGGAAGCTT 
               
               
                   
               
               
                 TTACGGCCGGCTGTTTCCCGAGGAAAGCATGCACTTCTTACACAGTTGTTATTGTTTGCAT 
               
               
                   
               
               
                 TGGCTGTCCCAGGTGCCTAGTGGGTTAGTAACCGAGCTCGGGATCAGTGCCAATAAAGG 
               
               
                   
               
               
                 CTGTATCTACTCTAGCAAAGCGAGCCGGCCTCCAATCCAAAAAGCGTACCTGGATCAGTT 
               
               
                   
               
               
                 TACTAAGGACTTTACGACATTCCTGCGTATCCATAGCGAAGAATTAATCTCGCGCGGTCG 
               
               
                   
               
               
                 CATGCTGCTGACCTGGATCTGTAAGGAAGATGAGTTCGAAAACCCAAATAGTATAGATC 
               
               
                   
               
               
                 TCCTCGAGATGAGCATTAACGATCTCGTGATAGAGGGTCACTTAGAGGAGGAAAAACTG 
               
               
                   
               
               
                 GACAGTTTCAATGTCCCAATCTATGCGCCATCCACGGAGGAAGTCAAGTGCATAGTGGA 
               
               
                   
               
               
                 AGAAGAAGGCTCCTTTGAGATTCTTTATCTTGAGACTTTCAAAGTACCGTATGACGCGGG 
               
               
                   
               
               
                 ATTTAGCATCGATGATGATTACCAAGGAAGATCTCACTCTCCAGTTTCATGCGATGAACA 
               
               
                   
               
               
                 CGCAAGAGCGGCGCATGTAGCCAGCGTTGTCCGTTCTATATTTGAGCCAATTGTGGCGTC 
               
               
                   
               
               
                 CCACTTTGGCGAGGCTATCCTGCCTGATCTGAGCCATCGGATAGCCAAGAATGCGGCTAA 
               
               
                   
               
               
                 AGTTTTACGTTCTGGTAAAGGGTTCTATGATTCAGTCATCATCTCGCTGGCTAAAAAGCC 
               
               
                   
               
               
                 TGAGAAGGCAGATATGTAA 
               
               
                   
               
               
                 Polypeptide sequence encoded by the polynucleotide of SEQ ID NO: 39:  
               
               
                 (SEQ ID NO: 40) 
                   
               
               
                 MELQEVLHMNGGEGDTSYAKNSFYNLFLIRVKPILEQCIQELLRANLPNINKCIKVADLGCAS 
                   
               
               
                   
               
               
                 GPNTLLTVRDIVQSIDKVGQEKKNELERPTIQIFLNDLFQNDFNSVFKSLPSFYRKLEKENGCK 
               
               
                   
               
               
                 IGSCLIGAMPGSFYGRLFPEESMHFLHSCYCLHWLSQVPSGLVTELGISANKGCIYSSKASRPPI 
               
               
                   
               
               
                 QKAYLDQFTKDFTTFLRIHSEELISRGRMLLTWICKEDEFENPNSIDLLEMSINDLVIEGHLEEE 
               
               
                   
               
               
                 KLDSFNVPIYAPSTEEVKCIVEEEGSFEILYLETFKVPYDAGFSIDDDYQGRSHSPVSCDEHAR 
               
               
                   
               
               
                 AAHVASVVRSIFEPIVASHFGEAILPDLSHRIAKNAAKVLRSGKGFYDSVIISLAKKPEKADM 
               
               
                   
               
               
                 DXMT_19:  
               
               
                 (SEQ ID NO: 41) 
                   
               
               
                 ATGGAATTGCAAGAGGTTTTACGCATGAATGGCGGTGAAGGCGACACTAGCTATGCTAA 
                   
               
               
                   
               
               
                 AAATTCGTCATACAACCTGTTTCTGATTCGGGTCAAACCGGTACTTGAACAATGCATTCA 
               
               
                   
               
               
                 AGGGTTACTCAGAGCCAACCTGCCTAACATTAACAAATGCATTAAAGTAGCCGATTTAG 
               
               
                   
               
               
                 GATGCGCAAGTGGAAGCAATACATTAAGTACGGTCAGAGATATAGTGCAATCTATAGAC 
               
               
                   
               
               
                 AAGGTTGGACAAGAAAAGAAGAATGAATTGGAAAGACCAACAATTCAAGTCTTTCTGAA 
               
               
                   
               
               
                 CGACTTGTTTCAGAACGACTTTAATTCCGTGTTTAAGCTGTTGCCGTCCTTTTATCGGAAA 
               
               
                   
               
               
                 CTGGAAAAGGAAAATGGCCGGAAAATTGGAAGTTGCTTGATTGGGGCCATGCCTGGTTC 
               
               
                   
               
               
                 CTTCTATGGTCGGCTGTTCCCAGAGGAAAGTATGCACTTTCTTCACTCCTGTTATTGCCTG 
               
               
                   
               
               
                 CATTGGCTCTCTCAGGTACCATCAGGCCTGGTTACAGAGTTGGGAATTTCAGCAAATAAG 
               
               
                   
               
               
                 GGGTGCATTTATTCGTCCAAAGCCAGCAGACCGCCGATCAAAAAGGCCTATCTTGACCA 
               
               
                   
               
               
                 ATTCACGAAGGACTTCACTACGTTTTTACGGGTTCACAGCGAAGAATTGATAAGTCGTGG 
               
               
                   
               
               
                 AAGAATGTTGTTGACTTGGATCTGTAAAGAAGACGAGTTTGAAAACCCAAATTCAATTG 
               
               
                   
               
               
                 ATCTGCTGGAGATGTCGCTTAATGATCTGGTTATTGAGGGCCATCTCGAGGAAGAAAAAC 
               
               
                   
               
               
                 TGGATTCCTTTAACGTACCGATATTCGCCCCGTCCACGGAAGAGGTCAAATGTATAGTAG 
               
               
                   
               
               
                 AAGAAGAAGGGTCATTTGAGATACTTTACTTAGAGACATTCAAAACACCATACGACGCA 
               
               
                   
               
               
                 GGGTTTTCAATCGACGATGATTATCAGGGTAGAAGCCATTCGCCGGTTTCATGTGACGAA 
               
               
                   
               
               
                 CATGCGATTGCAGAACATGTCGCCGCAGTGGTGAGATCGATTTACGAGCCTATATTAGCT 
               
               
                   
               
               
                 TCACATTTTGGTGAGGCAATTATGCCGGATCTTAGTCATCGTATAGCCAAAAATGCTGCG 
               
               
                   
               
               
                 AAGGTCTTGCGCTCAGGTAAGGGTTTTTATGACTCAATTATCATAAGTCTTGCCAAGAAG 
               
               
                   
               
               
                 CCGGAGAAATCAGATGTTAATCATTAA 
               
               
                   
               
               
                 Polypeptide sequence encoded by the polynucleotide of SEQ ID NO: 41:  
               
               
                 (SEQ ID NO: 42) 
                   
               
               
                 MELQEVLRMNGGEGDTSYAKNSSYNLFLIRVKPVLEQCIQGLLRANLPNINKCIKVADLGCA 
                   
               
               
                   
               
               
                 SGSNTLSTVRDIVQSIDKVGQEKKNELERPTIQVFLNDLFQNDFNSVFKLLPSFYRKLEKENGR 
               
               
                   
               
               
                 KIGSCLIGAMPGSFYGRLFPEESMHFLHSCYCLHWLSQVPSGLVTELGISANKGCIYSSKASRP 
               
               
                   
               
               
                 PIKKAYLDQFTKDFTTFLRVHSEELISRGRMLLTWICKEDEFENPNSIDLLEMSLNDLVIEGHL 
               
               
                   
               
               
                 EEEKLDSFNVPIFAPSTEEVKCIVEEEGSFEILYLETFKTPYDAGFSIDDDYQGRSHSPVSCDEH 
               
               
                   
               
               
                 AIAEHVAAVVRSIYEPILASHFGEAIMPDLSHRIAKNAAKVLRSGKGFYDSIIISLAKKPEKSDV 
               
               
                   
               
               
                 NH  
               
               
                   
               
               
                 DXMT_20:  
               
               
                 (SEQ ID NO: 43) 
                   
               
               
                 ATGGAAGTGCAGGAAGTCCTTAGAATGAATGGTGGCGAAGGTGATACATCATACGCGAA 
                   
               
               
                   
               
               
                 AAATTCAAGCTATAACCTCTTCCTTATTCGGGTCAAACCCGTCCTCGAACAGTGCATTCA 
               
               
                   
               
               
                 AGAACTGTTAAGAGCAAATCTGCCTAACATAAATAAATGTATTAAAGTTGCTGACCTCGG 
               
               
                   
               
               
                 CTGCGCGTCTGGGTCAAACACTCTTTCAACCGTACGGGGCATAGTCCAGATCATCGATAA 
               
               
                   
               
               
                 AGTGGGTCAGGAAAAGAAAAATGAACTTGAACGCCCGACAATACAGGTGTTTTTAAACG 
               
               
                   
               
               
                 ATCTGTTTCAAAACGACTTTAACTCTGTCTTTAAATCACTTCCTTCTTTCTACCGCAAGCT 
               
               
                   
               
               
                 GGAAAAGGAAAACGGACGCAAAATTGGCTCCTGCTTAATCGGGGCAATGCCGGGGAGCT 
               
               
                   
               
               
                 TTTATGGTCGTCTGTTCCCCGAAGAAAGCATGCACTTCTTGCATTCATGTTATTGCTTGCA 
               
               
                   
               
               
                 CTGGCTGTCTCAGGTGCCGAGTGGCTTAGTGACTGAGCTGGGTATTTCTGCGAACAAAGG 
               
               
                   
               
               
                 GTGTATTTATTCGTCAAAGGCGTCACGGCCACCTATAAAGAAGGCATATCTGGATCAATT 
               
               
                   
               
               
                 CACGAAGGATTTTACAACCTTCCTGAAAATACACAGTGAGGAGTTGATTTCTCGCGGTCG 
               
               
                   
               
               
                 CATGCTGCTGACGTGGATCTGCAAGGAAGATGAGTTTGAGAATCCCAATTCAATTGATCT 
               
               
                   
               
               
                 GCTCGAAATGTCCCTGAATGATTTGGTGACAGAGGGCCTCTTGGAAGAAGAGAAGCTGG 
               
               
                   
               
               
                 ACTCTTTTAATGTGCCTATCTATGCCCCATCGACAGAAGTGGTTAAATGCATTGTAGAAG 
               
               
                   
               
               
                 AAGAAGGCTCATTTGAAATACTCTATTTGAAAACATTCAAAGCTCCGTACGATGCAGGAT 
               
               
                   
               
               
                 TTTCGACCGATGACGATTATCAAGGGCGTTCTCATAGCCCAGCGAGTTGTGACGAACATG 
               
               
                   
               
               
                 CTCGTGCCGCTCATGTAGCTTCTGTGGCACGCTCTATCTTTGAGCCGATAGTAGCCTCCCA 
               
               
                   
               
               
                 TTTTGGAGAAGCAATAATGCCAGACTTGTCCCATCGCATAGCTAAAAATGCGGCAAAAG 
               
               
                   
               
               
                 TTTTACGCAGCGGAAAGGGCTTTTTCGACAGTATTATAATTAGCCTGGCGAAAAAGCCAG 
               
               
                   
               
               
                 AAAAATCAGATATGTAA 
               
               
                   
               
               
                 Polypeptide sequence encoded by the polynucleotide of SEQ ID NO: 43:  
               
               
                 (SEQ ID NO: 44) 
                   
               
               
                 MEVQEVLRMNGGEGDTSYAKNSSYNLFLIRVKPVLEQCIQELLRANLPNINKCIKVADLGCA 
                   
               
               
                   
               
               
                 SGSNTLSTVRGIVQIIDKVGQEKKNELERPTIQVFLNDLFQNDFNSVFKSLPSFYRKLEKENGR 
               
               
                   
               
               
                 KIGSCLIGAMPGSFYGRLFPEESMHFLHSCYCLHWLSQVPSGLVTELGISANKGCIYSSKASRP 
               
               
                   
               
               
                 PIKKAYLDQFTKDFTTFLKIHSEELISRGRMLLTWICKEDEFENPNSIDLLEMSLNDLVTEGLL 
               
               
                   
               
               
                 EEEKLDSFNVPIYAPSTEVVKCIVEEEGSFEILYLKTFKAPYDAGFSTDDDYQGRSHSPASCDE 
               
               
                   
               
               
                 HARAAHVASVARSIFEPIVASHFGEAIMPDLSHRIAKNAAKVLRSGKGFFDSIIISLAKKPEKSDM 
               
               
                   
               
               
                 DXMT_21:  
               
               
                 (SEQ ID NO: 45) 
                   
               
               
                 CTGCAGGAAGTCCTGCACATGAACGGCGGAGAAGGAGAAGCTAGCTATGCTAAGAATTC 
                   
               
               
                   
               
               
                 CAGTTTCAATCAACTGGTGCTGGCCAAGGTGAAACCTGTCTTAGAGCAGTGCGTACGTGA 
               
               
                   
               
               
                 ACTGCTGCGGGCCAATTTACCAAACATCAACAAGTGTATAAAGGTTGCCGATTTGGGCTG 
               
               
                   
               
               
                 CGCTTCGGGCCCAAATACACTGTTAACGGTATGGGATACAGTACAGTCTATTGATAAGGT 
               
               
                   
               
               
                 TAAACAGGAAATGAAAAACGAACTGGAGCGCCCCACTATTCAAGTGTTTCTGACGGACC 
               
               
                   
               
               
                 TTTTCCAGAACGATTTCAATTCCGTGGTGATGTTGTTGCCATCCTTTTACCGGAAACTGGA 
               
               
                   
               
               
                 GAAGGAGAACGGACGTAAAATCGGATCTTGTCTGATCGCGGCAATGCCGGGCTCTTTTC 
               
               
                   
               
               
                 ACGGACGCTTATTTCCAGAAGAATCCATGCACTTCTTACATTCCTCTTATTCCATCCAATT 
               
               
                   
               
               
                 CCTGTCACAAGTTCCGAGCGGGTTGGTTACGGAACTCGGAATCACGGCAAATAACCGTTC 
               
               
                   
               
               
                 AATTTATTCGAGTAAAGCGTCCCCGCCTCCGGTCCAGAAAGCGTACTTAGACCAGTTCAC 
               
               
                   
               
               
                 TAAAGACTTCACGACGTTTTTACGGATGAGATCGGAGGAACTGCTCAGTCGTGGCAGAA 
               
               
                   
               
               
                 TGCTGCTGACCTGCATTTGCAAGGGGGACGAGTGCGATGGTCCAAATACAATGGATTTGT 
               
               
                   
               
               
                 TGGAAATGGCTATCAACGACTTAGTAGCTGAGGGTCGTCTGGGTGAAGAAAAATTAGAT 
               
               
                   
               
               
                 TCATTTAACGTGCCCATCTATACAGCGTCCGTGGAAGAAGTCAAATGCATGGTCGAGGA 
               
               
                   
               
               
                 AGAGGGTAGCTTTGAGATACTGTACCTGCAGACTTTTAAATTACGCTATGATGCAGGTTT 
               
               
                   
               
               
                 TAGTATCGACGATGATTGTCAAGTACGCTCCCATAGTCCGGTTTATTCTGATGAGCACGC 
               
               
                   
               
               
                 CAGAGCTGCACATGTAGCATCTCTCATACGCTCAGTTTATGAACCAATCTTAGCATCCCA 
               
               
                   
               
               
                 TTTTGGTGAAGTGATAAAACCGGATATCTTCCATCGTTTTGCGACCAACGCGGCGAAAGT 
               
               
                   
               
               
                 AATACGGCTGGGTAAAGGCTTTTACAACAATTTGATAATTAGCCTTGCCAAGAAACCCGA 
               
               
                   
               
               
                 GAAATCAGATATTTAA 
               
               
                   
               
               
                 Polypeptide sequence encoded by the polynucleotide of SEQ ID NO: 45:  
               
               
                 (SEQ ID NO: 46)  
                   
               
               
                 MQEVLHMNGGEGEASYAKNSSFNQLVLAKVKPVLEQCVRELLRANLPNINKCIKVADLGCA 
                   
               
               
                   
               
               
                 SGPNTLLTVWDTVQSIDKVKQEMKNELERPTIQVFLTDLFQNDFNSVVMLLPSFYRKLEKEN 
               
               
                   
               
               
                 GRKIGSCLIAAMPGSFHGRLFPEESMHFLHSSYSIQFLSQVPSGLVTELGITANNRSIYSSKASP 
               
               
                   
               
               
                 PPVQKAYLDQFTKDFTTFLRMRSEELLSRGRMLLTCICKGDECDGPNTMDLLEMAINDLVAE 
               
               
                   
               
               
                 GRLGEEKLDSFNVPIYTASVEEVKCMVEEEGSFEILYLQTFKLRYDAGFSIDDDCQVRSHSPV 
               
               
                   
               
               
                 YSDEHARAAHVASLIRSVYEPILASHFGEVIKPDIFHRFATNAAKVIRLGKGFYNNLIISLAKKP 
               
               
                   
               
               
                 EKSDI 
               
               
                   
               
               
                 DXMT_22:  
               
               
                 (SEQ ID NO: 47) 
                   
               
               
                 ATGGAACTCCAGGAGGTTCTCCACATGAATGGTGGCGAAGGAGAGGCAAGTTACGCAAA 
                   
               
               
                   
               
               
                 GAACTCCTCATTCAATCAATTGGTCTTAGCGAAGGTGAAACCCGTTCTGGAACAATGTGT 
               
               
                   
               
               
                 GCGTGAACTGCTTCGCGCAAATCTTCCGAATATCAATAAATGCATTAAGGTAGCGGATCT 
               
               
                   
               
               
                 TGGGTGCGCGTCAGGTCCGAATACCCTCTTAACGGTCTGGGATACCGTTCAATCCATCGA 
               
               
                   
               
               
                 TAAAGTCAAGCAGGAAATGAAAAATGAGTTGGAACGCCCGACCATACAGGTGTTTCTGA 
               
               
                   
               
               
                 CCGATCTTTTCCAAAACGATTTTAACTCGGTGTTCATGTTGCTGCCCTCATTTTATCGCAA 
               
               
                   
               
               
                 ATTAGAGAAGGAAAATGGACGCAAAATTGGCTCTTGTCTTATTGCCGCTATGCCCGGAA 
               
               
                   
               
               
                 GCTTTCATGGTCGGCTTTTCCCAGAGGAGTCCATGCATTTCTTACATTCCAGCTACTCTTT 
               
               
                   
               
               
                 GCAGTTTCTCAGCCAAGTCCCCTCTGGGTTGGTCACCGAGTTAGGGATAACAGCTAATAA 
               
               
                   
               
               
                 ACGCTCAATATACTCTTCGAAAGCAAGTCCGCCTCCAGTCCAGAAAGCATACCTTGACCA 
               
               
                   
               
               
                 GTTCACCAAAGATTTCACGACATTCCTCCGCATGCGTTCCGAAGAGTTACTCAGTCGGGG 
               
               
                   
               
               
                 CCGCATGTTGCTTACCTGTATTTGCAAAGGTGATGAATGTGATGGGCCCAATACGATGGA 
               
               
                   
               
               
                 CTTGCTGGAAATGGCGATTAATGATTTGGTGGCTGAAGGGCGTCTGGGAGAGGAGAAAT 
               
               
                   
               
               
                 TGGATTCTTTTAACGTTCCAATCTACACAGCCAGCGTTGAAGAGGTTAAATGTATGGTGG 
               
               
                   
               
               
                 AAGAAGAAGGCTCTTTCGAAATACTCTATCTTCAGACATTTAAACTGCGGTATGATGCCG 
               
               
                   
               
               
                 GTTTTTCCATTGACGATGACTGCCAAGTTAGAAGCCATTCGCCCGTCTACAGCGATGAAC 
               
               
                   
               
               
                 ATGCACGTGCCGCTCATGTTGCCAGCTTAATTCGCTCAGTGTACGAACCGATCCTGGCGT 
               
               
                   
               
               
                 CGCATTTCGGCGAGGCTATAATACCGGATATATTTCACCGTTTTGCAACTAACGCGGCCA 
               
               
                   
               
               
                 AGGTGATTCGCTTGGGGAAAGGGTTCTACAACAACCTTATTATATCACTTGCTAAGAAAC 
               
               
                   
               
               
                 CTGAAAAGAGTGACATCTAA 
               
               
                   
               
               
                 Polypeptide sequence encoded by the polynucleotide of SEQ ID NO: 47:  
               
               
                 (SEQ ID NO: 48) 
                   
               
               
                 MELQEVLHMNGGEGEASYAKNSSFNQLVLAKVKPVLEQCVRELLRANLPNINKCIKVADLG 
                   
               
               
                   
               
               
                 CASGPNTLLTVWDTVQSIDKVKQEMKNELERPTIQVFLTDLFQNDFNSVFMLLPSFYRKLEK 
               
               
                   
               
               
                 ENGRKIGSCLIAAMPGSFHGRLFPEESMHFLHSSYSLQFLSQVPSGLVTELGITANKRSIYSSK 
               
               
                   
               
               
                 ASPPPVQKAYLDQFTKDFTTFLRMRSEELLSRGRMLLTCICKGDECDGPNTMDLLEMAINDL 
               
               
                   
               
               
                 VAEGRLGEEKLDSFNVPIYTASVEEVKCMVEEEGSFEILYLQTFKLRYDAGFSIDDDCQVRSH 
               
               
                   
               
               
                 SPVYSDEHARAAHVASLIRSVYEPILASHFGEAIIPDIFHRFATNAAKVIRLGKGFYNNLIISLA 
               
               
                   
               
               
                 KKPEKSDI 
               
               
                   
               
               
                 DXMT_23:  
               
               
                 (SEQ ID NO: 49) 
                   
               
               
                 ATGGAACTCCAGGAAGTTCTGCACATGAACGGTGGCGAAGGTGATGCTTCGTATGCTAA 
                   
               
               
                   
               
               
                 AAATTCAAGCTTTAATCAGTTGGTTCTGGCTAAAGTGAAGCCGGTACTTGAACAATGCGT 
               
               
                   
               
               
                 GGGAGAGCTCTTACGCGCAAATCTCCCCAATATTAACAAATGTATAAAAGTTGCGGATTT 
               
               
                   
               
               
                 AGGGTGTGCCTCCGGCCCGAACACCTTGTTAACCGTCCGTGATATCGTACAGTCAATCGA 
               
               
                   
               
               
                 TAAAGTTAGACAGGAAATGAAGAATGAATTGGAACGCCCCACCATCCAAGTCTTTCTTA 
               
               
                   
               
               
                 CGGACCTGTTCCAGAACGATTTCAACAGCGTGTTCATGCTGTTACCGTCATTCTACCGCA 
               
               
                   
               
               
                 AATTAGAAAAGGAGAACGGTCGGAAGATCGGTTCTTGTCTGATAGCAGCAATGCCCGGC 
               
               
                   
               
               
                 TCTTTTCATGGTCGTCTTTTCCCCGAAGAATCGATGCATTTCCTCCACAGCAGCTATTCAC 
               
               
                   
               
               
                 TGCAGTTCTTATCACAAGTTCCGTCAGGACTGGTTACTGAGTTGGGTATAACTGCGAACA 
               
               
                   
               
               
                 AACGCTCTATCTATAGCTCAAAAGCAAGTCCACCGCCAGTGCAAAAGGCCTACTTGGATC 
               
               
                   
               
               
                 AGTTTACTAAAGACTTTACGACCTTCCTGCGCATACGGAGTGAAGAACTCCTTTCTCGTG 
               
               
                   
               
               
                 GTAGAATGTTATTGACATGCATCTGCAAAGGCGATGAGTTCGATGGACCAAACACTATG 
               
               
                   
               
               
                 GATCTGTTAGAAATGGCAATAAACGATCTCGTCGTGGAAGGCCACCTTGAGGAAGAAAA 
               
               
                   
               
               
                 ACTGGACAGCTTCAACGTCCCCATTTATGCTGCTTCGGTTGAAGAGCTGAAGTGTATTGT 
               
               
                   
               
               
                 GGAAGAAGAGGGTTCATTTGAGATCTTATATTTAGAAACCTTCAAACTCCGCTACGATGC 
               
               
                   
               
               
                 GGGTTTTTCGATTGATGATGACTGCCAGGTACGTAGTCATAGTCCAGAATATTCCGATGA 
               
               
                   
               
               
                 GCATGCAAGAGCAGCGCATGTCGCGTCATTACTGCGGTCCGTATATGAACCGATCTTAGC 
               
               
                   
               
               
                 GAACCACTTTGGCGAAGCGATAATCCCTGATATCTTTCATCGTTTTGCGACTAATGCAGC 
               
               
                   
               
               
                 GAAAGTGATTAGATTGGGGAAGGGTTTTTACAATAACCTCATAATTAGCCTGGCTAAAA 
               
               
                   
               
               
                 AGCCCGAGAAGAGCGATATCTAA 
               
               
                   
               
               
                 Polypeptide sequence encoded by the polynucleotide of SEQ ID NO: 49:  
               
               
                 (SEQ ID NO: 50) 
                   
               
               
                 MELQEVLHMNGGEGDASYAKNSSFNQLVLAKVKPVLEQCVGELLRANLPNINKCIKVADLG 
                   
               
               
                   
               
               
                 CASGPNTLLTVRDIVQSIDKVRQEMKNELERPTIQVFLTDLFQNDFNSVFMLLPSFYRKLEKE 
               
               
                   
               
               
                 NGRKIGSCLIAAMPGSFHGRLFPEESMHFLHSSYSLQFLSQVPSGLVTELGITANKRSIYSSKAS 
               
               
                   
               
               
                 PPPVQKAYLDQFTKDFTTFLRIRSEELLSRGRMLLTCICKGDEFDGPNTMDLLEMAINDLVVE 
               
               
                   
               
               
                 GHLEEEKLDSFNVPIYAASVEELKCIVEEEGSFEILYLETFKLRYDAGFSIDDDCQVRSHSPEYS 
               
               
                   
               
               
                 DEHARAAHVASLLRSVYEPILANHFGEAIIPDIFHRFATNAAKVIRLGKGFYNNLIISLAKKPE 
               
               
                   
               
               
                 KSDI  
               
               
                   
               
               
                 DXMT_25:  
               
               
                 (SEQ ID NO: 51) 
                   
               
               
                 CTGCAAGAAGTCCTTCACATGAACGGTGGCGAAGGGGATACTAGCTACGCTAAAAACTC 
                   
               
               
                   
               
               
                 CAGTTACAATCTGGTGCTGACAAAAGTTAAACCTGTGCTGGAACAATGCATTAGAGAGC 
               
               
                   
               
               
                 TCCTGAGAGCGAACCTTCCGAATATTAATAAATGCATTAAAGTAGCCGACTTGGGTTGCG 
               
               
                   
               
               
                 CTTCAGGCCCTAACACGCTTCTCACTGTTCGCGATATTGTCCAGTCCATAGATAAGGTTG 
               
               
                   
               
               
                 GTCAGGAGGAGAAGAATGAATTGGAGCATCCTACCATTCAGATCTTCTTGAATGACCTTT 
               
               
                   
               
               
                 TTCAAAATGATTTCAACAGCGTATTCAAGCTGCTCCCTAGTTTTTATCGGAAACTTGAGA 
               
               
                   
               
               
                 AAGAGAACGGGAGAAAAATAGGCAGTTGTTTAATCTGGGCAATGCCTGGCAGCTTTTAC 
               
               
                   
               
               
                 AGCCGGCTTTTCCCAGAAGAAAGTATGCACTTTCTTCACTCATGCTATTGTCTGCAGTGGT 
               
               
                   
               
               
                 TAAGTCAAGTCCCTAGTGGCTTAGTTACAGAGCTGGGTATTAGTGCCAATAAAGGCATAA 
               
               
                   
               
               
                 TATACTCTTCTAAGGCTTCTCCACCACCGGTGCAGAAGGCCTATCTGGATCAATTCACCA 
               
               
                   
               
               
                 AAGATTTTACCACATTTCTGCGTATTCACTCTGAAGAACTCCTTTCCAGAGGACGTATGCT 
               
               
                   
               
               
                 GTTAACTTGTATCTGCAAAGGAGATGAAAGTGACGGGTTGAACACAATAGACCTTCTGG 
               
               
                   
               
               
                 AGCGGGCAATTAACGACCTCGTAGTAGAAGGTTTGTTAGAAGAGGAAAAGTTAGATTCA 
               
               
                   
               
               
                 TTCAACTTGCCATTATATACTCCATCGCTCGAAGTGGTCAAATGCATGGTGGAAGAATAA 
               
               
                   
               
               
                 Polypeptide sequence encoded by the polynucleotide of SEQ ID NO: 51:  
               
               
                 (SEQ ID NO: 52) 
                   
               
               
                 MQEVLHMNGGEGDTSYAKNSSYNLVLTKVKPVLEQCIRELLRANLPNINKCIKVADLGCAS 
                   
               
               
                   
               
               
                 GPNTLLTVRDIVQSIDKVGQEEKNELEHPTIQIFLNDLFQNDFNSVFKLLPSFYRKLEKENGRK 
               
               
                   
               
               
                 IGSCLIWAMPGSFYSRLFPEESMHFLHSCYCLQWLSQVPSGLVTELGISANKGIIYSSKASPPPV 
               
               
                   
               
               
                 QKAYLDQFTKDFTTFLRIHSEELLSRGRMLLTCICKGDESDGLNTIDLLERAINDLVVEGLLEE 
               
               
                   
               
               
                 EKLDSFNLPLYTPSLEVVKCMVEE  
               
               
                   
               
               
                 DXMT_26:  
               
               
                 (SEQ ID NO: 53) 
                   
               
               
                 CTGCAGGAAGTATTGCACATGAATGAAGGTGAGGGTGATACAAGTTATGCCAAGAATGC 
                   
               
               
                   
               
               
                 ATCTTATAATCTCGCTTTGGCGAAAGTGAAGCCATTTCTTGAGCAGTGCATTCGTGAATT 
               
               
                   
               
               
                 GCTCCGTGCAAATCTTCCGAATATCAATAAGTGCATTAAAGTCGCCGATCTTGGATGTGC 
               
               
                   
               
               
                 TTCAGGACCAAATACTCTGCTTACAGTGCGGGACATAGTACAATCCATTGACAAAGTAG 
               
               
                   
               
               
                 GACAGGAGGAGAAGAATGAGCTGGAACGCCCAACGATACAGATATTCCTTAATGATCTG 
               
               
                   
               
               
                 TTTCAGAACGATTTCAATAGCGTTTTTAAGCTGTTACCCTCATTCTACAGAAAACTGGAG 
               
               
                   
               
               
                 AAGGAAAACGGGCGCAAAATTGGGTCTTGCTTAATAAGTGCCATGCCTGGTTCCTTCTAT 
               
               
                   
               
               
                 GGTCGCTTATTTCCTGAAGAAAGTATGCACTTTCTGCATAGTTGCTATTCGGTTCATTGGC 
               
               
                   
               
               
                 TTTCTCAGGTTCCAAGCGGACTTGTTATTGAATTGGGTATCGGCGCTAACAAGGGTTCCA 
               
               
                   
               
               
                 TTTATAGTAGTAAAGGATGTCGTCCGCCAGTTCAGAAAGCTTATCTTGATCAATTCACCA 
               
               
                   
               
               
                 AAGACTTTACGACGTTCTTGCGTATTCATTCCAAGGAGCTGTTTTCTCGGGGACGTATGCT 
               
               
                   
               
               
                 GCTGACGTGTATATGCAAAGTGGATGAATTCGATGAACCCAATCCGCTGGACCTGCTGG 
               
               
                   
               
               
                 ATATGGCAATAAATGACCTCATCGTAGAAGGCAGATTAGGGGAAGAGAAACTTGATTCA 
               
               
                   
               
               
                 TTTAATGTCCCCATTTATACCGCTAGCGTCGAAGAAGTAAAATGCATGGTTGAAGAATAA 
               
               
                   
               
               
                 Polypeptide sequence encoded by the polynucleotide of SEQ ID NO: 53:  
               
               
                 (SEQ ID NO: 54) 
                   
               
               
                 MQEVLHMNEGEGDTSYAKNASYNLALAKVKPFLEQCIRELLRANLPNINKCIKVADLGCAS 
                   
               
               
                   
               
               
                 GPNTLLTVRDIVQSIDKVGQEEKNELERPTIQIFLNDLFQNDFNSVFKLLPSFYRKLEKENGRK 
               
               
                   
               
               
                 IGSCLISAMPGSFYGRLFPEESMHFLHSCYSVHWLSQVPSGLVIELGIGANKGSIYSSKGCRPP 
               
               
                   
               
               
                 VQKAYLDQFTKDFTTFLRIHSKELFSRGRMLLTCICKVDEFDEPNPLDLLDMAINDLIVEGRL 
               
               
                   
               
               
                 GEEKLDSFNVPIYTASVEEVKCMVEE 
               
               
                   
               
               
                 DXMT_27:  
               
               
                 (SEQ ID NO: 55) 
                   
               
               
                 ATGGAAGTAAAGGAAGCGCTGTTCATGAATAGAGGTGAAGGCGAATCCTCATACGCTCA 
                   
               
               
                   
               
               
                 AAACAGTAGTTTTACTCAGAAGGTTGCGTCTATGACTATGCCGGTATTGGAGAATGCCGT 
               
               
                   
               
               
                 AGAAACCTTATTTAGCAAGGATTTCCATCTTTTTCAGGCACTGAATGCCGCGGATCTGGG 
               
               
                   
               
               
                 TTGCGCTACAAGTCCAAATACATTCACGGTGATTTCGACCATTAAACGTATGATGGAGAA 
               
               
                   
               
               
                 GAAATGCCGCGAATTGAACTGTCAGACGTTAGAACTGCAAGTTTACTTGAATGACCTGCC 
               
               
                   
               
               
                 CGGAAATGACTTCAACACTCTGTTCAAAGGACTTTTGTCTAAGGTAGTGGTGGGAAATAA 
               
               
                   
               
               
                 GTGCGAAGAAGTCTCATGCTATGTGATGGGCGTGCCGGGTAGCTTCCATGGTCGGCTTTT 
               
               
                   
               
               
                 TCCTAGAAATAGCTTACACCTTGTCCACTCATGCTACTCAGCCCACTGGTTATCTCAAGCT 
               
               
                   
               
               
                 CCTAAAGGCCTGACGTCTCGGGAAGGTTTACCGCTTAACAAAGGAAAGATTTACATTTCA 
               
               
                   
               
               
                 AAACGCAGCCCGCCGGTGGTACGGGAAGCCTATTTGAGTCAGTTTCATGATGATTTTACG 
               
               
                   
               
               
                 ATGTTTCTTAATGCACGTTCCCAGGAAGTGGTGCCGCATGGGTGTATGGTGCTCATCCTG 
               
               
                   
               
               
                 CCTAGTAGACAATCCAGCGATCCAAGTTCTATGGAATCCTGCTTCACCTGGGAACTTTTG 
               
               
                   
               
               
                 GCAATTGCTATTGCCGAACTCGTATCACAAGGCCTTATTGATGAGGATAAACTGGACACC 
               
               
                   
               
               
                 TTCAATGTACCATCATACTTTCCCAGTTTAGAAGAAGTAAAGGATATCGTAGAGCGCGAT 
               
               
                   
               
               
                 GGCTCTTTCACTATCGATCACATGGAGGGTTTCGAGCTGGATACACTGCAGATGCAGGAA 
               
               
                   
               
               
                 AATGACAAGTGGATACGCGGAGAGAAATTAGCCAAAGCAGTTAGAGCGTTCACGGAGCC 
               
               
                   
               
               
                 TATCATTTCAAACCAGTTCGGCCATGAGATAATGGATAAGCTGTATGACAAATTTACACA 
               
               
                   
               
               
                 TATAGTCGCGAGCGATCTGGAAGGGAAAATCCCCAAATCAACGTCCATAGTTTTGGTGCT 
               
               
                   
               
               
                 GAGCAAGATTGTCGGCTAA 
               
               
                   
               
               
                 Polypeptide sequence encoded by the polynucleotide of SEQ ID NO: 55:  
               
               
                 (SEQ ID NO: 56) 
                   
               
               
                 MEVKEALFMNRGEGESSYAQNSSFTQKVASMTMPVLENAVETLFSKDFHLFQALNAADLGC 
                   
               
               
                   
               
               
                 ATSPNTFTVISTIKRMMEKKCRELNCQTLELQVYLNDLPGNDFNTLFKGLLSKVVVGNKCEE 
               
               
                   
               
               
                 VSCYVMGVPGSFHGRLFPRNSLHLVHSCYSAHWLSQAPKGLTSREGLPLNKGKIYISKRSPPV 
               
               
                   
               
               
                 VREAYLSQFHDDFTMFLNARSQEVVPHGCMVLILPSRQSSDPSSMESCFTWELLAIAIAELVS 
               
               
                   
               
               
                 QGLIDEDKLDTFNVPSYFPSLEEVKDIVERDGSFTIDHMEGFELDTLQMQENDKWIRGEKLAK 
               
               
                   
               
               
                 AVRAFTEPIISNQFGHEIMDKLYDKFTHIVASDLEGKIPKSTSIVLVLSKIVG 
               
               
                   
               
               
                 DXMT_28:  
               
               
                 (SEQ ID NO: 57) 
                   
               
               
                 ATGGAGGTGAAAGAGGCGCTGTTCATGAATCGGGGAGAAGGTGAGAATAGTTATGCACA  
                   
               
               
                   
               
               
                 AAACTCCTCCTTTACACAGAAGGTTGCGAGTATGACCATGCCGGTACTCGAAAACGCTGT  
               
               
                   
               
               
                 GGAAACCCTTTTCTCTAAAGATTTCCATTTGCTTCAGGCGCTGAACGTAGTAGATCTGGG  
               
               
                   
               
               
                 ATGCGCTACGAGTCCGAATACTTTCACGGTAATCAGCACCATCAAGCGGATGATGGAAA  
               
               
                   
               
               
                 AGAAGTGCCGGGAACTCAATTGTCAGACACTTGAACTGCAGGTTTATCTCAATGATCTGC  
               
               
                   
               
               
                 CAGGTAATGACTTCAATACACTGTTTAAAGGCCTTTTGTCTAAAGTTGTAGTCGGCAACA  
               
               
                   
               
               
                 AGTGCGAAGAAGTGTCATGCTATGTTATGGGCGTTCCTGGGTCATTTCACGGTCGTTTAT  
               
               
                   
               
               
                 TTCCGAGAAATTCATTGCGCTTGGTTCACTCTTGCTATTCTGCTCACTGGTTATCTCAGGC  
               
               
                   
               
               
                 GCCCAAGGGGTTGACATCACGTGAAGGTTTAGCATTGAACCGCCGCAAAATATACATTTC  
               
               
                   
               
               
                 CAAAACCAGCCCTCTGGTAGTGCGTGAAGCGTATCTTTCCCAGTTTCACGAAGATTTCAC  
               
               
                   
               
               
                 TATGTTCTTAAATGCCCGTAGTCAGGAAGTAGTTCCCAATGGCTGCATGGTCCTGATACT  
               
               
                   
               
               
                 TCCGGGGCGTCAGTCTTCAAATCCGTCATCAATGGAGAGCTGCTTTACCTGGGAACTGTT  
               
               
                   
               
               
                 AGCGATAGCCATAGGAGAGCTCGTGAGCCAAGGCCTCATCGATGAGGACAAGCTCGATA  
               
               
                   
               
               
                 CATTTAACGTGCCGAGTTATTTCCCGAGCTTAGAAGAGGTTAAGGACATAGTCGAGAGA  
               
               
                   
               
               
                 GATGGTAGTTTTACAATAGATCACATGGTTGGCTTCGAACTGGATACGCCCCAGATGCAA  
               
               
                   
               
               
                 GAGAATGATAAATGGGTACGTGTAGAAAAGTTAGCTAAGGCGGTTAGAGCTTTTACTGA  
               
               
                   
               
               
                 GCCAATCATAAGTAATCAGTTTGGTCACGAAATTATGGACAAACTCTACGACAAATTCAC  
               
               
                   
               
               
                 TTACATCGTGGTAAGTGATTTGGAAGGGAAGATCCCGAAAACTACGTCGATAGTACTGG  
               
               
                   
               
               
                 TGCTGTCGAAAATTATCGGATAA  
               
               
                   
               
               
                 Polypeptide sequence encoded by the polynucleotide of SEQ ID NO: 57:  
               
               
                 (SEQ ID NO: 58) 
                   
               
               
                 MEVKEALFMNRGEGENSYAQNSSFTQKVASMTMPVLENAVETLFSKDFHLLQALNVVDLG 
                   
               
               
                   
               
               
                 CATSPNTFTVISTIKRMMEKKCRELNCQTLELQVYLNDLPGNDFNTLFKGLLSKVVVGNKCE 
               
               
                   
               
               
                 EVSCYVMGVPGSFHGRLFPRNSLRLVHSCYSAHWLSQAPKGLTSREGLALNRRKIYISKTSPL 
               
               
                   
               
               
                 VVREAYLSQFHEDFTMFLNARSQEVVPNGCMVLILPGRQSSNPSSMESCFTWELLAIAIGELV 
               
               
                   
               
               
                 SQGLIDEDKLDTFNVPSYFPSLEEVKDIVERDGSFTIDHMVGFELDTPQMQENDKWVRVEKL 
               
               
                   
               
               
                 AKAVRAFTEPIISNQFGHEIMDKLYDKFTYIVVSDLEGKIPKTTSIVLVLSKIIG 
               
               
                   
               
               
                 DXMT_29:  
               
               
                 (SEQ ID NO: 59) 
                   
               
               
                 ATGAAAGAAGTAAAAGAAGCTCTGTTTATGAACAAAGGCGAAGGTGAATCCAGTTACGC 
                   
               
               
                   
               
               
                 TCAGAATAGCTCGTTCACTCAGACCGTAACGTCCATGACCATGCCGGTGTTAGAGAATGC 
               
               
                   
               
               
                 CGTTGAGACATTATTCTCCAAGGATTTTCACTTGCTGCAAGCTCTTAATGCAGTAGATTTA 
               
               
                   
               
               
                 GGATGCGCAGCTGGACCAACTACATTTACAGTGATTTCGACTATCAAACGTATGATGGAG 
               
               
                   
               
               
                 AAGAAATGTCGCGAACTCAATTGTCAAACTTTAGAACTTCAGGTATACCTGAACGATTTA 
               
               
                   
               
               
                 CCTGGTAACGACTTTAATACACTGTTTAAAGGTCTTCCGTCTAAAGTCGTCGGTAATAAA 
               
               
                   
               
               
                 TGCGAAGAAGTCAGCTGCTACGTAGTAGGTGTTCCAGGTTCATTTCATGGTCGGTTATTT 
               
               
                   
               
               
                 CCTCGTAATTCCCTTCACTTGGTGCATTCATGTTACAGTGTTCATTGGTTGACTCAGGCTC 
               
               
                   
               
               
                 CGAAAGGTTTGACCAGTAAGGAGGGGTTAGCGCTCAACAAAGGTAAGATCTATATTAGT 
               
               
                   
               
               
                 AAGACATCCCCTCCAGTGGTTAGAGAGGCATACTTGTCTCAGTTTCACGAGGATTTTACT 
               
               
                   
               
               
                 ATGTTTCTGAACTCACGGAGCCAGGAAGTTGTTCCAAATGGCTGCATGGTATTGATTCTG 
               
               
                   
               
               
                 AGAGGTCGTCTTTCGAGTGATCCTAGCGATATGGGTTCATGTTTTACTTGGGAACTGCTG 
               
               
                   
               
               
                 GCCGTGGCGATCGCAGAACTCGTGAGCCAAGGTTTAATCGATGAAGACAAGCTGGACAC 
               
               
                   
               
               
                 CTTTAACGTGCCGTCATATTTCCCTTCCCTTGAAGAGGTGAAAGACATAGTTGAACGCAA 
               
               
                   
               
               
                 TGGCTCTTTCACTATTGACCACATGGAGGGCTTCGAATTGGATTCACCCGAGATGCAGGA 
               
               
                   
               
               
                 AAATGATAAATGGGTTCGGGGCGAAAAATTTGCTACAGTTGCGCGGGCGTTCACGGAAC 
               
               
                   
               
               
                 CGATTATTTCAAATCAGTTTGGGCACGAAATCATGGATAAACTTTATGAGAAATTTACAC 
               
               
                   
               
               
                 ACATCGTGGTGAGTGATTTCGAAGCCAAAATACCGAAAATTACTTCTATAATCTTGGTTC 
               
               
                   
               
               
                 TCAGTAAAATTGTGGGCTAA 
               
               
                   
               
               
                 Polypeptide sequence encoded by the polynucleotide of SEQ ID NO: 59:  
               
               
                 (SEQ ID NO: 60) 
                   
               
               
                 MKEVKEALFMNKGEGESSYAQNSSFTQTVTSMTMPVLENAVETLFSKDFHLLQALNAVDLG 
                   
               
               
                   
               
               
                 CAAGPTTFTVISTIKRMMEKKCRELNCQTLELQVYLNDLPGNDFNTLFKGLPSKVVGNKCEE 
               
               
                   
               
               
                 VSCYVVGVPGSFHGRLFPRNSLHLVHSCYSVHWLTQAPKGLTSKEGLALNKGKIYISKTSPPV 
               
               
                   
               
               
                 VREAYLSQFHEDFTMFLNSRSQEVVPNGCMVLILRGRLSSDPSDMGSCFTWELLAVAIAELV 
               
               
                   
               
               
                 SQGLIDEDKLDTFNVPSYFPSLEEVKDIVERNGSFTIDHMEGFELDSPEMQENDKWVRGEKFA 
               
               
                   
               
               
                 TVARAFTEPIISNQFGHEIMDKLYEKFTHIVVSDFEAKIPKITSIILVLSKIVG 
               
               
                   
               
               
                 MXMT_30:  
               
               
                 (SEQ ID NO: 61) 
                   
               
               
                 ATGGAGGTAAAAGAAGCCTTGTTTATGAACAAGGGAGAGGGCGAAAGTTCCTACGCTCA 
                   
               
               
                   
               
               
                 GAGTTCTAGTTTTACGGAAACAGTTACTAGTATGACTATGCCAGTGCTTGAGAATGCTGT 
               
               
                   
               
               
                 TGAAACTCTGTTCTCAAAAGATTTCCATCTTTTACAAGCATTGAACGCAGCCGACCTTGG 
               
               
                   
               
               
                 CTGTGCAGCAGGTCCTACCACGTTTACGGTAATCAGCACCATAAAACGTATGATGGAGA 
               
               
                   
               
               
                 AGAAGTGCCGGGAGCTGAATTGTCAGACGTTAGAACTCCAGGTATACCTGAACGACTTG 
               
               
                   
               
               
                 CCCGGCAATGACTTCAACACCCTGTTTAAAGGGTTGTCGAGTAAGGTGGTGGGCAACAA 
               
               
                   
               
               
                 GTGCGAAGAAGTGCCATGTTATGTTGTAGGCGTACCCGGGAGCTTTCATGGTAGACTTTT 
               
               
                   
               
               
                 TCCCCGTAACAGCCTGCACTTAGTTCACTCGTGTTATTCAGTTCACTGGTTGACTCAGGCA 
               
               
                   
               
               
                 CCTAAAGGACTGACTAGTAAAGAGGGTCTGGCCCTGAATAAAGGTAAAATCTACATAAG 
               
               
                   
               
               
                 CAAGACCTCTCCGCCAGTAGTGCGGGAAGCCTACTTGTCACAGTTTCATGAGGATTTTAC 
               
               
                   
               
               
                 AATGTTTCTTAATTCGCGCTCGCAAGAAGTTGTTCCAAATGGGTGTATGGTATTAATTTTA 
               
               
                   
               
               
                 CGTGGACGTCTGTCTTCCGATCCGAGCGACATGGAGTCATGTTTTACTTGGGAACTCTTA 
               
               
                   
               
               
                 GCAGTGGCCATAGCTGAGCTGGTGTCACAGGGTCTGATTGATGAGGATAAGCTCGACAC 
               
               
                   
               
               
                 ATTTAACGTACCGTCCTATTTTCCGAGTCTGGAGGAAGTTAAAGATATAGTCGAGCGCAA 
               
               
                   
               
               
                 TGGCTCCTTCACGATAGATCACATGGAGGGTTTCGAACTTGACAGTCCACAGATGCAGGA 
               
               
                   
               
               
                 AAATGACAAATGGGTTCGTGGTGAAAAGTTTGCGACAGTGGCACGCGCTTTTACAGAGC 
               
               
                   
               
               
                 CCATTATTAGCAATCAGTTTGGCCATGAAATTATGGACAAACTCTATGAGAAATTCACCC 
               
               
                   
               
               
                 ACATTGTAGTGTCAGACTTAGAAGCTAAAATCCCGAAAATAACCTCAATCATCCTGGTTT 
               
               
                   
               
               
                 TATCGAAAATTGTAGGCTAA 
               
               
                   
               
               
                 Polypeptide sequence encoded by the polynucleotide of SEQ ID NO: 61:  
               
               
                 (SEQ ID NO: 62) 
                   
               
               
                 MEVKEALFMNKGEGESSYAQSSSFTETVTSMTMPVLENAVETLFSKDFHLLQALNAADLGC 
                   
               
               
                   
               
               
                 AAGPTTFTVISTIKRMMEKKCRELNCQTLELQVYLNDLPGNDFNTLFKGLSSKVVGNKCEEV 
               
               
                   
               
               
                 PCYVVGVPGSFHGRLFPRNSLHLVHSCYSVHWLTQAPKGLTSKEGLALNKGKIYISKTSPPVV 
               
               
                   
               
               
                 REAYLSQFHEDFTMFLNSRSQEVVPNGCMVLILRGRLSSDPSDMESCFTWELLAVAIAELVSQ 
               
               
                   
               
               
                 GLIDEDKLDTFNVPSYFPSLEEVKDIVERNGSFTIDHMEGFELDSPQMQENDKWVRGEKFAT 
               
               
                   
               
               
                 VARAFTEPIISNQFGHEIMDKLYEKFTHIVVSDLEAKIPKITSIILVLSKIVG 
               
               
                   
               
               
                 MXMT_31:  
               
               
                 (SEQ ID NO: 63) 
                   
               
               
                 ATGATGGAAGTGAAAGAAGCCCTGTTTATGAATCGGGGTGAAGGGGAAAGCAGCTACGC 
                   
               
               
                   
               
               
                 GCAAAACTCGTCATTTACTCAAAAAGTTGCATCATTAACCATGCCAGTTCTTGAGAATGC 
               
               
                   
               
               
                 CGTGGAGACTCTGTTCTCAAAAGATTTCCACCTTCTGCAGGCATTGAATGCCGCCGATCT 
               
               
                   
               
               
                 GGGTTGTGCCGCAGGGCCGAACACATTTACCGTTATATTCACAATTAAACGCATGATGGA 
               
               
                   
               
               
                 GAAGAAATGTAGAGAACTGAATTGCCAGACCCTGGAGCTGCAAGTGTATCTCAACGACC 
               
               
                   
               
               
                 TGCCTGGGAACGATTTTAACACATTGTTTAAGGGTCTGTCGTCAAAAGTCGTAGGTAACA 
               
               
                   
               
               
                 AATGCGAAGAGGTATCGTACTATGTCATGGGAGTGCCAGGTTCCTTTCATGGCCGCTTGT 
               
               
                   
               
               
                 TTCCACGCAATAGTCTGCATCTGGTACACTCGAGTTATAGCGTACATTGGTTGTCTCAAG 
               
               
                   
               
               
                 CACCTAAGGGTTTGAGATCCCGCGAAGGCTTGGCTCTGAATAAGGGCAAAATTTACATAT 
               
               
                   
               
               
                 CGAAAACGTCTCCTCCGGTTGTCCGGGAAGCCTACTTATCACAATTCCACGAGGATTTTA 
               
               
                   
               
               
                 CTATGTTCCTTAATGCCCGTAGCCAAGAAGTAGTGCCTAATGGATGTATGGTGCTTATCC 
               
               
                   
               
               
                 TTCACGGTCGTAAATCATCAGACCCGTCGAATATGGAAAGTTGCTTTACGTGGGAACTCT 
               
               
                   
               
               
                 TAGCCATCGCAATTAGCGAGCTTGTGTCACAGGGCTTGATCGATGAGGATAAACTCGATA 
               
               
                   
               
               
                 CCTTCAACGTGCCATATTATACGCCTAGCCTTGAGGAGATGAAAGATATCGTAGAACGTG 
               
               
                   
               
               
                 AAGGATCATTTACAATTGACCATATAGAGGGCTTTGAGCTTGATTCCCCGCACATGCAAG 
               
               
                   
               
               
                 AAAAAGACAAGTGGGCGGGTAGAGAAAAGCTTGCAAAAGCCATACGCGCTTTTACCGAG 
               
               
                   
               
               
                 CCGATTATCTCCAATCAGTTCGGCCATGAGATTATGGACAAGTTATATGACAAGTTCACA 
               
               
                   
               
               
                 CATATAGTTGTCTCTGACTTAGAGGCTAAAATCCCAAAAACCACCTCAATCATCCTGGTC 
               
               
                   
               
               
                 TTGTCTAAAATTGTTGGGTAA 
               
               
                   
               
               
                 Polypeptide sequence encoded by the polynucleotide of SEQ ID NO: 63:  
               
               
                 (SEQ ID NO: 64)  
                   
               
               
                 MMEVKEALFMNRGEGESSYAQNSSFTQKVASLTMPVLENAVETLFSKDFHLLQALNAADLG 
                   
               
               
                   
               
               
                 CAAGPNTFTVIFTIKRMMEKKCRELNCQTLELQVYLNDLPGNDFNTLFKGLSSKVVGNKCEE 
               
               
                   
               
               
                 VSYYVMGVPGSFHGRLFPRNSLHLVHSSYSVHWLSQAPKGLRSREGLALNKGKIYISKTSPP 
               
               
                   
               
               
                 VVREAYLSQFHEDFTMFLNARSQEVVPNGCMVLILHGRKSSDPSNMESCFTWELLAIAISELV 
               
               
                   
               
               
                 SQGLIDEDKLDTFNVPYYTPSLEEMKDIVEREGSFTIDHIEGFELDSPHMQEKDKWAGREKLA 
               
               
                   
               
               
                 KAIRAFTEPIISNQFGHEIMDKLYDKFTHIVVSDLEAKIPKTTSIILVLSKIVG 
               
               
                   
               
               
                 MXMT_32:  
               
               
                 (SEQ ID NO: 65) 
                   
               
               
                 ATGAATCGGGGCGAAGGAGAATCTAGCGATGCCCAGAATAGCTCCTTCACACAGAAAGG 
                   
               
               
                   
               
               
                 CGCATCCATGACTATGCCGGTGCTCGAGAATGCGGTGGAAACCCTGTTCTCGAAAGATTT 
               
               
                   
               
               
                 CCATTTGCTGCAAGCGTTAAATGCCGCTGATTTTGGATGTGCTGCCGGCCCGAATACTGT 
               
               
                   
               
               
                 CATTTCGACAATAAAAAGAATGATGGAGAAAAAGTGTCGCGAGCTGAATTGTCAGACGC 
               
               
                   
               
               
                 TCGAGTTGCAGGTTTACCTGAACGATCTCCCGGGTAATGACTTCAACACCCTGTTCAAGG 
               
               
                   
               
               
                 GTCTTAGCTCAAAAATTGTTGTGGGAAACAAGTGCGAGGAGGTAAGTTGTTATGCGATG 
               
               
                   
               
               
                 GGCGTTCCGGGCTCTTTCCACGGAAGATTATTTCCCCGTAACTCGCTCCATCTGGTGCATT 
               
               
                   
               
               
                 CAAGTTATTCCGTCCATTGGCTCTCACAGGCACCGAAAGGCTTAAGATCACGCGAGGGA 
               
               
                   
               
               
                 CTGGCCCTCAACAAAGGCAAAATTTACATATCAAAAACATCACCTCCGGTTGTTCGCGAA 
               
               
                   
               
               
                 GCGTATTTAAGCCAGTTCCATGAAGACTTTACGATGTTCTTAAACGCCAGAAGTCAAGAG 
               
               
                   
               
               
                 GTGGTACCGAACGGGTGCATGGTGTTAATTTTGCATGGCAGAAAGTCTTCCGACCCGTCT 
               
               
                   
               
               
                 AACATGGAATCGTGTTTCACTTGGGAACTGTTAGCTATCGCGATCGCGGAGCTGGTATCA 
               
               
                   
               
               
                 CAAGGGCTCATTGACGAGGACAAGCTTGACACGTTTAATGTGCCATATTACACGCCTAGT 
               
               
                   
               
               
                 CTGGAAGAAATGAAAGATATTGTAGAACGCGAGGGGTCTTTTACCATTGACCACATTGA 
               
               
                   
               
               
                 GGGTGTGGAATTAGATAGCCCCCACATGCAAGAAAAAGATAAATGGGCAGGCAGAGAG 
               
               
                   
               
               
                 AAGTTAGCCAAAGCTATTCGCGCGTTTACTGAACCAATCATCTCAAACCAGTTCGGTCAT 
               
               
                   
               
               
                 GAGATCATGGATAAACTGTACGATAAGTTTACGCACATTGTTGTAAGTGATCTGGAGGCA 
               
               
                   
               
               
                 AAAATACCAAAAACTACTTCGATTATCCTCGTCCTGTCAAAAATAGTTGGCTAA 
               
               
                   
               
               
                 Polypeptide sequence encoded by the polynucleotide of SEQ ID NO: 65:  
               
               
                 (SEQ ID NO: 66) 
                   
               
               
                 MNRGEGESSDAQNSSFTQKGASMTMPVLENAVETLFSKDFHLLQALNAADFGCAAGPNTVI 
                   
               
               
                   
               
               
                 STIKRMMEKKCRELNCQTLELQVYLNDLPGNDFNTLFKGLSSKIVVGNKCEEVSCYAMGVP 
               
               
                   
               
               
                 GSFHGRLFPRNSLHLVHSSYSVHWLSQAPKGLRSREGLALNKGKIYISKTSPPVVREAYLSQF 
               
               
                   
               
               
                 HEDFTMFLNARSQEVVPNGCMVLILHGRKSSDPSNMESCFTWELLAIAIAELVSQGLIDEDKL 
               
               
                   
               
               
                 DTFNVPYYTPSLEEMKDIVEREGSFTIDHIEGVELDSPHMQEKDKWAGREKLAKAIRAFTEPII 
               
               
                   
               
               
                 SNQFGHEIMDKLYDKFTHIVVSDLEAKIPKTTSIILVLSKIVG 
               
               
                   
               
               
                 MXMT_33:  
               
               
                 (SEQ ID NO: 67) 
                   
               
               
                 ATGATGGAAGTTAAGGAAGCACTGTTCATGAATGGTGGTGAGGGCGAATCCTCTTATGC 
                   
               
               
                   
               
               
                 GCAAAATTCCAGTTTCACACAGAAAGTGGCGAGTATGACAATTCCTGTGTTGGAAATAG 
               
               
                   
               
               
                 CTGTGGAGACAATATTTTCTAAGGATTTCCATCTTTTACAAGCACTTAATGCCGCTGATCT 
               
               
                   
               
               
                 GGGGTGCGCAGCCGGACCAAATACATTTACGGTTATTTCAACTATTAAGCGCATGATGGA 
               
               
                   
               
               
                 AAAGAAATGCCGGGAGCTCAACTGCGAAACTTTGGAATTACAAGTATATCTTAATGATCT 
               
               
                   
               
               
                 TCCCGGCAATGACTTCAATACGTTGTTTAAAGGCCTGAGCAGTACGGATGTGGTTGGAAA 
               
               
                   
               
               
                 TAAGTGCGAAGAAGTTTCCTGTTATGTTATGGGTGTCCCAGGCTCGTTTCATGGTCGTCTG 
               
               
                   
               
               
                 TTTCCGCGTAACTCATTGCATTTGGTACATAGTTCTTATAGCGTTCATTGGTTATCCCAGG 
               
               
                   
               
               
                 CCCCAAAGGGCTTACGGTCTAGAGAAGGCCTGGCATTGAACAAAGGTAAAATCTACATT 
               
               
                   
               
               
                 AGTAAGACCTCACCACCTGTTGTTAGAGAGGCGTATCTGAGTCAGTTCCATGAAGATTTC 
               
               
                   
               
               
                 ACAATGTTCTTAAACGCCCGTAGTCAAGAAGTGGTTCCTAATGGGTGTATGGTCCTCATT 
               
               
                   
               
               
                 CTCCATGGAAGAAAATCATCCGATCCCTCCAAAATTGAATGCTGCTTTACTTGGGAATTA 
               
               
                   
               
               
                 TTGGCCATTGCTATCGCCGAACTTGTTTCCCAGGGGCTGATCGACGAGGATAAATTAGAC 
               
               
                   
               
               
                 ACCTTCAACGTGCCATACTACACGCCATCTCTGGAAGAGGTTAAGGACATTGTAGAACGC 
               
               
                   
               
               
                 GAGGGCTCGTTCACTATCGATCACATGGAGGGCCTGGAATTAGACTCTCCACAAATGCA 
               
               
                   
               
               
                 GGAAAAAGATAAATGGGTACGGGGTGAAAAACTGGCGAAAGCGGTACGCGCATTCACG 
               
               
                   
               
               
                 GAACCAATAATATCCAACCAGTTTGGTCACGAAATTATGGACAAGCTTTATGACAAATTC 
               
               
                   
               
               
                 ACTCACATCGTAGTATCAGACCTTGAAGCCAAAAAGCCTAAAACTACCAGTATAATTTTG 
               
               
                   
               
               
                 GTGCTGAGCAAAATTGTTGGCTAA 
               
               
                   
               
               
                 Polypeptide sequence encoded by the polynucleotide of SEQ ID NO: 67:  
               
               
                 (SEQ ID NO: 68) 
                   
               
               
                 MMEVKEALFMNGGEGESSYAQNSSFTQKVASMTIPVLEIAVETIFSKDFHLLQALNAADLGC 
                   
               
               
                   
               
               
                 AAGPNTFTVISTIKRMMEKKCRELNCETLELQVYLNDLPGNDFNTLFKGLSSTDVVGNKCEE 
               
               
                   
               
               
                 VSCYVMGVPGSFHGRLFPRNSLHLVHSSYSVHWLSQAPKGLRSREGLALNKGKIYISKTSPPV 
               
               
                   
               
               
                 VREAYLSQFHEDFTMFLNARSQEVVPNGCMVLILHGRKSSDPSKIECCFTWELLAIAIAELVS 
               
               
                   
               
               
                 QGLIDEDKLDTFNVPYYTPSLEEVKDIVEREGSFTIDHMEGLELDSPQMQEKDKWVRGEKLA 
               
               
                   
               
               
                 KAVRAFTEPIISNQFGHEIMDKLYDKFTHIVVSDLEAKKPKTTSIILVLSKIVG 
               
               
                   
               
               
                 MXMT_34:  
               
               
                 (SEQ ID NO: 69) 
                   
               
               
                 ATGATGGAGGTGAAAGAGGCCCTTTTTATGAATGGTGGCGAGGGAGAATCGTCTTACGC 
                   
               
               
                   
               
               
                 CCAGAACAGTTCATTTACGCAAAAGGTTGCCTCTATGACTATGCCTGTGCTTGAAATTGC 
               
               
                   
               
               
                 AGTTGAAACGTTACTGAGCAAAGACTTCCATTTACTGCAGGCCCTGAACGTAGCGGATCT 
               
               
                   
               
               
                 GGGGTGTGCGGCCGGTCCGAATACATTTACCGTAATATCCACCATTAAACGGATGATGG 
               
               
                   
               
               
                 AAAAGAAATGTCGCGAACTGAATTGTCAGACGCTGGAATTGCAAGTTTACCTTAACGAT 
               
               
                   
               
               
                 CTGCCGGGGAATGATTTTAACACACTGTTCAAAGGCCTCAGCTCAAAGGTTGTTGTAGGT 
               
               
                   
               
               
                 AACAAATGCGAGGAAGTTAGCTGTTATGCTATGGGCGTCCCAGGTAGCTTCCACGGTAG 
               
               
                   
               
               
                 ATTATTTCCACGGAATTCGTTACACTTGGTCCACTCCAGCTATTCAGTGCACTGGCTGTCC 
               
               
                   
               
               
                 CAAGCACCTAAAGGCCTCCGGTCAAGAGAAGGGCTGGCGCTTAACAAAGGTAAAATCTA 
               
               
                   
               
               
                 CATAAGTAAGACATCTCCCCCAGTTGTTAGAGAAGCGTATTTGTCCCAGTTTCATGAAGA 
               
               
                   
               
               
                 CTTTACAATGTTCTTGAATGCTCGCTCCCAGGAGGTTGTACCCAATGGATGCATGGTCCT 
               
               
                   
               
               
                 GATCTTGCACGGAAGAAAATCAAGTGATCCTAGCAACATGGAGTCATGCTTCACATGGG 
               
               
                   
               
               
                 AACTGTTAGCGATTGCGATTGCCGGGCTTGTCTCACAGGGCTTAATAGACGAAGACAAA 
               
               
                   
               
               
                 CTCGATACGTTTAACGTGCCCTATTACACCCCGAGCCTCGAAGAAGTAAAAGACATAGTG 
               
               
                   
               
               
                 GAACGCGAAGGCAGTTTCACTATCGATCACATGGAAGGATTAGAATTAGATAATCCTCA 
               
               
                   
               
               
                 CATGCAGGAAAAAGACAAATGGGTACGTGGTGCTAAACTGGCTAAAGCTGTGCGCGCGT 
               
               
                   
               
               
                 TTACGGAGCCGATTATCAGCAAACAATTCGGCCATGAGATTATGAATAAGCTGTATGATA 
               
               
                   
               
               
                 AATTCACACATATTGTCGTTAGTGAGCTCGAGGCCAAGAAACCTAAGACTACCAGTATA 
               
               
                   
               
               
                 ATTCTTGTCTTGAGCAAAATAGTTGGGTAA 
               
               
                   
               
               
                 Polypeptide sequence encoded by the polynucleotide of SEQ ID NO: 69:  
               
               
                 (SEQ ID NO: 70) 
                   
               
               
                 MMEVKEALFMNGGEGESSYAQNSSFTQKVASMTMPVLEIAVETLLSKDFHLLQALNVADLG 
                   
               
               
                   
               
               
                 CAAGPNTFTVISTIKRMMEKKCRELNCQTLELQVYLNDLPGNDFNTLFKGLSSKVVVGNKCE 
               
               
                   
               
               
                 EVSCYAMGVPGSFHGRLFPRNSLHLVHSSYSVHWLSQAPKGLRSREGLALNKGKIYISKTSPP 
               
               
                   
               
               
                 VVREAYLSQFHEDFTMFLNARSQEVVPNGCMVLILHGRKSSDPSNMESCFTWELLAIAIAGL 
               
               
                   
               
               
                 VSQGLIDEDKLDTFNVPYYTPSLEEVKDIVEREGSFTIDHMEGLELDNPHMQEKDKWVRGAK 
               
               
                   
               
               
                 LAKAVRAFTEPIISKQFGHEIMNKLYDKFTHIVVSELEAKKPKTTSIILVLSKIVG 
               
               
                   
               
               
                 MXMT_35:  
               
               
                 (SEQ ID NO: 71) 
                   
               
               
                 ATGGGCAAAGTTAACGAAGTTTTATTCATGAACCGCGGAGAGGGGGAGATCTCATACGC 
                   
               
               
                   
               
               
                 ACAGAATTCAGCGTTTACCCAAAAAGTTGCGAGCATGGCAATGCCGGCCTTGGAGAACG 
               
               
                   
               
               
                 CGGTTGAGACTTTGTTTAGCAAAGACTTTCATTTACTTCAGGCACTTACTGCTGCTGATCT 
               
               
                   
               
               
                 TGGCTGTGCTGCCGGGCCGAATACCTTCGCCGTTATTTCTACGATTAAGCGGATGATGGA 
               
               
                   
               
               
                 GAAGAAATGTAGAGAATTATACTGCCAAACGCTCGAACTGCAGGTATATTTGAACGACC 
               
               
                   
               
               
                 TGTTCGGAAATGATTTCAATACCCTCTTCAAAGGCCTCTCATCAGAAGTTGTCGGCAATA 
               
               
                   
               
               
                 AGTGCGAAGAAGTATCCTGCTATGTTATGGGTGTTCCTGGGTCATTCCATGGACGTTTAT 
               
               
                   
               
               
                 TTCCCCGCAATTCATTGCATTTAGTTCACTCAAGCTACTCAGTGCATTGGCTGACCCAGGC 
               
               
                   
               
               
                 CCCAAAAGGCTTAACAAGTCGGGAAGGCCTCGCATTGAACAAAGGCAAGATATATATCT 
               
               
                   
               
               
                 CTAAAACATCACCGCCAGTTGTGAAAGAAGCGTACCTGTCGCAGTTTCACGAAGATTTTA 
               
               
                   
               
               
                 CTATGTTCTTAAATGCGCGCTCTCAGGAAGTAGTGCCCAATGGTTGCATGGTTTTGATCCT 
               
               
                   
               
               
                 GCATGGACGTCAAAGTTCCGATCCCTCAGAAATGGAGTCCTGCTTTACTTGGGAGCTGCT 
               
               
                   
               
               
                 CGCGATTGCTATTGCAGAGTTAGTGTCGCAAGGTTTGATCGATGAAGACAAATTGGATAC 
               
               
                   
               
               
                 CTTTAACGTGCCAAGCTATTGGCCATCTCTTGAAGAAGTGAAAGATATCGTCGAACGTGA 
               
               
                   
               
               
                 TGGCAGTTTCACTATTGACCATTTGGAGGGTTTCGAATTGGACTCTCTGGAGATGCAGGA 
               
               
                   
               
               
                 AAACGACAAATGGGTTCGCGGAGATAAATTTGCTAAGATGGTGCGGGCCTTTACTGAAC 
               
               
                   
               
               
                 CGATTATTTCAAACCAGTTCGGCCACGAGATTATGGACAAACTGTATGATAAATTTACCC 
               
               
                   
               
               
                 ACATTCTGGTTAGTGACCTTGAAGCAGAACTGCCGAAGACAACCAGCATTATTCTGGTAT 
               
               
                   
               
               
                 TGTCGAAGATAGTTGGGTAA 
               
               
                   
               
               
                 Polypeptide sequence encoded by the polynucleotide of SEQ ID NO: 71:  
               
               
                 (SEQ ID NO: 72) 
                   
               
               
                 MGKVNEVLFMNRGEGEISYAQNSAFTQKVASMAMPALENAVETLFSKDFHLLQALTAADL 
                   
               
               
                   
               
               
                 GCAAGPNTFAVISTIKRMMEKKCRELYCQTLELQVYLNDLFGNDFNTLFKGLSSEVVGNKCE 
               
               
                   
               
               
                 EVSCYVMGVPGSFHGRLFPRNSLHLVHSSYSVHWLTQAPKGLTSREGLALNKGKIYISKTSPP 
               
               
                   
               
               
                 VVKEAYLSQFHEDFTMFLNARSQEVVPNGCMVLILHGRQSSDPSEMESCFTWELLAIAIAEL 
               
               
                   
               
               
                 VSQGLIDEDKLDTFNVPSYWPSLEEVKDIVERDGSFTIDHLEGFELDSLEMQENDKWVRGDK 
               
               
                   
               
               
                 FAKMVRAFTEPIISNQFGHEIMDKLYDKFTHILVSDLEAELPKTTSIILVLSKIVG 
               
               
                   
               
               
                 DXMT_36:  
               
               
                 (SEQ ID NO: 73) 
                   
               
               
                 ATGGAACTCGCTACTGCCGGTAAGGTTAATGAGGTTCTGTTTATGAACAGAGGCGAGGG 
                   
               
               
                   
               
               
                 CGAATCTAGTTACGCACAAAACAGCTCATTTACACAGCAAGTCGCGAGCATGGCCCAGC 
               
               
                   
               
               
                 CCGCGCTCGAAAATGCAGTTGAAACGCTGTTTAGCAGAGATTTTCACTTACAAGCACTCA 
               
               
                   
               
               
                 ACGCTGCAGATCTGGGATGTGCTGCAGGCCCGAACACGTTTGCGGTAATCTCAACCATCA 
               
               
                   
               
               
                 AACGCATGATGGAGAAAAAGTGCCGGGAATTGAACTGTCAGACCCTGGAGTTACAGGTG 
               
               
                   
               
               
                 TACCTGAATGACCTGTTCGGCAATGACTTTAATACTCTGTTCAAGGGCCTCAGCAGTGAG 
               
               
                   
               
               
                 GTAATAGGTAATAAGTGCGAAGAAGTGAGCTGCTACGTAATGGGAGTGCCAGGTAGTTT 
               
               
                   
               
               
                 TCATGGACGGCTTTTCCCGCGCAATTCTCTTCACCTCGTTCACTCGAGCTATAGCGTTCAT 
               
               
                   
               
               
                 TGGTTAACACAAGCACCAAAGGGATTAACAAGCAGAGAGGGTTTAGCCTTGAACAAAGG 
               
               
                   
               
               
                 AAAAATCTACATCAGCAAAACTTCTCCGCCCGTAGTTAGAGAAGCGTACCTGTCACAATT 
               
               
                   
               
               
                 TCACGAGGACTTTACCATGTTCCTCAATGCGAGATCTCAGGAGGTGGTCCCCAACGGCTG 
               
               
                   
               
               
                 CATGGTTCTCATTCTGCGCGGGAGACAATGCTCAGATCCATCAGACATGCAATCTTGTTT 
               
               
                   
               
               
                 CACCTGGGAGCTGTTAGCCATGGCCATAGCCGAGCTCGTTTCGCAAGGCTTGATAGATGA 
               
               
                   
               
               
                 AGACAAGTTGGACACTTTTAATATACCCTCATATTTTGCTAGCCTGGAGGAGGTAAAGGA 
               
               
                   
               
               
                 CATTGTGGAGCGGGACGGCAGTTTTACAATCGACCATATAGAGGGGTTCGATCTCGATTC 
               
               
                   
               
               
                 ACTTGAGATGCAGGAGAACGACAAATGGGTCCGCGGCGAAAAATTTACTAAAGTAGTGC 
               
               
                   
               
               
                 GGGCCTTTACAGAACCCATTATCTCAAATCAGTTTGGACACGAAATCATGGATAAGCTGT 
               
               
                   
               
               
                 ATGATAAGTTCACTCACATCGTGGTCAGCGACTTGGAGGCGAAACTTCCCAAAACTACCA 
               
               
                   
               
               
                 GTATCTAA 
               
               
                   
               
               
                 Polypeptide sequence encoded by the polynucleotide of SEQ ID NO: 73:  
               
               
                 (SEQ ID NO: 74) 
                   
               
               
                 MELATAGKVNEVLFMNRGEGESSYAQNSSFTQQVASMAQPALENAVETLFSRDFHLQALNA 
                   
               
               
                   
               
               
                 ADLGCAAGPNTFAVISTIKRMMEKKCRELNCQTLELQVYLNDLFGNDFNTLFKGLSSEVIGN 
               
               
                   
               
               
                 KCEEVSCYVMGVPGSFHGRLFPRNSLHLVHSSYSVHWLTQAPKGLTSREGLALNKGKIYISK 
               
               
                   
               
               
                 TSPPVVREAYLSQFHEDFTMFLNARSQEVVPNGCMVLILRGRQCSDPSDMQSCFTWELLAM 
               
               
                   
               
               
                 AIAELVSQGLIDEDKLDTFNIPSYFASLEEVKDIVERDGSFTIDHIEGFDLDSLEMQENDKWVR 
               
               
                   
               
               
                 GEKFTKVVRAFTEPIISNQFGHEIMDKLYDKFTHIVVSDLEAKLPKTTSI 
               
               
                   
               
               
                 DXMT_37:  
               
               
                 (SEQ ID NO: 75) 
                   
               
               
                 ATGAATACCGGTGAGGGTGAAAGCTCATATCTTCTTAACTCCAAATTTACCAACGTGACG 
                   
               
               
                   
               
               
                 GCAATCAAGAGCATCCCTACCCTGAAGCGCGCCATTGAATCACTCTTTAAAGAGGAAAG 
               
               
                   
               
               
                 CCCGCCCTTTGAGCATTTACTGAACGTAGCGGATCTTGGATGTGCGTCTGGATCAACATC 
               
               
                   
               
               
                 GAATACCATTATGCCAACCGTAGTCCAGACGGTGGTTAATAAATGCCGTGAACTCAACC 
               
               
                   
               
               
                 ATAAAATTCCAGAATTCCAATTCTATCTGAATGATCTCCCTAGCAACGACTTTAATACTCT 
               
               
                   
               
               
                 GTTCAAGGGTCTGAACGGATTTGTGGGAAGCGGAGGAGAAGAGTTCGAGAATACGTCTT 
               
               
                   
               
               
                 GCCTTGTAATGGGTGCACCTGGCAGTTTTCATGGGCGCTTATTTCCACTCAACACGATAC 
               
               
                   
               
               
                 ATCTGGTATACTCAAATTATTCGGTTCACTGGTTGAGTAAAGTTCCCGATTTGCGCGACG 
               
               
                   
               
               
                 AAAAAGGTAACCCCATCAACAAAGGGACATTCTACATTAGCAAAACAAGCCCCAGTGGA 
               
               
                   
               
               
                 GTGCGTGAAGCTTATTTGGCACAATTTCAGAAAGATTTTACATTATTCTTGAAGTCCCGT 
               
               
                   
               
               
                 GCAGAAGAAATGGTTTCAAACGGTCGCGTAGTTCTCGTCTTGCACGGTCGTCTGAGTCAA 
               
               
                   
               
               
                 GACTTTAGCTGCGAAAAAGAGCTTCAACTGCCCTGGCTGATTTTGAGTCAAGCCATATCG 
               
               
                   
               
               
                 CGCCTGGTATCAAAAGGCTTGATCGACGAAGAGAAACTCGACTCATTTGAAGTACCGTA 
               
               
                   
               
               
                 CTATACTCCAAGCGTGCAGGAAGTGAAGGAATTGGTCGAAGGAGAAGGGTCGTACGCTG 
               
               
                   
               
               
                 TAGAGTTGATGGAAACTTTTACTATCCGTATCGGGGCTCGGAATGAAGGTATTTGGTCCG 
               
               
                   
               
               
                 ATGCAAGAGGTTTTGGAAATAACCTGCGTTCCATCACGGAAACGATGATAAGCCACCAC 
               
               
                   
               
               
                 TTCGGCCCGCAGATACTCGATGAGTTGTACGATGAGATTCAGGATTTACCTCTGCAGGAC 
               
               
                   
               
               
                 TTTGCAACACAGTGCTCATTCGTTGTCGGCTTAAAAAGAAATTAA 
               
               
                   
               
               
                 Polypeptide sequence encoded by the polynucleotide of SEQ ID NO: 75:  
               
               
                 (SEQ ID NO: 76) 
                   
               
               
                 MNTGEGESSYLLNSKFTNVTAIKSIPTLKRAIESLFKEESPPFEHLLNVADLGCASGSTSNTIMP 
                   
               
               
                   
               
               
                 TVVQTVVNKCRELNHKIPEFQFYLNDLPSNDFNTLFKGLNGFVGSGGEEFENTSCLVMGAPG 
               
               
                   
               
               
                 SFHGRLFPLNTIHLVYSNYSVHWLSKVPDLRDEKGNPINKGTFYISKTSPSGVREAYLAQFQK 
               
               
                   
               
               
                 DFTLFLKSRAEEMVSNGRVVLVLHGRLSQDFSCEKELQLPWLILSQAISRLVSKGLIDEEKLD 
               
               
                   
               
               
                 SFEVPYYTPSVQEVKELVEGEGSYAVELMETFTIRIGARNEGIWSDARGFGNNLRSITETMISH 
               
               
                   
               
               
                 HFGPQILDELYDEIQDLPLQDFATQCSFVVGLKRN  
               
               
                   
               
               
                 DXMT_38:  
               
               
                 (SEQ ID NO: 77) 
                   
               
               
                 ATGGATATGAAAGACGTGCTTTGCATGAATACCGGTGAGGGCGAGAGTTCGTACTTGCT 
                   
               
               
                   
               
               
                 GAATAGCAAGTTCACAAACGTAACAGCTATCAAATCTATCCCCACTCTTAAGAGAGCAA 
               
               
                   
               
               
                 TTGAATCGCTCTTCAAGGAAGAATCCCCTCCATTTGAACACTTATTGAATGTAGCCGATT 
               
               
                   
               
               
                 TAGGATGCGCCTCCGGCAGTACGAGTAATACGATAATGCCTACCGTGGTCCAAACGGTG 
               
               
                   
               
               
                 GTAAACAAATGTCGCGAACTGAACCACAAAATTCCTGAATTTCAATTCTACCTGAATGAC 
               
               
                   
               
               
                 TTGCCGTCAAATGACTTCAATACGTTGTTCAAGGGACTTAATGGATTTGTAGGTAGCGGT 
               
               
                   
               
               
                 GGTGAGGAATTTGAAAATACGAGTTGTCTCGTGATGGGTGCGCCCTAA 
               
               
                   
               
               
                 Polypeptide sequence encoded by the polynucleotide of SEQ ID NO: 77:  
               
               
                 (SEQ ID NO: 78) 
                   
               
               
                 MDMKDVLCMNTGEGESSYLLNSKFTNVTAIKSIPTLKRAIESLFKEESPPFEHLLNVADLGCA 
                   
               
               
                 SGSTSNTIMPTVVQTVVNKCRELNHKIPEFQFYLNDLPSNDFNTLFKGLNGFVGSGGEEFENT 
               
               
                 SCLVMGAP 
               
               
                   
               
               
                 DXMT_39:  
               
               
                 (SEQ ID NO: 79) 
                   
               
               
                 ATGGAACTGGCAACCGCAGGAAAAGTAAATGAAGTACTCTTTATGAACCGCGGCGAAGG 
                   
               
               
                   
               
               
                 AGAAAGCTCGTATGCCCAGAATTCAAGCTTTACACAGCAAGTTGCTTCTATGGCCCAGCC 
               
               
                   
               
               
                 AGCTCTTGAAAACGCTGTCGAAACTTTGTTCTCCCGGGATTTTCATCTCCAGGCTCTTAAC 
               
               
                   
               
               
                 GCTGCTGATTTGGGGTGCGCTGCAGGACCTAATACTTTCGCGGTCATCTCAACAATTAAA 
               
               
                   
               
               
                 CGCATGATGGAGAAGAAGTGTCGCGAACTCAACTGCCAGACGCTCGAACTCCAAGTCTA 
               
               
                   
               
               
                 CCTCAACGACCTCTTTGGGAACGACTTTAACACGCTGTTTAAAGGCTTGTCGAGTGAAGT 
               
               
                   
               
               
                 CATCGGAAATAAGTGTGAGGAGGTTAGTTGCTACGTGATGGGAGTACCGGGGTCATTCC 
               
               
                   
               
               
                 ACGGTCGTCTGTTTCCCAGAAACTCTCTGCATCTTGTCCATTCCTCATACTCAGTACATTG 
               
               
                   
               
               
                 GCTTACTCAGGCCCCAAAGGGCCTTACAAGCCGTGAAGGTCTGGCACTGAACAAGGGCA 
               
               
                   
               
               
                 AAATTTATATATCCAAGACTAGCCCTCCCGTTGTAAGAGAATCCTATTTATCCCAGTTCC 
               
               
                   
               
               
                 ATGAGGATTCCCAATGTTTTAGCATGTTAGACCCACGCGGGGGCTCACAGTGGTAA 
               
               
                   
               
               
                 Polypeptide sequence encoded by the polynucleotide of SEQ ID NO: 79:  
               
               
                 (SEQ ID NO: 80) 
                   
               
               
                 MELATAGKVNEVLFMNRGEGESSYAQNSSFTQQVASMAQPALENAVETLFSRDFHLQALNA 
                   
               
               
                   
               
               
                 ADLGCAAGPNTFAVISTIKRMMEKKCRELNCQTLELQVYLNDLFGNDFNTLFKGLSSEVIGN 
               
               
                   
               
               
                 KCEEVSCYVMGVPGSFHGRLFPRNSLHLVHSSYSVHWLTQAPKGLTSREGLALNKGKIYISK 
               
               
                   
               
               
                 TSPPVVRESYLSQFHEDSQCFSMLDPRGGSQW 
               
               
                   
               
               
                 DXMT_40:  
               
               
                 (SEQ ID NO: 81) 
                   
               
               
                 ATGGAAGTGAAAGAGATGTTATTCATGAATAAAGGCGATGGCGAAAATTCATACGTGAA 
                   
               
               
                   
               
               
                 AACATCGGGTTACACTCAGAAAGTGGCGGCCGTGACGCAACCCGTTGTATATCGGGCAG 
               
               
                   
               
               
                 CTCAGAGCCTGTTCACTGGTCGGAATTCTTGTAGTTATCAGGTTCTCAATGTCGCGGATTT 
               
               
                   
               
               
                 AGGGTGCTCAAGCGGACCTAATACCTTTACAGTGATGAGCACAGTGATTGAATCAACTC 
               
               
                   
               
               
                 GTGACAAATGCAGTGAGCTCAACTGGCAGATGCCAGAAATCCAGTTTTATCTGAATGATC 
               
               
                   
               
               
                 TGGTCGGTAACGATTTTAACACCTTGTTTAAAGGCCTGTCAGTTATACAGGATAAGTACA 
               
               
                   
               
               
                 AAAATGTAAGCTGTTTCGCCATGGGAGCTCCGGGCTCATTTCATGGACGTTTATTTCCCC 
               
               
                   
               
               
                 AAAACAGCATGCACCTCATACATAGCAGCTATGGGGTACAGTGGCTCTCTAAAGTACCG 
               
               
                   
               
               
                 AAAATGACCTCAGAAGGTGGTTTATCGCCGCCAAATAAAGGCAAAATTTATATCTCGAA 
               
               
                   
               
               
                 AACGTCTCCGCCCGCCGTGTGGAAAGCTTACCTCAGTCAATTTCAGGAGGACTTTTTAAG 
               
               
                   
               
               
                 TTTCTTGCGTTGTCGCAGTCCGGAGCTGGTTCCAGATGGACGCATGGTGCTCATTATTCAT 
               
               
                   
               
               
                 GGCCGTAAATCAGCTGACCCGACCACTAGAGAAAGCTGTTATACATGGGAAGTGCTTGC 
               
               
                   
               
               
                 AGATGCTATATCCTACCAGGTATCGCAAGGCTTAATTGACGAGGAAAAACTGAACTCCTT 
               
               
                   
               
               
                 CAATGTCCCTTACTATATTCCTAGTCAGGAAGAGGTACGGGATTTGGTTAATAAAGAAGG 
               
               
                   
               
               
                 CAGCTTCTTAACGGAGTTTGTAGACACAATCGAAGTAGAACTGGAGGGAATCTGGACTG 
               
               
                   
               
               
                 GCCCGGAAAACGGTGCCAAAAACCTGCGCAGCTTCACAGAACCAATGATTTCCCATCAG 
               
               
                   
               
               
                 TTCGGTGAGGAAGTCATGGACAAGCTGTATGACAAGGTCAAAGATATTCTGGTTGAGGA 
               
               
                   
               
               
                 CTGCAAACAAGAAAAACAATCTACGAGAGGAGTCTCTATAGTACTTGAGCTCAAAAAGA 
               
               
                   
               
               
                 AAGAGAGCCACCTTAGCTAA 
               
               
                   
               
               
                 Polypeptide sequence encoded by the polynucleotide of SEQ ID NO: 81:  
               
               
                 (SEQ ID NO: 82) 
                   
               
               
                 MEVKEMLFMNKGDGENSYVKTSGYTQKVAAVTQPVVYRAAQSLFTGRNSCSYQVLNVAD 
                   
               
               
                   
               
               
                 LGCSSGPNTFTVMSTVIESTRDKCSELNWQMPEIQFYLNDLVGNDFNTLFKGLSVIQDKYKN 
               
               
                   
               
               
                 VSCFAMGAPGSFHGRLFPQNSMHUHSSYGVQWLSKVPKMTSEGGLSPPNKGKIYISKTSPPA 
               
               
                   
               
               
                 VWKAYLSQFQEDFLSFLRCRSPELVPDGRMVLIIHGRKSADPTTRESCYTWEVLADAISYQVS 
               
               
                   
               
               
                 QGLIDEEKLNSFNVPYYIPSQEEVRDLVNKEGSFLTEFVDTIEVELEGIWTGPENGAKNLRSFT 
               
               
                   
               
               
                 EPMISHQFGEEVMDKLYDKVKDILVEDCKQEKQSTRGVSIVLELKKKESHLS 
               
               
                   
               
               
                 XMT_41:  
               
               
                 (SEQ ID NO: 83) 
                   
               
               
                 ATGGAGCTCCAAGAAGTCCTGCGGATGAATGGAGGCGAAGGCGATACAAGCTACGCCAA 
                   
               
               
                   
               
               
                 GAATTCAGCCTACAATCAACTGGTTCTCGCCAAGGTGAAACCTGTCCTTGAACAATGCGT 
               
               
                   
               
               
                 ACGGGAATTGTTGCGGGCCAACTTGCCCAACATCAACAAGTGCATTAAAGTTGCGGATTT 
               
               
                   
               
               
                 GGGATGCGCTTCTGGACCAAACACACTTTTAACGGTTCGGGACATTGTCCAAAGTATTGA 
               
               
                   
               
               
                 CAAAGTTGGCCAGGAAAAGAAGAATGAATTAGAACGTCCCACCATTCAGATTTTTCTGA 
               
               
                   
               
               
                 ATGATCTTTTCCCAAATGATTTCAATTCGGTTTTCAAGTTGCTGCCAAGCTTCTACCGCAA 
               
               
                   
               
               
                 ACTTGAGAAAGAAAATGGACGCAAAATAGGATCGTGCCTAATAGGGGCAATGCCCGGCT 
               
               
                   
               
               
                 CTTTCTACAGCAGACTCTTCCCCGAGGAGTCCATGCATTTTTTACACTCTTGTTACTGTCT 
               
               
                   
               
               
                 TCAATGGTTATCTCAGGTTCCTAGCGGTTTGGTGACTGAATTGGGGATCGGCACGAACAA 
               
               
                   
               
               
                 AGGGAGCATTTACTCTTCCAAAGCAAGTCGTCTGCCCGTCCAGAAGGCATATTTGGATCA 
               
               
                   
               
               
                 ATTTACGAAAGATTTTACCACATTTCTAAGGATTCATTCGGAAGAGTTGTTTTCACATGG 
               
               
                   
               
               
                 CCGAATGCTCCTTACTTGCATTTGTAAAGGAGTTGAATTAGACGCCCGGAATGCCATAGA 
               
               
                   
               
               
                 CTTACTTGAGATGGCAATAAACGACTTGGTTGTTGAGGGACATCTGGAGGAAGAAAAAT 
               
               
                   
               
               
                 TGGATAGTTTCAATCTTCCAGTCTATATACCTTCAGCAGAAGAAGTAAAGTGCATAGTTG 
               
               
                   
               
               
                 AGGAGGAAGGTTCTTTTGAAATTTTATACCTGGAGACTTTTAAGGTCCTTTACGATGCTG 
               
               
                   
               
               
                 GCTTCTCTATTGACGATGAACATATTAAAGCAGAGTATGTTGCATCTTCCGTTAGAGCAG 
               
               
                   
               
               
                 TTTACGAACCCATCCTCGCAAGTCATTTTGGAGAAGCTATTATACCTGACATATTCCACA 
               
               
                   
               
               
                 GGTTTGCGAAGCATGCAGCAAAGGTTCTCCCCTTGGGCAAAGGCTTCTATAATAATCTTA 
               
               
                   
               
               
                 TCATTTCTCTCGCCAAAAAGCCAGAGAAGTCAGACATGTAA 
               
               
                   
               
               
                 Polypeptide sequence encoded by the polynucleotide of SEQ ID NO: 83:  
               
               
                 (SEQ ID NO: 84) 
                   
               
               
                 MELQEVLRMNGGEGDTSYAKNSAYNQLVLAKVKPVLEQCVRELLRANLPNINKCIKVADLG 
                   
               
               
                   
               
               
                 CASGPNTLLTVRDIVQSIDKVGQEKKNELERPTIQIFLNDLFPNDFNSVFKLLPSFYRKLEKEN 
               
               
                   
               
               
                 GRKIGSCLIGAMPGSFYSRLFPEESMHFLHSCYCLQWLSQVPSGLVTELGIGTNKGSIYSSKAS 
               
               
                   
               
               
                 RLPVQKAYLDQFTKDFTTFLRIHSEELFSHGRMLLTCICKGVELDARNAIDLLEMAINDLVVE 
               
               
                   
               
               
                 GHLEEEKLDSFNLPVYIPSAEEVKCIVEEEGSFEILYLETFKVLYDAGFSIDDEHIKAEYVASSV 
               
               
                   
               
               
                 RAVYEPILASHFGEAIIPDIFHRFAKHAAKVLPLGKGFYNNLIISLAKKPEKSDM 
               
            
           
         
       
     
     Example 1 
     Guanine Deaminase (GDA) Gene Acquisition and Plasmid Construction 
     Nine genes with putative guanine deaminase activity were codon optimized and synthesized (SEQ ID NOS: 1, 3, 5, 7, 9, 11, 13, 15, and 17). Additionally, GDA genes were PCR amplified from both  E. coli  W3110 and  E. coli  BL-21 gDNA (SEQ ID NOS19 and 21). The nine synthetic and two PCR amplified (11 total) GDA genes were cloned into the pCK110900 vector system (See e.g., US Patent Application Publication 2006/0195947) under the control of a lac promoter. This expression vector also contains the P15a origin of replication and the chloramphenicol resistance gene. The resulting plasmids were transformed into  E. coli  W3110 using standard methods known in the art and the enzymes produced as described in Example 2. 
     Example 2 
     High-Throughput (HTP) Expression and Activity Assays of Guanine Deaminase (GDA) Variants 
     The putative guanine deaminase (GDA) polypeptides described in Example 1, were produced in host  E. coli  W3110 as an intracellular protein expressed under the control of the lac promoter. The polypeptides are designed to accumulate primarily as soluble cytosolic enzymes. 
     High-Throughput Growth and Expression (HTP) 
     Single  E. coli  colonies of each variant were picked and grown for approximately 16-18 hours in LB media containing 1% glucose and 30 μg/mL chloramphenicol (CAM) under culture conditions of 30° C., 200 rpm, and 85% humidity. A 20 μL aliquot of this overnight growth was transferred to a deep well plate containing 380 μL Terrific Broth (TB) growth media containing 30 μg/mL CAM. The culture was incubated in a shaker for 2 hours at 30° C. and at 250 rpm to an OD 600  of about 0.6 to 0.8. The expression of the heterologous GDA genes was then induced with IPTG (1 mM final concentration). Incubation was continued for about 18 hours under the same conditions. After expression, cell cultures were centrifuged at 4000 rpm, 4° C. for 10 min., and the media discarded. Cell pellets were resuspended in 300 μL Lysis Buffer (20 mM Tris-HCl pH=7.5 containing 500 μg/mL polymyxin B sulfate (PMBS) and 500 μg/mL lysozyme) and shaken at room temperature for two hours. After lysis, cell debris was centrifuged at 4000 rpm, 4° C. for 10 min., and the resulting lysates were stored at 4° C. 
     HTP Assay for GDA Activity 
     For each plate, 30 μL of HTP GDA lysates produced as describe above, were diluted into 1 mL of water. Twenty microliters of diluted lysates were then added to 180 μL of guanine solution (50 mM Tris-HCl pH=7.5, 30 μM guanine) at room temperature and absorbance measurements were immediately tracked at 245 nm and at 15 second intervals. GDA activity was determined based on the rate of depletion of the absorbance signal at 245 nm resulting from the conversion of guanine (with absorption peaks at about 245 and 270 nm) to xanthine (with a single absorption peak at about 270 nm only). After reacting for about 1 hr., the reactions were quenched with 50 μL of acetonitrile plus 0.2% formic acid, spun down at 4000 rpm for 5 min. and the supernatants were run on the HPLC to confirm the conversion of guanine to xanthine. 
     After one hour, GDA assay reactions with all nine GDA variants resulted in the complete conversion of guanine to xanthine as confirmed by HPLC analysis. 
     
       
         
           
               
             
               
                 TABLE 2 
               
               
                   
               
               
                 Relative Activities 1  for Guanine Deaminase (GDA) Variants 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 GDA_01 
                 (SEQ ID NO: 2) 
                 +++ 
               
               
                   
                 GDA_02 
                 (SEQ ID NO: 4) 
                 +++ 
               
               
                   
                 GDA_03 
                 (SEQ ID NO: 6) 
                 +++ 
               
               
                   
                 GDA_04 
                 (SEQ ID NO: 8) 
                 +++ 
               
               
                   
                 GDA_05 
                 (SEQ ID NO: 10) 
                 + 
               
               
                   
                 GDA_06 
                 (SEQ ID NO: 12) 
                 +++ 
               
               
                   
                 GDA_07 
                 (SEQ ID NO: 14) 
                 ++ 
               
               
                   
                 GDA_08 
                 (SEQ ID NO: 16) 
                 ++ 
               
               
                   
                 GDA_09 
                 (SEQ ID NO: 18) 
                 + 
               
               
                   
                 GDA_10 
                 (SEQ ID NO: 20) 
                 +++ 
               
               
                   
                 GDA_11 
                 (SEQ ID NO: 22) 
                 +++ 
               
               
                   
                   
               
               
                   
                   1 Key: 
               
               
                   
                 + = full conversion of 30 μM guanine to xanthine in &gt;10 minutes 
               
               
                   
                 ++ = full conversion of 30 μM guanine to xanthine in &lt;10 minutes 
               
               
                   
                 +++ = full conversion of 30 μM guanine to xanthine in &lt;3 minutes 
               
            
           
         
       
     
     Example 3 
     HPLC Analysis of Assay Samples 
     After running the high-throughput (HTP) or shake flask (SF) assays as described above, samples were quenched with acetonitrile (final concentration of acetonitrile was 20% v/v), shaken for minutes and spun to precipitate any particulates. The samples were then analyzed using an LC-UV assay by injecting 10 μL of the quenched reaction onto a 5 μL loop and resolved using the method described below. 
     Briefly, conversion to products of interest was determined using an Agilent 1200 HPLC equipped with a Phenomenex Luna C18 (2) column (4.6×250 mm, Sum). Solvents for LC analysis were 0.1% formic acid in water (A) and methanol (B). Products were resolved using the following gradient: t=0 min, 1% B; 7 min, 50% B; 7.75 min, 90% B; 8.0 min, 1% B, total run time is 10 min. The flow rate for the separation was 1.5 ml/min and a column temperature was ambient (approximately 21° C.). Retention times for key products: guanine=3.1 min; xanthine=4.5 min; 7-methyl-xanthine=5.4 min; 3-methyl-xanthine=5.8 min; 1-methyl-xanthine=6.2 min; theobromine=6.5 min; 1,7-dimethyl-xanthine=7.3 min; 1,3-dimethyl-xanthine=7.6 min; caffeine=8.3 min. Products in the eluant were determined as the peak area at 265 nm, with a path length of 1 cm. 
     Example 4 
     Methyltransferase (MT) Gene Acquisition and Plasmid Construction 
     Thirty-one genes with putative methyltransferase (MT) activities toward xanthine derivatives were codon optimized and synthesized as the gene sequences of SEQ ID NOS:23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 65, 77, 79, and 81. Additionally, one gene with putative methyltransferase activity was synthesized with native sequence (not codon optimized; SEQ ID NO:83). These 32 synthetic MT genes were cloned into the pCK110900 vector system as described for the GDA genes in Example 1. 
     Example 5 
     High-Throughput (HTP) Expression and Activity Assay of Methyltransferase (MT) Enzymes on Caffeine Precursors 
     The putative methyltransferase (MT) polypeptides described in Example 4 were produced in host  E. coli  W3110 as an intracellular protein expressed under the control of the lac promoter. The polypeptides are designed to accumulate as soluble cytosolic enzymes. 
     High-Throughput Growth and Expression (HTP) 
     Single  E. coli  colonies for each variant were picked and grown for approximately 16-18 hours (overnight) in LB media containing 1% glucose and 30 μg/mL chloramphenicol (CAM) under culture conditions of 30° C., 200 rpm, and 85% humidity. A 20 μL aliquot of overnight growth was transferred to a deep well plate containing 380 μL TB growth media containing 30 μg/mL CAM. The culture was incubated in a shaker for 2 hours at 30° C. and at 250 rpm to an OD 600  of about 0.6 to 0.8. The expression of the heterologous GDA genes was then induced with IPTG (IPTG) (1 mM final concentration). Incubation was continued for about 18 hours under the same conditions. After expression, cell cultures were centrifuged at 4000 rpm, 4° C. for 10 min., and the media discarded. Cell pellets were resuspended in 300 μL Lysis Buffer (20 mM Tris-HCl pH=7.5 containing 500 μg/mL PMBS and 500 μg/mL Lysozyme) and shaken at room temperature for two hours. After lysis, cell debris was centrifuged at 4000 rpm, 4° C. for 10 min., and the resulting lysates were stored at 4° C. 
     HTP Assay for MT Activity 
     Xanthosine, xanthine, 7-methylxanthine, and theobromine were each diluted to about 400 μM in 50 mM Tris-HCl at pH=7.5. Twenty microliters of 10×S-adenosyl methionine (SAM) buffer (30 mM SAM, 50 mM Tris-HCl pH=7.5, 1 mM DTT) was added to each well on a 96-well plate along with 20 μl HTP lysate and 160 μl substrate. The final reaction plates (with about 320 μM substrate, 3 mM SAM, and 50 mM Tris-HCl pH=7.5) were sealed and incubated at 30° C. and 300 RPM for 24 hrs. in a Thermotron incubator. Reactions were quenched by adding 50 μl acetonitrile plus 0.2% formic acid to a final concentration of 20% acetonitrile. Reactions were spun down at 4000 RPM for 5 min. and the supernatants were analyzed on HPLC. 
     All 32 putative methyltransferase enzymes were tested for methyltransferase activity toward the natural caffeine precursors xanthosine, 7-methylxanthine, and theobromine, as well as the non-native precursor xanthine. Conversions for the major methylated products for each MT variant with each substrate are shown below: 
     
       
         
           
               
             
               
                 TABLE 5-A 
               
             
            
               
                   
               
               
                 Relative Activity 1  of Each Methyltransferase Enzyme for 
               
               
                 Methylating Xanthosine to the Indicated Products 
               
            
           
           
               
               
               
               
               
               
            
               
                   
                 3- 
                   
                   
                   
                 1,3-Me- 
               
               
                   
                 Me-X 
                 7-Me-X 
                 Theo 
                 Caff 
                 X 
               
               
                   
                   
               
            
           
           
               
               
               
               
               
               
               
            
               
                 MXMT_10 
                 (SEQ ID NO: 24) 
                 ++ 
                 + 
                 + 
                 −− 
                 −− 
               
               
                 MXMT_11 
                 (SEQ ID NO: 26) 
                 −− 
                 −− 
                 −− 
                 −− 
                 −− 
               
               
                 XMT_12 
                 (SEQ ID NO: 28) 
                 −− 
                 −− 
                 −− 
                 −− 
                 −− 
               
               
                 XMT_13 
                 (SEQ ID NO: 30) 
                 −− 
                 −− 
                 −− 
                 −− 
                 −− 
               
               
                 MXMT_14 
                 (SEQ ID NO: 32) 
                 −− 
                 −− 
                 −− 
                 −− 
                 −− 
               
               
                 DXMT_15 
                 (SEQ ID NO: 34) 
                 −− 
                 −− 
                 −− 
                 −− 
                 −− 
               
               
                 DXMT_16 
                 (SEQ ID NO: 36) 
                 −− 
                 −− 
                 −− 
                 −− 
                 −− 
               
               
                 DXMT_17 
                 (SEQ ID NO: 38) 
                 −− 
                 −− 
                 −− 
                 −− 
                 −− 
               
               
                 DXMT_18 
                 (SEQ ID NO: 40) 
                 −− 
                 −− 
                 −− 
                 −− 
                 −− 
               
               
                 DXMT_19 
                 (SEQ ID NO: 42) 
                 −− 
                 −− 
                 −− 
                 −− 
                 −− 
               
               
                 DXMT_20 
                 (SEQ ID NO: 44) 
                 −− 
                 −− 
                 −− 
                 −− 
                 −− 
               
               
                 DXMT_21 
                 (SEQ ID NO: 46) 
                 −− 
                 −− 
                 −− 
                 −− 
                 −− 
               
               
                 DXMT_22 
                 (SEQ ID NO: 48) 
                 −− 
                 −− 
                 −− 
                 −− 
                 −− 
               
               
                 DXMT_23 
                 (SEQ ID NO: 50) 
                 −− 
                 −− 
                 −− 
                 −− 
                 −− 
               
               
                 DXMT_25 
                 (SEQ ID NO: 52) 
                 −− 
                 −− 
                 −− 
                 −− 
                 −− 
               
               
                 DXMT_26 
                 (SEQ ID NO: 54) 
                 −− 
                 −− 
                 −− 
                 −− 
                 −− 
               
               
                 DXMT_27 
                 (SEQ ID NO: 56) 
                 −− 
                 −− 
                 −− 
                 −− 
                 −− 
               
               
                 DXMT_28 
                 (SEQ ID NO: 58) 
                 −− 
                 −− 
                 −− 
                 −− 
                 −− 
               
               
                 DXMT_29 
                 (SEQ ID NO: 60) 
                 −− 
                 +++ 
                 −− 
                 −− 
                 −− 
               
               
                 MXMT_30 
                 (SEQ ID NO: 62) 
                 −− 
                 −− 
                 −− 
                 −− 
                 −− 
               
               
                 MXMT_31 
                 (SEQ ID NO: 64) 
                 −− 
                 −− 
                 −− 
                 −− 
                 −− 
               
               
                 MXMT_32 
                 (SEQ ID NO: 66) 
                 −− 
                 −− 
                 −− 
                 −− 
                 −− 
               
               
                 MXMT_33 
                 (SEQ ID NO: 68) 
                 + 
                 −− 
                 −− 
                 −− 
                 −− 
               
               
                 MXMT_34 
                 (SEQ ID NO: 70) 
                 + 
                 −− 
                 −− 
                 −− 
                 −− 
               
               
                 MXMT_35 
                 (SEQ ID NO: 72) 
                 + 
                 −− 
                 −− 
                 −− 
                 −− 
               
               
                 DXMT_36 
                 (SEQ ID NO: 74) 
                 −− 
                 −− 
                 −− 
                 −− 
                 −− 
               
               
                 DXMT_37 
                 (SEQ ID NO: 76) 
                 −− 
                 −− 
                 −− 
                 −− 
                 −− 
               
               
                 DXMT_38 
                 (SEQ ID NO: 78) 
                 −− 
                 −− 
                 −− 
                 −− 
                 −− 
               
               
                 DXMT_39 
                 (SEQ ID NO: 80) 
                 −− 
                 −− 
                 −− 
                 −− 
                 −− 
               
               
                 DXMT_40 
                 (SEQ ID NO: 82) 
                 −− 
                 −− 
                 −− 
                 −− 
                 −− 
               
               
                 XMT_41 
                 (SEQ ID NO: 84) 
                 −− 
                 +++ 
                 −− 
                 −− 
                 −− 
               
               
                   
               
               
                   1 Key: 
               
               
                 −− = conversion of &lt;1% of substrate 
               
               
                 + = conversion of &gt;1 to 10% of substrate 
               
               
                 ++ = conversion of &gt;10 to 50% of substrate 
               
               
                 +++ conversion of &gt;50% of substrate 
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 5-B 
               
             
            
               
                   
               
               
                 Relative Activity 1  of Each Methyltransferase Enzyme for 
               
               
                 Methylating Xanthine to the Indicated Products 
               
            
           
           
               
               
               
               
               
               
            
               
                   
                   
                   
                   
                   
                 1,3- 
               
               
                   
                 3-Me-X 
                 7-Me-X 
                 Theo 
                 Caff 
                 Me-X 
               
               
                   
                   
               
            
           
           
               
               
               
               
               
               
               
            
               
                 MXMT_10 
                 (SEQ ID NO: 24) 
                 +++ 
                 + 
                 + 
                 −− 
                 −− 
               
               
                 MXMT_11 
                 (SEQ ID NO: 26) 
                 ++ 
                 −− 
                 −− 
                 −− 
                 −− 
               
               
                 XMT_12 
                 (SEQ ID NO: 28) 
                 −− 
                 −− 
                 −− 
                 −− 
                 −− 
               
               
                 XMT_13 
                 (SEQ ID NO: 30) 
                 −− 
                 −− 
                 −− 
                 −− 
                 −− 
               
               
                 MXMT_14 
                 (SEQ ID NO: 32) 
                 −− 
                 −− 
                 −− 
                 −− 
                 −− 
               
               
                 DXMT_15 
                 (SEQ ID NO: 34) 
                 −− 
                 −− 
                 −− 
                 −− 
                 −− 
               
               
                 DXMT_16 
                 (SEQ ID NO: 36) 
                 −− 
                 −− 
                 −− 
                 −− 
                 −− 
               
               
                 DXMT_17 
                 (SEQ ID NO: 38) 
                 + 
                 + 
                 −− 
                 + 
                 ++ 
               
               
                 DXMT_18 
                 (SEQ ID NO: 40) 
                 −− 
                 −− 
                 −− 
                 −− 
                 −− 
               
               
                 DXMT_19 
                 (SEQ ID NO: 42) 
                 + 
                 −− 
                 −− 
                 −− 
                 −− 
               
               
                 DXMT_20 
                 (SEQ ID NO: 44) 
                 −− 
                 −− 
                 −− 
                 −− 
                 −− 
               
               
                 DXMT_21 
                 (SEQ ID NO: 46) 
                 −− 
                 −− 
                 −− 
                 −− 
                 −− 
               
               
                 DXMT_22 
                 (SEQ ID NO: 48) 
                 −− 
                 −− 
                 −− 
                 −− 
                 −− 
               
               
                 DXMT_23 
                 (SEQ ID NO: 50) 
                 −− 
                 −− 
                 −− 
                 −− 
                 −− 
               
               
                 DXMT_25 
                 (SEQ ID NO: 52) 
                 −− 
                 −− 
                 −− 
                 −− 
                 −− 
               
               
                 DXMT_26 
                 (SEQ ID NO: 54) 
                 −− 
                 −− 
                 −− 
                 −− 
                 −− 
               
               
                 DXMT_27 
                 (SEQ ID NO: 56) 
                 −− 
                 −− 
                 −− 
                 −− 
                 −− 
               
               
                 DXMT_28 
                 (SEQ ID NO: 58) 
                 −− 
                 −− 
                 −− 
                 −− 
                 −− 
               
               
                 DXMT_29 
                 (SEQ ID NO: 60) 
                 −− 
                 −− 
                 −− 
                 −− 
                 −− 
               
               
                 MXMT_30 
                 (SEQ ID NO: 62) 
                 −− 
                 −− 
                 −− 
                 −− 
                 −− 
               
               
                 MXMT_31 
                 (SEQ ID NO: 64) 
                 + 
                 −− 
                 −− 
                 −− 
                 −− 
               
               
                 MXMT_32 
                 (SEQ ID NO: 66) 
                 −− 
                 −− 
                 −− 
                 −− 
                 −− 
               
               
                 MXMT_33 
                 (SEQ ID NO: 68) 
                 ++ 
                 −− 
                 −− 
                 −− 
                 −− 
               
               
                 MXMT_34 
                 (SEQ ID NO: 70) 
                 + 
                 −− 
                 −− 
                 −− 
                 −− 
               
               
                 MXMT_35 
                 (SEQ ID NO: 72) 
                 +++ 
                 −− 
                 −− 
                 −− 
                 −− 
               
               
                 DXMT_36 
                 (SEQ ID NO: 74) 
                 −− 
                 −− 
                 −− 
                 −− 
                 −− 
               
               
                 DXMT_37 
                 (SEQ ID NO: 76) 
                 −− 
                 −− 
                 −− 
                 −− 
                 −− 
               
               
                 DXMT_38 
                 (SEQ ID NO: 78) 
                 −− 
                 −− 
                 −− 
                 −− 
                 −− 
               
               
                 DXMT_39 
                 (SEQ ID NO: 80) 
                 −− 
                 −− 
                 −− 
                 −− 
                 −− 
               
               
                 DXMT_40 
                 (SEQ ID NO: 82) 
                 −− 
                 −− 
                 −− 
                 −− 
                 −− 
               
               
                 XMT_41 
                 (SEQ ID NO: 84) 
                 −− 
                 −− 
                 −− 
                 −− 
                 −− 
               
               
                   
               
               
                   1 Key: 
               
               
                 −− = conversion of &lt;1% of substrate 
               
               
                 + = conversion of &gt;1 to 10% of substrate 
               
               
                 ++ = conversion of &gt;10 to 50% of substrate 
               
               
                 +++ conversion of &gt;50% of substrate 
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 5-C 
               
             
            
               
                   
               
               
                 Relative Activity 1  of Each Methyltransferase Enzyme for 
               
               
                 Methylating 7-Methylxanthine to the Indicated Products 
               
            
           
           
               
               
               
            
               
                   
                 Theo 
                 Caff 
               
               
                   
                   
               
            
           
           
               
               
               
               
               
            
               
                   
                 MXMT_10 
                 (SEQ ID NO: 24) 
                 +++ 
                 −− 
               
               
                   
                 MXMT_11 
                 (SEQ ID NO: 26) 
                 +++ 
                 −− 
               
               
                   
                 XMT_12 
                 (SEQ ID NO: 28) 
                 −− 
                 −− 
               
               
                   
                 XMT_13 
                 (SEQ ID NO: 30) 
                 −− 
                 −− 
               
               
                   
                 MXMT_14 
                 (SEQ ID NO: 32) 
                 −− 
                 −− 
               
               
                   
                 DXMT_15 
                 (SEQ ID NO: 34) 
                 −− 
                 −− 
               
               
                   
                 DXMT_16 
                 (SEQ ID NO: 36) 
                 −− 
                 −− 
               
               
                   
                 DXMT_17 
                 (SEQ ID NO: 38) 
                 −− 
                 +++ 
               
               
                   
                 DXMT_18 
                 (SEQ ID NO: 40) 
                 −− 
                 −− 
               
               
                   
                 DXMT_19 
                 (SEQ ID NO: 42) 
                 ++ 
                 ++ 
               
               
                   
                 DXMT_20 
                 (SEQ ID NO: 44) 
                 −− 
                 −− 
               
               
                   
                 DXMT_21 
                 (SEQ ID NO: 46) 
                 −− 
                 −− 
               
               
                   
                 DXMT_22 
                 (SEQ ID NO: 48) 
                 −− 
                 −− 
               
               
                   
                 DXMT_23 
                 (SEQ ID NO: 50) 
                 −− 
                 −− 
               
               
                   
                 DXMT_25 
                 (SEQ ID NO: 52) 
                 −− 
                 −− 
               
               
                   
                 DXMT_26 
                 (SEQ ID NO: 54) 
                 −− 
                 −− 
               
               
                   
                 DXMT_27 
                 (SEQ ID NO: 56) 
                 −− 
                 −− 
               
               
                   
                 DXMT_28 
                 (SEQ ID NO: 58) 
                 −− 
                 −− 
               
               
                   
                 DXMT_29 
                 (SEQ ID NO: 60) 
                 + 
                 −− 
               
               
                   
                 MXMT_30 
                 (SEQ ID NO: 62) 
                 −− 
                 −− 
               
               
                   
                 MXMT_31 
                 (SEQ ID NO: 64) 
                 + 
                 −− 
               
               
                   
                 MXMT_32 
                 (SEQ ID NO: 66) 
                 −− 
                 −− 
               
               
                   
                 MXMT_33 
                 (SEQ ID NO: 68) 
                 ++ 
                 −− 
               
               
                   
                 MXMT_34 
                 (SEQ ID NO: 70) 
                 + 
                 −− 
               
               
                   
                 MXMT_35 
                 (SEQ ID NO: 72) 
                 +++ 
                 −− 
               
               
                   
                 DXMT_36 
                 (SEQ ID NO: 74) 
                 −− 
                 −− 
               
               
                   
                 DXMT_37 
                 (SEQ ID NO: 76) 
                 −− 
                 −− 
               
               
                   
                 DXMT_38 
                 (SEQ ID NO: 78) 
                 −− 
                 −− 
               
               
                   
                 DXMT_39 
                 (SEQ ID NO: 80) 
                 −− 
                 −− 
               
               
                   
                 DXMT_40 
                 (SEQ ID NO: 82) 
                 −− 
                 −− 
               
               
                   
                 XMT_41 
                 (SEQ ID NO: 84) 
                 −− 
                 −− 
               
               
                   
                   
               
               
                   
                   1 Key: 
               
               
                   
                 −− = conversion of &lt;1% of substrate 
               
               
                   
                 + = conversion of &gt;1 to 10% of substrate 
               
               
                   
                 ++ = conversion of &gt;10 to 50% of substrate 
               
               
                   
                 +++ conversion of &gt;50% of substrate 
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 5-D 
               
             
            
               
                   
               
               
                 Relative Activity 1  of Each Methyltransferase Enzyme 
               
               
                 for Methylating Theobromine to Caffeine 
               
            
           
           
               
               
            
               
                   
                 Caff 
               
               
                   
                   
               
            
           
           
               
               
               
               
            
               
                   
                 MXMT_10 
                 (SEQ ID NO: 24) 
                 −− 
               
               
                   
                 MXMT_11 
                 (SEQ ID NO: 26) 
                 −− 
               
               
                   
                 XMT_12 
                 (SEQ ID NO: 28) 
                 −− 
               
               
                   
                 XMT_13 
                 (SEQ ID NO: 30) 
                 −− 
               
               
                   
                 MXMT_14 
                 (SEQ ID NO: 32) 
                 −− 
               
               
                   
                 DXMT_15 
                 (SEQ ID NO: 34) 
                 −− 
               
               
                   
                 DXMT_16 
                 (SEQ ID NO: 36) 
                 −− 
               
               
                   
                 DXMT_17 
                 (SEQ ID NO: 38) 
                 +++ 
               
               
                   
                 DXMT_18 
                 (SEQ ID NO: 40) 
                 + 
               
               
                   
                 DXMT_19 
                 (SEQ ID NO: 42) 
                 +++ 
               
               
                   
                 DXMT_20 
                 (SEQ ID NO: 44) 
                 −− 
               
               
                   
                 DXMT_21 
                 (SEQ ID NO: 46) 
                 −− 
               
               
                   
                 DXMT_22 
                 (SEQ ID NO: 48) 
                 −− 
               
               
                   
                 DXMT_23 
                 (SEQ ID NO: 50) 
                 −− 
               
               
                   
                 DXMT_25 
                 (SEQ ID NO: 52) 
                 −− 
               
               
                   
                 DXMT_26 
                 (SEQ ID NO: 54) 
                 −− 
               
               
                   
                 DXMT_27 
                 (SEQ ID NO: 56) 
                 −− 
               
               
                   
                 DXMT_28 
                 (SEQ ID NO: 58) 
                 −− 
               
               
                   
                 DXMT_29 
                 (SEQ ID NO: 60) 
                 −− 
               
               
                   
                 MXMT_30 
                 (SEQ ID NO: 62) 
                 −− 
               
               
                   
                 MXMT_31 
                 (SEQ ID NO: 64) 
                 −− 
               
               
                   
                 MXMT_32 
                 (SEQ ID NO: 66) 
                 −− 
               
               
                   
                 MXMT_33 
                 (SEQ ID NO: 68) 
                 −− 
               
               
                   
                 MXMT_34 
                 (SEQ ID NO: 70) 
                 −− 
               
               
                   
                 MXMT_35 
                 (SEQ ID NO: 72) 
                 −− 
               
               
                   
                 DXMT_36 
                 (SEQ ID NO: 74) 
                 −− 
               
               
                   
                 DXMT_37 
                 (SEQ ID NO: 76) 
                 −− 
               
               
                   
                 DXMT_38 
                 (SEQ ID NO: 78) 
                 −− 
               
               
                   
                 DXMT_39 
                 (SEQ ID NO: 80) 
                 −− 
               
               
                   
                 DXMT_40 
                 (SEQ ID NO: 82) 
                 −− 
               
               
                   
                 XMT_41 
                 (SEQ ID NO: 84) 
                 −− 
               
               
                   
                   
               
               
                   
                   1 Key: 
               
               
                   
                 −− = conversion of &lt;1% of substrate 
               
               
                   
                 + = conversion of &gt;1 to 10% of substrate 
               
               
                   
                 ++ = conversion of &gt;10 to 50% of substrate 
               
               
                   
                 +++ conversion of &gt;50% of substrate 
               
            
           
         
       
     
     Example 6 
     Shake-Flask Expression and Activity Assay of Methyltransferase (MT) Enzymes with Xanthine as the Substrate 
     In addition to the HTP assay for primary screening, in some cases a secondary screening was carried out using shake-flask lysates of the methyltransferase variants. Shake flask lysates are prepared using mechanical lysis and are generally substantially more concentrated compared to the cell lysate used in HTP assays. 
     Shake-Flask (SF) Expression 
     For preparing SF lysates, a single microbial colony of  E. coli  containing a plasmid encoding an methyltransferase of interest was inoculated into 5 mL Luria Bertani broth containing 30 μg/mL chloramphenicol (CAM) and 1% glucose. Cells were grown overnight (at least 16 hours) in an incubator at 30° C. with shaking at 250 rpm. The 5 mL culture was diluted into 250 mL of TB media containing 30 μg/ml CAM in a 1000 mL flask and was grown at 30° C. Expression of the methyltransferase genes were induced by addition of IPTG to a final concentration of 1 mM when the optical density at 600 nm (OD 600 ) of the culture was 0.6 to 0.8. Incubation was then continued overnight (at least 16 hours). Cells were harvested by centrifugation (7000 rpm, 6 min, 4° C.) and the supernatant discarded. The cell pellet was resuspended with 30 mL of cold (4° C.) 25 mM triethanolamine (TEA), pH 7.5 and passed once through a microfluidizer. Cell debris was removed by centrifugation (10000 rpm, 40 minutes, 4° C.). The clear lysate supernatant was collected and stored at 4° C. Alternatively, the clear lysate supernatant can be frozen at −80° C. and lyophilized to produce a dry shake-flask powder which is relatively stable when stored at −20° C. 
     Assay for MT Activity on Xanthine Using Shake-Flask Lysates 
     Xanthine was diluted to about 400 μM in 50 mM Tris-HCl at pH=7.5. Twenty microliters of 10×S-Adenosyl methionine (SAM) buffer (30 mM SAM, 50 mM Tris-HCl pH=7.5, 1 mM DTT) was added to each well on a 96-well plate along with 50 μl HTP lysate and 130 μl substrate. The final reaction plates (with about 260 μM substrate, 3 mM SAM, and 50 mM Tris-HCl pH=7.5) were sealed and incubated at 30° C. and 300 RPM for 24 hrs. in a Thermotron incubator. Reactions were quenched by adding 50 μl acetonitrile plus 0.2% formic acid to a final concentration of 20% acetonitrile. Reactions were spun down at 4000 RPM for 5 min. and the supernatants were analyzed on HPLC. 
     Five MT variants (comprising SEQ ID NOS:24, 26, 38, 42, and 72) showing initial activity on xanthine in the HTP assay were scaled up and tested at shake-flask level. As shown in the table below, variants MXMT_10, MXMT_11, and MXMT_35 were shown to perform two methylations, converting xanthine to the dimethylated xanthine product theobromine (3,7-dimethylxanthine). Further, variants DXMT_17 and DXMT_19 were shown to perform three methylations, converting xanthine to the trimethylated xanthine product caffeine (1,3,7-trimethylxanthine). The table below shows some of the methylated products (as a percentage of initial xanthine peak area) from the methyltransferase reactions with each of the MT enzymes and xanthine as the substrate. 
     
       
         
           
               
             
               
                 TABLE 6 
               
             
            
               
                   
               
               
                 Relative Activity 1  of Each Methyltransferase Enzyme for 
               
               
                 Methylating Xanthine to the Indicated Products 
               
            
           
           
               
               
               
               
               
               
            
               
                   
                   
                   
                   
                   
                 1,3- 
               
               
                   
                 3-Me-X 
                 7-Me-X 
                 Theo 
                 Caff 
                 Me-X 
               
               
                   
                   
               
            
           
           
               
               
               
               
               
               
               
            
               
                 MXMT_10 
                 (SEQ ID NO: 24) 
                 ++ 
                 ++ 
                 ++ 
                 −− 
                 −− 
               
               
                 MXMT_11 
                 (SEQ ID NO: 26) 
                 +++ 
                 ++ 
                 + 
                 −− 
                 −− 
               
               
                 DXMT_17 
                 (SEQ ID NO: 38) 
                 + 
                 ++ 
                 −− 
                 ++ 
                 ++ 
               
               
                 DXMT_19 
                 (SEQ ID NO: 42) 
                 + 
                 + 
                 −− 
                 + 
                 ++ 
               
               
                 MXMT_35 
                 (SEQ ID NO: 72) 
                 +++ 
                 ++ 
                 −− 
                 −− 
                 −− 
               
               
                   
               
               
                   1  Key: 
               
               
                 −− = conversion &lt;1% of substrate 
               
               
                 + = conversion &gt;1 to 10% of substrate 
               
               
                 ++ = conversion &gt;10 to 50% of substrate 
               
               
                 +++ = conversion &gt;50% of substrate 
               
            
           
         
       
     
     Example 7 
     Conversion of 7-Methylxanthine to Theobromine and Caffeine with the Alternate Methyl Donor S-Methylmethionine (SMM) 
     In addition to the native methyl donor (SAM), five methyltransferase enzymes were tested for activity with the alternate methyl donor S-methylmethionine (SMM). 
     In this preliminary experiment, 7-Methylxanthine was diluted to about 400 μM in 50 mM Tris-HCl at pH=7.5. Twenty microliters of 10×S-methylmethionine (SMM) buffer (300 mM SMM, 50 mM Tris-HCl pH=7.5, 1 mM DTT) was added to each well on a 96-well plate along with 50 μl HTP lysate and 130 μl substrate. The final reaction plates (with about 260 μM substrate, 30 mM SMM, and 50 mM Tris-HCl pH=7.5) were sealed and incubated at 30° C. and 300 RPM for 24 hrs. in a Thermotron incubator. Reactions were quenched by adding 50 μl acetonitrile plus 0.2% formic acid to a final concentration of 20% acetonitrile. Reactions were spun down at 4000 RPM for 5 min. and the supernatants were analyzed on HPLC. 
     As shown in the table below, MXMT_10 (SEQ ID NO:24) was shown to methylate 7-methylxanthine in the presence of a composition containing the alternate methyl donor SMM to produce theobromine (3,7-dimethylxanthine). Further, DXMT_17 (SEQ ID NO:38) was shown to methylate 7-methylxanthine in the presence of a composition containing the alternate methyl donor SMM to produce the trimethylated product (1,3,7-trimethylxanthine). The table below summarized the primary methylated products (as a percentage of initial 7-methylxanthine peak area) from the methyltransferase reactions with the presence of a composition comprising the SMM methyl donor. 
     
       
         
           
               
             
               
                 TABLE 7 
               
             
            
               
                   
               
               
                 Relative Activity 1  of Each Methyltransferase Enzyme for 
               
               
                 Methylating 7-Methylxanthine to the Indicated Products with S- 
               
               
                 Methylmethionine (SMM) Methyl Donor 
               
            
           
           
               
               
               
            
               
                   
                 Theo 
                 Caff 
               
               
                   
                   
               
            
           
           
               
               
               
               
               
            
               
                   
                 MXMT_10 
                 (SEQ ID NO: 24) 
                 ++ 
                 −− 
               
               
                   
                 MXMT_11 
                 (SEQ ID NO: 26) 
                 −− 
                 −− 
               
               
                   
                 DXMT_17 
                 (SEQ ID NO: 38) 
                 ++ 
                 + 
               
               
                   
                 DXMT_19 
                 (SEQ ID NO: 42) 
                 −− 
                 −− 
               
               
                   
                 MXMT_35 
                 (SEQ ID NO: 72) 
                 −− 
                 −− 
               
               
                   
                   
               
               
                   
                   1 Key: 
               
               
                   
                 −− = conversion &lt;1% of substrate 
               
               
                   
                 + = conversion &gt;1 to 10% of substrate 
               
               
                   
                 ++ = conversion &gt;10 to 50% of substrate 
               
               
                   
                 +++ = conversion &gt;50% of substrate 
               
            
           
         
       
     
     Example 8 
     Conversion of 7-Methylxanthine to Theobromine and Caffeine with the Alternate Methyl Donor Gamma-Butyrobetaine 
     In addition to the native methyl donor (SAM), five methyltransferase enzymes were tested for activity with the alternate methyl donor gamma-butyrobetaine. 
     In this preliminary experiment, 7-Methylxanthine was diluted to about 400 μM in 50 mM Tris-HCl at pH=7.5. Twenty microliters of 10× gamma-butyrobetaine buffer (300 mM gamma-butyrobetaine, 50 mM Tris-HCl pH=7.5) was added to each well on a 96-well plate along with 50 μl HTP lysate and 130 μl substrate. The final reaction plates (with about 260 μM substrate, 30 mM gamma-butyrobetaine, and 50 mM Tris-HCl pH=7.5) were sealed and incubated at 30° C. and 300 RPM for 24 hrs. in a Thermotron incubator. Reactions were quenched by adding 50 μl acetonitrile plus 0.2% formic acid to a final concentration of 20% acetonitrile. Reactions were spun down at 4000 RPM for 5 min. and the supernatants were analyzed on HPLC. 
     As shown in the table below, DXMT_17 was shown to methylate 7-methylxanthine in the presence of a composition comprising the alternate methyl donor gamma-butyrobetaine to produce the trimethylated product (1,3,7-trimethylxanthine). 
     
       
         
           
               
             
               
                 TABLE 8 
               
             
            
               
                   
               
               
                 Relative Activity 1  of Each Methyltransferase Enzyme for 
               
               
                 Methylating 7-Methylxanthine to the Indicated Products with Gamma- 
               
               
                 Butyrobetaine Methyl Donor 
               
            
           
           
               
               
               
            
               
                   
                 Theo 
                 Caff 
               
               
                   
                   
               
            
           
           
               
               
               
               
               
            
               
                   
                 MXMT_10 
                 (SEQ ID NO: 24) 
                 −− 
                 −− 
               
               
                   
                 MXMT_11 
                 (SEQ ID NO: 26) 
                 −− 
                 −− 
               
               
                   
                 DXMT_17 
                 (SEQ ID NO: 38) 
                 ++ 
                 + 
               
               
                   
                 DXMT_19 
                 (SEQ ID NO: 42) 
                 −− 
                 −− 
               
               
                   
                 MXMT_35 
                 (SEQ ID NO: 72) 
                 −− 
                 −− 
               
               
                   
                   
               
               
                   
                   1 Key: 
               
               
                   
                 −− = conversion &lt;1% of substrate 
               
               
                   
                 + = conversion &gt;1 to 10% of substrate 
               
               
                   
                 ++ = conversion &gt;10 to 50% of substrate 
               
               
                   
                 +++ = conversion &gt;50% of substrate 
               
            
           
         
       
     
     Example 9 
     Conversion of Xanthine (or 7-Methylxanthine) to Theobromine and Caffeine with the Alternate Methyl Donor Trimethylglycine (TMG Aka Betaine) 
     In addition to the native methyl donor (SAM), methyltransferase enzymes are tested for activity with the alternate methyl donor trimethylglycine (TMG). 
     For these experiments, xanthine (or 7-methylxanthine) is diluted to about 400 μM in 50 mM Tris-HCl at pH=7.5. Twenty microliters of 10×TMG buffer (300 mM TMG, 50 mM Tris-HCl pH=7.5) is added to each well on a 96-well plate along with 50 μl HTP lysate and 130 μl substrate. The final reaction plates (with about 260 μM substrate, 30 mM TMG, and 50 mM Tris-HCl pH=7.5) are sealed and incubated at 30° C. and 300 RPM for 24 hrs. in a Thermotron incubator. Reactions are quenched by adding 50 μl acetonitrile plus 0.2% formic acid to a final concentration of 20% acetonitrile. Reactions are spun down at 4000 RPM for 5 min. and the supernatants are analyzed by HPLC. 
     While the present invention has been described with reference to the specific embodiments, various changes can be made and equivalents can be substituted to adapt to a particular situation, material, composition of matter, process, process step or steps, thereby achieving benefits of the invention without departing from the scope of what is claimed. 
     For all purposes in the United States of America, each and every publication and patent document cited in this application is incorporated herein by reference as if each such publication or document was specifically and individually indicated to be incorporated herein by reference. Citation of publications and patent documents is not intended as an indication that any such document is pertinent prior art, nor does it constitute an admission as to its contents or date.