Biosynthesis of betalains

Abstract

Aspects of the disclosure relate to tyrosine hydroxylases, including engineered enzymes, and their use in catalyzing chemical reactions to produce betalain. Additional aspects of the disclosure relate to genetic modifications of host cells to improve betalain production.

Description

[0001] Attorney Docket No. G0919.70121WO00   BIOSYNTHESIS OF BETALAINS     CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit under 35 U.S.C. § 119(e) of U.S. Provisional Application No.63 / 563,199, filed March 8, 2024, entitled, “BIOSYNTHESIS OF BETALAINS,” the entire disclosure of which is hereby incorporated by reference in its entirety. REFERENCE TO AN ELECTRONIC SEQUENCE LISTING The contents of the electronic sequence listing (G091970121WO00-SEQ-KVC.xml; Size: 1,072,177 bytes; and Date of Creation: March 6, 2025) is herein incorporated by reference in its entirety. FIELD The present disclosure relates to the use of engineered tyrosine hydroxylases for production of one or more betalains. BACKGROUND Betalains are a class of red and yellow tyrosine-derived pigments found in plants. Betalains can be used as natural food dyes and have useful pharmacological properties as antioxidants. The two categories of betalains are: (1) betacyanins, which include betanin, isobetanin, betanidin, probetanin, and neobetanin; and (2) betaxanthins, which include vulgaxanthin, miraxanthin, portulaxanthin, and indicaxanthin. Chemical synthesis of betalains, including betacyanins and betaxanthins, can be laborious and often results in low yields. SUMMARY Aspects of the present disclosure relate, at least in part, to variant tyrosine hydroxylases [such as Cytochrome P45076AD1 (“AD1”) variants capable of hydroxylating tyrosine], host cells comprising heterologous polynucleotides encoding variant tyrosine hydroxylases, and methods of using host cells comprising variant tyrosine hydroxylases to biosynthesize betalains. Aspects of the present disclosure also relate to various genetic modifications of host cells which can result in higher betalain production. Attorney Docket No. G0919.70121WO00   Aspects of the present disclosure relate to a variant tyrosine hydroxylase, wherein the variant tyrosine hydroxylase comprises an amino acid sequence that is at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, or at least 99% identical to SEQ ID NO: 1 and wherein the amino acid sequence of the variant tyrosine hydroxylase comprises an amino acid substitution relative to SEQ ID NO: 1 at one or more residues corresponding to position 26, 31, 95, 114, 115, 147, 198, 228, 240, 254, 259, 280, 288, 346, 403, 405, 409, 418, 459 and / or 467 of SEQ ID NO: 1. In some embodiments, the amino acid sequence of the variant tyrosine hydroxylase comprises: a) the amino acid serine (S) at a residue corresponding to position 13 in the sequence of SEQ ID NO: 1; b) the amino acid serine (S) at the residue corresponding to position 26 in the sequence of SEQ ID NO: 1; c) the amino acid arginine (R) at the residue corresponding to position 26 in the sequence of SEQ ID NO: 1; d) the amino acid threonine (T) at the residue corresponding to position 26 in the sequence of SEQ ID NO: 1; e) the amino acid leucine (L) at the residue corresponding to position 26 in the sequence of SEQ ID NO: 1; f) the amino acid arginine (R) at the residue corresponding to position 31 in the sequence of SEQ ID NO: 1; g) the amino acid alanine (A) at the residue corresponding to position 95 in the sequence of SEQ ID NO: 1; h) the amino acid leucine (L) at the residue corresponding to position 95 in the sequence of SEQ ID NO: 1; i) the amino acid serine (S) at the residue corresponding to position 114 in the sequence of SEQ ID NO: 1; j) the amino acid leucine (L) at the residue corresponding to position 115 in the sequence of SEQ ID NO: 1; k) the amino acid leucine (L) at the residue corresponding to position 147 in the sequence of SEQ ID NO: 1; l) the amino acid asparagine (N) at the residue corresponding to position 198 in the sequence of SEQ ID NO: 1; m) the amino acid aspartate (D) at the residue corresponding to position 198 in the sequence of SEQ ID NO: 1; n) the amino acid serine (S) at the residue corresponding to position 198 in the sequence of SEQ ID NO: 1; o) the amino acid glutamate (E) at the residue corresponding to position 198 in the sequence of SEQ ID NO: 1; p) the amino acid glycine (G) at the residue corresponding to position 198 in the sequence of SEQ ID NO: 1; q) the amino acid lysine (K) at the residue corresponding to position 228 in the sequence of SEQ ID NO: 1; r) the amino acid serine (S) at the residue corresponding to position 240 in the sequence of SEQ ID NO: 1; s) the amino acid lysine (K) at the residue corresponding to position 240 in the sequence of SEQ ID NO: 1; t) the amino acid asparagine (N) at the residue corresponding to position 240 in the sequence of SEQ ID NO: 1; u) the amino acid aspartate (D) at the residue corresponding to position 254 in the sequence of SEQ ID NO: 1; v) the amino acid glutamate (E) at the residue corresponding to Attorney Docket No. G0919.70121WO00   position 254 in the sequence of SEQ ID NO: 1; w) the amino acid glycine (G) at the residue corresponding to position 254 in the sequence of SEQ ID NO: 1; x) the amino acid asparagine (N) at the residue corresponding to position 254 in the sequence of SEQ ID NO: 1; y) the amino acid alanine (A) at the residue corresponding to position 254 in the sequence of SEQ ID NO: 1; z) the amino acid glutamine (Q) at the residue corresponding to position 254 in the sequence of SEQ ID NO: 1; aa) the amino acid arginine (R) at the residue corresponding to position 254 in the sequence of SEQ ID NO: 1; bb) the amino acid alanine (A) at the residue corresponding to position 259 in the sequence of SEQ ID NO: 1; cc) the amino acid leucine (L) at the residue corresponding to position 259 in the sequence of SEQ ID NO: 1; dd) the amino acid lysine (K) at the residue corresponding to position 259 in the sequence of SEQ ID NO: 1; ee) the amino acid serine (S) at the residue corresponding to position 259 in the sequence of SEQ ID NO: 1; ff) the amino acid valine (V) at the residue corresponding to position 259 in the sequence of SEQ ID NO: 1; gg) the amino acid threonine (T) at the residue corresponding to position 259 in the sequence of SEQ ID NO: 1; hh) the amino acid asparagine (N) at the residue corresponding to position 259 in the sequence of SEQ ID NO: 1; ii) the amino acid methionine (M) at the residue corresponding to position 280 in the sequence of SEQ ID NO: 1; jj) the amino acid tyrosine (Y) at the residue corresponding to position 280 in the sequence of SEQ ID NO: 1; kk) the amino acid aspartate (D) at the residue corresponding to position 288 in the sequence of SEQ ID NO: 1; ll) the amino acid serine (S) at the residue corresponding to position 346 in the sequence of SEQ ID NO: 1; mm) the amino acid valine (V) at the residue corresponding to position 403 in the sequence of SEQ ID NO: 1; nn) the amino acid proline (P) at the residue corresponding to position 405 in the sequence of SEQ ID NO: 1; oo) the amino acid glutamate (E) at the residue corresponding to position 405 in the sequence of SEQ ID NO: 1; pp) the amino acid valine (V) at the residue corresponding to position 409 in the sequence of SEQ ID NO: 1; qq) the amino acid lysine (K) at the residue corresponding to position 409 in the sequence of SEQ ID NO: 1; rr) the amino acid serine (S) at the residue corresponding to position 418 in the sequence of SEQ ID NO: 1; ss) the amino acid serine (S) at the residue corresponding to position 459 in the sequence of SEQ ID NO: 1; tt) the amino acid glycine (G) at the residue corresponding to position 459 in the sequence of SEQ ID NO: 1; uu) the amino acid glycine (G) at the residue corresponding to position 467 in the sequence of SEQ ID NO: 1; or vv) any combination thereof. In some embodiments, the amino acid sequence of the variant tyrosine hydroxylase comprises amino acid substitutions at residues corresponding to the following positions in the Attorney Docket No. G0919.70121WO00   amino acid sequence of SEQ ID NO: 1: i. positions 26 and 254; ii. positions 26 and 459; iii. positions 26, 31, and 254; iv. positions 26, 198, and 254; v. positions 26, 147, 254, 259, and 459; vi. positions 26, 147, 198, 254, 280, and 459; vii. positions 26, 198, 254, 259, 403, 409, and 459; viii. positions 26, 114, 198, 240, 254, 259, 403, 405, 409, and 459; ix. positions 95, 254, and 418; x. positions 95, 114, 147, 198, 228, 254, 259, 280, 405, and 459; xi. positions 114, 240, 254, 259, 405, and 459; xii. positions 114, 228, 240, 254, 259, 405, 409, 418, and 459; xiii. positions 147, 254, 459; xiv. positions 198 and 259; xv. positions 198 and 403; xvi. positions 198 and 405; xvii. positions 198, 240, and 254; xviii. positions 198, 254, 259, 459, and 467; xix. positions 198, 228, 240, 254, 403, and 459; xx. positions 198, 240, 254, 409, 418, and 459; xxi. positions 240, 254, and 259; xxii. positions 254 and 259; xxiii. positions 254 and 280; xxiv. positions 254 and 403; xxv. positions 254 and 459; xxvi. positions 254, 259, and 409; or xxvii. positions 254, 259, 280, 403, 405, 409, and 459. In some embodiments, the amino acid sequence of the variant tyrosine hydroxylase comprises the following amino acid substitutions relative to the sequence of SEQ ID NO: 1: i. Q26R and C254D; ii. Q26L and F459S; iii. Q26S, L31R, and C254N; iv. Q26S, H198S, and C254N; v. Q26S, F147L, C254D, P259K, and F459S; vi. Q26R, F147L, H198N, C254D, F280M, and F459S; vii. Q26R, H198G, C254R, P259L, G288D, I409V, and F459S; viii. Q26S, H198N, C254N, P259L, G288D, I409V, and F459S; ix. Q26S, H198G, C254N, P259L, A403V, I409V, and F459S; x. Q26S, T114S, H198E, C240N, C254D, P259S, A403V, Q405P, I409V, and F459S; xi. P95A, C254N, and C418S; xii. P95L, T114S, F147L, H198E, C228K, C254N, P259L, F280M, Q405P, and F459S; xiii. T114S, C240N, C254D, P259A, Q405P, and F459S; xiv. T114S, C228K, C240K, C254A, P259S, Q405P, I409V, C418S, and F459S; xv. F147L, C254N, and F459S; xvi. H198D and P259N; xvii. H198D and A403V; xviii. H198S and Q405E; xix. H198N , C240S, and C254D; xx. H198N, C254D, and P259L; xxi. H198N , C254D, and P259S; xxii. H198N, C254D, P259L, F459S, and D467G; xxiii. H198G , C228K, C240K, C254A, A403V, and F459S; xxiv. H198G , C240K, C254A, I409K, C418S, and F459G; xxv. C240S, C254D, and P259K; xxvi. C254D and P259V; xxvii. C254D and P259L; xxviii. C254D and P259K; xxix. C254D and F280Y; xxx. C254D and A403V; xxxi. C254D and F459S; xxxii. C254E, P259T , and I409V; xxxiii. C254E, P259S, and I409V; or xxxiv. C254D, P259A, F280M, A403V, Q405P, I409V, and F459S. In some embodiments, the variant tyrosine hydroxylase is a cytochrome P450 enzyme. Attorney Docket No. G0919.70121WO00   In some embodiments, the cytochrome P450 enzyme is a cytochrome P45076AD1 enzyme (CYP76AD1). In some embodiments, the variant tyrosine hydroxylase comprises an amino acid sequence that is at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, or at least 99% identical to any one of SEQ ID NOs: 1-258 and 523-525. In some embodiments, the variant tyrosine hydroxylase comprises the amino acid sequence of any one of: SEQ ID NOs: 2-258 and 523-525. In some embodiments, the variant tyrosine hydroxylase comprises the amino acid sequence of any one of SEQ ID NOs: 2-258 and 523-525. In some embodiments, the variant tyrosine hydroxylase is capable of indirectly producing more betalain than a tyrosine hydroxylase comprising the amino acid sequence of SEQ ID NO: 1. In some embodiments, the variant tyrosine hydroxylase is capable of indirectly producing at least 1-fold, at least 1.5-fold, at least 2-fold, at least 2.5-fold, at least 3-fold, at least 3.5-fold, at least 4-fold, at least 4.5-fold, at least 5-fold, at least 6-fold, at least 7-fold, at least 8-fold, at least 9-fold, or at least 10-fold more betalain than a tyrosine hydroxylase comprising the sequence of SEQ ID NO: 1. In some embodiments, the betalain is a betacyanin or a betaxanthin. In some embodiments, the betacyanin is betanin, isobetanin, betanidin, isobetanidin, probetanin, or neobetanin. In some embodiments, the betaxanthin is vulgaxanthin, miraxanthin, portulaxanthin, or indicaxanthin. Aspects of the present disclosure relate to a host cell that comprises a heterologous polynucleotide encoding the variant tyrosine hydroxylase of any one of the above embodiments or aspects. In some embodiments, the host cell is a bacterial cell, an archaebacterial cell, an algal cell, a fungal cell, a yeast cell, a plant cell, an animal cell, a mammalian cell, or a human cell. In some embodiments, the host cell is a filamentous fungal cell or a yeast cell. In some embodiments, the yeast cell is a Saccharomyces cell, a Yarrowia cell, a Komagataella cell, a Pichia cell, or a Fusarium cell. In some embodiments, the Saccharomyces cell is a Saccharomyces cerevisiae cell. In some embodiments, the Yarrowia cell is a Yarrowia lipolytica cell. In some embodiments, the host cell is a bacterial cell. Attorney Docket No. G0919.70121WO00   In some embodiments, the bacterial cell is an Escherichia coli (E. coli) cell, a Bacillus subtilis cell, or a Corynebacterium glutamicum cell. In some embodiments, the plant cell is a sugar beet cell. In some embodiments, the sugar beet cell is a Beta vulgaris cell. In some embodiments, the plant cell is a Solanum lycopersicum cell. In some embodiments, the host cell comprises a genetic modification that results in reduced or eliminated expression of the gene CYP76AD5 in the host cell relative to a cell that does not comprise the genetic modification, or wherein the host cell does not comprise a gene encoding a CYP76AD5 enzyme. In some embodiments, the host cell comprises a genetic modification that results in increased expression of a polynucleotide encoding ALD6, ATR1, ATR2, LDS2, PEX19, PGM1, TPI1 or ZWF1, or any combination of such genetic modification or increased expression, relative to a cell that does not comprise the genetic modification. In some embodiments, the host cell comprises a genetic modification that results in reduced or eliminated expression of a polynucleotide encoding CYP76AD5, ARO5, ATF1, BUD17, CTA1, DAL7, EXG1, GCN4, GPH1, GRX4, MCK1, PUT1 or YDC1, or any combination of such genetic modification or reduced or eliminated expression, relative to a cell that does not comprise the genetic modification. In some embodiments, the host cell is capable of producing more betalain than a host cell that expresses a heterologous polynucleotide encoding a tyrosine hydroxylase comprising the amino acid sequence of SEQ ID NO: 1. In some embodiments, the host cell is capable of producing at least 1-fold, at least 1.5-fold, at least 2-fold, at least 2.5-fold, at least 3-fold, at least 3.5-fold, at least 4-fold, at least 4.5-fold, at least 5-fold, at least 6-fold, at least 7-fold, at least 8-fold, at least 9-fold, or at least 10-fold more betalain than a host cell that expresses a heterologous polynucleotide encoding a tyrosine hydroxylase comprising the amino acid sequence of SEQ ID NO: 1. In some embodiments, the betalain is a betacyanin or a betaxanthin. In some embodiments, the betacyanin is betanin, isobetanin, betanidin, isobetanidin, probetanin, or neobetanin. In some embodiments, the betaxanthin is vulgaxanthin, miraxanthin, portulaxanthin, or indicaxanthin. In some embodiments, expression of the gene EXG1 in the host cell is increased. Attorney Docket No. G0919.70121WO00   In some embodiments, the host cell is capable of producing more betalain than a host cell that expresses a heterologous polynucleotide encoding a tyrosine hydroxylase comprising the amino acid sequence of SEQ ID NO: 1. In some embodiments, the host cell is capable of producing at least 1-fold, at least 1.5-fold, at least 2-fold, at least 2.5-fold, at least 3-fold, at least 3.5-fold, at least 4-fold, at least 4.5-fold, at least 5-fold, at least 6-fold, at least 7-fold, at least 8-fold, at least 9-fold, or at least 10-fold more betalain than a host cell that expresses a heterologous polynucleotide encoding a tyrosine hydroxylase comprising the amino acid sequence of SEQ ID NO: 1. In some embodiments, the betalain is betanidin or isobetanidin. In some embodiments, the host cell comprises more than one copy of a polynucleotide encoding ALD6, ATR1, ATR2, LDS2, PEX19, PGM1, TPI1 or ZWF1, or any combination thereof, relative to a corresponding wild-type or control host cell. In some embodiments, the host cell comprises a deletion in or of a polynucleotide encoding CYP76AD5, ARO5, ATF1, BUD17, CTA1, DAL7, EXG1, GCN4, GPH1, GRX4, MCK1, PUT1 or YDC1, or any combination of such deletion. In some embodiments, the ATR1 is AtATR1 and / or the ATR2 is AtATR2. Aspects of the present disclosure relate to a method of producing a betalain, comprising contacting tyrosine with the variant tyrosine hydroxylase of any one of the above embodiments or aspects. Aspects of the present disclosure relate to a method of producing a betalain, comprising culturing the host cell of any one of the above embodiments or aspects. In some embodiments, the betalain is a betacyanin or a betaxanthin. In some embodiments, the betacyanin is betanin, isobetanin, betanidin, isobetanidin, probetanin, or neobetanin. In some embodiments, the betaxanthin is vulgaxanthin, miraxanthin, portulaxanthin, or indicaxanthin. In some embodiments, the betalain is betanidin or isobetanidin. In some embodiments, the method further comprises isolating the betalain. Aspects of the present disclosure relate to a host cell that comprises a heterologous polynucleotide encoding a tyrosine hydroxylase, wherein the tyrosine hydroxylase is a tyrosine hydroxylase of Table 2, or wherein the tyrosine hydroxylase comprises an amino acid sequence having at least 70% or at least 75% sequence identity to a tyrosine hydroxylase of Table 2, to CYP76AD1 (SEQ ID NO: 1), or to CYP76AD5 (SEQ ID NO: 517). Attorney Docket No. G0919.70121WO00   In some embodiments, the tyrosine hydroxylase comprises an amino acid sequence having at least 80% or at least 85% sequence identity to CYP76AD1, to a tyrosine hydroxylase of Table 2, or to CYP76AD5. In some embodiments, the tyrosine hydroxylase comprises an amino acid sequence having at least 90%, at least 95%, at least 98%, or at least 99% sequence identity to CYP76AD1, to a tyrosine hydroxylase of Table 2, or to CYP76AD5. In some embodiments, the tyrosine hydroxylase is CYP76AD1, a tyrosine hydroxylase of Table 2, or CYP76AD5. In some embodiments, the host cell is a bacterial cell, an archaebacterial cell, an algal cell, a fungal cell, a yeast cell, a plant cell, an animal cell, a mammalian cell, or a human cell. In some embodiments, the host cell is a filamentous fungal cell or a yeast cell. In some embodiments, the yeast cell is a Saccharomyces cell, a Yarrowia cell, a Komagataella cell, a Pichia cell, or a Fusarium cell. In some embodiments, the Saccharomyces cell is a Saccharomyces cerevisiae cell. In some embodiments, the Yarrowia cell is a Yarrowia lipolytica cell. In some embodiments, the host cell is a bacterial cell. In some embodiments, the bacterial cell is an Escherichia coli (E. coli) cell, a Bacillus subtilis cell, or a Corynebacterium glutamicum cell. In some embodiments, the plant cell is a sugar beet cell. In some embodiments, the sugar beet cell is a Beta vulgaris cell. In some embodiments, the plant cell is a Solanum lycopersicum cell. In some embodiments, the host cell comprises a genetic modification that results in increased expression of a polynucleotide encoding ALD6, ATR1, ATR2, LDS2, PEX19, PGM1, TPI1 or ZWF1, or any combination of such genetic modification or increased expression, relative to a cell that does not comprise the genetic modification. In some embodiments, the host cell comprises a genetic modification that results in reduced or eliminated expression of a polynucleotide encoding CYP76AD5, ARO5, ATF1, BUD17, CTA1, DAL7, EXG1, GCN4, GPH1, GRX4, MCK1, PUT1 or YDC1, or any combination of such genetic modification or reduced or eliminated expression, relative to a cell that does not comprise the genetic modification. In some embodiments, the host cell does not comprise a polynucleotide encoding CYP76AD5, ARO5, ATF1, BUD17, CTA1, DAL7, EXG1, GCN4, GPH1, GRX4, MCK1, PUT1 or YDC1, or any combination thereof. Attorney Docket No. G0919.70121WO00   In some embodiments, the host cell comprises more than one copy of a polynucleotide encoding ALD6, ATR1, ATR2, LDS2, PEX19, PGM1, TPI1 or ZWF1, or any combination thereof, relative to a corresponding wild-type or control host cell. In some embodiments, the host cell comprises a deletion in or of a polynucleotide encoding CYP76AD5, ARO5, ATF1, BUD17, CTA1, DAL7, EXG1, GCN4, GPH1, GRX4, MCK1, PUT1 or YDC1, or any combination of such deletion. In some embodiments, the host cell comprises (a) a first genetic modification that results in increased expression of a polynucleotide(s) encoding ALD6, ATR1, ATR2, LDS2, PEX19, or PGM1, or any combination of such first genetic modification or increased expression, relative to a cell that does not comprise the first genetic modification or such combination; (b) a second genetic modification that results in reduced or eliminated expression of a polynucleotide(s) encoding GCN4, ARO5, ATF1, BUD17, GRX4, YDC1, or EXG1, or any combination of such second genetic modification or reduced or eliminated expression, relative to a cell that does not comprise the second genetic modification or such combination; or (c) any combination of (a) and (b). In some embodiments, the ATR1 is AtATR1 and / or the ATR2 is AtATR2. In some embodiments, the host cell comprises (a) a first genetic modification that results in increased expression of a polynucleotide(s) encoding TPI1, ZWF1, or TPI1 and ZWF1, relative to a cell that does not comprise the first genetic modification; (b) a second genetic modification that results in reduced or eliminated expression of a polynucleotide(s) encoding GPH1, CTA1, DAL7, PUT1, or MCK1, or any combination of such second genetic modification or reduced or eliminated expression, relative to a cell that does not comprise the second genetic modification or such combination; or (c) any combination of (a) and (b). In some embodiments, the tyrosine hydroxylase comprises an amino acid substitution at one or more positions that correspond to one or more positions selected from W13, H18, S25, Q26, T29, L31, R70, K92, H94, P95, T114, M115, F147, Q164, K185, H198, Y219, C228, S232, C240, S241, C254, P259, D260, Q278, F280, T286, G288, I346, A403, Q405, A407, I409, I416, C418, F459, and D467 of SEQ ID NO: 1. In some embodiments, the tyrosine hydroxylase comprises an amino acid substitution at one or more positions that correspond to one or more positions selected from W13L, H18L, S25R, Q26D, Q26G, Q26H, Q26I, Q26K, Q26L, Q26N, Q26R, Q26S, Q26T, T29K, T29N, T29S, L31K, L31R, R70K, K92H, H94Q, P95A, P95I, P95L, P95N, P95S, P95V, T114S, C144S, T146A, T146G, T146S, F147I, F147L, Q164K, K185N, H198D, H198E, H198G, H198K, H198N, H198S, Y219L, C228F, C228K, C228Y, S232L, C240A, C240D, Attorney Docket No. G0919.70121WO00   C240F, C240G, C240I, C240K, C240N, C240S, C240V, S241Y, C254A, C254D, C254E, C254G, C254N, C254Q, C254R, C254T, A258S, P259A, P259E, P259F, P259K, P259L, P259R, P259S, P259T, P259V, D260S, D270N, Q278D, Q278K, Q278N, F280H, F280I, F280M, F280N, F280S, F280Y, T286S, G288D, I346S, A403V, Q405E, Q405P, Q405S, A407P, I409A, I409E, I409K, I409L, I409S, I409V, I416L, C418S, F459G, F459S, and D467G of SEQ ID NO: 1. In some embodiments, the host cell is capable of producing more betalain than a host cell that expresses a heterologous polynucleotide encoding a tyrosine hydroxylase comprising the amino acid sequence of SEQ ID NO: 1. In some embodiments, the host cell is capable of producing at least 1-fold, at least 1.5-fold, at least 2-fold, at least 2.5-fold, at least 3-fold, at least 3.5-fold, at least 4-fold, at least 4.5-fold, at least 5-fold, at least 6-fold, at least 7-fold, at least 8-fold, at least 9-fold, or at least 10-fold more betalain than a host cell that expresses a heterologous polynucleotide encoding a tyrosine hydroxylase comprising the amino acid sequence of SEQ ID NO: 1. In some embodiments, the betalain is a betacyanin or a betaxanthin. In some embodiments, the betacyanin is betanin, isobetanin, betanidin, isobetanidin, probetanin, or neobetanin. In some embodiments, the betaxanthin is vulgaxanthin, miraxanthin, portulaxanthin, or indicaxanthin. In some embodiments, expression of the gene EXG1 in the host cell is increased. In some embodiments, the host cell is capable of producing more betalain than a host cell that expresses a heterologous polynucleotide encoding a tyrosine hydroxylase comprising the amino acid sequence of SEQ ID NO: 1. In some embodiments, the host cell is capable of producing at least 1-fold, at least 1.5-fold, at least 2-fold, at least 2.5-fold, at least 3-fold, at least 3.5-fold, at least 4-fold, at least 4.5-fold, at least 5-fold, at least 6-fold, at least 7-fold, at least 8-fold, at least 9-fold, or at least 10-fold more betalain than a host cell that expresses a heterologous polynucleotide encoding a tyrosine hydroxylase comprising the amino acid sequence of SEQ ID NO: 1. In some embodiments, the betalain is betanidin or isobetanidin. Aspects of the present disclosure relate to a method of producing a betalain using the host cell of any one of claims 48-80, the method comprising culturing the host cell under conditions effective to produce betalain. In some embodiments, the method further comprises isolating the betalain from the host cell. Attorney Docket No. G0919.70121WO00   In some embodiments, the betalain is a betacyanin or betaxanthin. In some embodiments, the betaxanthin is indicaxanthin. In some embodiments, the betacyanin is betanin, isobetanin, betanidin, isobetanidin, probetanin, or neobetanin. In some embodiments, (a) the genetic modification, (b) the polynucleotide encoding ALD6, ATR1, ATR2, LDS2, PEX19, PGM1, TPI1 or ZWF1, or (c) any combination of the genetic modification and polynucleotide encoding ALD6, ATR1, ATR2, LDS2, PEX19, PGM1, TPI1 or ZWF1 comprise a sequence heterologous to the host cell. In some embodiments, the polynucleotide encoding ALD6, ATR1, ATR2, LDS2, PEX19, PGM1, TPI1 or ZWF1 or any combination of such polynucleotide comprises a sequence heterologous to the host cell. Each of the limitations of the invention can encompass various embodiments of the invention. It is, therefore, anticipated that each of the limitations of the invention involving any one element or combinations of elements can be included in each aspect of the invention. This invention is not limited in its application to the details of construction and the arrangement of components set forth in the following description or illustrated in the drawings. The invention is capable of other embodiments and of being practiced or of being carried out in various ways. Also, the phraseology and terminology used in this disclosure is for the purpose of description and should not be regarded as limiting. The use of “including,” “comprising,” or “having,” “containing,” “involving,” and variations of thereof in this disclosure, is meant to encompass the items listed thereafter and equivalents thereof as well as additional items. As used in this specification and the appended claims, the singular forms "a," "an" and "the" include plural referents unless the content clearly dictates otherwise. BRIEF DESCRIPTION OF THE DRAWINGS The following drawings form part of the present specification and are included to further demonstrate certain aspects of the present disclosure, which may be better understood by reference to one or more of these drawings in combination with the detailed description of specific embodiments presented in this disclosure. The accompanying drawings are not intended to be drawn to scale. The drawings are illustrative only and are not required for enablement of the disclosure. For purposes of clarity, not every component may be labeled in every drawing. In the drawings: FIGs.1A-1B are diagrams showing a biosynthetic pathway from tyrosine to a betaxanthin and betacyanin (FIG.1A), including the betaxanthin indicaxanthin (FIG.1B) Attorney Docket No. G0919.70121WO00   and two betacyanins, in particular, betanidin and betanin (FIG.1B), in which the tyrosine hydroxylase enzyme is AD1 or AD5 [cytochrome P45076AD1 (CYP76AD1) or 76AD5 (CYP76AD5), respectively], DODA is DOPA 4,5-dioxygenase (also known as 4,5-DOPA dioxygenase extradiol), and UGT is a UDP-glucosyltransferase. FIGs.2A-2B show screening results from Example 1. FIG.2A shows a comparison of betanin production in two background strains. Top performing CYP76AD1 variants are within the oval. FIG.2B shows a comparison of betanin and betalamic acid production by a background strain lacking CYP76AD5 (“AD5”). Data is normalized to wild-type CYP76AD1 (“AD1”) activity. In this and other Figures: In various experiments described herein, unless otherwise noted, betanin production measurements are based on the assumption that all absorbance at 540nm in all samples is due to the presence of betanin. In this and other Figures: In various experiments described herein, unless otherwise noted, betalamic acid production measurements are based on the assumption that all absorbance at 405nm in all samples is due to the presence of betalamic acid. FIG.3 shows fold change in betanin production catalyzed by tyrosine hydroxylase CYP76AD1 variants that exhibited at least a 2-fold improvement in activity over the wild- type CYP76AD1. FIG.4 shows the distribution of amino acid substitutions in tyrosine hydroxylase CYP76AD1 single amino acid substitution variants identified in the screen described in Example 1. The Y-axis indicates the frequency a particular amino acid position was found substituted in the various tyrosine hydroxylase variants. In this Figure and in FIGs.6 and 9, the amino acid residues that were introduced into wild type BvCYP76AD1 (SEQ ID NO: 1) at each position to form the substitution variants are indicated. FIG.5 is a list of top tyrosine hydroxylase CYP76AD1 variants identified in the screen described in Example 1 in a background strain lacking CYP76AD5 expression. Fold improvement over wild-type CYP76AD1 is shown. FIG.6 shows the distribution of amino acid substitutions in the top 24 tyrosine hydroxylase CYP76AD1 substitution variants identified in the screen described in Example 1 in a background strain lacking CYP76AD5 expression. The Y-axis indicates the frequency an amino acid position was found substituted in the top 24 tyrosine hydroxylase variants. The amino acid residues that were introduced into the wild type BvCYP76AD1 (SEQ ID NO: 1) sequence at each position to generate the top 24 variant enzymes are also shown. Attorney Docket No. G0919.70121WO00   FIG.7 shows fold change of betanin and betalamic acid production compared to wild-type CYP76AD1 in CYP76AD1 variants identified in the screen described in Example 2. FIG.8 shows fold change of betanin production in the top 20 tyrosine hydroxylase CYP76AD1 variants identified in the screen described in Example 2. FIG.9 shows the distribution of amino acid substitutions within the top 20 tyrosine hydroxylase CYP76AD1 variants identified in Example 2. The frequency and nature of the substitution at each amino acid position are shown. FIG.10 shows relative indicaxanthin production in a strain with a deletion of mck1, as described (along with FIGs.11 and 12) in Example 5. In various experiments described herein, unless otherwise noted, indicaxanthin measurements are based on the assumption that the absorbance at 480nm is due to indicaxanthin. Values of indicaxanthin production are normalized relative to averaged indicaxanthin production (each representing a value of “1”). FIG.11 shows growth (indicated in this and other Figures by OD660), as well as relative indicaxanthin and betalamic acid production in a control strain and in a strain with deletion of mck1 (“mck1 del” in this and other figures) as measured in an Ambr fermentation. Values of indicaxanthin and betalamic acid production are normalized relative to indicaxanthin and betalamic acid production, respectively, in control at the final time point (each representing a value of “1”). Values for OD660in this and other figures are normalized relative to that of control at the final time point (each representing a value of “1”). FIG.12 shows growth, as well as relative betacyanin (betanin, betanidin) and betalamic acid production in a control strain and in a strain with deletion of mck1 as measured in an Ambr fermentation. Values of betacyanin and betalamic acid production are normalized relative to betacyanin and betalamic acid production, respectively, in control at the final time point (each representing a value of “1”). FIG.13 shows growth, as well as relative betanin and betanidin production in a control strain and in a strain with deletion of exg1 (“EXG1”) as measured in an Ambr fermentation, as described in Example 6. Values of betanidin, betanin and betalamic acid production are normalized relative to betanidin, betanin and betalamic acid production, respectively, in control at the final time point (each representing a value of “1”). FIG.14 shows replicate results for betacyanin (based on UV at 540nm) production for various variants of BvCYP76AD1, as described in Example 3. Non-producer control (circles), AD1 wild type control (SEQ ID NO: 1, squares), AD1 variants from generation 1, as described in Example 1 (crosses), AD1 variants from generation 2, Example 2 Attorney Docket No. G0919.70121WO00   (diamonds); AD1 variants from generation 3, Example 3 (star). Values of betacyanin production are normalized relative to averaged betacyanin production in AD1 wild type control (SEQ ID NO: 1) (each representing a value of “1”). FIG.15 shows the positive impact of AtATR2 overexpression on betacyanin (betanin, betanidin) production in an Ambr fermentation, as described in Example 4. Values of betacyanin and betalamic acid production are normalized relative to betacyanin and betalamic acid production, respectively, in control at the final time point (each representing a value of “1”). FIG.16 shows that the knockdown of gcn4 (“gcn4 KD”) led to an increase in betacyanin (betanin, betanidin) production relative to the control in an Ambr fermentation, as described in Example 7. Time is presented in hours. Values of betacyanin and betalamic acid production are normalized relative to betacyanin and betalamic acid production in control at the final time point (each representing a value of “1”). FIG.17 shows that the deletion of ARO5 (“ARO5 del”) led to an increase in betacyanin (betanin, betanidin) production relative to the control in an Ambr fermentation, as described in Example 8. Values of betacyanin and betalamic acid production are normalized relative to betacyanin and betalamic acid production, respectively, in control at the final time point (each representing a value of “1”). FIG.18 shows the impact of the deletion of cta1 (cross), dal7 (square) or gph1 (star) on betaxanthin production compared to control base strain (circle), as described in Example 9. Values of betaxanthin production are normalized relative to betaxanthin production in control base strain (each representing a value of “1”). FIG.19 shows the positive impact of overexpressing ZWF1 (“zwf1 +”) and TPI1 (“tpi1 +”) on betacyanin (betanin, betanidin) and betalamic acid production in an Ambr fermentation, as described in Example 9. Values of betacyanin and betalamic acid production are normalized relative to betacyanin and betalamic acid production, respectively, in control at the final time point (each representing a value of “1”). FIG.20 shows the positive impact of simultaneously deleting cta1 (“cta1-”) and overexpressing ZWF1 (“zwf1+”) and TPI1 (“tpi1 +”) on indicaxanthin production in an Ambr fermentation, as described in Example 9. Values of betaxanthin and betalamic acid production are normalized relative to betaxanthin and betalamic acid production, respectively, in control at the final time point (each representing a value of “1”). FIG.21 shows the positive impact of deleting YDC1 (“YDC1-”), while overexpressing PEX19 (“PEX19+”) on betacyanin (betanin, betanidin) production in an Attorney Docket No. G0919.70121WO00   Ambr fermentation, as described in Example 10. This Figure also shows the positive impact of deleting BUD17 (“BUD17-”), while overexpressing ALD6 (“ALD6+”) on betanin production in an Ambr fermentation, as described in Example 10. Values of betacyanin and betalamic acid production are normalized relative to betacyanin and betalamic acid production, respectively, in control at the final time point (each representing a value of “1”). FIG.22 shows the impact of the deletion of ATF1 (“ATF1-”) and / or GRX4 (“GRX4- ”), while simultaneously overexpressing PGM1 (“PGM1+”) and / or LDS2 (“LDS2+”), respectively on betacyanin (betanin, betanidin) production in an Ambr fermentation, as described in Example 10. Values of betacyanin and betalamic acid production are normalized relative to betacyanin and betalamic acid production, respectively, in control at the final time point (each representing a value of “1”). FIG.23 shows the positive impact of put1 (“put1 del”) deletion on indicaxanthin production in an Ambr fermentation, as described in Example 11. Values of betaxanthin and betalamic acid production are normalized relative to proline level in control at the final time point (each representing a value of “1”). DETAILED DESCRIPTION The present disclosure provides, in some aspects, engineered tyrosine hydroxylase enzymes that are capable of increased production of one or more betalains. The present disclosure also provides various genetic modifications to host cells which can increase production of one or more betalains. Betalains (e.g., betanin and indicaxanthin) can be useful as natural food dyes or as antioxidants in pharmacological applications. Tyrosine hydroxylase enzymes described herein, which are capable of using tyrosine as a substrate to produce betalains, and host cells expressing such tyrosine hydroxylase enzymes, are useful for production of increased quantities of one or more betalains. Betalains Aspects of the disclosure are useful for the production of betalains. As used in this disclosure, the term “betalain” refers to a class of red and yellow tyrosine-derived pigments that are derivatives of betalamic acid. Betalains naturally occur in plants of the order Caryophyllales and in higher order fungi. Betalains contribute to pigments that give the deep red color seen in beets. Betalains can be grouped into two categories: betacyanins and betaxanthins. Attorney Docket No. G0919.70121WO00   A betacyanin is a derivative of betalamic acid that has a conjugated substituted aromatic nucleus to the 1,7-diazaheptamethinium chromophore. See, e.g., Goldman et al. J. Amer. Soc. Hort. Sci. 121(1):23–26. 1996. In some embodiments, betacyanins are derivatives of betanidin, which is an iminium adduct of cyclodioxyphenylalnine (cyclo-DOPA). In some embodiments, a betacyanin is a compound of Formula 1: , in which R1and R2are hydrogen or sugar moieties. Non-limiting examples of betacyanins include betanin, isobetanin, probetanin, and neobetanin. In some embodiments, a betacyanin is amaranthine, iso-amarathine, bougainvillein-r-I, betanin, iso-bougainvillein-r-I, isobetanin, 2-apiosyl-betanin, betanidin, isobetanidin, 2-apiosyl-isoisobetanin, phyllocactin, 4-malonyl- betanin, neobetanin, isophyllocactin, 4-malonyl-iso-betanin, 2-apiosyl-phyllocactin, 2- apiosyl-isophyllocactin, sinapoyl-apiosyl-betanin, sinapoyl-apiosyl-betanin-isomer, glycosyl- glycosyl-(caffeoyl-glycosyl)-betanidin, Glycosyl-glycosyl-(caffeoyl-glycosyl)-betanidin- isomer, (caffeoyl-glucosyl)-betanidin, feruloyl-glycosyl-betanin, glycosyl-(Caffeoyl- glycosyl)-betanidin, caffeoyl-glycosyl-(coumaroyl-glycosyl)-betanin-type, caffeoyl-glycosyl- (coumaroyl-glycosyl)-betanin-type, glycosyl-(caffeoyl-glycosyl)-betanidin-isomer, (caffeoyl- glucosyl)-betanidin-isomer, glycosyl-(coumaroyl-glycosyl)-betanidin, caffeoyl-glycosyl- (coumaroyl-glycosyl)-betanin-type, glycosyl-(coumaroyl-glycosyl)-betanidin-isomer, caffeoyl-glycosyl-(coumaroyl-glycosyl)-betanin-type, betanidin-6-O-(6'-O-trans-4- coumaroyl-glycosyl)-b-sophoroside, lampranthin II, betanidin-6-O-(6'-O-trans-4-coumaroyl- glycosyl)-b-sophoroside-isomer, or isolampranthin II. A betaxanthin is a derivative of betalamic acid that does not have a conjugated substituted aromatic nucleus to the 1,7-diazaheptamethinium chromophore. In some embodiments, betaxanthins are condensation products of betalamic acid with alpha-amino Attorney Docket No. G0919.70121WO00   acids or amines. Non-limiting examples of betaxanthins include indicaxanthin, portulacaxanthin II, and phenylalanine-betaxanthin. See also, e.g., US Patent No. 6,353,156. In some embodiments, a betaxanthin is a compound of Formula 2: in which R3 is an amine or amino acid group and R4 is usually hydrogen. In some embodiments, a betaxanthin is glutamine-betaxanthin, glutamic acid-betaxanthin, proline- betaxanthin, dopa-betaxanthin I, dopa-betaxanthin II, tyrosine-betaxanthin, dopamine- betaxanthin, valine-betaxanthin, tyramine-betaxanthin, 3- methoxytyramine-betaxanthin, iso- leucine-betaxanthin, leucine-betaxanthin, phenylalanine-betaxanthin, or tryptophan- betaxanthin. The betalains of this disclosure can be produced by enzymatic activity either in vitro or in vivo as illustrated in Fig. 1. Naturally-occurring L-tyrosine is converted to L-DOPA by tyrosine hydroxylases such as CYP76AD1 (“AD1”) or CYP76AD5 (“AD5”). L-DOPA is then converted to either cyclo-DOPA by CYP76AD1 or betalamic acid by DOPA 4,5- dioxygenase. Cyclo-DOPA is converted to cDOPA 5-O-glucoside by cyclo-DOPA-5-O- glucosyltransferase, after which it spontaneously reacts with betalamic acid to form betanin. Betalamic acid spontaneously reacts with cycloDOPA or an alpha-amino acid or an amine to generate either betanidin or one or more betaxanthins, respectively. Betanidin is converted to betanin by betanidin-5-O-glucosyltransferase. In some embodiments, the betalain is a betacyanin. In some embodiments, the betacyanin is betanin. In some embodiments, the betacyanin is isobetanin. In some embodiments, the betacyanin is probetanin. In some embodiments, the betacyanin is neobetanin. In some embodiments, the betacyanin is betanidin. In some embodiments, the betalain is a betaxanthin. In some embodiments, the betaxanthin is vulgaxanthin. In some embodiments, the betaxanthin is miraxanthin. In some embodiments, the betaxanthin is Attorney Docket No. G0919.70121WO00   portulaxanthin. In some embodiments, the betaxanthin is indicaxanthin. In some embodiments, more than one betalain is produced. In some embodiments, any combination of: betacyanin, betanin, isobetanin, betanidin probetanin, neobetanin, vulgaxanthin, indicaxanthin, miraxanthin, and / or portulaxanthin is produced. Tyrosine Hydroxylases As used in this disclosure, a “tyrosine hydroxylase” refers to an enzyme that catalyzes the conversion of L-tyrosine to L-DOPA and / or L-DOPA to cyclo-DOPA. Naturally occurring tyrosine hydroxylases include cytochrome P450s and tyrosine 3-monooxygenase. Tyrosine hydroxylase variants of the disclosure include Cytochrome P45076AD1 (“CYP76AD1” or “AD1”) variants capable of hydroxylating tyrosine. In some embodiments, the tyrosine hydroxylase is a variant of Cytochrome P45076AD1 from Beta vulgaris, or BvCYP76AD1. In some embodiments, the tyrosine hydroxylase is a variant of Cytochrome P45076AD1 from Beta vulgaris, or BvCYP76AD1 which comprises a mutation at any of the positions W13, H18, S25, Q26, T29, L31, R70, K92, H94, P95, T114, M115, F147, Q164, K185, H198, Y219, C228, S232, C240, S241, C254, P259, D260, Q278, F280, T286, G288, I346, A403, Q405, A407, I409, I416, C418, F459, and / or D467, or any combination thereof, wherein the number indicates the position and the letter preceding the number indicates the amino acid at that position in the wildtype sequence (e.g., SEQ ID NO: 1). In some embodiments, a mutation is a substitution. In some embodiments a substitution is any of: W13L, H18L, S25R, Q26D, Q26G, Q26H, Q26I, Q26K, Q26L, Q26N, Q26R, Q26S, Q26T, T29K, T29N, T29S, L31K, L31R, R70K, K92H, H94Q, P95A, P95I, P95L, P95N, P95S, P95V, T114S, M115L, C144S, T146A, T146G, T146S, F147I, F147L, Q164K, K185N, H198D, H198E, H198G, H198K, H198N, H198S, Y219L, C228F, C228K, C228Y, S232L, C240A, C240D, C240F, C240G, C240I, C240K, C240N, C240S, C240V, S241Y, C254A, C254D, C254E, C254G, C254N, C254Q, C254R, C254T, A258S, P259A, P259E, P259F, P259K, P259L, P259R, P259S, P259T, P259V, D260S, D270N, Q278D, Q278K, Q278N, F280H, F280I, F280M, F280N, F280S, F280Y, T286S, G288D, I346S, A403V, Q405E, Q405P, Q405S, A407P, I409A, I409E, I409K, I409L, I409S, I409V, I416L, C418S, F459G, F459S, and / or D467G, wherein the number indicates the position and the letter preceding the number indicates the amino acid at that position in the wildtype sequence (e.g., SEQ ID NO: 1), and wherein the letter following the number indicates the substitution. A tyrosine hydroxylase of the disclosure can use L-tyrosine as a substrate. In some embodiments, a tyrosine hydroxylase exhibits specificity for L-tyrosine compared to other Attorney Docket No. G0919.70121WO00   amino acids (e.g., L-phenylalanine or L-histidine). In some embodiments, a tyrosine hydroxylase produces L-DOPA from L-tyrosine. In some embodiments, a tyrosine hydroxylase produces cyclo-DOPA from L-DOPA. In some embodiments, increased processing of L-tyrosine by a tyrosine hydroxylase results in increased quantities of one or more betalains. In some embodiments, a tyrosine hydroxylase predominantly consumes L- tyrosine relative to one or more other amino acids; e.g., may consume L-tyrosine at a rate at least 1.1-fold, 1.2-fold, 1.3-fold, 1.4-fold, 1.5-fold, 2-fold, 2.5-fold, 3-fold, 3.5-fold, 4-fold, 4.5-fold, 5-fold, 5.5-fold, 6-fold, 7-fold, 8-fold, 9-fold or 10-fold higher (e.g., 2-fold to 10- fold more) relative to one or more other amino acids (e.g., relative to L-phenylalanine or L- histidine). In some embodiments, a tyrosine hydroxylase of the disclosure can indirectly increase production of a betalain. As used herein, indirectly increasing production of a betalain refers to increasing production of L-DOPA and / or cyclo-DOPA. L-DOPA is converted by DODA (DOPA dioxygenase, EC: 1.13.11.29; also referred to as “stizolobate synthase”) to betalamic acid, which then spontaneously condenses to form betalains. Cyclo-DOPA can either spontaneously condense with betalamic acid, forming betanidin, or can be glycosylated by a UGT (UDPG:cyclo-DOPA 5-O-glucosyltransferase, EC: 2.4.1; also referred to as “cDOPA5GT”), resulting in cyclo-DOPA-o-glucoside, which spontaneously condenses with betalamic acid, leading to increased betacyanin production. In some embodiments, the tyrosine hydroxylase is engineered. The term “engineered,” as used in the disclosure, refers to the product of modifying, mutating, or otherwise changing the native structure of a protein or enzyme. In some embodiments, the tyrosine hydroxylase is an engineered tyrosine hydroxylase. In some embodiments, an engineered tyrosine hydroxylase comprises one or more amino acid additions, deletions, or substitutions relative to a wild-type tyrosine hydroxylase. In some embodiments, an engineered tyrosine hydroxylase is encoded by an engineered polynucleotide. In some embodiments, an engineered polynucleotide comprises one or more nucleotide additions, deletions, or point mutations relative to a reference polynucleotide. In some embodiments, a tyrosine hydroxylase is a tyrosine hydroxylase from Beta vulgaris or a variant thereof (e.g., described herein). In some embodiments, the tyrosine hydroxylase from Beta vulgaris is BvCYP76AD1. The amino acid sequence of BvCYP76AD1 is provided by SEQ ID NO: 1 below, which corresponds to the sequence provided by UniProtKB Accession No. I3PFJ5: Attorney Docket No. G0919.70121WO00   MDHATLAMILAIWFISFHFIKLLFSQQTTKLLPPGPKPLPIIGNILEVGKKPHRSFANLAKIHGPLIS LRLGSVTTIVVSSADVAKEMFLKKDHPLSNRTIPNSVTAGDHHKLTMSWLPVSPKWRNFRKITAVHLL SPQRLDACQTFRHAKVQQLYEYVQECAQKGQAVDIGKAAFTTSLNLLSKLFFSVELAHHKSHTSQEFK ELIWNIMEDIGKPNYADYFPILGCVDPSGIRRRLACSFDKLIAVFQGIICERLAPDSSTTTTTTTDDV LDVLLQLFKQNELTMGEINHLLVDIFDAGTDTTSSTFEWVMTELIRNPEMMEKAQEEIKQVLGKDKQI QESDIINLPYLQAIIKETLRLHPPTVFLLPRKADTDVELYGYIVPKDAQILVNLWAIGRDPNAWQNAD IFSPERFIGCEIDVKGRDFGLLPFGAGRRICPGMNLAIRMLTLMLATLLQFFNWKLEGDISPKDLDMD EKFGIALQKTKPLKLIPIPRY (SEQ ID NO: 1) BvCYP76AD1 (SEQ ID NO: 1) is expressed in strains discussed in Examples 1, 2 and 3, for example. A non-limiting example of a nucleotide sequence encoding SEQ ID NO: 1 is provided by SEQ ID NO: 259: atggatcatgctactttggccatgattttggccatttggtttatttcgttccatttcattaagttatt attttcacaacaaaccactaagctattgccaccaggtccaaagccattacctattatcggaaatatat tagaagtcggtaagaaaccacacagatcttttgctaacttggctaaaattcacggtcctttgatctcc ttaagattaggttctgttaccactatcgtagttagtagcgctgatgttgctaaagaaatgttcctaaa gaaggatcaccctctgtcaaacagaactataccaaacagcgttactgctggtgaccaccataagctga ctatgtcctggttaccagtgtctccaaaatggaggaacttccgtaagattacagctgtgcacttatta tccccacaacgtttagacgcctgtcaaactttcagacacgcaaaggttcaacaattgtacgaatacgt tcaagaatgtgcacaaaagggccaagctgtcgatattggaaaggcagccttcacaacttcccttaacc ttttgtctaagttatttttctctgtagaattagcccaccacaagtcccacacttcgcaagaatttaag gaactgatttggaacattatggaagatatcggcaaaccaaattacgccgactacttccctattcttgg ttgcgtagatccatcaggtatcagaagaaggttggcctgttctttcgacaagttgattgccgttttcc aaggtatcatttgtgaaagattggctcctgacagtagcacaaccactactacaactaccgacgatgta ttggacgtcttgttgcaattgttcaagcaaaatgaactgactatgggtgaaataaaccacttgttggt tgacatcttcgacgctggtactgataccacgagtagtacctttgaatgggttatgactgaattgatca gaaacccagaaatgatggaaaaagcccaagaagagattaaacaagtgctgggtaaggacaagcaaatt caagaatccgacatcattaacttaccatacctacaagccattattaaggaaaccttaagattgcaccc accaactgtttttctactaccaagaaaggctgatactgatgttgaactttacggttatatcgttccta aggatgctcaaatcttggtcaacttgtgggccattggtagagatccaaacgcttggcaaaatgctgat attttctctccagaaagattcatcggttgtgagatagatgtcaagggtagagattttggtctattgcc attcggtgctggtagaagaatctgtccaggaatgaatcttgctatcagaatgttaactcttatgttag caacgttattgcaattctttaattggaaactggaaggcgacatttctcctaaggaccttgacatggac gaaaaattcggtatcgcattacaaaaaactaagccattgaaattgatccctataccaagatactaa (SEQ ID NO: 259) In some embodiments, a tyrosine hydroxylase is BvCYP76AD5, the amino acid sequence of which is provided below as SEQ ID NO: 517. MDNTTLALILSSLFVCFQLIRSFINHAKKSNKLPPGPKRMPIFGNIFDLGEKPHRSFANLAKIHGPLV SLQLGSVTTVVVSSADVAKEMFLKNDQALANRTIPDSVRAGDHDKLSMSWLPVSAKWRNLRKISAVQL LSTQRLDASQAHRQSKVQQLLEYVHDCSKKGQPVDIGRAAFTTSLNLLSNTFFSVELASHESSASQEF KQLMWNIMEEIGRPNYADFFPILGYLDPFGIRRRLAGYFDQLIAVFQDIIGERQKIRSANLSGGKQTT NDILDTLLNLYDEKELSMGEINHLLVDIFDAGTDTTASTLEWAMAELVKNPDMMVKVQDEIEQAIGKG CSMVQESDISKLPYLQAIIKETLRLHPPTVFLLPRKADADVELYGYVVPKNAQVLVNLWAIGRDPKVW KNPEVFSPERFLESNIDYKGRDFELLPFGAGRRICPGLTLAYRMLNLMMANFLHSYDWKLEDGMHPKD LDMDEKFGITLQKVKPLQVIPVPRK* (SEQ ID NO: 517) A non-limiting example of a nucleotide sequence encoding SEQ ID NO: 517 is provided by SEQ ID NO: 520 below. Attorney Docket No. G0919.70121WO00   atggacaacactaccttagcattaattttatcttcattattcgtttgctttcaattgatcagatcttt cattaatcatgctaagaaatctaacaaattgcctccaggtcctaagagaatgccaattttcggtaaca tttttgacttgggtgaaaagcctcatagatcatttgctaatttagctaagattcacggtcctttggtt tcattgcaattgggttcagttactactgttgttgtttcctcagctgacgttgccaaggaaatgttttt gaagaatgatcaagctttagctaacagaactatccctgactctgtccgtgccggtgaccacgacaagt tatctatgtcctggttgccagtttctgccaagtggagaaacttaagaaaaatatccgctgttcaattg ttgtctacccaaagattggacgcttcacaagctcatagacaatctaaggttcaacagttgttggaata cgtccatgactgttctaaaaaaggtcaaccagtcgatatcggtagagctgctttcactacctccttga acttgttatccaacacttttttttcagttgagttggcttcccatgaatcttctgcttcccaagagttc aaacaattaatgtggaatattatggaagaaattggtagaccaaactacgctgacttctttcctatctt aggttacttggatccattcggtataagaagacgtttggctggttacttcgaccaattgatagctgtct tccaagatattatcggtgagagacaaaagattagatcagctaacttatctggtggtaagcaaaccacc aacgatatcttggacactttgttgaacttatatgacgaaaaggaattatctatgggtgaaataaacca cttgttggttgatatttttgatgctggtactgacactaccgcctctaccttggagtgggccatggctg aattggttaagaaccctgacatgatggttaaggttcaagacgaaatcgagcaagccattggtaagggt tgttccatggtccaagaatctgacatctctaagttgccatacttacaagctatcatcaaggaaacctt aagattacatccaccaaccgttttcttattaccaagaaaagctgacgccgatgttgaattatatggtt atgttgttccaaaaaacgcccaagtcttggttaatttatgggcaattggtcgtgatcctaaagtctgg aaaaatccagaagttttctccccagaaagattcttagaatccaatattgactacaagggtagagattt tgagttgttaccattcggtgccggtagaagaatttgtcctggtttgaccttggcttacagaatgttaa atttaatgatggctaactttttacactcatacgattggaagttggaagatggtatgcatcctaaggat ttggatatggatgaaaagtttggtatcacattgcagaaggttaagccattgcaagttattcctgttcc aagaaagtaa (SEQ ID NO: 520) In some embodiments, a tyrosine hydroxylase is one shown in Table 2. Tyrosine hydroxylase variants for increased production of one or more betalains As described in Examples 1, 2 and 3, variant tyrosine hydroxylases that contain one or more amino acid substitutions relative to BvCYP76AD1 (SEQ ID NO: 1) were identified that were capable of producing increased amounts of one or more betalains (e.g., betanin and indicaxanthin). Aspects of the present disclosure relate to improving the expression, solubility, stability or enzyme activity of a tyrosine hydroxylase such that it is capable of producing increased amounts of one or more betalains relative to a parent tyrosine hydroxylase, as well as the resulting improved tyrosine hydroxylase enzymes, which are disclosed herein. The surprising and unexpected findings described in the present disclosure, including in Examples 1, 2, and 3, may lead to improved production of one or more betalains. In some embodiments, a tyrosine hydroxylase associated with the disclosure comprises at least 1, at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 21, at least 22, at least 23, at least 24, at least 25, at least 26, at least 27, at least 28, at least 29, at least 30, at least 31, at least 32, at least Attorney Docket No. G0919.70121WO00   33, at least 34, at least 35, at least 36, at least 37, at least 38, at least 39, at least 40, at least 41, at least 42, at least 43, at least 44, at least 45, at least 46, at least 47, at least 48, at least 49, at least 50, at least 60, at least 70, at least 80, at least 90, or at least 100 amino acid substitutions, deletions, insertions, or additions relative to SEQ ID NO: 1. In some embodiments, a variant tyrosine hydroxylase disclosed herein may increase conversion of L-tyrosine indirectly to one or more betalains (e.g., betanin or indicaxanthin) by approximately 1.1-fold, 1.2-fold, 1.3-fold, 1.4-fold, 1.5-fold, 2-fold, 2.5-fold, 3-fold, 3.5- fold, 4-fold, 4.5-fold, 5-fold, 5.5-fold, 6-fold, 7-fold, 8-fold, 9-fold, or 10-fold more (e.g., 2- fold to 10-fold or more) relative to a control. In some embodiments, the control is a tyrosine hydroxylase comprising or having the sequence of SEQ ID NO: 1. In some embodiments, a tyrosine hydroxylase comprises an amino acid sequence, or is encoded by a polynucleotide sequence, that is at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or is 100% identical to (a) any amino acid sequence or any polynucleotide sequence, respectively, set forth in SEQ ID NOs: 1-258 or 523-525 or 259-516 or 526-528, (b) an amino acid or a polynucleotide sequence, respectively, of a tyrosine hydroxylase in Table 7, or (c) a tyrosine hydroxylase or its polynucleotide coding sequence, respectively, that is otherwise described in this disclosure. In some embodiments, the amino acid sequence of a tyrosine hydroxylase comprises or consists of any amino acid sequence set forth in of SEQ ID NOs: 1-258 or 523- 525, or a conservatively substituted variant thereof. In some embodiments, the polynucleotide coding sequence of a tyrosine hydroxylase comprises or consists of any polynucleotide sequence set forth in SEQ ID NOs: 259-516, 526-528, or a conservatively substituted variant thereof. In some embodiments, a conservatively substituted variant of a polynucleotide sequence is one in which the codon is changed without changing the amino acid encoded. In various sequences herein, an optional asterisk (*) indicates the end of a sequence. In some embodiments, the sequence of a tyrosine hydroxylase associated with the disclosure comprises one or more amino acid substitutions relative to SEQ ID NO: 1, wherein at least one of the amino acid substitutions is at a position corresponding to position 13, 26, Attorney Docket No. G0919.70121WO00   31, 95, 114, 115, 147, 198, 228, 240, 254, 259, 280, 288, 346, 403, 405, 407, 409, 416, 418, 459 and / or 467 in SEQ ID NO: 1. In some embodiments, a tyrosine hydroxylase comprises any one or more of the following amino acid substitutions: the amino acid serine (S) at a residue corresponding to position 13 in the sequence of SEQ ID NO: 1 (e.g., 13S); the amino acid serine (S) at the residue corresponding to position 26 in the sequence of SEQ ID NO: 1; the amino acid arginine (R) at the residue corresponding to position 26 in the sequence of SEQ ID NO: 1; the amino acid threonine (T) at the residue corresponding to position 26 in the sequence of SEQ ID NO: 1; the amino acid leucine (L) at the residue corresponding to position 26 in the sequence of SEQ ID NO: 1; the amino acid arginine (R) at the residue corresponding to position 31 in the sequence of SEQ ID NO: 1; the amino acid alanine (A) at the residue corresponding to position 95 in the sequence of SEQ ID NO: 1; the amino acid leucine (L) at the residue corresponding to position 95 in the sequence of SEQ ID NO: 1; the amino acid serine (S) at the residue corresponding to position 114 in the sequence of SEQ ID NO: 1; the amino acid leucine (L) at the residue corresponding to position 115 in the sequence of SEQ ID NO: 1; the amino acid leucine (L) at the residue corresponding to position 147 in the sequence of SEQ ID NO: 1; the amino acid asparagine (N) at the residue corresponding to position 198 in the sequence of SEQ ID NO: 1; the amino acid aspartate (D) at the residue corresponding to position 198 in the sequence of SEQ ID NO: 1; the amino acid serine (S) at the residue corresponding to position 198 in the sequence of SEQ ID NO: 1; the amino acid glutamate (E) at the residue corresponding to position 198 in the sequence of SEQ ID NO: 1; the amino acid glycine (G) at the residue corresponding to position 198 in the sequence of SEQ ID NO: 1; the amino acid lysine (K) at the residue corresponding to position 228 in the sequence of SEQ ID NO: 1; the amino acid serine (S) at the residue corresponding to position 240 in the sequence of SEQ ID NO: 1; the amino acid lysine (K) at the residue corresponding to position 240 in the sequence of SEQ ID NO: 1; the amino acid asparagine (N) at the residue corresponding to position 240 in the sequence of SEQ ID NO: 1; the amino acid aspartate (D) at the residue corresponding to position 254 in the sequence of SEQ ID NO: 1; the amino acid glutamate (E) at the residue corresponding to position 254 in the sequence of SEQ ID NO: 1; the amino acid glycine (G) at the residue corresponding to position 254 in the sequence of SEQ ID NO: 1; the amino acid asparagine (N) at the residue corresponding to position 254 in the sequence of SEQ ID NO: 1; the amino acid alanine (A) at the residue corresponding to position 254 in the sequence of SEQ ID NO: 1; the amino acid glutamine (Q) at the residue corresponding to position 254 in the sequence of SEQ ID NO: 1; the amino Attorney Docket No. G0919.70121WO00   acid arginine (R) at the residue corresponding to position 254 in the sequence of SEQ ID NO: 1; the amino acid alanine (A) at the residue corresponding to position 259 in the sequence of SEQ ID NO: 1; the amino acid leucine (L) at the residue corresponding to position 259 in the sequence of SEQ ID NO: 1; the amino acid lysine (K) at the residue corresponding to position 259 in the sequence of SEQ ID NO: 1; the amino acid serine (S) at the residue corresponding to position 259 in the sequence of SEQ ID NO: 1; the amino acid valine (V) at the residue corresponding to position 259 in the sequence of SEQ ID NO: 1; the amino acid threonine (T) at the residue corresponding to position 259 in the sequence of SEQ ID NO: 1; the amino acid asparagine (N) at the residue corresponding to position 259 in the sequence of SEQ ID NO: 1; the amino acid methionine (M) at the residue corresponding to position 280 in the sequence of SEQ ID NO: 1; the amino acid tyrosine (Y) at the residue corresponding to position 280 in the sequence of SEQ ID NO: 1; the amino acid aspartate (D) at the residue corresponding to position 288 in the sequence of SEQ ID NO: 1; the amino acid serine (S) at the residue corresponding to position 346 in the sequence of SEQ ID NO: 1; the amino acid valine (V) at the residue corresponding to position 403 in the sequence of SEQ ID NO: 1; the amino acid proline (P) at the residue corresponding to position 405 in the sequence of SEQ ID NO: 1; the amino acid glutamate (E) at the residue corresponding to position 405 in the sequence of SEQ ID NO: 1; the amino acid valine (V) at the residue corresponding to position 409 in the sequence of SEQ ID NO: 1; the amino acid lysine (K) at the residue corresponding to position 409 in the sequence of SEQ ID NO: 1; the amino acid serine (S) at the residue corresponding to position 418 in the sequence of SEQ ID NO: 1; the amino acid serine (S) at the residue corresponding to position 459 in the sequence of SEQ ID NO: 1; the amino acid glycine (G) at the residue corresponding to position 459 in the sequence of SEQ ID NO: 1; the amino acid glycine (G) at the residue corresponding to position 467 in the sequence of SEQ ID NO: 1; or any combination thereof. In some embodiments, a tyrosine hydroxylase comprises amino acid substitutions at  residues corresponding to the following positions in the amino acid sequence of SEQ ID NO: 1: positions 26 and 254; positions 26 and 459; positions 26, 31, and 254; positions 26, 198, and 254; positions 26, 147, 254, 259, and 459; positions 26, 147, 198, 254, 280, and 459; positions 26, 198, 254, 259, 403, 409, and 459; positions 26, 114, 198, 240, 254, 259, 403, 405, 409, and 459; positions 95, 254, and 418; positions 95, 114, 147, 198, 228, 254, 259, 280, 405, and 459; positions 114, 240, 254, 259, 405, and 459; positions 114, 228, 240, 254, 259, 405, 409, 418, and 459; positions 147, 254, 459; positions 198 and 259; positions 198 and 403; positions 198 and 405; positions 198, 240, and 254; positions 198, 254, 259, 459, Attorney Docket No. G0919.70121WO00   and 467; positions 198, 228, 240, 254, 403, and 459; positions 198, 240, 254, 409, 418, and 459; positions 240, 254, and 259; positions 254 and 259; positions 254 and 280; positions 254 and 403; positions 254 and 459; positions 254, 259, and 409; or positions 254, 259, 280, 403, 405, 409, and 459. In some embodiments, a tyrosine hydroxylase comprises the following amino acid substitutions relative to the sequence of SEQ ID NO: 1: Q26R [the amino acid Glutamine (Q) at Position 26 has been replaced by Arginine (R)] and C254D; Q26L and F459S; Q26S, L31R, and C254N; Q26S, H198S, and C254N; Q26S, F147L, C254D, P259K, and F459S; Q26R, F147L, H198N, C254D, F280M, and F459S; Q26R, H198G, C254R, P259L, G288D, I409V, and F459S; Q26S, H198N, C254N, P259L, G288D, I409V, and F459S, Q26S, H198G, C254N, P259L, A403V, I409V, and F459S; Q26S, T114S, H198E, C240N, C254D, P259S, A403V, Q405P, I409V, and F459S; P95A, C254N, and C418S; P95L, T114S, F147L, H198E, C228K, C254N, P259L, F280M, Q405P, and F459S; T114S, C240N, C254D, P259A, Q405P, and F459S; T114S, C228K, C240K, C254A, P259S, Q405P, I409V, C418S, and F459S; F147L, C254N, and F459S; H198D and P259N; H198D and A403V; H198S and Q405E; H198N, C240S, and C254D; H198N, C254D, and P259L; H198N, C254D, and P259S; H198N, C254D, P259L, F459S, and D467G; H198G, C228K, C240K, C254A, A403V, and F459S; H198G, C240K, C254A, I409K, C418S, and F459G; C240S, C254D, and P259K; C254D and P259V; C254D and P259L; C254D and P259K; C254D and F280Y; C254D and A403V; C254D and F459S; C254E, P259T, and I409V; C254E, P259S, and I409V; or C254D, P259A, F280M, A403V, Q405P, I409V, and F459S; or C254D, I416L, and D467G; or any other combination of mutations disclosed herein. In some embodiments, a variant tyrosine hydroxylase described herein may exhibit at least 1.1-fold, 1.2-fold, 1.3-fold, 1.4-fold, 1.5-fold, 2-fold, 2.5-fold, 3-fold, 3.5-fold, 4-fold, 4.5-fold, 5-fold, 5.5-fold, 6-fold, 7-fold, 8-fold, 9-fold, or 10-fold more (e.g., 2-fold to 10- fold or more) activity on L-tyrosine (e.g., production of one or more betalains indirectly from L-tyrosine) relative to another tyrosine hydroxylase (e.g., a wild-type tyrosine hydroxylase). Variants Aspects of the disclosure relate to variant tyrosine hydroxylases. As used in this disclosure, a "variant" polynucleotide refers to a polynucleotide that differs from a reference polynucleotide by one or more nucleotides in its sequence. As used in this disclosure, a "variant" polypeptide refers to a polypeptide that differs from a reference polypeptide by one or more amino acids in its sequence. Attorney Docket No. G0919.70121WO00   A variant may share at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity with a reference sequence, including all values in between. Unless otherwise noted, the term “sequence identity” refers to the relatedness of the sequences of two polypeptides or polynucleotides when the sequences are aligned, and the term “percent identity” refers to the percentage of residues (amino acids or nucleotides) that are identical when two polypeptide or polynucleotide sequences are aligned. In some embodiments, sequence identity and / or percent identity is determined across the entire length of a sequence, while in other embodiments, sequence identity and / or percent identity is determined over a region of a sequence. Percent identity of polypeptide or polynucleotide sequences can be calculated by any of the methods known to one of ordinary skill in the art. For example, percent identity can be determined using the algorithm of Karlin and Altschul Proc. Natl. Acad. Sci. USA 87:2264- 68, 1990, modified as in Karlin and Altschul Proc. Natl. Acad. Sci. USA 90:5873-77, 1993. Such an algorithm is incorporated into the NBLAST®and XBLAST®programs (version 2.0) of Altschul et al., J. Mol. Biol.215:403-10, 1990. BLAST®protein searches can be performed, for example, with the XBLAST program, score=50, wordlength=3. Where gaps exist between two sequences, Gapped BLAST®can be utilized, for example, as described in Altschul et al., Nucleic Acids Res.25(17):3389-3402, 1997. When utilizing BLAST®and Gapped BLAST®programs, the default parameters of the respective programs (e.g., XBLAST®and NBLAST®) can be used, or the parameters can be adjusted appropriately as would be understood by one of ordinary skill in the art. A second example of a local alignment technique is based on the Smith-Waterman algorithm (Smith, T.F. & Waterman, M.S. (1981) J. Mol. Biol.147:195-197). An example of a global alignment technique is the Needleman–Wunsch algorithm (Needleman, S.B. & Wunsch, C.D. (1970) J. Mol. Biol.48:443-453), which is based on dynamic programming. A further example of a global alignment technique is the Fast Optimal Global Sequence Alignment Algorithm (FOGSAA). Attorney Docket No. G0919.70121WO00   In some embodiments, the identity of two polypeptide sequences is determined by aligning the amino acid sequences of the polypeptides, calculating the number of identical amino acids, and dividing by the length of one of the polypeptide sequences. In some embodiments, the identity of two polynucleotide sequences is determined by aligning the nucleotide sequences of the polynucleotides, calculating the number of identical nucleotides and dividing by the length of one of the polynucleotide sequences. For multiple sequence alignments, computer programs including Clustal Omega (Sievers et al., Mol Syst Biol.2011 Oct 11;7:539) may be used. In some embodiments, sequence identity is determined using the algorithm of Karlin and Altschul Proc. Natl. Acad. Sci. USA 87:2264-68, 1990, modified as in Karlin and Altschul Proc. Natl. Acad. Sci. USA 90:5873-77, 1993 (e.g., BLAST®, NBLAST®, XBLAST® or Gapped BLAST® programs, using default parameters of the respective programs). In some embodiments, the sequence identity of two amino acid or polynucleotide sequences is determined using the Smith-Waterman algorithm (Smith, T.F. & Waterman, M.S. (1981) J. Mol. Biol.147:195-197) or the Needleman–Wunsch algorithm (Needleman, S.B. & Wunsch, C.D. (1970) J. Mol. Biol.48:443-453). In some embodiments, the sequence identity of two amino acid or polynucleotide sequences is determined using a Fast Optimal Global Sequence Alignment Algorithm (FOGSAA). In some embodiments, the sequence identity of two amino acid or polynucleotide sequences is determined using Clustal Omega (Sievers et al., Mol Syst Biol.2011 Oct 11;7:539). As used in this application, a residue (such as a nucleic acid residue or an amino acid residue) in sequence “X” is referred to as corresponding to a position or residue (such as a nucleic acid residue or an amino acid residue) “Z” in a different sequence “Y” when the residue in sequence “X” is at the counterpart position of “Z” in sequence “Y” when sequences X and Y are aligned using sequence alignment tools known in the art. In some embodiments, a polypeptide variant (e.g., a tyrosine hydroxylase variant) comprises the same or substantially similar secondary structure (e.g., alpha helix, beta sheet) as that of a reference polypeptide (e.g., a reference tyrosine hydroxylase). In some embodiments, a polypeptide variant (e.g., a tyrosine hydroxylase variant) comprises the same or substantially similar tertiary structure as that of a reference polypeptide (e.g., a reference tyrosine hydroxylase). As a non-limiting example, a variant polypeptide may have low Attorney Docket No. G0919.70121WO00   primary sequence identity (e.g., less than 80%, less than 75%, less than 70%, less than 65%, less than 60%, less than 55%, less than 50%, less than 45%, less than 40%, less than 35%, less than 30%, less than 25%, less than 20%, less than 15%, less than 10%, or less than 5% sequence identity) compared to a reference polypeptide, but comprise one or more secondary structures (e.g., including but not limited to loops, alpha helices, or beta sheets) or the same tertiary structure as that of a reference polypeptide. For example, a loop may be located between a beta sheet and an alpha helix, between two alpha helices, or between two beta sheets. Homology modeling may be used to compare two or more tertiary structures. Mutations can be made in a nucleotide sequence using any method known to one of ordinary skill in the art. For example, mutations can be made using gene editing tools, PCR, site-directed mutagenesis (e.g., according to Kunkel, Proc. Nat. Acad. Sci. U.S.A.82: 488- 492, 1985), chemical synthesis of a gene or polypeptide, or by insertions, such as insertion of a tag (e.g., a HIS tag or a GFP tag), as well as using chemical mutagens or ultraviolet light. Mutations can include, for example, one or more substitutions, deletions, additions, insertions, fusions, translocations, or any combination thereof, generated using any method known in the art. In some embodiments, methods for producing variants include methods for generating circular permutation of a sequence (Yu and Lutz, Trends Biotechnol.2011 Jan;29(1):18-25). To generate a circular permutation of a polypeptide sequence, the linear primary sequence of a polypeptide can be circularized (e.g., by joining the N-terminal and C-terminal ends of the sequence) and the resulting circular polypeptide can be re-linearized, i.e. is severed (“broken”) at a different location, to generate a linear polypeptide with different N and C termini, the resulting polypeptide being a circular permutation of the original sequence. Thus, the linear primary sequence of the new polypeptide may have low sequence identity (e.g., less than 80%, less than 75%, less than 70%, less than 65%, less than 60%, less than 55%, less than 50%, less than 45%, less than 40%, less than 35%, less than 30%, less than 25%, less than 20%, less than 15%, less than 10%, less or less than 5%, including all values in between) compared to the linear sequence of the polypeptide before it was circularized and severed as determined by linear sequence alignment methods (e.g., Clustal Omega or BLAST). Topological analysis of the two polypeptides, however, may reveal that the tertiary structure of the two polypeptides is similar or dissimilar. Without being bound by a particular theory, a variant polypeptide created through circular permutation of a reference polypeptide and with a similar tertiary structure as the reference polypeptide can share similar functional characteristics (e.g., enzymatic activity, enzyme kinetics, substrate specificity or product Attorney Docket No. G0919.70121WO00   specificity). In some instances, circular permutation may alter the secondary structure, tertiary structure or quaternary structure and produce a polypeptide with different functional characteristics (e.g., increased or reduced enzymatic activity, different substrate specificity, or different product specificity). See, e.g., Yu and Lutz, Trends Biotechnol.2011 Jan;29(1):18-25. It should be appreciated that in a polypeptide that has undergone circular permutation, the linear amino acid sequence of the polypeptide would differ from a reference polypeptide that has not undergone circular permutation. However, one of ordinary skill in the art would be able to determine which residues in the polypeptide that has undergone circular permutation correspond to residues in the reference polypeptide that has not undergone circular permutation by, for example, aligning the sequences and detecting conserved motifs, and / or by comparing the structures or predicted structures of the polypeptides, e.g., by homology modeling. In some embodiments, an algorithm that determines the percent identity between a sequence of interest and a reference sequence described in this application accounts for the presence of circular permutation between the sequences. The presence of circular permutation may be detected using any method known in the art, including, for example, RASPODOM (Weiner et al., Bioinformatics.2005 Apr 1;21(7):932-7). In some embodiments, the presence of circulation permutation is corrected for (e.g., the domains in at least one sequence are rearranged) prior to calculation of the percent identity between a sequence of interest and a sequence described in this application. Functional variants of tyrosine hydroxylases disclosed in this application are also encompassed by the present disclosure. For example, functional variants may bind one or more of the same substrates (e.g., tyrosine) or produce one or more of the same products (e.g., betalain precursors). Functional variants may be identified using any method known in the art. For example, the algorithm of Karlin and Altschul Proc. Natl. Acad. Sci. USA 87:2264-68, 1990 described above may be used to identify homologous proteins (e.g., homologs). Putative functional variants may also be identified by searching for polypeptides with functionally annotated domains. Databases including Pfam (Sonnhammer et al., Proteins. 1997 Jul;28(3):405-20) may be used to identify polypeptides with a particular domain. Homology modeling may also be used to identify amino acid residues that are amenable to mutation without affecting function. A non-limiting example of such a method may include Attorney Docket No. G0919.70121WO00   use of position-specific scoring matrix (PSSM) and an energy minimization protocol. See, e.g.¸Stormo et al., Nucleic Acids Res.1982 May 11;10(9):2997-3011. PSSM may be paired with calculation of a Rosetta energy function, which determines the difference between the wild-type and a mutant, such as a point mutant. Without being bound by a particular theory, potentially stabilizing mutations can be desirable for protein engineering (e.g., production of functional homologs). In some embodiments, a potentially stabilizing mutation has a ΔΔGcalcvalue of less than -0.1 (e.g., less than -0.2, less than -0.3, less than -0.35, less than -0.4, less than -0.45, less than -0.5, less than -0.55, less than -0.6, less than -0.65, less than -0.7, less than -0.75, less than -0.8, less than -0.85, less than -0.9, less than -0.95, or less than -1.0) Rosetta energy units (R.e.u.). See, e.g., Goldenzweig et al., Mol Cell.2016 Jul 21;63(2):337-346. doi: 10.1016 / j.molcel.2016.06.012. In some embodiments, a polynucleotide sequence encoding a tyrosine hydroxylase associated with the disclosure comprises a mutation at 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100 or more than 100 nucleotide positions corresponding to a reference sequence. In some embodiments, the polynucleotide sequence encoding a tyrosine hydroxylase associated with the disclosure comprises a mutation in 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100 or more codons of a coding sequence relative to a reference coding sequence. As will be understood by one of ordinary skill in the art, a mutation within a codon may or may not change the amino acid that is encoded by the codon due to degeneracy of the genetic code. In some embodiments, the one or more mutations in the coding sequence do not alter the amino acid sequence of the coding sequence relative to the amino acid sequence of a reference polypeptide. In some embodiments, the one or more mutations in a polynucleotide sequence encoding a tyrosine hydroxylase alters the amino acid sequence of the polypeptide relative to the amino acid sequence of a reference polypeptide. In some embodiments, the one or more mutations alter the amino acid sequence of the polypeptide relative to the amino acid Attorney Docket No. G0919.70121WO00   sequence of a reference polypeptide and alter (enhance or reduce) an activity of the polypeptide relative to the reference polypeptide. The activity, including specific activity, of any of the polypeptides described in this application may be measured using methods known in the art. As a non-limiting example, a polypeptide’s activity may be determined by measuring its substrate specificity, product(s) produced, the concentration of product(s) produced, or any combination thereof. As used in this application, “specific activity” of a polypeptide refers to the amount (e.g., concentration) of a particular product produced for a given amount (e.g., concentration) of the polypeptide per unit time. Mutations in a polypeptide coding sequence may result in conservative amino acid substitutions. As used in this application, a “conservative amino acid substitution,” or “conservatively substituted amino acid” refers to an amino acid substitution that does not alter the relative charge or size characteristics or functional activity of the protein in which the amino acid substitution is made. In some instances, an amino acid is characterized by its R group (see, e.g., Table 1). For example, an amino acid may comprise a nonpolar aliphatic R group, a positively charged R group, a negatively charged R group, a nonpolar aromatic R group, or a polar uncharged R group. Non-limiting examples of an amino acid comprising a nonpolar aliphatic R group include alanine, glycine, valine, leucine, methionine, and isoleucine. Non-limiting examples of an amino acid comprising a positively charged R group include lysine, arginine, and histidine. Non-limiting examples of an amino acid comprising a negatively charged R group include aspartate and glutamate. Non-limiting examples of an amino acid comprising a nonpolar, aromatic R group include phenylalanine, tyrosine, and tryptophan. Non-limiting examples of an amino acid comprising a polar uncharged R group include serine, threonine, cysteine, proline, asparagine, and glutamine. Functionally equivalent variants of polypeptides may include conservative amino acid substitutions. Non-limiting examples of conservative substitutions of amino acids include substitutions made amongst amino acids within the following groups: (a) M, I, L, V; (b) F, Y, W; (c) K, R, H; (d) A, G; (e) S, T; (f) Q, N; and (g) E, D. Additional non-limiting examples of conservative amino acid substitutions are provided in Table 1. In some embodiments, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 or more than 20 residues can be changed when preparing variant polypeptides. In some embodiments, amino acids are replaced by conservative amino acid substitutions. Attorney Docket No. G0919.70121WO00   Table 1. Non-limiting examples of conservative amino acid substitutions Attorney Docket No. G0919.70121WO00   Amino acid substitutions in the amino acid sequence of a polypeptide to produce a polypeptide variant having a desired property and / or activity can be made by alteration of the coding sequence of the polypeptide. Similarly, conservative amino acid substitutions in the amino acid sequence of a polypeptide to produce functionally equivalent variants of the polypeptide typically are made by alteration of the coding sequence of the polypeptide (e.g., tyrosine hydroxylase). In some embodiments, a tyrosine hydroxylase comprises an amino acid sequence at least 60%, at least 70%, at least 80% or at least 90% identical to that of BvCYP76AD1 and has one or more mutations at positions corresponding to one or more positions selected from W13, H18, S25, Q26, T29, L31, R70, K92, H94, P95, T114, M115, F147, Q164, K185, H198, Y219, C228, S232, C240, S241, C254, P259, D260, Q278, F280, T286, G288, I346, A403, Q405, A407, I409, I416, C418, F459, and D467 relative to SEQ ID NO: 1, or any combination thereof. In some embodiments, a mutation is an amino acid substitution. In some embodiments, a tyrosine hydroxylase is a homolog of BvCYP76AD1 or is one provided in Table 2. In some embodiments, a tyrosine hydroxylase comprises an amino acid sequence at least 60%, at least 70%, at least 80% or at least 90% identical to that provided in Table 2 and has one or more mutations at positions corresponding to one or more positions selected from W13, H18, S25, Q26, T29, L31, R70, K92, H94, P95, T114, M115, F147, Q164, K185, H198, Y219, C228, S232, C240, S241, C254, P259, D260, Q278, F280, T286, G288, I346, A403, Q405, A407, I409, I416, C418, F459, and D467 relative to SEQ ID NO: 1, or any combination thereof. In some embodiments, a mutation is an amino acid substitution. Polynucleotides Encoding Tyrosine Hydroxylases Aspects of the present disclosure relate to recombinant enzymes, functional modifications and variants thereof, polynucleotides encoding said enzymes, as well as uses relating to any thereof. These enzymes include variants of tyrosine hydroxylases, such as Cytochrome P45076AD1 (“AD1”) variants capable of hydroxylating tyrosine. For example, the enzymes and cells described in this application may be used to promote L-tyrosine processing, e.g., by converting L-tyrosine indirectly to one or more betalains. The methods may comprise using a host cell comprising one or more enzymes disclosed in this application, a cell lysate, isolated enzymes, or any combination thereof. Methods comprising recombinant expression of polynucleotides encoding an enzyme disclosed in this application in a host cell are encompassed by the present disclosure. In vitro methods comprising reacting one or more Attorney Docket No. G0919.70121WO00   tyrosine hydroxylases in a reaction mixture disclosed in this application are also encompassed by the present disclosure. The term “heterologous” with respect to a polynucleotide, such as a polynucleotide comprising a gene, is used interchangeably with the term “exogenous” and the term “recombinant” and refers to: a polynucleotide that has been artificially supplied to a biological system such as a cell; a polynucleotide that has been modified within a biological system; or a polynucleotide whose expression or regulation has been manipulated within a biological system. A heterologous polynucleotide that is introduced into or expressed in a host cell may be a synthetic polynucleotide, a polynucleotide that comes from a different organism or species from the host cell, or a polynucleotide that results from modification or selective editing within the host cell of a polynucleotide that is endogenous to the host cell. A polynucleotide comprising a sequence that is endogenous to a host cell also may be considered heterologous when it is, for example: situated non-naturally in the host cell; expressed recombinantly in the host cell, either stably or transiently; present in a copy number that differs from the naturally occurring copy number within the host cell; or expressed in a non-natural way or at a non-natural level within the host cell, such as through manipulation of regulatory regions that control expression of the polynucleotide. In some embodiments, a heterologous polynucleotide is a polynucleotide that comprises a sequence endogenous to a host cell but whose expression is driven by a promoter that does not naturally regulate expression of the polynucleotide. In other embodiments, a heterologous polynucleotide is a polynucleotide that comprises a sequence endogenous to the host cell and whose expression is driven by a promoter that does naturally regulate expression of the polynucleotide, but the promoter driving its expression or another regulatory region regulating its expression has been modified. In some embodiments, the promoter is recombinantly activated or repressed. For example, gene-editing techniques may be used to regulate expression of a polynucleotide in a cell, including an endogenous polynucleotide, from a promoter, including an endogenous promoter. See, e.g., Chavez et al., Nat Methods. 2016 Jul; 13(7): 563–567. A heterologous polynucleotide may comprise a wild-type sequence or a mutant sequence as compared with a reference polynucleotide sequence. A polynucleotide encoding a tyrosine hydroxylase associated with the disclosure, may be incorporated into any appropriate vector through any method known in the art. For example, the vector may be an expression vector, including but not limited to a viral vector (e.g., a lentiviral, retroviral, adenoviral, or adeno-associated viral vector), any vector suitable for transient expression, any vector suitable for constitutive expression, or any vector suitable Attorney Docket No. G0919.70121WO00   for inducible expression (e.g., a galactose-inducible or doxycycline-inducible vector). The vector may be a cloning vector, such as a plasmid, fosmid, phagemid, virus genome or artificial chromosome. As used in this application, the term "expression vector" or "expression construct" refers to a nucleic acid construct, generated recombinantly or synthetically, with a series of specified nucleic acid elements that permit transcription of a particular polynucleotide in a host cell, such as a yeast cell or bacterial cell. In some embodiments, a polynucleotide associated with the disclosure is inserted into an expression vector or expression construct such that it is operably joined to regulatory sequences and, in some embodiments, expressed as an RNA transcript. In some embodiments, the expression vector or expression construct comprises one or more markers, such as a selectable marker, to identify cells transformed or transfected with the expression vector or expression construct. A polynucleotide encoding a polypeptide associated with the disclosure is “operably joined” or “operably linked” to a regulatory sequence when the polynucleotide and the regulatory sequence are covalently linked, and the expression or transcription of the polynucleotide is under the influence or control of the regulatory sequence. In some embodiments, a polynucleotide encoding any of the polypeptides described in this application is under the control of regulatory sequences (e.g., enhancer sequences). In some embodiments, a polynucleotide (e.g., a polynucleotide comprising a gene) is expressed under the control of a promoter. In some embodiments, the promoter is a native promoter, corresponding to the promoter of the gene in its endogenous context. In other embodiments, the promoter is not the native promoter of the gene, e.g., the promoter is different from the promoter of the gene in its endogenous context. In some embodiments, the promoter is a eukaryotic promoter. Non-limiting examples of eukaryotic promoters include TDH3, PGK1, PKC1, PDC1, TEF1, TEF2, RPL18B, SSA1, TDH2, PYK1,TPI1 GAL1, GAL10, GAL7, GAL3, GAL2, MET3, MET25, HXT3, HXT7, ACT1, ADH1, ADH2, CUP1-1, ENO2, and SOD1, as would be known to one of ordinary skill in the art (see, e.g., Addgene website: blog.addgene.org / plasmids-101-the-promoter- region). In some embodiments, the promoter is a prokaryotic promoter (e.g., bacteriophage or bacterial promoter). Non-limiting examples of bacteriophage promoters include Pls1con, T3, T7, SP6, and PL. Non-limiting examples of bacterial promoters include Pbad, PmgrB, Ptrc2, Plac / ara, Ptac, and Pm. In some embodiments, the promoter is an inducible promoter. As used in this application, an “inducible promoter” is a promoter controlled by the presence or absence of a Attorney Docket No. G0919.70121WO00   molecule. Non-limiting examples of inducible promoters include chemically regulated promoters and physically regulated promoters. For chemically regulated promoters, the transcriptional activity can be regulated by one or more compounds, such as alcohol, an antibiotic such as tetracycline, a carbon source such as galactose, a steroid, a metal, or other compounds. For physically regulated promoters, transcriptional activity can be regulated by a phenomenon such as light or temperature. Non-limiting examples of tetracycline-regulated promoters include anhydrotetracycline (aTc)-responsive promoters and other tetracycline- responsive promoter systems (e.g., a tetracycline repressor protein (tetR), a tetracycline operator sequence (tetO) and a tetracycline transactivator fusion protein (tTA)). Non-limiting examples of steroid-regulated promoters include promoters based on the rat glucocorticoid receptor, human estrogen receptor, moth ecdysone receptors, and promoters from the steroid / retinoid / thyroid receptor superfamily. Non-limiting examples of metal-regulated promoters include promoters derived from metallothionein (proteins that bind and sequester metal ions) genes. Non-limiting examples of pathogenesis-regulated promoters include promoters induced by salicylic acid, ethylene or benzothiadiazole (BTH). Non-limiting examples of temperature / heat-inducible promoters include heat shock promoters. Non- limiting examples of light-regulated promoters include light responsive promoters from plant cells. In certain embodiments, the inducible promoter is a galactose-inducible promoter. In some embodiments, the inducible promoter is induced by one or more physiological conditions (e.g., pH, temperature, radiation, osmotic pressure, saline gradients, cell surface binding, or concentration of one or more extrinsic or intrinsic inducing agents). Non-limiting examples of an extrinsic inducer or inducing agent include amino acids and amino acid analogs, saccharides and polysaccharides, nucleic acids, protein transcriptional activators and repressors, cytokines, toxins, petroleum-based compounds, metal containing compounds, salts, ions, enzyme substrate analogs, hormones or any combination thereof. In some embodiments, the promoter is a constitutive promoter. As used in this application, a “constitutive promoter” refers to an unregulated promoter that allows continuous transcription of a gene. Non-limiting examples of a constitutive promoter include TDH3, PGK1, PKC1, PDC1, TEF1, TEF2, RPL18B, SSA1, TDH2, PYK1, TPI1, HXT3, HXT7, ACT1, ADH1, ADH2, ENO2, and SOD1. Other inducible promoters or constitutive promoters known to one of ordinary skill in the art are also contemplated. In some embodiments, introduction of a polynucleotide, such as a polynucleotide encoding a tyrosine hydroxylase associated with the disclosure, into a host cell results in Attorney Docket No. G0919.70121WO00   genomic integration of the polynucleotide. In some embodiments, a host cell (e.g., a yeast cell or a bacterial cell) comprises at least 1 copy, at least 2 copies, at least 3 copies, at least 4 copies, at least 5 copies, at least 6 copies, at least 7 copies, at least 8 copies, at least 9 copies, at least 10 copies, at least 11 copies, at least 12 copies, at least 13 copies, at least 14 copies, at least 15 copies, at least 16 copies, at least 17 copies, at least 18 copies, at least 19 copies, at least 20 copies, at least 21 copies, at least 22 copies, at least 23 copies, at least 24 copies, at least 25 copies, at least 26 copies, at least 27 copies, at least 28 copies, at least 29 copies, at least 30 copies, at least 31 copies, at least 32 copies, at least 33 copies, at least 34 copies, at least 35 copies, at least 36 copies, at least 37 copies, at least 38 copies, at least 39 copies, at least 40 copies, at least 41 copies, at least 42 copies, at least 43 copies, at least 44 copies, at least 45 copies, at least 46 copies, at least 47 copies, at least 48 copies, at least 49 copies, at least 50 copies, at least 60 copies, at least 70 copies, at least 80 copies, at least 90 copies, at least 100 copies, or more, including any values in between, of a polynucleotide sequence, such as a polynucleotide sequence encoding any of the polypeptides described in this application, in its genome. Said copies may be inserted into the same locus or into different loci of a recombinant host cell of the disclosure. In some embodiments, the sequence of a polynucleotide (e.g., a polynucleotide comprising a gene) is codon optimized. Codon optimization may increase expression of a gene by at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100%, including all values in between) relative to a reference sequence that is not codon-optimized. In some embodiments, a polynucleotide encoding a tyrosine hydroxylase comprises a sequence that is at least 50% (e.g., at least 55%, 60%, 65%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more than 99%, including all values in between) identical to any one of SEQ ID NOs: 259-516 or 526-528. In certain embodiments, a polynucleotide encoding a tyrosine hydroxylase comprises any one of SEQ ID NOs: 259- 516 and 526-528. In certain embodiments a polynucleotide encoding a tyrosine hydroxylase consists of or consists essentially of any one of SEQ ID NOs: 259-516 and 526-528. Host Cells Any of the polynucleotides or polypeptides of the disclosure may be expressed in a host cell. As used in this application, the term “host cell” refers to a cell that can be used to Attorney Docket No. G0919.70121WO00   express a polynucleotide, such as a polynucleotide that encodes a polypeptide used in production of one or more betalains and precursors thereof. Any suitable host cell may be used to express any of the recombinant polypeptides, including tyrosine hydroxylases, and other polypeptides disclosed in this application, including eukaryotic cells or prokaryotic cells. Suitable host cells include, but are not limited to, fungal cells (e.g., yeast cells), bacterial cells (e.g., E. coli cells), algal cells, plant cells, insect cells, and animal cells, including mammalian cells. Suitable yeast host cells include, but are not limited to: Candida, Hansenula, Saccharomyces, Schizosaccharomyces, Pichia, Kluyveromyces, Yarrowia and Fusarium. In some embodiments, the yeast cell is Hansenula polymorpha, Saccharomyces cerevisiae, Saccharomyces carlsbergensis, Saccharomyces diastaticus, Saccharomyces norbensis, Saccharomyces kluyveri, Schizosaccharomyces pombe, Pichia pastoris, Pichia finlandica, Pichia trehalophila, Pichia kodamae, Pichia membranaefaciens, Pichia opuntiae, Pichia thermotolerans, Pichia salictaria, Pichia quercuum, Pichia pijperi, Pichia stipitis, Pichia methanolica, Pichia angusta, Kluyveromyces lactis, Candida albicans, Yarrowia lipolytica, or Fusarium venenatum. In some embodiments, the yeast strain is an industrial polyploid yeast strain. Other non-limiting examples of fungal cells include cells obtained from Aspergillus spp., Penicillium spp., Fusarium spp., Rhizopus spp., Acremonium spp., Neurospora spp., Sordaria spp., Magnaporthe spp., Allomyces spp., Ustilago spp., Botrytis spp., and Trichoderma spp. In some embodiments, the host cell is an algal cell such as Chlamydomonas (e.g., C. Reinhardtii) and Phormidium (P. sp. ATCC29409). The present disclosure is also suitable for use with a variety of plant cell types. In some embodiments, the host cell is a plant cell such as Beta vulgaris. In some embodiments, the host cell is a plant cell such as a tomato cell. In some embodiments, the host cell is a plant cell such as Solanum lycopersicum cell. In other embodiments, the host cell is a prokaryotic cell. Suitable prokaryotic cells include gram positive, gram negative, and gram-variable bacterial cells. The host cell may be a species of, but not limited to: Agrobacterium, Alicyclobacillus, Anabaena, Anacystis, Acinetobacter, Acidothermus, Arthrobacter, Azotobacter, Bacillus, Bifidobacterium, Brevibacterium, Butyrivibrio, Buchnera, Campestris, Campylobacter, Clostridium, Corynebacterium, Chromatium, Coprococcus, Escherichia, Enterococcus, Enterobacter, Erwinia, Fusobacterium, Faecalibacterium, Francisella, Flavobacterium, Geobacillus, Haemophilus, Helicobacter, Klebsiella, Lactobacillus, Lactococcus, Ilyobacter, Micrococcus, Attorney Docket No. G0919.70121WO00   Microbacterium, Mesorhizobium, Methylobacterium, Methylobacterium, Mycobacterium, Neisseria, Pantoea, Pseudomonas, Prochlorococcus, Rhodobacter, Rhodopseudomonas, Rhodopseudomonas, Roseburia, Rhodospirillum, Rhodococcus, Scenedesmus, Streptomyces, Streptococcus, Synecoccus, Saccharomonospora, Saccharopolyspora, Staphylococcus, Serratia, Salmonella, Shigella, Thermoanaerobacterium, Tropheryma, Tularensis, Temecula, Thermosynechococcus, Thermococcus, Ureaplasma, Xanthomonas, Xylella, Yersinia, and Zymomonas. In some embodiments, the bacterial host strain is an industrial strain. Numerous bacterial industrial strains are known and suitable for the methods and compositions described in this application. In some embodiments, the bacterial host cell is of the Agrobacterium species (e.g., A. radiobacter, A. rhizogenes, A. rubi), the Arthrobacterspecies (e.g., A. aurescens, A. citreus, A. globformis, A. hydrocarboglutamicus, A. mysorens, A. nicotianae, A. paraffineus, A. protophonniae, A. roseoparaffinus, A. sulfureus, A. ureafaciens), the Bacillus species (e.g., B. thuringiensis, B. anthracis, B. megaterium, B. subtilis, B. lentus, B. circulars, B. pumilus, B. lautus, B. coagulans, B. brevis, B. firmus, B. alkaophius, B. licheniformis, B. clausii, B. stearothermophilus, B. halodurans, B. amyloliquefaciens). In particular embodiments, the host cell will be an industrial Bacillus strain including but not limited to B. subtilis, B. pumilus, B. licheniformis, B. megaterium, B. clausii, B. stearothermophilus and B. amyloliquefaciens. In some embodiments, the host cell will be an industrial Clostridium species (e.g., C. acetobutylicum, C. tetani E88, C. lituseburense, C. saccharobutylicum, C. perfringens, C. beijerinckii). In some embodiments, the host cell will be an industrial Corynebacterium species (e.g., C. glutamicum, C. acetoacidophilum). In some embodiments, the host cell will be an industrial Escherichia species (e.g., E. coli). In some embodiments, the host cell will be an industrial Erwinia species (e.g., E. uredovora, E. carotovora, E. ananas, E. herbicola, E. punctata, E. terreus). In some embodiments, the host cell will be an industrial Pantoea species (e.g., P. citrea, P. agglomerans). In some embodiments, the host cell will be an industrial Pseudomonas species, (e.g., P. putida, P. aeruginosa, P. mevalonii). In some embodiments, the host cell will be an industrial Streptococcus species (e.g., S. equisimiles, S. pyogenes, S. uberis). In some embodiments, the host cell will be an industrial Streptomyces species (e.g., S. ambofaciens, S. achromogenes, S. avermitilis, S. coelicolor, S. aureofaciens, S. aureus, S. fungicidicus, S. griseus, S. lividans). In some embodiments, the host cell will be an industrial Zymomonas species (e.g., Z. mobilis, Z. lipolytica). Attorney Docket No. G0919.70121WO00   The present disclosure is also suitable for use with a variety of animal cell types, including mammalian cells, for example, human (including 293, HeLa, WI38, PER.C6 and Bowes melanoma cells), mouse (including 3T3, NS0, NS1, Sp2 / 0), hamster (CHO, BHK), monkey (COS, FRhL, Vero), and hybridoma cell lines. In various embodiments, cell types or strains that may be used in the practice of the disclosure including both prokaryotic and eukaryotic cell or strains, and are readily accessible to the public from a number of culture collections such as American Type Culture Collection (ATCC), Deutsche Sammlung von Mikroorganismen and Zellkulturen GmbH (DSM), Centraalbureau Voor Schimmelcultures (CBS), and Agricultural Research Service Patent Culture Collection, Northern Regional Research Center (NRRL). The term “cell,” as used in this application, may refer to a single cell or a population of cells, such as a population of cells belonging to the same cell line or strain. Use of the singular term “cell” should not be construed to refer explicitly to a single cell rather than a population of cells. The host cell may comprise genetic modifications relative to a wild-type counterpart. A vector or polynucleotide encoding any one or more of the polypeptides (e.g., tyrosine hydroxylases) described in this application may be introduced into a suitable host cell using any method known in the art. Host cells may be cultured under any conditions suitable as would be understood by one of ordinary skill in the art. For example, any media, temperature, and incubation conditions known in the art may be used. For host cells carrying an inducible vector, cells may be cultured with an appropriate inducible agent to promote expression. Any of the cells disclosed in this application can be cultured in media of any type (rich or minimal) and any composition prior to, during, and / or after contact and / or integration of a nucleic acid. The conditions of the culture or culturing process can be optimized through routine experimentation as would be understood by one of ordinary skill in the art. In some embodiments, the selected media is supplemented with various components. In some embodiments, the concentration and amount of a supplemental component is optimized. In some embodiments, other aspects of the media and growth conditions (e.g., pH, temperature, etc.) are optimized through routine experimentation. In some embodiments, the frequency that the media is supplemented with one or more supplemental components, and the amount of time that the cell is cultured, is optimized. Culturing of the cells described in this application can be performed in culture vessels known and used in the art. In some embodiments, an aerated reaction vessel (e.g., a stirred Attorney Docket No. G0919.70121WO00   tank reactor) is used to culture the cells. In some embodiments, a bioreactor or fermenter is used to culture the cells. Thus, in some embodiments, the cells are used in fermentation. As used in this application, the terms “bioreactor” and “fermenter” are interchangeably used and refer to an enclosure, or partial enclosure, in which a biological, biochemical and / or chemical reaction takes place, involving a living organism or part of a living organism, or purified proteins. Any type of bioreactor or fermenter known in the art may be compatible with aspects of the disclosure. Any suitable host cell may be used to produce any of the recombinant polypeptides (e.g., tyrosine hydroxylase) disclosed in this application, including eukaryotic cells or prokaryotic cells. In some embodiments, a host cell that expresses a heterologous polynucleotide encoding a variant tyrosine hydroxylase disclosed herein may increase conversion of L- tyrosine indirectly to one or more betalains (e.g., betanin or indicaxanthin) by approximately 1.1-fold, 1.2-fold, 1.3-fold, 1.4-fold, 1.5-fold, 2-fold, 2.5-fold, 3-fold, 3.5-fold, 4-fold, 4.5- fold, 5-fold, 5.5-fold, 6-fold, 7-fold, 8-fold, 9-fold, or 10-fold more (e.g., approximately 2- fold to approximately 10-fold more) relative to a control. In some embodiments, the control is a host cell that expresses a heterologous polynucleotide encoding a tyrosine hydroxylase comprising or having the sequence of SEQ ID NO: 1. In some embodiments, a host cell expresses a heterologous polynucleotide encoding a variant tyrosine hydroxylase that comprises an amino acid sequence that is at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or is 100% identical to any one of SEQ ID NOs: 1-258 and 523-525, an amino acid or polynucleotide sequence of a tyrosine hydroxylase in Table 7, or a tyrosine hydroxylase otherwise described in this disclosure. In some embodiments, the amino acid sequence of a tyrosine hydroxylase comprises or consists of any one of SEQ ID NOs: 1-258 and 523-525, or a conservatively substituted version thereof. In some embodiments, a host cell that expresses a heterologous polynucleotide encoding a variant tyrosine hydroxylase described herein may exhibit at least 1.1-fold, 1.2- fold, 1.3-fold, 1.4-fold, 1.5-fold, 2-fold, 2.5-fold, 3-fold, 3.5-fold, 4-fold, 4.5-fold, 5-fold, Attorney Docket No. G0919.70121WO00   5.5-fold, 6-fold, 7-fold, 8-fold, 9-fold, or 10-fold more (e.g., at least 2-fold to at least 10-fold more) activity on L-tyrosine (e.g., production of one or more betalains indirectly from L- tyrosine) relative to a corresponding cell expressing a polynucleotide encoding another tyrosine hydroxylase (e.g., a wild-type tyrosine hydroxylase). Genetic modifications of the host cell In some embodiments, a host cell producing a betalain can comprise one or more genetic modifications that result in an increase in expression from one or more polynucleotides. In some embodiments, a host cell producing a betalain can comprise one or more genetic modifications that result in a reduction or elimination of expression from one or more other polynucleotides. In some embodiments, a host cell producing a betalain can comprise one or more genetic modifications that result in an increase in expression from one or more polynucleotides and a reduction or elimination of expression from one or more other polynucleotides. In some embodiments, a host cell producing a betalain can be one in which expression of a polynucleotide encoding a selected enzyme is absent or the polynucleotide encoding the selected enzyme is absent. In some embodiments, a host cell producing a betalain can comprise one or more genetic modifications that result in an increase in expression from one or more polynucleotides, a reduction or elimination of expression from one or more other polynucleotides and the host cell is one in which a polynucleotide encoding a selected enzyme is absent. In some embodiments, the reduction or elimination of expression from a polynucleotide encoding an enzyme (e.g., a gene) may be achieved using any method known in the art, including, by way of non-limiting example, by reducing promoter strength, knocking out the gene, replacing a native gene with a less active or abundant homolog from another species, and / or mutating a native or heterologous gene to attenuate expression or activity, or any other common molecular biology technique known to one of ordinary skill in the art. In some embodiments, the reduction or elimination of expression from a polynucleotide encoding an enzyme can be accomplished using any technique known in the art. In some embodiments, a technique known in the art for the reduction or elimination of expression from a polynucleotide encoding an enzyme may include: deleting the gene or a Attorney Docket No. G0919.70121WO00   part thereof so that the gene no longer expresses a functional protein; making a frameshift mutation in the coding segment; deleting the promoter for the gene; replacing the native promoter with a weak or weaker promoter, or a regulatable promoter which is then regulated to be inactive; deleting the start codon; deleting or altering the native ribosome binding site of the gene or the region between the native ribosome binding site and the translational start of the gene; introducing a premature stop codon in the gene; introducing a heterologous nucleic acid and / or making an alteration to the sequence of the gene such that the protein product thereof (or the mRNA encoding it) is unstable, inactive, less active, or no longer transported to a cellular compartment wherein it would normally function; introducing a promoter which is downstream (3') of the gene, is oriented in the opposite direction, and is stronger than the native promoter; altering the codon usage such that a decreased amount of the mRNA of the gene is translated; altering one or more of the intercistronic regions; introducing an agent such as a siRNA or antibody which interferes with and / or causes the destruction of the mRNA and / or protein corresponding to the gene; or using any other method known in the art now or in the future. As a non-limiting example, polymerase chain reaction (PCR)-based methods may be used (see, e.g., Gardner et al.2014 Methods Mol Biol., 1205:45-78) or gene- editing techniques may be used to genetically modify the host cells of the disclosure. For example, genes may be deleted through gene replacement (e.g., with a marker, including a selection marker). A gene may also be truncated through the use of a transposon system (see, e.g., Poussu et al.2005 Nucleic Acids Res., 33(12): el04). A non-limiting example of a host cell producing a betalain that comprises one or more genetic modifications is one in which: (a) expression of a polynucleotide(s) encoding one or more of the following enzymes (or a variant or homolog thereof) is increased: ALD6, ATR1, ATR2, LDS2, PEX19, PGM1, TPI1, or ZWF1 [e.g., increased relative to a cell (e.g., a host cell such as a wild-type or a control host cell) that does not comprise the genetic modification], or any combination thereof; or (b) expression of a polynucleotide(s) encoding one or more of the following enzymes (or a variant or homolog thereof) is reduced, eliminated or absent: CYP76AD5, ARO5, ATF1, BUD17, CTA1, DAL7, EXG1, GCN4, GPH1, GRX4, MCK1, PUT1, or YDC1 [e.g., reduced to eliminated relative to a cell (e.g., a host cell such as a wild-type or a control host cell) that does not comprise the genetic modification], or any combination thereof; or (c) any combination of (a) and (b). In some embodiments, in a host cell in which expression of a polynucleotide(s) encoding one or more of the following enzymes (or a variant or homolog thereof) is increased: ALD6, ATR1, ATR2, LDS2, PEX19, PGM1, TPI1, or ZWF1, the source organism Attorney Docket No. G0919.70121WO00   of the sequence of the polynucleotide(s) encoding ALD6, ATR1, ATR2, LDS2, PEX19, PGM1, TPI1, or ZWF1 is different from the source organism of the host cell [e.g., the polynucleotide(s) encoding ALD6, ATR1, ATR2, LDS2, PEX19, PGM1, TPI1, or ZWF1 may be heterologous to the host cell]. As a non-limiting example: the host cell is Saccharomyces cerevisiae, but the source organism for the sequence of the polynucleotide(s) encoding ATR1 is Arabidopsis thaliana. As a non-limiting example: the host cell is Saccharomyces cerevisiae, but the source organism for the sequence of the polynucleotide(s) encoding ATR2 is Arabidopsis thaliana. As another non-limiting example: the host cell is Saccharomyces cerevisiae, but the source organism for the sequence of the polynucleotide(s) encoding ZWF1 is Yarrowia. In some embodiments, a host cell in which the expression of a polynucleotide encoding an enzyme is described as reduced, eliminated or absent, is a host cell that, in its wild-type form, does not comprise or express such a polynucleotide. Thus, a host cell in which a polynucleotide encoding an enzyme is described as absent includes a host cell in which the polynucleotide is not present in the host cell’s wild-type form. As a non-limiting example, wild-type Saccharomyces cerevisiae does not comprise a polynucleotide encoding CYP76AD5 (“AD5”), and thus the expression of a polynucleotide encoding AD5 is absent from this wild-type host. In some embodiments, production by a host cell of a betalain can be increased by increasing production of L-DOPA and / or cyclo-DOPA. L-DOPA is converted by DODA (DOPA dioxygenase, EC: 1.13.11.29; also referred to as “stizolobate synthase”) to betalamic acid, which then spontaneously condenses to form betalains. In some embodiments, in a host cell for production of a betalain, expression of a polynucleotide(s) encoding DODA (or a variant or homolog thereof) is increased. In some embodiments, DODA is MjDODA from Mirabilis jalapa (SEQ ID NO: 565) or a variant or homolog thereof. In some embodiments, DODA is stizolobate synthase [Amaranthus cruentus (Purple amaranth)] (AcDODA), A0A0U1YJM3. In some embodiments, DODA is 4,5-dioxygenase- like protein [Conophytum uviforme] (CuDODA), QED20600.1. In some embodiments, these changes in expression may be considered to be genetic modifications. Examples 1-3 show that mutations in Cytochrome P45076AD1 can improve betalain production; and Examples 4-11 show that gene modifications in host cells can improve betalain production mediated by wild-type Cytochrome P45076AD1 and / or Cytochrome P45076AD5. Attorney Docket No. G0919.70121WO00   In Examples 1, 6 and 9, some of the host cells comprise polynucleotides which encode both AD1 and AD5, and some of the host cells comprise a polynucleotide that encodes AD1 but not AD5. In Examples 2, 3, 4, 5, 7, 8, and 10, the host cells comprise a polynucleotide encoding AD1 but not AD5. In Example 11, the host cells comprise a polynucleotide encoding AD5 but not AD1. In some embodiments, an AD5 is BvCYP76AD5, SEQ ID NO: 517. In some embodiments, the mutations in Cytochrome P45076AD1 can be combined with the genetic modifications in host cells to improve betalain production. In some embodiments, depending on the type of betalain that is to be produced, it may be advantageous to increase or reduce the expression of various genes in the host cell. In some embodiments, a host cell for producing betacyanins comprises any one or more of the following genetic modifications: (a) an increase in expression of a polynucleotide(s) encoding one or more of the following: ALD6, ATR1 (e.g., AtATR1), ATR2 (e.g., AtATR2), LDS2, PEX19, or PGM1 [e.g., an increase relative to a cell (e.g., a host cell such as a wild- type or a control host cell) that does not comprise the genetic modification], or any combination thereof; or (b) a reduction, elimination or absence of expression of a polynucleotide encoding one or more of the following: GCN4, ARO5, ATF1, BUD17, GRX4, YDC1, or EXG1 [e.g., a reduction or elimination relative to a cell (e.g., a host cell such as a wild-type or a control host cell) that does not comprise the genetic modification], or any combination thereof; or (c) any combination of (a) and (b). In some embodiments, in a host cell for producing betacyanins and betaxanthins (e.g., indicaxanthin): (a) expression of a polynucleotide(s) encoding one or more of the following enzymes (or a variant or homolog thereof) is increased: TPI1 and / or ZWF1 (e.g., an increase relative to a host cell such as a wild-type or a control host cell); or (b) expression of a polynucleotide(s) encoding one or more of the following enzymes (or a variant or homolog thereof) is reduced, eliminated or absent: GPH1, CTA1, DAL7, PUT1, or MCK1 (e.g., reduced or eliminated relative to a host cell such as a wild-type or a control host cell), or any combination thereof; or (c) any combination of (a) and (b). In some embodiments, the selection of AD1 or AD5 for expression in the host cell can also depend on the desired betalain product. Without wishing to be bound by any particular theory, the present disclosure notes that AD5 (e.g., BvCYP76AD5) reportedly is a tyrosine hydroxylase, but does not perform the second reaction of converting L-DOPA to cyclo- DOPA (which is reportedly performed by AD1). Sunnadeniya et al.2016 PLoS ONE 11(2): Attorney Docket No. G0919.70121WO00   e0149417; and Polturak et al.2016 New Phytologist 210: 269–283. In some embodiments, a host cell for producing betacyanins can express a polynucleotide(s) encoding AD5, which can complement the expression of a polynucleotide encoding AD1 in making L-DOPA. In some embodiments, in a host cell for production betacyanins (e. g., betanin), expression of a polynucleotide(s) encoding CYP76AD1 (Cytochrome P45076AD1) (or a variant or homolog thereof) is increased. In some embodiments, in a host cell for production betacyanins (e. g., betanin), expression of a polynucleotide(s) encoding CYP76AD1 (Cytochrome P45076AD1, e.g., BvCYP76AD1) (or a variant or homolog thereof) and CYP76AD5 (Cytochrome P450 76AD1, e.g., BvCYP76AD5) are increased. In some embodiments, in a host cell for production of betaxanthins (e. g., indicaxanthin), expression of a polynucleotide(s) encoding CYP76AD5 (Cytochrome P45076AD5) is increased. In Example 1 and in various examples herein describing production of a betaxanthin (e.g., indicaxanthin), the host cells comprise a polynucleotide encoding AD5. In some embodiments, a host cell for producing a betalain can express CYP76AD1 and / or CYP76AD5, and can have multiple genetic modifications (e.g., modifications of the expression of one or more polynucleotides encoding one or more genes). In some embodiments, any of various genes in (or introduced into) a host cell can be a target of a genetic modification. In some embodiments, the gene is from Arabidopsis thaliana and is ATR2 (e.g., AtATR2), Acc. No. Q9SUM3, SEQ ID NO: 529, as described in Example 4; or the gene is from Saccharomyces cerevisiae and is: ALD6, P54115, SEQ ID NO: 538, Example 10; LDS2, Q08218, SEQ ID NO: 542, Example 10; PEX19, Q07418, SEQ ID NO: 540, Example 10; PGM1, P33401, SEQ ID NO: 544, Example 10; TPI1, P00942, SEQ ID NO: 536, Example 9; or ZWF1, P11412, SEQ ID NO: 535, Example 9. In some embodiments, the gene is from Saccharomyces cerevisiae and is: ARO5, P53133, SEQ ID NO: 531, Example 8; ATF1, P40353, SEQ ID NO: 543, Example 10; BUD17, P53727, SEQ ID NO: 537, Example 10; CTA1, P15202, SEQ ID NO: 532, Example 9; DAL7, P21826, SEQ ID NO: 533, Example 9; EXG1, NP_013403.1, SEQ ID NO: 519, Example 5; GCN4, P03069, SEQ ID NO: 530, Example 7; GPH1, P06738, SEQ ID NO: 534, Example 9; GRX4, P32642, SEQ ID NO: 541, Example 10; MCK1, NP_014092.1, SEQ ID NO: 518, Example 6; PUT1, P09368, SEQ ID NO: 545, Example 11; YDC1, Q02896, SEQ ID NO: 539, Example 10. In some embodiments, the selection of a genetic modification(s) to be made to a host cell may depend on the betalain desired to be produced. As shown herein, some genetic Attorney Docket No. G0919.70121WO00   modifications may increase production of one betalain while decreasing the production of another. As non-limiting examples: Without wishing to be bound by any theory, the present disclosure suggests that the overexpression of AtATR2 may shift the balance from betalamic acid to betacyanin production, as shown in Example 4. Without wishing to be bound by any theory, the present disclosure suggests that overexpression of AtATR1 may have a similar effect to overexpression of AtATR2, as their amino acid sequences (e.g., AtATR1 is represented by SEQ ID NO: 573, and AtATR2 is represented by SEQ ID NO: 529) have 86.8% similarity. Reportedly, AtATR1 (P450 reductase 1) and AtATR2 (P450 reductase 2) both have a Flavodoxin 1 region; both serve as an electron donor in several oxygenase systems; both are a component of nitric oxide synthases and methionine synthase reductases; and both also transfer two electrons from NADPH to the heme of cytochrome p450. See, for example: Urban P, et al. J Biol Chem.1997 Aug 1;272(31):19176-86; McBride et al. Mol Cell Proteomics.2017 Nov;16(11):1972-1989; Mayer et al. Nature.1999 Dec 16;402(6763):769-77; and Niu et al. FEBS J.2017 Mar;284(5):754-765. Without wishing to be bound by any theory, the present disclosure suggests that the BvATR1 and BvATR2 (from Beta vulgaris) may also have a similar effect to overexpression of AtATR2. The amino acid sequences of BvATR1 (SEQ ID NO: 575) and BvATR2 (SEQ ID NO: 577) have 90.4% and 88.2% similarity, respectively, to that of AtATR2 (SEQ ID NO: 529). Similarity was determined using the LALIGN sequence alignment, software version 36.3.8i Feb, 2025, available at: fasta.bioch.virginia.edu / fasta_www2 / fasta_www.cgi; see: X. Huang and W. Miller (1991) Adv. Appl. Math.12:373-381. Like AtATR2, BvATR1 and BvATR2 reportedly both have a Flavodoxin 1 region; both serve as an electron donor in several oxygenase systems; both are a component of nitric oxide synthases and methionine synthase reductases; and both also transfer two electrons from NADPH to the heme of cytochrome p450. See, for example: NCBI Reference Sequence: XP_010688489.1; and NCBI Reference Sequence: XP_010692385.3. In some embodiments, a homolog of AtATR2 is AtATR1, BvATR1, or BvATR2. In some embodiments, a homolog of AtATR1 is AtATR2, BvATR1, or BVATR2. Without wishing to be bound by any theory, the present disclosure suggests that the deletion of exg1 shifted the balance from betanidin to betanin production, as shown in Example 5. Without wishing to be bound by any particular theory, the present disclosure suggests that the knockout of PUT1 may be particularly useful for the production of indicaxanthin (see Example 11); PUT1 reportedly degrades proline (Nishimura et al.2021 Attorney Docket No. G0919.70121WO00   Microorg.9: 1650), which can be used as a precursor to indicaxanthin (and can be added to the medium as such). The knockout of PUT1 may also be useful for production of other betalains. The present disclosure also notes that a PUT1 knockout may, in at least some circumstances, decrease the growth rate of at least some host cells. In some embodiments, the host cell (i) comprises a genetic modification described herein; and (ii) comprises a polynucleotide encoding: (a) a wild-type tyrosine hydroxylase, e.g., BvCYP76AD1 (SEQ ID NO: 1); (b) a homolog of BvCYP76AD1; (c) a variant BvCYP76AD1 tyrosine hydroxylase that comprises one or more amino acid substitutions relative to BvCYP76AD1; or (d) a variant of a homolog of BvCYP76AD1. In some embodiments, a genetic modification results in: (a) an increase in the expression of a polynucleotide encoding one or more of the following enzymes (or a variant or homolog thereof): ALD6, ATR1, ATR2, LDS2, PEX19, PGM1, TPI1, or ZWF1, or any combination thereof; or (b) a reduction, elimination or absence of the expression of a polynucleotide encoding one or more of the following enzymes (or a variant or homolog thereof): CYP76AD5, ARO5, ATF1, BUD17, CTA1, DAL7, EXG1, GCN4, GPH1, GRX4, MCK1, PUT1, or YDC1, or any combination thereof; or (c) any combination of (a) and (b). In some embodiments, a genetic modification results in: (a) an increase in the expression of a polynucleotide encoding one or more of the following enzymes: ALD6, ATR1, ATR2, LDS2, PEX19, PGM1, TPI1, or ZWF1, or any combination thereof; or (b) a reduction, elimination or absence of the expression of a polynucleotide encoding one or more of the following enzymes: CYP76AD5, ARO5, ATF1, BUD17, CTA1, DAL7, EXG1, GCN4, GPH1, GRX4, MCK1, PUT1, or YDC1, or any combination thereof; or (c) any combination of (a) and (b). In some embodiments, a host cell for production of a betalain can comprise one or more UGTs. In some embodiments, a UGT is selected from: cyclo-DOPA 5-O- glucosyltransferase from Mirabilis jalapa, also known as MjcDOPA5GT, BAD91803.1 (SEQ ID NO: 567); Db5GT, WOB18973.1, SEQ ID NO: 569; or CqcDOPA5GT from Chenopodium quinoa, XP_021748306.1, SEQ ID NO: 571; or a variant or homolog of any of these. In some embodiments, a UGT can perform one or more different chemical steps in the biosynthesis of a betalain (see Figures 1A and 1B); a host cell can comprise two or more UGTs to perform all the relevant steps to produce a desired betalain. In some embodiments, a host cell can comprise one or more genetic modifications that result in altered expression of one or more selected polynucleotides such that expression can be increased, decreased or eliminated. Attorney Docket No. G0919.70121WO00   In some embodiments, the host cell has a genetic modification that results in an increase in expression of one or more selected sequences or a genetic modification that results in a decrease in expression of one or more selected sequences. In some embodiments, the host cell has a genetic modification that results in an increase in expression of one or more selected sequences and a genetic modification that results in a decrease in expression of one or more selected sequences. In some embodiments, the host cell has more than one genetic modification that results in any combination of the foregoing increase and decrease in expression of one or more selected sequences. In some embodiments, the genetic modification is more than one copy of a polynucleotide encoding a selected sequence. In some embodiments, the genetic modification is a deletion in or of a polynucleotide encoding a selected sequence. In some embodiments, the genetic modification that results in an increase in expression of one or more selected sequences is a strong promoter operably linked to the one or more selected sequences resulting in increased expression. In some embodiments, a genetic modification that results in a decrease in expression of one or more selected sequences is a weak promoter operably linked to the one or more selected sequences resulting in decreased expression. In some embodiments, expression of the gene ALD6 (or a variant or a homolog thereof) in the host cell is increased. In some embodiments, expression of the gene ATR1 (or a variant or a homolog thereof) in the host cell is increased. In some embodiments, expression of the gene ATR2 (or a variant or a homolog thereof) in the host cell is increased. In some embodiments, expression of the gene LDS2 (or a variant or a homolog thereof) in the host cell is increased. In some embodiments, expression of the gene PEX19 (or a variant or a homolog thereof) in the host cell is increased. In some embodiments, expression of the gene PGM1 (or a variant or a homolog thereof) in the host cell is increased. In some embodiments, expression of the gene TPI1 (or a variant or a homolog thereof) in the host cell is increased. In some embodiments, expression of the gene ZWF1 (or a variant or a homolog thereof) in the host cell is increased. In some embodiments, the host cell can comprise: (a) a polynucleotide encoding a variant tyrosine hydroxylase that comprises one or more amino acid substitutions relative to BvCYP76AD1 (SEQ ID NO: 1); or (b) a polynucleotide encoding a wild-type tyrosine hydroxylase, e.g., BvCYP76AD1 (SEQ ID NO: 1) or a homolog thereof. Example amino acid and nucleotide sequences for these genes are provided in Table 7. In some embodiments, an asterisk (*), if present, indicates the end of an amino acid or nucleotide sequence. Attorney Docket No. G0919.70121WO00   In some embodiments, wherein a gene (or a variant or homolog thereof) is not already present in a host cell, increasing the expression of the gene (or variant or homolog) may entail introducing a polynucleotide encoding the gene (or variant or homolog) into the host cell. In some embodiments, expression of the gene CYP76AD5 (or a homolog thereof) in the host cell is reduced, eliminated or absent. In some embodiments, expression of the gene ARO5 (or a homolog thereof) in the host cell is reduced, eliminated or absent. In some embodiments, expression of the gene ATF1 (or a homolog thereof) in the host cell is reduced, eliminated or absent. In some embodiments, expression of the gene BUD17 (or a homolog thereof) in the host cell is reduced, eliminated or absent. In some embodiments, expression of the gene CTA1 (or a homolog thereof) in the host cell is reduced, eliminated or absent. In some embodiments, expression of the gene DAL7 (or a homolog thereof) in the host cell is reduced, eliminated or absent. In some embodiments, expression of the gene EXG1 (or a homolog thereof) in the host cell is reduced, eliminated or absent. In some embodiments, expression of the gene GCN4 (or a homolog thereof) in the host cell is reduced, eliminated or absent. In some embodiments, expression of the gene GPH1 (or a homolog thereof) in the host cell is reduced, eliminated or absent. In some embodiments, expression of the gene GRX4 (or a homolog thereof) in the host cell is reduced, eliminated or absent. In some embodiments, expression of the gene MCK1 (or a homolog thereof) in the host cell is reduced, eliminated or absent. In some embodiments, expression of the gene PUT1 (or a homolog thereof) in the host cell is reduced, eliminated or absent. In some embodiments, expression of the gene YDC1 (or a homolog thereof) in the host cell is reduced, eliminated or absent. In some embodiments, the reduction, elimination or absence of the expression of a gene may be achieved by deleting or knocking out the gene. In some embodiments, the host cell can comprise: (a) a polynucleotide encoding a variant tyrosine hydroxylase that comprises one or more amino acid substitutions relative to BvCYP76AD1 (SEQ ID NO: 1); or (b) a polynucleotide encoding a wild-type tyrosine hydroxylase, e.g., BvCYP76AD1 (SEQ ID NO: 1) or a homolog thereof. Example amino acid and nucleotide sequences for these genes are provided in Table 7. In some embodiments, an asterisk (*), if present, indicates the end of an amino acid or nucleotide sequence. In some embodiments, the host cell which (a) expresses a heterologous polynucleotide encoding a tyrosine hydroxylase comprising the amino acid sequence of SEQ ID NO: 1, and (b) comprises at least one of the genetic modifications described herein is capable of Attorney Docket No. G0919.70121WO00   producing more betalain than a control host cell lacks the at least one of the genetic modifications described herein. In some embodiments, a control host cell is a cell used for comparison in an experiment. In some embodiments, a host cell comprises a polynucleotide encoding a tyrosine hydroxylase described herein (e.g., a CYP76AD1 variant described herein) and a polynucleotide encoding the tyrosine hydroxylase CYP76AD5 (SEQ ID NO: 517), or a variant thereof. In some embodiments, in a host cell for producing a betalain, the expression of a polynucleotide encoding BvCYP76AD5 (SEQ ID NO: 517) is increased. In some embodiments, a host cell comprises a polynucleotide encoding a tyrosine hydroxylase described herein (e.g., a CYP76AD1 variant described herein) but does not comprise a polynucleotide encoding CYP76AD5 or a variant thereof. In some embodiments, a host cell comprises a polynucleotide encoding a tyrosine hydroxylase described herein (e.g., a CYP76AD1 variant described herein), a polynucleotide encoding CYP76AD5 or a variant thereof, and a polynucleotide encoding MCK1 kinase (MCK1; SEQ ID NO: 518), or a variant thereof. In some embodiments, a host cell comprises a polynucleotide encoding a tyrosine hydroxylase described herein (e.g., a CYP76AD1 variant described herein), a polynucleotide encoding CYP76AD5 or a variant thereof, but does not comprise a polynucleotide encoding MCK1 or a variant thereof. In some embodiments, a host cell comprises a polynucleotide encoding a tyrosine hydroxylase described herein (e.g., a CYP76AD1 variant described herein), but does not comprise a polynucleotide encoding CYP76AD5 or MCK1 or variants thereof. In some embodiments, a host cell comprises a polynucleotide encoding a tyrosine hydroxylase described herein (e.g., a CYP76AD1 variant described herein), a polynucleotide encoding CYP76AD5 or a variant thereof, a polynucleotide encoding MCK1 or a variant thereof, and a polynucleotide encoding exo-1,3-beta-glucanase (EXG1; SEQ ID NO: 519), or a variant thereof. In some embodiments, a host cell comprises a polynucleotide encoding a tyrosine hydroxylase described herein (e.g., a CYP76AD1 variant described herein), a polynucleotide encoding CYP76AD5 or a variant thereof, and a polynucleotide encoding MCK1 or a variant thereof, but does not comprise a polynucleotide encoding EXG1 or a variant or homolog thereof, wherein a homolog of EXG1 is a gene whose amino acid sequence has a high degree of identity to that the Beta vulgaris EXG1 (e.g., at least 30%, at least 40%, or at least 50% sequence identity). In some embodiments, a host cell comprises a polynucleotide encoding a tyrosine hydroxylase described herein (e.g., a CYP76AD1 variant described herein), and a polynucleotide encoding CYP76AD5 or a variant thereof, but does Attorney Docket No. G0919.70121WO00   not comprise polynucleotides encoding MCK1 or EXG1 or variants thereof. In some embodiments, a host cell comprises a polynucleotide encoding a tyrosine hydroxylase described herein (e.g., a CYP76AD1 variant described herein), but does not comprise polynucleotides encoding CYP76AD5, MCK1, and / or EXG1 or variants thereof. In some embodiments, expression of a polynucleotide encoding a tyrosine hydroxylase described herein (CYP76AD5 or a variant thereof) is reduced, eliminated or absent. In some embodiments, reduction, elimination or absence of expression of a polynucleotide encoding a tyrosine hydroxylase described herein (CYP76AD5 or a variant thereof) is by gene deletion, gene knockout, or gene knockdown. In some embodiments, expression of a polynucleotide encoding MCK1, or a variant or homolog thereof is reduced, eliminated or absent. In some embodiments, reduction, elimination or absence of expression of a polynucleotide encoding MCK1 or a variant or homolog thereof is by gene deletion, gene knockout, or gene knockdown. In some embodiments, expression of a polynucleotide encoding EXG1, or a variant or homolog thereof is reduced, eliminated or absent. In some embodiments, reduction, elimination or absence of expression of a polynucleotide encoding EXG1 or a variant or homolog thereof is by gene deletion, gene knockout, or gene knockdown. In some embodiments, expression of a polynucleotide encoding EXG1, or a variant or homolog thereof is increased. In some embodiments, increased expression of a polynucleotide encoding EXG1 or a variant or homolog thereof is by overexpression. In some embodiments, increased expression of a polynucleotide encoding EXG1 or a variant or homolog thereof results in increased production of betanidin and / or isobetanidin. In some embodiments, in a host cell producing a betalain: (a) expression of a polynucleotide encoding one or more of the following enzymes (or a variant or homolog thereof) is increased: ALD6, ATR1, ATR2, LDS2, PEX19, PGM1, TPI1, or ZWF1, or any combination thereof; or (b) expression of a polynucleotide encoding one or more of the following enzymes (or a variant or homolog thereof) is reduced, eliminated or absent: CYP76AD5, ARO5, ATF1, BUD17, CTA1, DAL7, EXG1, GCN4, GPH1, GRX4, MCK1, PUT1, or YDC1, or any combination thereof; or (c) any combination of (a) and (b). Homologs of various genes In some embodiments, in a host cell producing a betalain: (a) expression of a polynucleotide encoding one or more of the following enzymes is increased: a homolog of any of: ALD6, ATR1, ATR2, LDS2, PEX19, PGM1, TPI1, or ZWF1, or any combination thereof; or (b) expression of a polynucleotide encoding one or more of the following enzymes Attorney Docket No. G0919.70121WO00   is reduced, eliminated or absent: a homolog of any of: CYP76AD5, ARO5, ATF1, BUD17, CTA1, DAL7, EXG1, GCN4, GPH1, GRX4, MCK1, PUT1, or YDC1, or any combination thereof; or (c) any combination of (a) and (b). As used in this application, homologs or homologous sequences are sequences (e.g., nucleic acid or amino acid sequences) that share a certain percent identity (e.g., at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% percent identity, including all values in between) and may be paralogous sequences, orthologous sequences, or sequences arising from convergent evolution. Paralogous sequences arise from duplication of a gene within a genome of a species, while orthologous sequences diverge after a speciation event. Two different species may have evolved independently but may each comprise a sequence that shares a certain percent identity with a sequence from the other species as a result of convergent evolution. In some embodiments, homologs of BvCYP76AD5 include but are not limited to: cytochrome P45076AD1-like protein [Abronia nealleyi], AKI33952.1; cytochrome P450 76AD1-like protein [Abronia nealleyi], AKI33845.1; cytochrome P45076AD1-like protein [Acleisanthes lanceolata], AKI33848.1; cytochrome P45076AD1-like protein [Acleisanthes obtusa], AKI33847.1; cytochrome P45076AD1-like protein, partial [Allionia incarnata], AKI33853.1; cytochrome P45076AD1-like protein, partial [Alternanthera caracasana], AKI33835.1; cytochrome P45076AD1-like protein, partial [Alternanthera ficoidea], AKI33831.1; cytochrome P45076AD1-like protein, partial [Alternanthera sessilis], AKI33829.1; cytochrome P45076AD1-like protein, partial [Amaranthus cruentus], AKI33932.1; CYP76AD2 [Amaranthus cruentus], AET43291.1; cytochrome P45076AD1- like [Amaranthus tricolor], XP_057542296.1; cytochrome P45076AD1-like [Amaranthus tricolor], XP_057541335.1; cytochrome P45076AD1-like [Amaranthus tricolor], XP_057527403.1; cytochrome P45076AD1-like protein [Anulocaulis leiosolenus], AKI33846.1; cytochrome P450 CYP76AD14 [Basella alba], AJD87470.1; cytochrome P450 76AD1-like protein, partial [Bassia scoparia], AKI33839.1; cytochrome P450 CYP76AD6 [Beta vulgaris], WIF23011.1; cytochrome P45076AD1-like protein, partial [Beta vulgaris subsp. maritima], AKI33834.1; hypothetical protein BVRB_9g222320 isoform A [Beta vulgaris subsp. vulgaris], KMT00967.1; Cytochrome P45076AD1 [Bienertia sinuspersici], Attorney Docket No. G0919.70121WO00   KAL2927655.1; Cytochrome P45076AD1 [Bienertia sinuspersici], KAL2927654.1; Cytochrome P45076AD1 [Bienertia sinuspersici], KAL2926580.1; cytochrome P450 76AD1-like protein, partial [Boerhavia coccinea], AKI33852.1; cytochrome P450 CYP76AD15 [Bougainvillea peruviana], BDZ29444.1; cytochrome p45076AD [Bougainvillea peruviana], BCD59210.1; cytochrome P45076AD1-like protein, partial [Bougainvillea spectabilis], AKI33941.1; hypothetical protein Cgig2_014657 [Carnegiea gigantea], KAJ8452894.1; CYP76AD4 [Celosia cristata], AGI78466.1; cytochrome P450 76AD1-like [Chenopodium quinoa], XP_021732600.1; cytochrome P45076AD1-like [Chenopodium quinoa], XP_021717192.1; cytochrome P45076AD1-like [Chenopodium quinoa], XP_021717175.1; cytochrome P450 CYP76AD12 [Cleretum bellidiforme], AJD87468.1; cytochrome P45076AD19 [Dianthus caryophyllus], AMA07825.1; cytochrome P45076AD1-like protein [Ercilla volubilis], AKI33916.1; cytochrome P450 76AD1-like protein [Froelichia latifolia], AKI33838.1; cytochrome P45076AD1-like protein, partial [Hypertelis cerviana], AKI33918.1; cytochrome P45076AD1-like protein, partial [Mirabilis jalapa], AKI33843.1; CYP76AD3 [Mirabilis jalapa], AET43292.1; cytochrome P45076AD1-like protein [Mirabilis multiflora], AKI33844.1; cytochrome P450 76AD17 [Mollugo verticillata], AMA07822.1; cytochrome P450 CYP76AD9 [Opuntia ficus- indica], AJD87465.1; cytochrome P450 CYP76AD10 [Phytolacca americana], AJD87466.1; cytochrome P45076AD1-like protein, partial [Phytolacca bogotensis], AKI33943.1; cytochrome P45076AD1-like protein [Phytolacca dioica], AKI33942.1; cytochrome P450 76AD1-like protein, partial [Portulaca cryptopetala], AKI33921.1; cytochrome P450 76AD1-like protein, partial [Portulaca molokiniensis], AKI33920.1; hypothetical protein RND81_14G194500 [Saponaria officinalis], KAK9666568.1; cytochrome P45076AD1-like protein, partial [Sesuvium portulacastrum], AKI33914.1; cytochrome P45076AD1-like [Spinacia oleracea], XP_021853403.2; cytochrome P45076AD1-like [Spinacia oleracea], XP_021848355.2; and cytochrome P45076AD1-like protein, partial [Talinum sp. YY-2015], AKI33923.1. In some embodiments, a variant of a homolog of BvCYP76AD5 comprises a mutation (e.g., a substitution) at one or more position corresponding to any of: W13, H18, S25, Q26, T29, L31, R70, K92, H94, P95, T114, M115, F147, Q164, K185, H198, Y219, C228, S232, C240, S241, C254, P259, D260, Q278, F280, T286, G288, I346, A403, Q405, A407, I409, I416, C418, F459, and D467. In some embodiments, homologs of ATR1 (cytochrome P450 reductase 1 from Arabidosis thaliana; SEQ ID NO: 573) include but are not limited to: unnamed protein Attorney Docket No. G0919.70121WO00   product [Arabidopsis halleri], CAL9226709.1; NADPH--cytochrome P450 reductase 1 [Arabidopsis lyrata subsp. lyrata], XP_020873336.1; FAD-binding domain ferredoxin reductase-type [Arabidopsis suecica], KAG7546321.1; hypothetical protein Bca4012_015118 [Brassica carinata], KAL0738908.1; hypothetical protein Bca4012_080278 [Brassica carinata], KAL0659693.1; hypothetical protein DY000_02038194 [Brassica cretica], KAF3532631.1; hypothetical protein DY000_02038193 [Brassica cretica], KAF3532636.1; NADPH--cytochrome P450 reductase 1 [Brassica napus], XP_013644219.2; unnamed protein product [Brassica napus], CAF2027779.1; NADPH--cytochrome P450 reductase 1- like [Brassica napus], XP_048600101.1; hypothetical protein HID58_001430 [Brassica napus], KAH0941793.1; hypothetical protein YC2023_087399 [Brassica napus], WZZ76029.1; hypothetical protein HID58_078129 [Brassica napus], KAH0871107.1; unnamed protein product, partial [Brassica oleracea], VDD49521.1; NADPH--cytochrome P450 reductase 1 [Brassica oleracea var. oleracea], XP_013598654.1; NADPH--cytochrome P450 reductase 1-like [Brassica oleracea var. oleracea], XP_013618645.1; unnamed protein product, partial [Brassica rapa], CAG7887521.1; NADPH--cytochrome P450 reductase 1 [Brassica rapa], XP_009138137.2; hypothetical protein IGI04_001426 [Brassica rapa subsp. trilocularis], KAG5413859.1; hypothetical protein IGI04_001425 [Brassica rapa subsp. trilocularis], KAG5413858.1; NADPH--cytochrome P450 reductase 1 isoform X1 [Camelina sativa], XP_010433757.1; NADPH--cytochrome P450 reductase 1 [Capsella rubella], XP_006285937.1; NADPH--cytochrome P450 reductase 1 [Cardamine amara subsp. amara], KAL1222506.1; NADPH--cytochrome P450 reductase 1 [Cardamine amara subsp. amara], KAL1222507.1; NADPH--cytochrome P450 reductase 1 [Citrus sinensis], KAH9756198.1; hypothetical protein WN944_007917 [Citrus x changshan-huyou], KAK9215911.1; hypothetical protein WN943_008119 [Citrus x changshan-huyou], KAK9219474.1; NADPH--cytochrome P450 reductase [Citrus x clementina], XP_006433816.1; Flavodoxin [Corchorus capsularis], OMO50775.1; hypothetical protein COLO4_35252 [Corchorus olitorius], OMO57587.1; NADPH--cytochrome P450 reductase- like [Durio zibethinus], XP_022768466.1; unnamed protein product [Eruca vesicaria subsp. sativa], CAH8363970.1; unnamed protein product [Eruca vesicaria subsp. sativa], CAH8384629.1; NADPH--cytochrome P450 reductase [Euphorbia lathyris], XP_065880562.1; NADPH--cytochrome P450 reductase 1 [Eutrema salsugineum], XP_006413419.1; hypothetical protein CXB51_011412 [Gossypium anomalum], KAG8494022.1; hypothetical protein B456_009G229300 [Gossypium raimondii], KJB58863.1; P450 reductase 1 [Hibiscus trionum], GMI82778.1; NADPH--cytochrome P450 Attorney Docket No. G0919.70121WO00   reductase 1 [Hirschfeldia incana], KAJ0263359.1; NADPH--cytochrome P450 reductase [Melia azedarach], KAJ4701468.1; unnamed protein product [Microthlaspi erraticum], CAA7037327.1; unnamed protein product [Microthlaspi erraticum], CAA7037328.1; NADPH--cytochrome P450 reductase 1 [Raphanus sativus], XP_018484557.1; NADPH-- cytochrome P450 reductase 1 [Raphanus sativus], KAJ4913076.1; NADPH--cytochrome P450 reductase [Senna tora], KAF7817035.1; hypothetical protein N665_0008s0129 [Sinapis alba], KAF8117784.1; hypothetical protein N665_0632s0024 [Sinapis alba], KAF8086204.1; hypothetical protein N665_0008s0130 [Sinapis alba], KAF8117785.1; truncated cytochrome P450 reductase 1, partial [synthetic construct], UGC41730.1; NADPH- -cytochrome P450 reductase 1-like [Tarenaya hassleriana], XP_010530279.1; NADPH-- cytochrome P450 reductase [Theobroma cacao], XP_007018234.2; and unnamed protein product [Thlaspi arvense], CAH2078069.1. In some embodiments, homologs of ATR2 (cytochrome P450 reductase from Arabidosis thaliana; SEQ ID NO: 529) include but are not limited to: unnamed protein product [Arabidopsis arenosa], CAE6168248.1; unnamed protein product [Arabidopsis halleri], CAL9227439.1; NADPH-cytochrome P450 reductase 2 [Arabidopsis lyrata subsp. lyrata], XP_002869386.1; nadph-ferrihemoprotein reductase [Arabis alpina], KFK29577.1; unnamed protein product [Arabis nemorensis], VVB11013.1; hypothetical protein Bca4012_022745 [Brassica carinata], KAL0726652.1; hypothetical protein F2Q69_00009846 [Brassica cretica], KAF3508290.1; hypothetical protein YC2023_087806 [Brassica napus], WZZ76436.1; unnamed protein product [Brassica oleracea], VDD00751.1; NADPH-cytochrome P450 reductase 2-like [Brassica oleracea var. oleracea], XP_013606073.1; hypothetical protein BRARA_H01415 [Brassica rapa], RID50708.1; hypothetical protein IGI04_000692 [Brassica rapa subsp. trilocularis], KAG5413125.1; NADPH-cytochrome P450 reductase 2-like [Camelina sativa], XP_010447751.1; NADPH- cytochrome P450 reductase 2 [Capsella rubella], XP_006283224.1; NADPH-cytochrome P450 reductase 2 [Cardamine amara subsp. amara], KAL1210563.1; NADPH-cytochrome P450 reductase 2 [Carica papaya], XP_021912724.1; NAD_binding_1 domain-containing protein / Flavodoxin_1 domain-containing protein / FAD_binding_1 domain-containing protein [Cephalotus follicularis], GAV59576.1; NADPH-cytochrome P450 reductase [Corylus avellana], XP_059459917.1; unnamed protein product [Eruca vesicaria subsp. sativa], CAH8322551.1; unnamed protein product [Eutrema halophilum], BAJ33878.1; NADPH- cytochrome P450 reductase 2 [Eutrema salsugineum], XP_006412733.1; NADPH:cytochrome P450 reductase [Gossypium hirsutum], ACN54324.1; NADPH- Attorney Docket No. G0919.70121WO00   cytochrome P450 reductase 2 [Hirschfeldia incana], KAJ0251731.1; unnamed protein product [Microthlaspi erraticum], CAA7048781.1; NADPH-cytochrome P450 reductase 2 [Morus notabilis], XP_010093854.1; Sulfite reductase [NADPH] flavoprotein alpha- component-like FAD-binding [Arabidopsis suecica], KAG7545630.1; hypothetical protein GBA52_004863 [Prunus armeniaca], KAH0993380.1; NADPH-cytochrome P450 reductase 2 [Prunus avium], XP_021810039.1; NADPH-cytochrome P450 reductase 2 [Prunus mume], XP_008223694.1; NADPH-cytochrome P450 reductase [Quillaja saponaria], KAJ7955784.1; NADPH-cytochrome P450 reductase 2 [Raphanus sativus], XP_018459848.1; NADPH-cytochrome P450 reductase 2-like [Raphanus sativus], XP_018448133.2; hypothetical protein FNV43_RR03218 [Rhamnella rubrinervis], KAF3452785.1; hypothetical protein N665_0699s0023 [Sinapis alba], KAF8084809.1; NADPH-cytochrome P450 reductase 2-like [Tarenaya hassleriana], XP_010526342.1; and unnamed protein product [Thlaspi arvense], CAH2077489.1. In some embodiments, homologs of DODA include but are not limited to: 4,5- dioxygenase-like protein [Abronia nealleyi], AKI33694.1; 4,5-dioxygenase-like protein [Abronia nealleyi], AKI33780.1; 4,5-dioxygenase-like protein [Acleisanthes lanceolata], AKI33697.1; 4,5-dioxygenase-like protein [Acleisanthes lanceolata], AKI33774.1; 4,5- dioxygenase-like protein [Acleisanthes obtusa], AKI33696.1; 4,5-dioxygenase-like protein [Acleisanthes obtusa], AKI33775.1; 4,5-dioxygenase-like protein [Allionia incarnata], AKI33781.1; 4,5-dioxygenase-like protein [Alternanthera brasiliana], AKI33718.1; stizolobate synthase [Amaranthus cruentus (Purple amaranth)], A0A0U1YJM3; 4,5-DOPA dioxygenase extradiol-like [Amaranthus tricolor], XP_057515191.1; 4,5-dioxygenase-like protein [Anulocaulis leiosolenus], AKI33692.1; 4,5-dioxygenase-like protein [Anulocaulis leiosolenus], AKI33771.1; 4,5-dioxygenase-like protein [Atriplex prostrata], AKI33710.1; 4,5-dioxygenase-like protein [Basella alba], AKI33740.1; 4,5-DOPA dioxygenase extradiol [Beta vulgaris subsp. vulgaris], XP_010674305.1; 4,5-DOPA dioxygenase extradiol [Beta vulgaris subsp. vulgaris], XP_010674305.1; 4,5-dioxygenase-like protein [Boerhavia burbidgeana], AKI33788.1; 4,5-dioxygenase-like protein [Boerhavia coccinea], AKI33772.1; DOPA 4,5-dioxygenase [Bougainvillea glabra], ASW22755.1; DOPA 4,5- dioxygenase [Bougainvillea glabra], BAG80687.1; DOPA 4,5-dioxygenase [Bougainvillea peruviana], BCD59214.1; DOPA 4,5-dioxygenase [Bougainvillea peruviana], BCD59217.1; 4,5-dioxygenase-like protein [Bougainvillea spectabilis], AKI33701.1; 4,5-dioxygenase-like protein [Bougainvillea spectabilis], AKI33762.1; 4,5-dioxygenase-like protein [Bougainvillea stipitata], AKI33763.1; Dopa 4,5-dioxygenase-like protein [Calandrinia Attorney Docket No. G0919.70121WO00   mirabilis], AIS23504.1; DODAa2 [Carnegiea gigantea], QED21474.1; 4,5-dioxygenase-like protein [Ceodes umbellifera], AKI33766.1; 4,5-DOPA dioxygenase extradiol 1-like [Chenopodium quinoa], XP_021732601.1; 4,5-dioxygenase-like protein [Conophytum uviforme], QED20600.1; 4,5-dioxygenase-like protein [Cyphomeris gypsophiloides], AKI33693.1; 4,5-dioxygenase-like protein [Cyphomeris gypsophiloides], AKI33778.1; 4,5- dioxygenase-like protein [Delosperma echinatum], AKI33791.1; 4,5-dioxygenase-like protein [Ercilla volubilis], AKI33759.1; 4,5-dioxygenase-like protein [Fenestraria rhopalophylla subsp. aurantiaca], QED20603.1; 4,5-dioxygenase-like protein [Froelichia latifolia], AKI33715.1; 4,5-dioxygenase-like protein [Glottiphyllum longum], QED20606.1; 4,5-dioxygenase-like protein [Guapira obtusata], AKI33764.1; 4,5-dioxygenase-like protein [Hilleria latifolia], AKI33768.1; 4,5-dioxygenase-like protein [Juttadinteria simpsonii], QED20608.1; 4,5-dioxygenase-like protein [Juttadinteria simpsonii], QED20610.1; DODAa2 [Kewa caespitosa], QED21488.1; DODA [Limeum aethiopicum], QED21489.1; 4,5-dioxygenase-like protein [Lophophora williamsii], AKI33738.1; DODA [Macarthuria australis], QED21491.1; DODAa1 [Mesembryanthemum crystallinum], QED21476.1; 4,5- dioxygenase-like protein [Mirabilis jalapa], AKI33700.1; 4,5-dioxygenase-like protein [Mirabilis jalapa], AKI33787.1; 4,5-dioxygenase-like protein [Mirabilis multiflora], AKI33699.1; 4,5-dioxygenase-like protein [Mirabilis multiflora], AKI33777.1; 4,5- dioxygenase-like protein [Petiveria alliacea], AKI33767.1; 4,5-dioxygenase-like protein [Phaulothamnus spinescens], AKI33708.1; 4,5-dioxygenase-like protein [Phytolacca americana], AKI33703.1; 4,5-DOPA dioxygenase [Phytolacca americana], BAH66635.1; 4,5-dioxygenase-like protein [Phytolacca americana], AKI33757.1; 4,5-dioxygenase-like protein [Phytolacca bogotensis], AKI33704.1; 4,5-dioxygenase-like protein [Phytolacca bogotensis], AKI33758.1; 4,5-dioxygenase-like protein [Phytolacca dioica], AKI33705.1; 4,5-dioxygenase-like protein [Phytolacca dioica], AKI33760.1; 4,5-dioxygenase-like protein [Pisonia aculeata], AKI33765.1; 4,5-dioxygenase-like protein [Portulaca amilis], AKI33748.1; 4,5-dioxygenase-like protein [Portulaca grandiflora], AKI33747.1; 4,5-DOPA dioxygenase extradiol [Portulaca grandiflora], Q7XA48.1; 4,5-dioxygenase-like protein [Portulaca oleracea], AKI33746.1; 4,5-dioxygenase-like protein [Portulaca oleracea], AKI33800.1; 4,5-dioxygenase-like protein [Portulaca pilosa], AKI33743.1; 4,5- dioxygenase-like protein [Portulaca suffruticosa], AKI33750.1; Dopa 4,5-dioxygenase-like protein [Ptilotus exaltatus var. semilanatus x Ptilotus nobilis], AIS23505.1; 4,5-dioxygenase- like protein [Rivina humilis], AKI33702.1; 4,5-dioxygenase-like protein [Sarcobatus vermiculatus], AKI33770.1; 4,5-dioxygenase-like protein [Seguieria aculeata], AKI33761.1; Attorney Docket No. G0919.70121WO00   4,5-DOPA dioxygenase [Selenicereus monacanthus], UYB77605.1; 4,5-dioxygenase-like protein [Sesuvium humifusum], AKI33795.1; 4,5-dioxygenase-like protein [Sesuvium portulacastrum], AKI33794.1; 4,5-dioxygenase-like protein [Sesuvium verrucosum], AKI33792.1; hypothetical protein SOVF_189620 [Spinacia oleracea], KNA05514.1; 4,5- DOPA dioxygenase extradiol [Spinacia oleracea], XP_021836119.2; DODAa2 [Stegnosperma halimifolium], QED21471.1; 4,5-dioxygenase-like protein [Stoeberia utilis], QED20616.1; 4,5-DOPA dioxygenase extradiol [Suaeda salsa], ACO59903.1; 4,5- dioxygenase-like protein [Talinum sp. YY-2015], AKI33739.1; 4,5-dioxygenase-like protein [Trianthema portulacastrum], AKI33797.1; 4,5-dioxygenase-like protein [Trichodiadema marlothii], QED20617.1; and 4,5-dioxygenase-like protein [Zaleya pentandra], AKI33796.1. In some embodiments, homologs of EXG1 (exo-1,3-beta-glucanase from Saccharomyces cerevisiae, SEQ ID NO: 519) include but are not limited to: glucan 1,3-beta- glucosidase [Henningerozyma blattae CBS 6284], XP_004180675.1; glucan 1,3-beta- glucosidase [Huiozyma naganishii CBS 8797], XP_022465230.1; glucan 1,3-beta- glucosidase [Kazachstania africana CBS 2517], XP_003955047.1; LADA_0A04148g1_1 [Lachancea dasiensis], SCU78157.1; LAFE_0C07536g1_1 [Lachancea fermentati], SCW00589.1; Glucan 1,3-beta-glucosidase; Exo-1,3-beta-glucanase; Flags: Precursor [Lachancea kluyveri NRRL Y-12651], Q875R9.1; glucan 1,3-beta-glucosidase [Lachancea lanzarotensis], XP_022629254.1; LAME_0C06722g1_1 [Lachancea meyersii CBS 8951], SCU83801.1; LAMI_0C00716g1_1 [Lachancea mirantina], SCU82746.1; LANO_0F03026g1_1 [Lachancea nothofagi CBS 11611], SCU99660.1; LAQU0S02e09560g1_1 [Lachancea quebecensis], CUS21255.1; LAFA_0C04830g1_1 [Lachancea sp. 'fantastica'], SCU81424.1; glucan 1,3-beta-glucosidase [Lachancea thermotolerans CBS 6340], XP_002556182.1; similar to Saccharomyces cerevisiae YOR190W SPR1 Sporulation-specific exo-1,3-beta-glucanase [Maudiozyma saulgeensis], SMN22873.1; glucan 1,3-beta-glucosidase I / II [Monosporozyma unispora], CAL9732893.1; uncharacterized protein RNJ42_01296 [Nakaseomyces bracarensis], XP_070907490.1; glucan 1,3-beta-glucosidase [Nakaseomyces glabratus], XP_447274.1; glucan 1,3-beta- glucosidase [Naumovozyma castellii], XP_003676253.1; glucan 1,3-beta-glucosidase [Naumovozyma dairenensis CBS 421], XP_003671991.1; exg1p [Saccharomyces arboricola H-6], EJS42561.1; glucan 1,3-beta-glucosidase [Saccharomyces eubayanus], XP_018219402.1; glucan 1,3-beta-glucosidase [Saccharomyces kudriavzevii IFO 1802], XP_056083891.1; hypothetical protein SKDZ_12G3300 [Saccharomyces kudriavzevii ZP591], CAI4046746.1; glucan 1,3-beta-glucosidase [Saccharomyces mikatae IFO 1815], Attorney Docket No. G0919.70121WO00   XP_056078328.1; glucan 1,3-beta-glucosidase [Saccharomyces paradoxus], XP_033768043.1; exo-1,3-beta-glucanase [Saccharomyces pastorianus], QID86860.1; hypothetical protein SUVZ_12G3300 [Saccharomyces uvarum], CAI4048056.1; glucan 1,3- beta-glucosidase [Tetrapisispora phaffii CBS 4417], XP_003686194.1; uncharacterized protein TDEL_0G03720 [Torulaspora delbrueckii], XP_003682950.1; glucan 1,3-beta- glucosidase [Torulaspora globosa], XP_037141681.1; uncharacterized protein Kpol_530p49 [Vanderwaltozyma polyspora DSM 70294], XP_001644937.1; and uncharacterized protein HG535_0G02180 [Zygotorulaspora mrakii], XP_037146059.1. In some embodiments, homologs of MCK1 (a dual-specificity S / T and tyrosine protein kinase from S. cerevisiae, SEQ ID NO: 518) include but are not limited to: AaceriADL168Cp [Ashbya aceris (nom. inval.)], AGO11614.1; protein kinase Mck1p [Candida anglica], CAK7913294.1; serine / threonine protein kinase YGK3 [Arxiozyma heterogenica], XP_064713747.1; uncharacterized protein BABINDRAFT_137420 [Babjeviella inositovora NRRL Y-12698], XP_018985252.1; Protein kinase MCK1 [Cyberlindnera fabianii], ONH68812.1; serine / threonine protein kinase YGK3 [Cyberlindnera jadinii NRRL Y-1542], XP_020072413.1; unnamed protein product [Debaryomyces tyrocola], CUM54060.1; Hypothetical protein Ecym_2042 [Eremothecium cymbalariae DBVPG#7215], XP_003644616.1; ADL168Cp [Eremothecium gossypii ATCC 10895], NP_983928.1; HBL292Cp [Eremothecium sinecaudum], XP_017985606.1; Protein kinase MCK1 [Hanseniaspora osmophila], OEJ81950.1; uncharacterized protein TBLA_0A07770 [Henningerozyma blattae CBS 6284], XP_004178085.1; serine / threonine protein kinase YGK3 [Huiozyma naganishii CBS 8797], XP_022462068.1; serine / threonine protein kinase YGK3 [Kazachstania africana CBS 2517], XP_003956300.1; unnamed protein product [Kluyveromyces dobzhanskii CBS 2104], CDO94524.1; Ygk3 / Mck1 [Kluyveromyces lactis], QEU62794.1; Protein kinase MCK1 [Kluyveromyces marxianus], KAL2710898.1; LADA_0H10506g1_1 [Lachancea dasiensis], SCU98087.1; LAFE_0G18074g1_1 [Lachancea fermentati], SCW03781.1; serine / threonine / tyrosine protein kinase MCK1 [Lachancea lanzarotensis], XP_022628633.1; LAME_0F15280g1_1 [Lachancea meyersii CBS 8951], SCU96194.1; LAMI_0G07140g1_1 [Lachancea mirantina], SCV00760.1; LANO_0E05094g1_1 [Lachancea nothofagi CBS 11611], SCU93895.1; LAFA_0G19592g1_1 [Lachancea sp. 'fantastica'], SCU98684.1; serine / threonine / tyrosine protein kinase MCK1 [Lachancea thermotolerans CBS 6340], XP_002555009.1; serine / threonine protein kinase YGK3 [Maudiozyma barnettii], XP_041408649.1; putative protein kinase Mck1p [Maudiozyma bulderi], CAL1762513.1; Attorney Docket No. G0919.70121WO00   protein kinase mck1 [Maudiozyma exigua], KAG0670221.1; serine / threonine / tyrosine protein kinase [Maudiozyma humilis], GMM57881.1; similar to Saccharomyces cerevisiae YOL128C YGK3 Protein kinase related to mammalian glycogen synthase kinases of the GSK-3 family [Maudiozyma saulgeensis], SMN22451.1; protein kinase Mck1p [Monosporozyma servazzii], CAL9733429.1; protein kinase mck1 [Monosporozyma unispora], KAG0665300.1; Protein kinase MCK1 [Nakaseomyces bracarensis], XP_070908605.1; Serine / Threonine protein kinases active-site signature [Nakaseomyces glabratus], KAH7606135.1; serine / threonine protein kinase YGK3 [Naumovozyma castellii], XP_003675808.1; serine / threonine protein kinase YGK3 [Naumovozyma dairenensis CBS 421], XP_003671412.2; mck1p [Saccharomyces arboricola H-6], EJS42106.1; serine / threonine / tyrosine protein kinase MCK1 [Saccharomyces eubayanus], XP_018219592.1; serine / threonine / tyrosine protein kinase MCK1 [Saccharomyces kudriavzevii IFO 1802], XP_056084512.1; serine / threonine / tyrosine protein kinase MCK1 [Saccharomyces mikatae IFO 1815], XP_056078943.1; serine / threonine / tyrosine protein kinase MCK1 [Saccharomyces paradoxus], XP_033768660.1; protein kinase mck1 [Saccharomyces pastorianus], QID81848.1; hypothetical protein N7582_004685 [Saccharomyces uvarum], WBF15191.1; serine / threonine / tyrosine protein kinase MCK1 [Saccharomycodes ludwigii], XP_045932632.1; serine / threonine / tyrosine protein kinase [Saccharomycopsis crataegensis], XP_064852651.1; uncharacterized protein TPHA_0P01380 [Tetrapisispora phaffii CBS 4417], XP_003688730.1; serine / threonine / tyrosine protein kinase MCK1 [Torulaspora delbrueckii], XP_003678603.1; serine / threonine / tyrosine protein kinase MCK1 [Torulaspora globosa], XP_037140001.1; serine / threonine / tyrosine protein kinase MCK1 [Vanderwaltozyma polyspora DSM 70294], XP_001642181.1; uncharacterized protein WICANDRAFT_34029 [Wickerhamomyces anomalus NRRL Y-366-8], XP_019037500.1; uncharacterized protein BN7_4005 [Wickerhamomyces ciferrii], XP_011273709.1; hypothetical protein WICMUC_001597 [Wickerhamomyces mucosus], KAH3678316.1; hypothetical protein WICPIJ_006561 [Wickerhamomyces pijperi], KAH3682468.1; protein kinase mck1 [Zygosaccharomyces mellis], GCE99923.1; MCK1 (YNL307C) and YGK3 (YOL128C) [Zygosaccharomyces parabailii], AQZ09316.1; serine / threonine / tyrosine protein kinase MCK1 [Zygosaccharomyces rouxii], XP_002495775.1; and serine / threonine / tyrosine protein kinase MCK1 [Zygotorulaspora mrakii], XP_037145426.1. In some embodiments, homologs of PUT1 (proline oxidase from Saccharomyces cerevisiae; SEQ ID NO: 545) include but are not limited to: proline dehydrogenase Attorney Docket No. G0919.70121WO00   [Saccharomyces eubayanus], XP_018220566.1; PUT1-like protein [Saccharomyces kudriavzevii IFO 1802], EJT41967.1; proline dehydrogenase [Saccharomyces mikatae IFO 1815], XP_056078189.1; proline dehydrogenase [Saccharomyces paradoxus], XP_033767910.1; proline dehydrogenase [Saccharomyces pastorianus], QID81110.1; hypothetical protein SUVC_12G1950 [Saccharomyces uvarum], CAI4046533.1; proline dehydrogenase [Torulaspora delbrueckii], XP_003682494.1; proline dehydrogenase [Zygosaccharomyces mellis], GCF00867.1; and proline dehydrogenase [Zygosaccharomyces rouxii], XP_002497808.1. In some embodiments, homologs of TPI1 (triose phosphate isomerase from Saccharomyces cerevisiae, SEQ ID NO: 536) include but are not limited to: AaceriAGL201Cp [Ashbya aceris (nom. inval.)], AGO13674.1; triose-phosphate isomerase TPI1 [Arxiozyma heterogenica], XP_064712962.1; triosephosphate isomerase [Candida tropicalis MYA-3404], XP_002551310.1; CYFA0S35e00386g1_1 [Cyberlindnera fabianii], CDR47632.1; triose-phosphate isomerase TPI1 [Cyberlindnera jadinii NRRL Y-1542], XP_020072739.1; Triosephosphate isomerase [Dipodascopsis uninucleata], KAK9453410.1; triose-phosphate isomerase TPI1 Ecym_2666 [Eremothecium cymbalariae DBVPG#7215], XP_003645193.1; triose-phosphate isomerase TPI1 [Eremothecium gossypii ATCC 10895], NP_986466.2; triose-phosphate isomerase TPI1 [Eremothecium sinecaudum], XP_017989376.1; hypothetical protein DV451_002095 [Geotrichum candidum], KAF5101732.1; probable Triosephosphate isomerase [Hanseniaspora guilliermondii], SGZ41315.1; hypothetical protein QEN19_001036 [Hanseniaspora menglaensis], XBW35463.1; Triosephosphate isomerase [Hanseniaspora opuntiae], OEJ83523.1; Triosephosphate isomerase [Hanseniaspora osmophila], OEJ80747.1; triose-phosphate isomerase [Hanseniaspora uvarum], GMM40634.1; triose phosphate isomerase [Hanseniaspora valbyensis NRRL Y-1626], OBA27498.1; triose-phosphate isomerase TPI1 [Henningerozyma blattae CBS 6284], XP_004182381.1; triose-phosphate isomerase TPI1 [Huiozyma naganishii CBS 8797], XP_022465767.1; triose-phosphate isomerase TPI1 [Kazachstania africana CBS 2517], XP_003958676.1; unnamed protein product [Kluyveromyces dobzhanskii CBS 2104], CDO96232.1; Tpi1 [Kluyveromyces lactis], QEU62332.1; triosephosphate isomerase [Kluyveromyces marxianus], QGN15883.1; triosephosphate isomerase [Komagataella kurtzmanii], KAI0462487.1; BA75_03555T0 [Komagataella pastoris], ANZ76720.1; GQ67_04079T0 [Komagataella phaffii], AOA63935.1; uncharacterized protein KUCA_T00002396001 [Kuraishia capsulata CBS 1993], XP_022458428.1; LADA_0H06480g1_1 [Lachancea dasiensis], SCU97474.1; Attorney Docket No. G0919.70121WO00   LAFE_0E04830g1_1 [Lachancea fermentati], SCW01675.1; triose-phosphate isomerase TPI1 [Lachancea lanzarotensis], XP_022629042.1; LAME_0E02718g1_1 [Lachancea meyersii CBS 8951], SCU89250.1; LAMI_0G00936g1_1 [Lachancea mirantina], SCU99802.1; LANO_0F12970g1_1 [Lachancea nothofagi CBS 11611], SCV01677.1; LAQU0S03e03488g1_1 [Lachancea quebecensis], CUS21477.1; LAFA_0D04214g1_1 [Lachancea sp. 'fantastica'], SCU83546.1; triose-phosphate isomerase TPI1 [Lachancea thermotolerans CBS 6340], XP_002552447.1; Triosephosphate isomerase [Lipomyces japonicus], XP_066782442.1; triose-phosphate isomerase [Martiniozyma asiatica (nom. inval.)], GMM28113.1; triose-phosphate isomerase TPI1 [Maudiozyma barnettii], XP_041405150.1; putative triosephosphate isomerase [Maudiozyma bulderi], CAL1761863.1; triosephosphate isomerase [Maudiozyma exigua], KAG0670516.1; triose- phosphate isomerase [Maudiozyma humilis], GMM58371.1; similar to Saccharomyces cerevisiae YDR050C TPI1 Triose phosphate isomerase, abundant glycolytic enzyme [Maudiozyma saulgeensis], SMN20339.1; Piso0_002650 [Millerozyma farinosa CBS 7064], CCE82894.1; hypothetical protein MOSE0_H02388 [Monosporozyma servazzii], CAL9735287.1; triosephosphate isomerase [Monosporozyma unispora], KAG0661222.1; Triosephosphate isomerase [Nadsonia fulvescens var. elongata DSM 6958], ODQ65763.1; Triosephosphate isomerase [Nakaseomyces bracarensis], XP_070911181.1; triose-phosphate isomerase TPI1 [Nakaseomyces glabratus], XP_447161.1; triose-phosphate isomerase TPI1 [Naumovozyma castellii], XP_003674013.1; triose-phosphate isomerase TPI1 [Naumovozyma dairenensis CBS 421], XP_003667954.1; hypothetical protein CANINC_002831 [Pichia inconspicua], TID26136.1; triose-phosphate isomerase [Pichia kluyveri], GMM45028.1; uncharacterized protein C5L36_0A00870 [Pichia kudriavzevii], XP_029318956.1; uncharacterized protein PRCAT00004626001 [Priceomyces carsonii], XP_062811317.1; tpi1p [Saccharomyces arboricola H-6], EJS44263.1; triose-phosphate isomerase TPI1 [Saccharomyces eubayanus], XP_018223620.1; triose-phosphate isomerase TPI1 [Saccharomyces mikatae IFO 1815], XP_056081051.1; triose-phosphate isomerase TPI1 [Saccharomyces paradoxus], XP_033765300.1; hypothetical protein N7582_000258 [Saccharomyces uvarum], WBF11037.1; triose-phosphate isomerase TPI1 [Saccharomycodes ludwigii], XP_045934646.1; triose-phosphate isomerase TPI1 [Tetrapisispora phaffii CBS 4417], XP_003688130.1; triose-phosphate isomerase TPI1 [Torulaspora delbrueckii], XP_003681133.1; hypothetical protein HG537_0D04450 [Torulaspora globosa], QLQ80445.1; triose-phosphate isomerase TPI1 [Vanderwaltozyma polyspora DSM 70294], XP_001642963.1; triose-phosphate isomerase TPI1 [Wickerhamomyces anomalus NRRL Y- Attorney Docket No. G0919.70121WO00   366-8], XP_019037099.1; triose-phosphate isomerase TPI1 [Wickerhamomyces ciferrii], XP_011273813.1; hypothetical protein WICMUC_003413 [Wickerhamomyces mucosus], KAH3674172.1; hypothetical protein WICPIJ_003771 [Wickerhamomyces pijperi], KAH3685297.1; TIM, Triose-phosphate isomerase [Zygosaccharomyces bailii], Q9C401.1; triosephosphate isomerase [Zygosaccharomyces mellis], GCE98569.1; TPI1 (YDR050C) [Zygosaccharomyces parabailii], AQZ13823.1; triose-phosphate isomerase TPI1 [Zygosaccharomyces rouxii], XP_002498527.1; hypothetical protein ZYGR_0AZ00610 [Zygosaccharomyces rouxii], GAV55890.1; and triose-phosphate isomerase TPI1 [Zygotorulaspora mrakii], XP_037142139.1. In some embodiments a homolog of a UGT is selected from: UDP-glycosyltransferase 92A1 [Abeliophyllum distichum], KAL2485420.1; UDP-glycosyltransferase 92A1 [Abeliophyllum distichum], KAL2485421.1; anthocyanidin 3-O-glucoside 2''-O- glucosyltransferase-like [Abrus precatorius], XP_027338749.1; hypothetical protein LWI28_015900 [Acer negundo], KAI9181533.1; hypothetical protein Q3G72_008237 [Acer saccharum], KAK1558915.1; hypothetical protein EZV62_011254 [Acer yangbiense], TXG64260.1; UFGT6b [Actinidia chinensis], AYJ72754.1; scopoletin glucosyltransferase- like [Actinidia eriantha], XP_057465240.1; UDP-Glycosyltransferase superfamily protein [Actinidia rufa], GFS45635.1; scopoletin glucosyltransferase-like [Alnus glutinosa], XP_062177295.1; glucosyltransferase [Amaranthus hypochondriacus], AHV78225.1; cyanidin 3-O-galactoside 2''-O-xylosyltransferase FGGT1-like [Amaranthus tricolor], XP_057525449.1; cyanidin 3-O-galactoside 2''-O-xylosyltransferase FGGT1-like [Amaranthus tricolor], XP_057525449.1; cyanidin 3-O-galactoside 2''-O-xylosyltransferase FGGT1-like [Amaranthus tricolor], XP_057544661.1; hypothetical protein L6164_013507 [Bauhinia variegata], KAI4334798.1; cyanidin 3-O-galactoside 2''-O-xylosyltransferase FGGT1 [Beta vulgaris subsp. vulgaris], XP_010695817.2; UDP-glucose:flavonoid-O- glucosyltransferase [Beta vulgaris], AAS94329.1; Scopoletin glucosyltransferase [Bienertia sinuspersici], KAL2939360.1; cyclo-DOPA-5-glucosyltransferase [Bougainvillea glabra], QSB37376.1; cyclo-DOPA 5-glucosyltransferase [Bougainvillea peruviana], BCD59220.1; cyclo-DOPA 5-O-glucosyltransferase [Bougainvillea spectabilis], AIS20905.1; hypothetical protein CsSME_00009638 [Camellia sinensis var. sinensis], GMP38376.1; unnamed protein product [Camellia sinensis], CAL5378925.1; hypothetical protein VNO77_30038 [Canavalia gladiata], KAK7320505.1; hypothetical protein Cgig2_032811 [Carnegiea gigantea], KAJ8424631.1; hypothetical protein Cgig2_001234 [Carnegiea gigantea], KAJ8434041.1; hypothetical protein FH972_000545 [Carpinus fangiana], KAE7995777.1; UDP- Attorney Docket No. G0919.70121WO00   glycosyltransferase 92A1-like [Carya illinoinensis], XP_042986555.1; hypothetical protein ACB092_07G120600 [Castanea dentata], KAL4615380.1; hypothetical protein CMV_004315 [Castanea mollissima], KAF3972154.1; cyclo-DOPA 5-O-glucosyltransferase [Celosia cristata], BAD91804.1; UDP-glycosyltransferase 79B30-like [Chenopodium quinoa], XP_021735841.1; hypothetical protein ACH5RR_032555 [Cinchona calisaya], KAL3507173.1; hypothetical protein CISIN_1g039043mg [Citrus sinensis], KDO77743.1; hypothetical protein WN944_012326 [Citrus x changshan-huyou], KAK9223877.1; UDP- glycosyltransferase 79B30 [Citrus x clementina], XP_006449434.1; RUBY [Cloning vector pCambia2300-RUBY], UYI58482.1; RUBY reporter protein [Cloning vector UAS- RUBY / pWB], WGJ63507.1; UDP-glycosyltransferase 92A1-like [Coffea eugenioides], XP_027165690.1; UDP-glucuronosyl / UDP-glucosyltransferase [Corchorus capsularis], OMO74617.1; scopoletin glucosyltransferase-like [Cornus florida], XP_059652917.1; UDP- glycosyltransferase 92A1-like [Corylus avellana], XP_059447302.1; UDP- glycosyltransferase 92A1-like [Corylus avellana], XP_059447745.1; scopoletin glucosyltransferase-like [Corylus avellana], XP_059448401.1; cyanidin 3-O-galactoside 2''- O-xylosyltransferase FGGT1 [Daucus carota subsp. sativus], XP_017231986.1; chalcononaringenin 2'-O-glucosyltransferase [Dianthus caryophyllus], WMS55853.1; UDP- glucuronosyl / UDP-glucosyltransferase [Dillenia turbinata], KAK6940172.1; hypothetical protein Drorol1_Dr00019347 [Drosera rotundifolia], GAB2214977.1; hypothetical protein RJ639_009762 [Escallonia herrerae], KAK3013221.1; hypothetical protein RJ640_016582 [Escallonia rubra], KAK2991547.1; cyanidin 3-O-galactoside 2''-O-xylosyltransferase FGGT1-like [Euphorbia lathyris], XP_065877306.1; UDP-glycosyltransferase 79B30 [Euphorbia peplus], WCJ27120.1; hypothetical protein TIFTF001_007424 [Ficus carica], GMN38200.1; hypothetical protein Fmac_030826 [Flemingia macrophylla], KAL2316950.1; UDP-glycosyltransferase 92A1 [Forsythia ovata], KAL2507288.1; crocetin glucosyltransferase 3 [Fragaria vesca subsp. vesca], XP_004296707.1; UDP- glycosyltransferase 92A1-like [Gastrolobium bilobum], XP_061352024.1; UDP- glycosyltransferase 92A1 [Glycine max], KAH1263495.1; hypothetical protein CXB51_006325 [Gossypium anomalum], KAG8499933.1; UDP-glycosyltransferase 92A1- like isoform X1 [Gossypium arboreum], XP_017631964.1; UDP-glycosyltransferase 92A1 isoform X1 [Gossypium hirsutum], XP_016714060.2; UDP-glycosyl transferase 1 [Haloxylon ammodendron], AIS71990.1; UDP-glucuronosyl and UDP-glucosyl transferase [Handroanthus impetiginosus], PIN21114.1; hypothetical protein KSS87_001089 [Heliosperma pusillum], KAH9626629.1; Inositol-3-phosphate synthase-like [Heracleum Attorney Docket No. G0919.70121WO00   sosnowskyi], KAK1400447.1; UDP-glycosyltransferase 92A1-like [Herrania umbratica], XP_021290328.1; scopoletin glucosyltransferase [Hevea brasiliensis], XP_021684532.2; hypothetical protein GQ457_01G046790 [Hibiscus cannabinus], KAL4310762.1; hypothetical protein V6N11_005995 [Hibiscus sabdariffa], KAK9014857.1; hypothetical protein like AT4G27570 [Hibiscus trionum], GMI72304.1; unnamed protein product [Ilex paraguariensis], CAK9181878.1; hypothetical protein JCGZ_21500 [Jatropha curcas], KDP21029.1; UDP-glycosyltransferase 92A1-like [Juglans microcarpa x Juglans regia], XP_041010274.1; cyanidin 3-O-galactoside 2''-O-xylosyltransferase FGGT1 [Juglans regia], XP_018838487.1; uridine diphosphate glycosyltransferase 2 [Kalopanax septemlobus], ART66192.1; unnamed protein product [Lactuca saligna], CAI9301304.1; UDP- glycosyltransferase 92A1 [Lactuca sativa], XP_023730908.1; unnamed protein product [Linum tenue], CAI0397247.1; hypothetical protein L1049_014893 [Liquidambar formosana], KAK9286495.1; hypothetical protein SO802_021772 [Lithocarpus litseifolius], KAK9997086.1; crocetin glucosyltransferase 3-like [Lotus japonicus], XP_057441528.1; putative UDP-glucuronosyl / UDP-glucosyltransferase, UDP-glycosyltransferase family [Lupinus albus], KAE9597152.1; UDP-glycosyltransferase 92A1-like [Lupinus angustifolius], XP_019433424.1; UDP-glycosyltransferase 92A1-like [Lupinus angustifolius], XP_019433424.1; unnamed protein product [Lupinus luteus], CAL0313933.1; scopoletin glucosyltransferase-like [Malania oleifera], XP_057963675.1; scopoletin glucosyltransferase [Manihot esculenta], XP_021624601.1; UDP-glycosyltransferase 92A1 [Medicago truncatula], XP_003617072.1; Glycosyltransferase [Melia azedarach], KAJ4716280.1; cyclo-DOPA 5-O-glucosyltransferase [Mirabilis jalapa], AZC85901.1; Scopoletin glucosyltransferase [Morella rubra], KAB1208500.1; scopoletin glucosyltransferase [Morus notabilis], XP_010107891.2; UDP-glycosyltransferase 92A1 [Mucuna pruriens], RDX83435.1; UDP-glycosyltransferase 79B30-like [Nelumbo nucifera], XP_010262362.1; hypothetical protein Nepgr_004699 [Nepenthes gracilis], GMH02860.1; hypothetical protein F0562_020706 [Nyssa sinensis], KAA8545843.1; OLC1v1021416C1 [Oldenlandia corymbosa var. corymbosa], CAI9087360.1; UDP-glycosyltransferase 92A1- like [Olea europaea var. sylvestris], XP_022873726.1; flavonoid 7-O-glucosyltransferase [Paeonia delavayi], ARA67362.1; UGTPg44 [Panax ginseng], AKA44594.1; hypothetical protein Pfo_016383 [Paulownia fortunei], KAI3459720.1; hypothetical protein VNO80_06040 [Phaseolus coccineus], KAK7372653.1; UDP-glycosyltransferase 92A1-like [Phaseolus vulgaris], XP_068485623.1; glucosyltransferase [Phytolacca americana], BAG71127.1; scopoletin glucosyltransferase-like [Pistacia vera], XP_031248387.1; Attorney Docket No. G0919.70121WO00   hypothetical protein NC651_026574 [Populus alba x Populus x berolinensis], KAJ6885952.1; anthocyanidin 3-O-glucoside 2''-O-glucosyltransferase-like [Populus euphratica], XP_011045872.1; hypothetical protein POTOM_040720 [Populus tomentosa], KAG6754917.1; unnamed protein product [Prunus armeniaca], CAB4290539.1; scopoletin glucosyltransferase-like [Prunus avium], XP_021823916.1; unnamed protein product [Prunus brigantina], CAL9015571.1; cyanidin 3-O-galactoside 2''-O-xylosyltransferase FGGT1-like [Prunus dulcis], XP_034213836.1; anthocyanidin 3-O-glucoside 2''-O- glucosyltransferase [Prunus persica], XP_007213494.2; hypothetical protein CerSpe_281550 [Prunus speciosa], BFG41881.1; anthocyanidin 3-O-glucoside 2-O-glucosyltransferase [Prunus yedoensis var. nudiflora], PQQ04568.1; Glycosyltransferase [Psidium guajava], KAI3420706.1; hypothetical protein VNO78_31782 [Psophocarpus tetragonolobus], KAK7385858.1; anthocyanidin 3-O-glucoside 2''-O-glucosyltransferase-like [Quercus lobata], XP_030937802.1; cyanidin 3-O-galactoside 2''-O-xylosyltransferase FGGT1-like [Quercus robur], XP_050256153.1; probable UDP-glucosyl transferase 73B6 [Quercus suber], XP_023885854.1; crocetin glucosyltransferase 3-like [Rhodamnia argentea], XP_048127969.1; hypothetical protein RHMOL_Rhmol11G0240300 [Rhododendron molle], KAI8532773.1; hypothetical protein RHMOL_Rhmol09G0073600 [Rhododendron molle], KAI8538078.1; hypothetical protein RHSIM_Rhsim09G0078400 [Rhododendron simsii], KAF7133081.1; crocetin glucosyltransferase 3-like [Rhododendron vialii], XP_058182801.1; scopoletin glucosyltransferase-like [Rhododendron vialii], XP_058191359.1; cyanidin 3-O- galactoside 2''-O-xylosyltransferase FGGT1 [Ricinus communis], XP_002522508.1; LOW QUALITY PROTEIN: crocetin glucosyltransferase 3-like [Rosa chinensis], XP_024175485.1; crocetin glucosyltransferase 3-like [Rosa rugosa], XP_061992206.1; hypothetical protein SLE2022_058730 [Rubroshorea leprosula], GLT87813.1; hypothetical protein M0R45_028219 [Rubus argutus], KAK9919633.1; hypothetical protein DKX38_017142 [Salix brachista], KAB5534056.1; ANTHOCYANIDIN 3-O-GLUCOSIDE 2''-O-GLUCOSYLTRANSFERASE-RELATED [Salix purpurea], KAJ6769910.1; hypothetical protein OIU78_024732 [Salix suchowensis], KAJ6292609.1; UDP- glycosyltransferase 92A1-like [Salvia divinorum], KAL1557025.1; UDP-glycosyltransferase 92A1 [Salvia hispanica], XP_047976286.1; UDP-glycosyltransferase 92A1-like [Salvia miltiorrhiza], XP_057779483.1; hypothetical protein RND81_11G160200 [Saponaria officinalis], KAK9677679.1; cyclo-DOPA 5-O glucosyltransferase [Selenicereus monacanthus], UYB77606.1; UDP-glycosyltransferase 92A1 [Senna tora], KAF7837089.1; UDP-glycosyltransferase 92A1 [Sesamum alatum], KAK4421562.1; UDP- Attorney Docket No. G0919.70121WO00   glycosyltransferase 92A1 [Sesamum alatum], KAK4421562.1; UDP-glycosyltransferase family, conserved site [Sesbania bispinosa], KAJ1394014.1; hypothetical protein SLA2020_523060 [Shorea laevis], GLT80895.1; UDP-glycosyltransferase 92A1 [Spatholobus suberectus], TKY57065.1; cyanidin 3-O-galactoside 2''-O-xylosyltransferase FGGT1-like [Spinacia oleracea], XP_021838808.2; cyanidin 3-O-galactoside 2''-O- xylosyltransferase FGGT1-like [Spinacia oleracea], XP_021845121.1; Bet5OGT [synthetic construct], WOB18973.1; hypothetical protein NL676_021536 [Syzygium grande], KAI6693826.1; UDP-glycosyltransferase 79B30 [Theobroma cacao], XP_007025501.2; unnamed protein product [Trifolium pratense], CAJ2653800.1; UDP-glycosyltransferase 92A1 [Trifolium repens], KAK2431310.1; cyanidin 3-O-galactoside 2''-O-xylosyltransferase FGGT1-like [Tripterygium wilfordii], XP_038689061.1; hypothetical protein Vadar_027281 [Vaccinium darrowii], KAH7841223.1; UDP-glycosyltransferase 92A1-like [Vicia villosa], XP_058743152.1; UDP-glycosyltransferase 92A1-like [Vigna umbellata], XP_047157167.1; UDP-glycosyltransferase 92A1-like [Vigna unguiculata], XP_027941888.1; scopoletin glucosyltransferase-like [Vitis riparia], XP_034682237.1; hypothetical protein VITISV_004870 [Vitis vinifera], CAN65903.1; UDP-glycosyltransferase 92A1 [Vitis vinifera], XP_003632051.1; or hypothetical protein JRO89_XS07G0109000 [Xanthoceras sorbifolium], KAH7567635.1. In some embodiments, homologs of ZWF1 (glucose-6-phosphate dehydrogenase from Saccharomyces cerevisiae, SEQ ID NO: 535) include but are not limited to: AaceriABL206Cp [Ashbya aceris (nom. inval.)], AGO10251.1; glucose-6-phosphate dehydrogenase [Arxiozyma heterogenica], XP_064713634.1; glucose-6-phosphate dehydrogenase [Eremothecium cymbalariae DBVPG#7215], XP_003647674.1; glucose-6- phosphate dehydrogenase [Eremothecium gossypii ATCC 10895], NP_982741.1; glucose-6- phosphate dehydrogenase [Huiozyma naganishii CBS 8797], XP_022464989.1; glucose-6- phosphate dehydrogenase [Kazachstania africana CBS 2517], XP_003955376.1; Zwf1 [Kluyveromyces lactis], QEU61133.1; Glucose-6-phosphate 1-dehydrogenase [Kluyveromyces marxianus], KAL2706811.1; LAFE_0H00716g1_1 [Lachancea fermentati], SCW03864.1; LAMI_0E00232g1_1 [Lachancea mirantina], SCU90022.1; uncharacterized protein KABA2_07S08360 [Maudiozyma barnettii], XP_041407804.1; putative glucose-6- phosphate 1-dehydrogenase [Maudiozyma bulderi], CAL1764217.1; Glucose-6-phosphate 1- dehydrogenase [Maudiozyma exigua], KAG0671413.1; hypothetical protein DAKH74_017800 [Maudiozyma humilis], GMM55164.1; similar to Saccharomyces cerevisiae YNL241C ZWF1 Glucose-6-phosphate dehydrogenase (G6PD), catalyzes the first Attorney Docket No. G0919.70121WO00   step of the pentose phosphate pathway [Maudiozyma saulgeensis], SMN21360.1; glucose-6- phosphate 1-dehydrogenase [Monosporozyma servazzii], CAL9738584.1; Glucose-6- phosphate 1-dehydrogenase [Monosporozyma unispora], KAG0667370.1; Glucose-6- phosphate 1-dehydrogenase [Nakaseomyces bracarensis], XP_070910547.1; glucose-6- phosphate dehydrogenase [Nakaseomyces glabratus], XP_448038.1; glucose-6-phosphate dehydrogenase [Naumovozyma castellii], XP_003673037.1; uncharacterized protein NDAI_0H04010 [Naumovozyma dairenensis CBS 421], XP_003671817.1; hypothetical protein SEUBUCD650_0N00930 [Saccharomyces eubayanus], CAI1670227.1; hypothetical protein SKDZ_14G0880 [Saccharomyces kudriavzevii ZP591], CAI4049472.1; glucose-6- phosphate dehydrogenase [Saccharomyces mikatae IFO 1815], XP_056079003.1; glucose-6- phosphate dehydrogenase [Saccharomyces paradoxus], XP_033768718.1; Glucose-6- phosphate 1-dehydrogenase [Saccharomyces pastorianus], QID87556.1; hypothetical protein N7582_004745 [Saccharomyces uvarum], WBF15251.1; glucose-6-phosphate dehydrogenase [Saccharomycodes ludwigii], XP_045935481.1; probable Glucose-6- phosphate 1-dehydrogenase [Saccharomycodes ludwigii], SSD59032.1; glucose-6-phosphate dehydrogenase [Tetrapisispora phaffii CBS 4417], XP_003688773.1; glucose-6-phosphate dehydrogenase [Torulaspora delbrueckii], XP_003681492.1; hypothetical protein HG537_0C00210 [Torulaspora globosa], QLQ79374.1; glucose-6-phosphate dehydrogenase [Vanderwaltozyma polyspora DSM 70294], XP_001643280.1; glucose-6-phosphate 1- dehydrogenase [Zygosaccharomyces mellis], GCF01275.1; ZWF1 (YNL241C) [Zygosaccharomyces parabailii], AQZ14618.1; hypothetical protein ZYGR_0AS06820 [Zygosaccharomyces rouxii], GAV55358.1; and glucose-6-phosphate dehydrogenase [Zygotorulaspora mrakii], XP_037144047.1. In some embodiments, a host cell for producing a betalain which comprises a genetic modification described herein comprises: (a) a wild-type CYP76AD1 (or homolog thereof); or (b) a variant of CYP76AD1 described herein. In some embodiments, a variant of CYP76AD1 is AD1_pe3M [BvCYP76AD1 (SEQ ID NO: 1) with substitutions: Q26S, T114S, H198E, C240N, C254D, P259S, A403V, Q405P, I409V, and F459S; SEQ ID NO: 523]; AD1_pe3N [BvCYP76AD1 (SEQ ID NO: 1) with substitutions: T114S, C228K, C240K, C254A, P259S, Q405P, I409V, C418S, and F459S; SEQ ID NO: 524], and AD1_pe3O [BvCYP76AD1 (SEQ ID NO: 1) with substitutions: P95L, T114S, F147L, H198E, C228K, C254N, P259L, F280M, Q405P, and F459S; SEQ ID NO: 525]. Homologs of BvCYP76AD1 Attorney Docket No. G0919.70121WO00   In some embodiments, a homolog of BvCYP76AD1 is a gene comprising an amino acid sequence similar to that of BvCYP76AD1, including but not limited to a gene of a similar function from an organism sharing a common ancestor to Beta vulgaris; homologs of BvCYP76AD1 include related genes which have resulted from an evolutionary gene duplication event followed by speciation or any other divergence in sequence and / or function. In some embodiments, a homolog of AD1 comprises an amino acid sequence at least about 50% identical to that of AD1. In some embodiments, a homolog of AD1 comprises an amino acid sequence at least about 40% identical to that of AD1. In some embodiments, a homolog of AD1 comprises an amino acid sequence at least about 30% identical to that of AD1. The genes encoding these proteins are also homologs. Various homologs of AD1 are known in the art. In some embodiments, homologs of AD1 can be identified by searching for sequences with similarity to the sequence of AD1 (e.g., SEQ ID NO: 1), for example, by using the Basic Local Alignment Search Tool (BLAST) in the National Center for Biotechnology Information (NCBI) database; such a search was performed to generate the list of homologs presented below. Additional homologs can be identified using additional sequence comparisons or searching in other databases known in the art. In some embodiments, an amino acid in a homolog of BvCYP76AD1 corresponding to W13, H18, S25, Q26, T29, L31, R70, K92, H94, P95, T114, M115, F147, Q164, K185, H198, Y219, C228, S232, C240, S241, C254, P259, D260, Q278, F280, T286, G288, I346, A403, Q405, A407, I409, I416, C418, F459, and / or D467 of BvCYP76AD1 (and / or any other amino acid position in BvCYP76AD1 variants disclosed herein) is an identical amino acid at the same position, a similar amino acid (e.g., an amino from the same R group, as described in Table 1) at the same position, or an identical or similar amino acid at a slightly different position. It is well understood in the art that homologs may be different lengths from each other, with various domains or positions shifted relative to each other in a linear sequence; however, sequence comparisons readily performed by one of skill in the art with available software can be used to identify the amino acids in a homolog corresponding to the above-listed amino acid positions in BvCYP76AD1. In some embodiments, a homolog of BvCYP76AD1 is any presented in Table 2 below. Table 2. Attorney Docket No. G0919.70121WO00   Attorney Docket No. G0919.70121WO00   Attorney Docket No. G0919.70121WO00   Attorney Docket No. G0919.70121WO00   In some embodiments, the term “homolog” (in reference to a particular gene) is intended to include variants (e.g., mutants) of homologs, e.g., any gene having 90% or more or 95% or more sequence identity to a homolog. As a non-limiting example, a homolog of BvCYP76AD1 includes various variants of cytochrome P450 CYP76AD8 [Opuntia ficus- indica] described in Li et al.2024 ACS Synth. Biol.13 (6): 1916-1924. A Variant of a Homolog of BvCYP76AD1 In some embodiments, a variant of a homolog of BvCYP76AD1 comprises a mutation(s) at an amino acid(s) corresponding to W13, H18, S25, Q26, T29, L31, R70, K92, H94, P95, T114, M115, F147, Q164, K185, H198, Y219, C228, S232, C240, S241, C254, P259, D260, Q278, F280, T286, G288, I346, A403, Q405, A407, I409, I416, C418, F459, and / or D467, or any combination thereof, of BvCYP76AD1 (“AD1”) (SEQ ID NO: 1). In some embodiments, a mutation is a substitution. In some embodiments, a variant of a tyrosine hydroxylase is a homolog of BvCYP76AD1 comprising a mutation(s) at an amino acid(s) corresponding to: W13L, H18L, S25R, Q26D, Q26G, Q26H, Q26I, Q26K, Q26L, Q26N, Q26R, Q26S, Q26T, T29K, T29N, T29S, L31K, L31R, R70K, K92H, H94Q, P95A, P95I, P95L, P95N, P95S, P95V, T114S, C144S, T146A, T146G, T146S, F147I, F147L, Q164K, K185N, H198D, H198E, H198G, H198K, H198N, H198S, Y219L, C228F, C228K, C228Y, S232L, C240A, C240D, C240F, C240G, C240I, C240K, C240N, C240S, C240V, S241Y, C254A, C254D, C254E, C254G, C254N, C254Q, C254R, C254T, A258S, P259A, P259E, P259F, P259K, P259L, P259R, P259S, P259T, P259V, D260S, D270N, Q278D, Q278K, Q278N, F280H, F280I, F280M, F280N, F280S, F280Y, T286S, G288D, I346S, A403V, Q405E, Q405P, Q405S, A407P, I409A, I409E, I409K, I409L, I409S, I409V, I416L, C418S, F459G, F459S, and / or D467G in the amino acid sequence of the homolog. In some embodiments, a mutation is a substitution. In some embodiments, a substitution is a substitution described herein for a variant of BvCYP76AD1. In some embodiments, a variant of a homolog of BvCYP76AD1 is a tyrosine hydroxylase which is not BvCYP76AD1 and which comprises a sequence at least 90% Attorney Docket No. G0919.70121WO00   identical to that of BvCYP76AD1 and which comprises a mutation(s) at an amino acid(s) corresponding to W13, H18, S25, Q26, T29, L31, R70, K92, H94, P95, T114, M115, F147, Q164, K185, H198, Y219, C228, S232, C240, S241, C254, P259, D260, Q278, F280, T286, G288, I346, A403, Q405, A407, I409, I416, C418, F459, and / or D467, or any combination thereof, of BvCYP76AD1 (“AD1”) (SEQ ID NO: 1). In some embodiments, a mutation is a substitution. In some embodiments, a variant of a homolog of BvCYP76AD1 is a tyrosine hydroxylase which is not BvCYP76AD1 and which comprises a sequence at least 80% identical to that of BvCYP76AD1 and which comprises a mutation(s) at an amino acid(s) corresponding to W13, H18, S25, Q26, T29, L31, R70, K92, H94, P95, T114, M115, F147, Q164, K185, H198, Y219, C228, S232, C240, S241, C254, P259, D260, Q278, F280, T286, G288, I346, A403, Q405, A407, I409, I416, C418, F459, and / or D467, or any combination thereof, of BvCYP76AD1 (“AD1”) (SEQ ID NO: 1). In some embodiments, a mutation is a substitution. In some embodiments, a variant of a homolog of BvCYP76AD1 is a tyrosine hydroxylase which is not BvCYP76AD1 and which comprises a sequence at least 70% identical to that of BvCYP76AD1 and which comprises a mutation(s) at an amino acid(s) corresponding to W13, H18, S25, Q26, T29, L31, R70, K92, H94, P95, T114, M115, F147, Q164, K185, H198, Y219, C228, S232, C240, S241, C254, P259, D260, Q278, F280, T286, G288, I346, A403, Q405, A407, I409, I416, C418, F459, and / or D467, or any combination thereof, of BvCYP76AD1 (“AD1”) (SEQ ID NO: 1). In some embodiments, a mutation is a substitution. In some embodiments, a variant of a homolog of BvCYP76AD1 is a tyrosine hydroxylase which is not BvCYP76AD1 and which comprises a sequence at least 60% identical to that of BvCYP76AD1 and which comprises a mutation(s) at an amino acid(s) corresponding to W13, H18, S25, Q26, T29, L31, R70, K92, H94, P95, T114, M115, F147, Q164, K185, H198, Y219, C228, S232, C240, S241, C254, P259, D260, Q278, F280, T286, G288, I346, A403, Q405, A407, I409, I416, C418, F459, and / or D467, or any combination thereof, of BvCYP76AD1 (“AD1”) (SEQ ID NO: 1). In some embodiments, a mutation is a substitution. Methods In some aspects, the disclosure provides methods of using host cells for producing products of interest. In some embodiments, the disclosure provides a method comprising Attorney Docket No. G0919.70121WO00   culturing a host cell described in this application (e.g., a host cell comprising a heterologous polynucleotide encoding a tyrosine hydroxylase). Methods for culturing cells are described elsewhere in this application. In some embodiments, the disclosure provides a method of producing one or more betalains from L-tyrosine comprising culturing a host cell described in this application (e.g., a host cell comprising a heterologous polynucleotide encoding a tyrosine hydroxylase). In some embodiments, the production occurs ex vivo, e.g., in an in vitro cell culture environment. Compositions, cells, enzymes, and methods described in this application are also applicable to industrial settings, including any application wherein there is a need for increased biosynthesis of one or more betalains. In some embodiments, methods associated with the disclosure include methods of producing one or more of the following products: betanin, isobetanin, betanidin, isobetanidin, probetanin, neobetanin, vulgaxanthin, miraxanthin, portulaxanthin, and / or indicaxanthin, or precursors or derivatives thereof. In some aspects, the disclosure provides a method of producing betalains for use as dyes, such as food dyes. For example, betalains provide red and yellow pigments found in nature, such as the deep red color of beets. In some aspects, the disclosure provides a method of producing betalains for use as antioxidants. The disclosure is directed, in part, to methods of producing one or more betalains using a tyrosine hydroxylase described in this disclosure, or a nucleic acid encoding the same, or a host cell comprising any thereof. In some embodiments, a tyrosine hydroxylase is engineered to produce increased titers of L-DOPA as a first step of producing one or more betalains, such as betanin or indicaxanthin. Without wishing to be bound by any theory, it is believed that increased titers of one or more betalains can be produced by increasing production of L-DOPA. L-tyrosine is converted to L-DOPA by either CYP76AD1 or CYP76AD5. L-DOPA is then converted to either cyclo-DOPA by CYP76AD1 or betalamic acid by DOPA 4,5-dioxygenase. Cyclo- DOPA is converted to cDOPA 5-O-glucoside by cyclo-DOPA-5-O-glucosyltransferase, which then spontaneously condenses with betalamic acid leading to betanin. Betalamic acid also spontaneously condenses with cyclo-DOPA leading to betanidin. Alternatively, betalamic acid also spontaneously condenses with an amine, such as amino acids, leading to the respective betaxanthin. Finally, betanidin is converted to betanin by betanidin-5-O- glucosyltransferase. In some embodiments, a host cell expressing a tyrosine hydroxylase also comprises any one of the enzymes required to produce one or more betalains from L-tyrosine. In some embodiments, a tyrosine hydroxylase may comprise one or more modifications to enhance its effectiveness [e.g., activity and / or stability (e.g., half-life)] in a Attorney Docket No. G0919.70121WO00   selected mode of biosynthesis. For example, a tyrosine hydroxylase may comprise a modification that increases stability and / or activity of the enzyme at acidic pH, e.g., to improve the effectiveness of the tyrosine hydroxylase when used in an industry-level batch culture. In some embodiments, the tyrosine hydroxylase is immobilized to another agent, e.g., a different enzyme, a polymer (e.g., polysaccharide (e.g., starch)), or an inorganic carrier (e.g., silica gel). Immobilization may increase enzyme stability and / or shelf-life. Compositions Further aspects of the disclosure relate to compositions containing one or more betalains (e.g., betanin and indicaxanthin). Culturing of host cells associated with the disclosure can result in compositions comprising products, including one or more betalains. In some embodiments, compositions obtained by culturing host cells associated with the disclosure result in compositions in which at least 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49%, 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% of the total products in the composition is / are one or more betalains. Compositions associated with the disclosure can further comprise additional components as would be understood by one of ordinary skill in the art. For example, it should be appreciated that in some embodiments, compositions comprising one or more betalains can include cell culture fermentation broth or cell culture supernatants. In other embodiments, compositions may include one or more betalains in a form that has been purified from cell culture fermentation broth or cell culture supernatants. In some embodiments, cells associated with the disclosure are cultured in the presence of an organic solvent overlay. As used in this disclosure, an organic solvent overlay refers to a layer comprising one or more organic solvents that is added to a cell culture sample. The organic solvent overlay may partially or fully cover the cell culture sample. The use of an organic solvent overlay can assist with reducing or alleviating host cell toxicity caused by increased concentrations of products. In some embodiments, compositions comprising one or more betalains further comprise one or more components of an organic solvent overlay (e.g., dodecane). Attorney Docket No. G0919.70121WO00   The present invention is further illustrated by the following Examples, which in no way should be construed as further limiting. The entire contents of all of the references (including literature references, issued patents, published patent applications, and co pending patent applications) cited throughout this application are hereby expressly incorporated by reference. EXAMPLES In order that the disclosure described in the present application may be more fully understood, the following examples are set forth. The examples described in this application are offered to illustrate the systems and methods provided in this disclosure and are not to be construed in any way as limiting their scope. Example 1. Identification of variant tyrosine hydroxylases (generation 1) that exhibit increased betanin production. This Example describes the identification of variant tyrosine hydroxylases that are capable of increasing betanin production relative to betanin production by a wild-type tyrosine hydroxylase from Beta vulgaris (BvCYP76AD1; SEQ ID NO: 1). To identify variant tyrosine hydroxylases capable of increased betanin production relative to BvCYP76AD1, a protein engineering library of approximately 700 variants was generated based on the BvCYP76AD1 sequence. The library included variants that contained single amino acid substitutions and variants that contained two or three amino acid substitutions. The protein engineering library was transformed into two CEN.PK Saccharomyces cerevisiae strains modified to increase tyrosine production. These strains expressed known genes (UGT (EC: 2.4.1) and DODA (EC: 1.13.11.29)) that allow betacyanin production. These modified strains were used as host strains to screen the protein engineering library. One of the screening strains had overexpression of BvCYP76AD5 (AD5) to ensure supply of L-DOPA for the conversion to betalamic acid by DODA. To initiate cell growth in preparation for screening, glycerol stocks of the tyrosine hydroxylase variant transformants were thawed at room temperature for approximately 1 hour.240 µL of preculture 1 media was added to each well of a deep well plate, and 10 µL aliquots of glycerol stock was added to each well. Plates containing glycerol stocks of the tyrosine hydroxylase variant transformants were incubated at 30℃ at 1,000 rpm and 80% humidity for 1 day.50 µL aliquots of the tyrosine hydroxylase variant transformants in Attorney Docket No. G0919.70121WO00   glycerol stocks were then transferred from wells of the first plate to wells of a second plate each containing 450 µL of preculture 2 media. The plates were incubated at 30℃ at 1,000 RPM and 80% humidity for 1 day.50 µL aliquots of the tyrosine hydroxylase variant transformants in glycerol stocks were then transferred from wells of the second plate to wells of a third plate each containing 450 µL of production media. The plates were incubated at 30℃ at 1,000 RPM and 80% humidity for 3 days. After 3 days, 5 µL of production cultures was transferred to plates containing PBS and measured at OD660. The plates were then spun down at 4,000 x g for 7 minutes and 5 µL of supernatant was transferred to wells of a 384- well plate at 10X dilution.10 µL of 10X diluted supernatant was then transferred to another 384-well plate at a 50X dilution and the plate was shaken at 1,000 rpm for 3 minutes. Plates were then analyzed for catalytic activity. Multiple tyrosine hydroxylase BvCYP76AD1 variants led to increased betanin production over the control (wild-type BvCYP76AD1; SEQ ID NO: 1). Expression of some of the tyrosine hydroxylase CYP76AD1 variants increased titers of betanin with or without the presence of CYP76AD5 expression (FIG.2A; indicated by the oval), while a subset of variants led to a more pronounced improvement of betanin production only in the absence of CYP76AD5 expression (FIG.2A, indicated along the x-axis). Expression of some tyrosine hydroxylase variants increased betalamic acid production as well as increased betanin production (FIG.2B). Multiple tyrosine hydroxylase CYP76AD1 variants comprising single amino acid substitutions were identified that exhibited at least a 2-fold improvement in betanin production over wild-type CYP76AD1, with variants comprising a W13S substitution showing the highest improvement over wild-type CYP76AD1 (FIG.3). The distribution of residues mutated in the tyrosine hydroxylase CYP76AD1 variants was calculated and the amino acid substitutions at those residues for the top 40 variants that comprised single amino acid substitutions in strains lacking CYP76AD5 expression was determined (FIG.4). Tyrosine hydroxylase CYP76AD1 variants comprising two or more amino acid substitutions that showed at least a 2.7-fold activity improvement over the wild-type CYP76AD1 when expressed in a strain lacking CYP76AD5 expression were also identified, along with selected variants comprising one amino acid substitution (FIG.5). The distribution of modified residues and the specific amino acid substitutions at those residues for the variants shown in FIG.5 is summarized in FIG.6. Attorney Docket No. G0919.70121WO00   Table 3. Mutations present in top betanin-producing tyrosine hydroxylase variants. Throughout this document, unless otherwise noted, the number indicates the position and the letter preceding the number indicates the amino acid at that position in the wildtype sequence (e.g., SEQ ID NO: 1) and the letter following the number indicates the amino acid substitution. Attorney Docket No. G0919.70121WO00   Attorney Docket No. G0919.70121WO00   Attorney Docket No. G0919.70121WO00   Attorney Docket No. G0919.70121WO00   Attorney Docket No. G0919.70121WO00   Attorney Docket No. G0919.70121WO00   Table 4. Betanin-producing tyrosine hydroxylase variants identified in a strain lacking CYP76AD5. Attorney Docket No. G0919.70121WO00   Example 2. Identification of additional variant tyrosine hydroxylases (generation 2) that exhibit increased betanin production. This Example describes the identification of additional variant tyrosine hydroxylases that are capable of increased betanin production relative to that produced by the wild-type tyrosine hydroxylase from Beta vulgaris (BvCYP76AD1; SEQ ID NO: 1). To identify additional variant tyrosine hydroxylases capable of increased betanin production relative to BvCYP76AD1, a subsequent protein engineering library of approximately 300 variants was generated based on the BvCYP76AD1 sequence and based on the results in Example 1. The protein engineering library was transformed into a Saccharomyces cerevisiae strain further modified to increase tyrosine production. This strain, which contained known genes (UGT and DODA) to allow betacyanin production, was used as the host strain to screen this protein engineering library. The protein engineering library design in this Example utilized the single and multi- amino acid substitution variants identified in Example 1 to generate new tyrosine hydroxylase variants that comprised 2-7 amino acid substitutions. Strains containing variant tyrosine hydroxylases from the resulting library were prepared, cultured, and measured for activity using the same methods as described in Example 1. Tyrosine hydroxylase CYP76AD1 variants were identified that led to increased titers of betanin and betalamic acid relative to the control (BvCYP76AD1; SEQ ID NO: 1) (FIG. 7). Some variants exhibited up to nearly a 6-fold activity improvement over the control (BvCYP76AD1; SEQ ID NO: 1) (FIG.8). The distribution of modified positions and the amino acid substitutions at those positions in 20 top betanin-producing variants is summarized in FIG.9. Table 5. Top betanin-producing tyrosine hydroxylase variants identified in Example 2 compared to wild-type CYP76AD1. Variant Fold Change in Molecule Protein Amino acid substitutions relative to SEQ ID NO: 1 Betanin ID SEQ ID Production NO: (based on UV Attorney Docket No. G0919.70121WO00   Example 3. Identification of additional variant tyrosine hydroxylases (generation 3) that exhibit increased betanin production. This Example describes the identification of additional variant tyrosine hydroxylases (generation 3) that are capable of increased betanin production relative to that produced by the wild-type tyrosine hydroxylase from Beta vulgaris (BvCYP76AD1; SEQ ID NO: 1). Attorney Docket No. G0919.70121WO00   A Saccharomyces cerevisiae strain modified to increase tyrosine production and which contained known genes (UGT and DODA) to allow betacyanin production, was used as the host strain to screen new tyrosine hydroxylase variants that comprised up to 9-10 amino acid substitutions. Strains expressing these variant tyrosine hydroxylases were prepared, cultured, and measured for activity using the same methods as described in Example 1. Tyrosine hydroxylase CYP76AD1 variants were identified that led to increased titers of betanin and betalamic acid relative to the control (BvCYP76AD1; SEQ ID NO: 1) (FIG. 14). A total of 10 variants of BvCYP76AD1 were produced in generation 3, and then tested in different backgrounds. The data shown in FIG.14 represents a comparison of selected variants from generation 3, along with some variants from generations 1 and 2 (described in Examples 1 and 2, respectively), all in the same genetic background. The 3 variants shown all performed better than the control; generation 3 variant SEQ ID NO: 524 exhibited up to nearly a 9- to 10-fold activity improvement over the control (BvCYP76AD1; SEQ ID NO: 1) (FIG.14). The sequence of each of the variants of BvCYP76AD1 in FIG.14 (referred to as SEQ ID NOs: 42, 44, 45, 47, 48, 51, 59, 238, 241, 245, 252, 258, 523, 524 and 525) is included in the specification and sequence listing with the corresponding SEQ ID NO (e.g., SEQ ID NOs: 42, 44, 45, 47, 48, 51, 59, 238, 241, 245, 252, 258, 523, 524 and 525, respectively). The mutations (relative to BvCYP76AD1; SEQ ID NO: 1) in these variants are described in Table 6, below: Table 6. Betanin-producing tyrosine hydroxylase variants Variant Fold Change in Molecule Protein ID SEQ ID NO: 6508549 17002764 59 7002816 45 . 7002845 47 C254D; P259L 7002869 48 C254D; P259V 7002930 44 C254D; A403V 2.26 7003078 51 Attorney Docket No. G0919.70121WO00   A comparison of betacyanin production by various enzymes from Examples 1, 2 and 3 are shown in FIG.14. A circle indicates production in the base strain; a square indicates production in a strain expressing the control enzyme (BvCYP76AD1; SEQ ID NO: 1); and a cross, diamond, and star indicate production in strains expressing an enzyme from Examples 1, 2 and 3, respectively. Replicate results for various enzymes are shown; for example, the production of betacyanin by SEQ524 (a variant of BvCYP76AD1 represented by SEQ ID NO: 524) in 10 replicates is shown. Example 4. Increased betanin production by overexpression of cytochrome P450 reductase. This Example describes the identification of cytochrome P450 reductase from Arabidosis thaliana (AtATR2; SEQ ID NO: 529), which also improves betacyanin production. To investigate the effect of overexpression of the AtATR2 (encoding a NADPH- cytochrome P450 reductase) on betacyanin production, engineered Saccharomyces cerevisiae strains with additional AtATR2 expression were created by integration of an overexpression cassette. Attorney Docket No. G0919.70121WO00   Integration of AtATR2 overexpression cassette was confirmed by sequencing. These engineered Saccharomyces cerevisiae strains had been modified to increase tyrosine production and expressed known genes (CYP76AD1, UGT and DODA) that allowed betacyanin production. The same protocol as described in Example 1 was used except the UV absorbance measurements were conducted in 96-well plates instead of 384-well plates. A fermentation protocol was used to grow strains and produce betalains. The fermentation was carried out in an Ambr ® 250 (small bioreactors available from Sartorius, Goettingen, Germany). Strains producing betaxanthin and strains producing betacyanin were grown using standard methods, modified from methods described in van Hoek et al.2000 Biotech. Bioeng.68(5), 517-523, the contents of which are hereby incorporated by reference in its entirety. Surprisingly, the overexpression of AtATR2 led to an increase in betanin production relative to the control in an Ambr fermentation. The observed improvements were ~39 to 66 % depending on the background strain used to overexpress AtATR2 (FIG.15). Without wishing to be bound by any theory, the present disclosure suggests that the overexpression of AtATR2 shifted the balance from betalamic acid to betacyanin production. Example 5. Investigation of the effect of mck1 deletion on betaxanthin and betacyanin production To investigate the effect of expression of the mck1 gene (encoding a dual-specificity S / T and tyrosine protein kinase) on betaxanthin production, engineered Saccharomyces cerevisiae strains lacking the mck1 gene were created by replacing the mck1 gene with an F- Cphl recognition site. Deletion of mck1 was confirmed by sequencing. These engineered Saccharomyces cerevisiae strains had been modified to increase tyrosine production and expressed known genes (CYP76AD1, UGT and DODA) that allowed betacyanin production, or known genes (CYP76AD5 and DODA) that allowed betaxanthin production. The same protocol as described in Example 1 was used except the UV absorbance measurements were conducted in 96-well plates instead of 384-well plates. The fermentation was carried out in an Ambr ® 250 (small bioreactors available from Sartorius, Goettingen, Germany). Strains producing betaxanthin and strains producing betacyanin were grown using standard methods, modified from methods described in van Hoek et al.2000 Biotech. Bioeng.68(5), 517-523, the contents of which is hereby incorporated by reference in its entirety. Attorney Docket No. G0919.70121WO00   Surprisingly, the deletion of mck1 led to an increase in betaxanthin production, specifically indicaxanthin, which is a type of betaxanthin (FIG.10). FIG.11 shows the positive impact of mck1 deletion on betaxanthin production in an Ambr fermentation. This result was also consistent for other betalains, including betacyanin (FIG.12). Example 6. Investigation of the effect of exg1 deletion on betacyanin production To investigate the effect of expression of the exg1 gene (encoding the major exo-1,3- beta-glucanase) on betacyanin production, engineered Saccharomyces cerevisiae strains lacking the exg1 gene were created by deleting the exg1 gene. Deletion of exg1 was confirmed by sequencing. These engineered Saccharomyces cerevisiae strains had been modified to increase tyrosine production and expressed known genes (CYP76AD1, UGT and DODA) that allowed betacyanin production The same protocol as described in Example 1 was used to measure the UV absorbance except UV absorbance measurements were conducted in 96-well plates instead of 384-well plates. A fermentation protocol was used to grow strains and produce betacyanin. The fermentation was carried out in an Ambr ® 250 (small bioreactors available from Sartorius, Goettingen, Germany). Strains producing betacyanin were grown using standard methods as described in Example 5. Surprisingly, results indicate the deletion of exg1 led to an increase in betanin production (FIG.13), while decreasing the betanidin content. Without wishing to be bound by any theory, the present disclosure suggests that the deletion of exg1 shifted the balance from betanidin to betanin production. In various other experiments, other glucanase(s) were deleted while EXG1 was not deleted, but an effect similar to that of the deletion of EXG1 was not observed. Without wishing to be bound by any particular theory, the presence of EXG1 could be masking the effect of the deletion of another glucanase. Example 7. Investigation of the effect of gcn4 knockdown on betacyanin production To investigate the effect of expression of gcn4 (SEQ ID NO: 530) a gene encoding a basic leucine zipper transcriptional activator of amino acid biosynthetic genes, on betacyanin production, engineered Saccharomyces cerevisiae strains with reduced gcn4 expression were created by mRNA perturbation via Nonsense Mediated Decay (NMD) as described in the literature [Schuldiner, M. et al. (2005) Cell 123: 507-519; Muhlrad, D. et al. (1999) RNA 5: 1299-1307]. Addition of the desired NMD sequence to gcn4 (SEQ ID NO: 549) was Attorney Docket No. G0919.70121WO00   confirmed by sequencing. These engineered S. cerevisiae strains had been modified to increase tyrosine production and expressed known genes (BvCYP76AD1 (SEQ ID NO: 1), UGT and DODA) that allowed betacyanin production. The same protocol as described in Example 1 was used except the UV absorbance measurements were conducted in 96-well plates instead of 384-well plates. The fermentation was carried out in an Ambr ® 250 (small bioreactors available from Sartorius, Goettingen, Germany). Strains producing betaxanthin and strains producing betacyanin were grown using standard methods, modified from methods described in van Hoek, P., et al. (2000). Biotech. Bioeng.68(5), 517-523. Fermentative capacity in high-cell-density fed-batch cultures of baker’s yeast. Biotechnology and Bioengineering, 68(5), 517-523, the contents of which is hereby incorporated by reference in its entirety. Surprisingly, results indicate the knockdown of gcn4 led to an increase in betanin production relative to the control in an Ambr fermentation. The observed improvements were ~8-22 % depending on the background strain used to downregulate gcn4 (FIG.16). FIG.16 shows the positive impact of gcn4 knockdown on betacyanin production in an Ambr fermentation. Example 8: Increased betanin production by deletion of a protein involved in aromatic amino acid biosynthesis This Example describes the deletion of ARO5, a gene involved in aromatic amino acid biosynthesis (SEQ ID NO: 531), and its impact on betacyanin production. To investigate the effect of knockout of ARO5 on betacyanin production, engineered Saccharomyces cerevisiae strains were created with a deletion of ARO5. The deletion of ARO5 was confirmed by sequencing. These engineered Saccharomyces cerevisiae strains had been modified to increase tyrosine production and expressed known genes (CYP76AD1, UGT and DODA) that allowed betacyanin production. The same protocol as described in Example 1 was used except the UV absorbance measurements were conducted in 96-well plates instead of 384-well plates. The fermentation was carried out in an Ambr ® 250 (small bioreactors available from Sartorius, Goettingen, Germany). Strains producing betacyanin were grown using standard methods, modified from methods described in van Hoek, et al. (van Hoek, P., et al. (2000). Fermentative capacity in high-cell-density fed-batch cultures of baker’s yeast. Biotechnology and Bioengineering, 68(5), 517-523, the contents of which is hereby incorporated by reference in its entirety). Attorney Docket No. G0919.70121WO00   Surprisingly, results indicate the deletion of ARO5 led to an increase in betanin production relative to the control in an Ambr fermentation. The observed improvements were ~9 % (FIG.17). FIG.17 shows the positive impact of ARO5 deletion on betacyanin production in an Ambr fermentation. Example 9: Increased betalain production by genetic modifications This Example describes the identification of genetic modifications that improve betalain production. To identify genetic modifications that were beneficial for betalain production, Saccharomyces cerevisiae strains able to produce betaxanthins and / or betacyanins, i.e., strains expressing BvCYP76AD5 (SEQ ID NO: 517), BvCYP76AD1, DODA and / or UGT, were used as host strains to determine betalain production. Some of the strains were tested in 96 well plate, so they were prepared, cultured and measured for activity using the same methods as described in Example 1. The same protocol as described in Example 1 was used except the UV absorbance measurements were conducted in 96-well plates instead of 384- well plates. The fermentation was carried out in an Ambr ® 250 (small bioreactors available from Sartorius, Goettingen, Germany). Strains producing betaxanthin and strains producing betacyanin were grown using standard methods, modified from methods described in van Hoek, et al. (van Hoek, P., et al. (2000). Fermentative capacity in high-cell-density fed-batch cultures of baker’s yeast. Biotechnology and Bioengineering, 68(5), 517-523, the contents of which is hereby incorporated by reference in its entirety). Surprisingly, results indicate the knockout of cta1 (catalase A, SEQ ID NO: 532), dal7 (malate synthase, SEQ ID NO: 533) or gph1 (glycogen phosphorylase, SEQ ID NO: 534) led to an increase in indicaxanthin (FIG.18). FIG.18 shows the positive impact of cta1, dal7 or gph1 on indicaxanthin production. The observed improvements were ~6-7% for each of the modifications. Surprisingly, results also indicate the overexpression of ZWF1 (glucose-6-phosphate dehydrogenase, SEQ ID NO: 535) and TPI1 (triose phosphate isomerase, SEQ ID NO: 536) led to an increase in betanin production (FIG.19). FIG.19 shows the positive impact of overexpressing ZWF1 and TPI1 on betanin production in an Ambr fermentation. The observed improvements were ~5-29% depending on the background strain used to overexpress ZWF1 and TPI1. When the knockout of cta1 was combined with the overexpression of ZWF1 and TPI1, further improvements in indicaxanthin production were observed (FIG.20). FIG.20 Attorney Docket No. G0919.70121WO00   shows the positive impact of simultaneously deleting cta1 and overexpressing ZWF1 and TPI1 on indicaxanthin production in an Ambr fermentation. The observed improvements were ~10%. Example 10: Increased betanin production by genetic modifications simultaneously deleting and overexpression genes of interest This Example describes the identification of genetic modifications that improve betalain production. To identify genetic modifications that were beneficial for betalain production, Saccharomyces cerevisiae strains able to produce betalains, i.e., strains expressing BvCYP76AD1, DODA and / or UGT, were used as host strain to determine betalain production. The genetic modification comprises the simultaneous deletion of a first gene and overexpression of a second gene in place of the first gene as summarized below. The same protocol as described in Example 1 was used except the UV absorbance measurements were conducted in 96-well plates instead of 384-well plates. The fermentation was carried out in an Ambr ® 250 (small bioreactors available from Sartorius, Goettingen, Germany). Strains producing betacyanin were grown using standard methods, modified from methods described in van Hoek, et al. (van Hoek, P., et al. (2000). Fermentative capacity in high-cell-density fed-batch cultures of baker’s yeast. Biotechnology and Bioengineering, 68(5), 517-523, the contents of which is hereby incorporated by reference in its entirety. Surprisingly, results indicated that deletion of BUD17 (putative pyridoxal kinase, SEQ ID NO: 537) and overexpression of ALD6 (aldehyde dehydrogenase, SEQ ID NO: 538) led to an increase in betanin production (FIG.21). FIG.21 shows the positive impact of deleting BUD17, while overexpressing ALD6 on betanin production in an Ambr fermentation. The observed improvements were ~11%. Surprisingly, results indicated that deletion of YDC1 (alkaline dihydroceramidase, SEQ ID NO: 539) and overexpression of PEX19 (peroxisome partitioning, SEQ ID NO: 540) also led to an increase in betanin production (FIG.21). FIG.21 shows the positive impact of deleting YDC1, while overexpressing PEX19 on betanin production in an Ambr fermentation. The observed improvements were ~9%. Surprisingly, results indicated that deletion of GRX4 (glutathione-dependent oxidoreductase, and glutathione S-transferase, SEQ ID NO: 541) and overexpression of LDS2 (spore wall assembly, SEQ ID NO: 542) led to an increase in betanin production (FIG. 22). FIG.22 shows the positive impact of deleting GRX4 while overexpressing LDS2 on Attorney Docket No. G0919.70121WO00   betanin production in an Ambr fermentation. In some experiments the observed improvements were ~3-14% depending on the background strain used. For example, an improvement of 40% was observed when GRX4 was deleted and LDS2 was overexpressed in a strain that already had deletion of ATF1 and overexpression of PGM1. Surprisingly, results indicated that deletion of ATF1 (alcohol acetyltransferase, SEQ ID NO: 543) and overexpression of PGM1 (phosphoglucomutase, SEQ ID NO: 544) can lead to an increase in betanin production (FIG.22). FIG.22 shows the impact of deleting ATF1, while overexpressing PGM1 on betanin production in an Ambr fermentation. The observed impact was ~ -5 to +15%. In addition, a deletion of ATF1 and overexpression of PGM1 in combination with deletion of GRX4 and overexpression of LDS2 led to a betanin improvement of 32% (over a control that did not include a deletion of ATF1 or GRX4, or overexpression of PGM1 or LDS2) (FIG.22). Example 11: Increased indicaxanthin production by knocking out proline degradation This Example describes the knockout of PUT1 (proline oxidase; SEQ ID NO: 545) and its effect on indicaxanthin production. To investigate the effect of a PUT1 knockout on indicaxanthin production, engineered Saccharomyces cerevisiae strains were created with a deletion of PUT1, which was confirmed by sequencing. These engineered Saccharomyces cerevisiae strains had been modified to increase tyrosine production and expressed known genes (BvCYP76AD5 SEQ ID NO: 517, and DODA) that allowed betaxanthin production. The same protocol as described in Example 1 was used except the UV absorbance measurements were conducted in 96-well plates instead of 384-well plates. The fermentation was carried out in an Ambr ® 250 (small bioreactors available from Sartorius, Goettingen, Germany). Strains producing betaxanthin were grown using standard methods, modified from methods described in van Hoek, et al. (van Hoek, P., et al. (2000). Fermentative capacity in high-cell-density fed-batch cultures of baker’s yeast. Biotechnology and Bioengineering, 68(5), 517-523, the contents of which is hereby incorporated by reference in its entirety). Surprisingly, the deletion of PUT1 led to an increase in indicaxanthin production relative to the control in an Ambr fermentation despite reducing the growth of the strain. The observed improvements were ~14 % (FIG.23). FIG.23 shows the positive impact of PUT1 deletion on indicaxanthin production in an Ambr fermentation.

[0002] ehtE S E S E S E S E S E S E S E S E S E S E S E S E S E S E S E S E S odnasesalyO xNorD dIy Q h E eSnid siocrA yotfni1 2 3 4 5 6 7 8 90111213141516171om:A O:N O:N O: : : : : : : : : : : : : :N O N O N O N O N O N O N O O O O O O O O seN N N N N N N NcD D D D D D D D D D D D D D D nI I I I I I I I I I I I I I IDIDIeuQ Q Q Q q E e S E S E S E Q S E Q S E Q S E Q S E Q S E Q S E Q Q Q Q Q Q Q S E S E S E S E S E S E S E S S.e7lue-lcroenem9409831839273754015995785243034201belea oDIGa 5N84025024 4 5 4 5 6 5 5 5 5 5 5 5 502020202 2 2 2 2 2 2 2 2 2 2M560707070700000000000000000000000T7 7 7 7 7 7 7 7 7 7 7 7

[0003] S S S S S S S S S S S S S S S S S S S S S 819102122 3 4 5 6 7 8 9 0 1 2 3 4 5 6 7 8: : : :2:2:2 2 2 2 2 2 3 3 3 3 3 3 3 3 3O O O O O O:O:O:O: : : : : : : : : : : :NN N N N N N N NO N O N O N O N O N O N O N O N O N O N O N O N DIDIDIDIDIDIDIDIDIDIDIDIDIDIDIDIDIDIDIDIDIQE QE Q Q Q Q Q Q Q Q Q Q Q Q Q Q Q Q Q Q S E S E S E S E S E S E S E S E Q S S E S E S E S E S E S E S E S E S E S E S E S 887841491336626 4 2 9 1 7 8 8 9 3 5 9 2 14 4 5 4 5 5 58595356 4 6 1 8 9 8 8 6 5 72 2 2 2 2 2 2 2 2 242525 5 5 4 4 4 5 7 00 0 0 0 0 0 0 0 0 0 0 02020202 2 2 2 2 30 0 0 0 0 0 0 0 0 0 0 0 0 0 00000000 0 07 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7070707

[0004] S S S S S S S S S S S S S S S S S S S S S 930414243 4 5 6 7 8 9 0 1 2 3 4 5 6 7 8 9: : : :4:4:4 4 4 4 4 5 5 5 5 5 5 5 5 5 5O O O O O O:O:O:O: : : : : : : : : : : :NN N N N N N N NO N O N O N O N O N O N O N O N O N O N O N O N DIDIDIDIDIDIDIDIDIDIDIDIDIDIDIDIDIDIDIDIDIQE QE Q Q Q Q Q Q Q Q Q Q Q Q Q Q Q Q Q Q S E S E S E S E S E S E S E S E Q S S E S E S E S E S E S E S E S E S E S E S E S 219766689003613 5 9 9 5 8 6 7 7 3 8 2 4 48 7 0 0 0 9 83948688 5 7 3 0 8 2 5 6 7 62 2 3 3 3 2 2 2 2 292720 9 0 9 0 7 8 7 70 0 0 0 0 0 0 0 0 0 0 03020302 3 2 2 2 20 0 0 0 0 0 0 0 0 0 0 0 0 0 00000000 0 07 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7070707

[0005] S S S S S S S S S S S S S S S S S S S S S 061626364 5 6 7 8 9 0 1 2 3 4 5 6 7 8 9 0: : : :6:6:6 6 6 6 7 7 7 7 7 7 7 7 7 7 8O O O O O O:O:O:O: : : : : : : : : : : :NN N N N N N N NO N O N O N O N O N O N O N O N O N O N O N O N DIDIDIDIDIDIDIDIDIDIDIDIDIDIDIDIDIDIDIDIDIQE QE Q Q Q Q Q Q Q Q Q Q Q Q Q Q Q Q Q Q S E S E S E S E S E S E S E S E Q S S E S E S E S E S E S E S E S E S E S E S E S 765705187950973 5 1 6 0 4 8 4 9 8 2 9 9 19 7 9 0 8 8 03870974 8 4 6 9 1 6 0 7 8 22 2 2 3 2 2 3 2 3 203030 0 9 0 8 8 9 8 00 0 0 0 0 0 0 0 0 0 0 03030203 2 2 2 2 30 0 0 0 0 0 0 0 0 0 0 0 0 0 00000000 0 07 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7070707

[0006] S S S S S S S S S S S S S S S S S S S S S 12 3 4 5 6 7 8 9 0 10 18 82 3 4 5 6 7 8 9 0 0: :8:8:8:8 8 8 8 9 9 9 9 9 9 9 9 9 9 1 1O O O O O:O:O:O: : : : : : : : : : : : :NN N N N N N NO N O N O N O N O N O N O N O N O N O N O N O N O N DIDIDIDIDIDIDIDIDIDIDIDIDIDIDIDIDIDIDIDIDIQE Q Q Q Q Q Q Q Q Q Q Q Q Q Q Q Q Q Q S E S E S E S E S E S E S E S E S E S E S E S E S E S E S E S E S E S E Q S E Q S E S 7601386518670 9 9 1 8 6 4 1 0 8 2 7 4 2 00 0 7 0 8 07078977 1 9 9 5 8 3 4 5 6 3 73 3 2 3 2 3 3 2 27292820 0 9 9 0 9 9 0 90 0 0 0 0 0 0 0 0 0 0 03030202 3 2 2 3 20 0 0 0 0 0 0 0 0 0 0 0 0 0 00000000 0 07 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7070707

[0007] S S S S S S S S S S S S S S S S S S S S S 203040506070809 0 1 2 3 4 5 6 7 8 9 0 1 21 1 1 1 1 1 1011111111 1 1 1 1 1 1 2 2 2: : : : : : : : : : :1:1:1:1:1 1 1 1 1 1O O O O O O O O O O O O O O O:O:O:O:O: :NN N N N N N N N N N N N N N N N N NO N O N DIDIDIDIDIDIDIDIDIDIDIDIDIDIDIDIDIDIDIDIDIQE QE QE QE QE QE QE QE QE QE QE QE QE QE Q Q Q Q Q Q Q S S S S S S S S S S S S S S E S E S E S E S E S E S E S 564 0 0 2 0 2 4 8 0 7 9 2 4 7 6 0 5 9 2 17879030009 2 0 3 2 4 4 2 1 8 3 5 1 2 6 32 2 3 3 3828203030 9 0 0 8 0 0 0 0 0 0 00 0 0 0 0 0 0 0 0302030302 3 3 3 3 3 3 30 0 0 0 0 0 0 0 0 0 0 0 0000000000 0 0 07 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 707070707

[0008] S S S S S S S S S S S S S S S S S S S S S 324252627282920 1 2 3 4 5 6 7 8 9 0 1 2 31 1 1 1 1 1 1313131313 3 3 3 3 3 4 4 4 4: : : : : : : : : : :1:1:1:1:1 1 1 1 1 1O O O O O O O O O O O O O O O:O:O:O:O: :NN N N N N N N N N N N N N N N N N NO N O N DIDIDIDIDIDIDIDIDIDIDIDIDIDIDIDIDIDIDIDIDIQE QE QE QE QE QE QE QE QE QE QE QE QE QE Q Q Q Q Q Q Q S S S S S S S S S S S S S S E S E S E S E S E S E S E S 563 6 6 8 9 9 3 9 5 1 4 2 6 6 4 7 3 2 2 50909020001 6 6 8 9 1 3 5 1 7 8 5 7 9 4 33 3 3 3 3920382030 0 0 0 0 8 0 0 7 9 8 00 0 0 0 0 0 0 0 0303030303 2 3 3 2 2 2 30 0 0 0 0 0 0 0 0 0 0 0 0000000000 0 0 07 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 707070707

[0009] S S S S S S S S S S S S S S S S S S S S S 445464748494051 2 3 4 5 6 7 8 9 0 1 2 3 41 1 1 1 1 1 1515151515 5 5 5 5 6 6 6 6 6: : : : : : : : : : :1:1:1:1:1 1 1 1 1 1O O O O O O O O O O O O O O O:O:O:O:O: :NN N N N N N N N N N N N N N N N N NO N O N DIDIDIDIDIDIDIDIDIDIDIDIDIDIDIDIDIDIDIDIDIQE QE QE QE QE QE QE QE QE QE QE QE QE QE Q Q Q Q Q Q Q S S S S S S S S S S S S S S E S E S E S E S E S E S E S 653 4 6 3 3 1 2 5 3 2 0 4 8 5 0 1 3 2 8 98806049705 6 7 5 4 8 4 4 5 6 6 4 9 7 4 42 3 3 2 3037203030 0 0 9 0 9 9 0 7 9 0 90 0 0 0 0 0 0 0 0303030203 2 2 3 2 2 3 20 0 0 0 0 0 0 0 0 0 0 0 0000000000 0 0 07 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 707070707

[0010] S S S S S S S S S S S S S S S S S S S S S 566676869607172 3 4 5 6 7 8 9 0 1 2 3 4 51 1 1 1 1 1 1717171717 7 7 7 8 8 8 8 8 8: : : : : : : : : : :1:1:1:1:1 1 1 1 1 1O O O O O O O O O O O O O O O:O:O:O:O: :NN N N N N N N N N N N N N N N N N NO N O N DIDIDIDIDIDIDIDIDIDIDIDIDIDIDIDIDIDIDIDIDIQE QE QE QE QE QE QE QE QE QE QE QE QE QE Q Q Q Q Q Q Q S S S S S S S S S S S S S S E S E S E S E S E S E S E S 957 2 6 1 9 5 6 1 2 6 3 3 2 5 0 2 1 8 3 47689057194 7 5 7 1 8 5 9 2 4 1 3 9 8 9 72 2 3 2 2729292829 7 7 8 9 0 8 9 0 0 9 00 0 0 0 0 0 0 0 0202020202 3 2 2 3 3 2 30 0 0 0 0 0 0 0 0 0 0 0 0000000000 0 0 07 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 707070707

[0011] S S S S S S S S S S S S S S S S S S S S S 687888980919293 4 5 6 7 8 9 0 1 2 3 4 5 61 1 1 1 1 1 1919191919 9 9 0 0 0 0 0 0 0: : : : : : : : : : :1:1:1:2:2 2 2 2 2 2O O O O O O O O O O O O O O O:O:O:O:O: :NN N N N N N N N N N N N N N N N N NO N O N DIDIDIDIDIDIDIDIDIDIDIDIDIDIDIDIDIDIDIDIDIQE QE QE QE QE QE QE QE QE QE QE QE QE QE Q Q Q Q Q Q Q S S S S S S S S S S S S S S E S E S E S E S E S E S E S 607 0 3 4 9 7 5 1 1 8 1 8 6 3 7 0 6 6 9 58906030081 4 5 3 6 1 2 5 0 2 1 8 6 8 5 92 3 3 3 2820382920 0 9 8 0 8 0 7 7 8 8 90 0 0 0 0 0 0 0 0303020203 2 3 2 2 2 2 20 0 0 0 0 0 0 0 0 0 0 0 0000000000 0 0 07 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 707070707

[0012] S S S S S S S S S S S S S S S S S S S S S 708090011121314 5 6 7 8 9 0 1 2 3 4 5 6 72 2 2 2 2 2 2121212121 1 2 2 2 2 2 2 2 2: : : : : : : : : : :2:2:2:2:2 2 2 2 2 2O O O O O O O O O O O O O O O:O:O:O:O: :NN N N N N N N N N N N N N N N N N NO N O N DIDIDIDIDIDIDIDIDIDIDIDIDIDIDIDIDIDIDIDIDIQE QE QE QE QE QE QE QE QE QE QE QE QE QE Q Q Q Q Q Q Q S S S S S S S S S S S S S S E S E S E S E S E S E S E S 008 4 3 3 1 7 7 5 3 9 9 7 5 9 5 3 2 9 8 39988959852 2 7 8 6 0 2 7 8 6 6 1 1 4 7 72 2 2 2 2828203927 9 9 9 7 9 8 8 0 8 7 80 0 0 0 0 0 0 0 0202020202 2 2 2 3 2 2 20 0 0 0 0 0 0 0 0 0 0 0 0000000000 0 0 07 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 707070707

[0013] S S S S S S S S S S S S S S S S S S S S S 829203132333435 6 7 8 9 0 1 2 3 4 5 6 7 82 2 2 2 2 2 2323232323 4 4 4 4 4 4 4 4 4: : : : : : : : : : :2:2:2:2:2 2 2 2 2 2O O O O O O O O O O O O O O O:O:O:O:O: :NN N N N N N N N N N N N N N N N N NO N O N DIDIDIDIDIDIDIDIDIDIDIDIDIDIDIDIDIDIDIDIDIQE QE QE QE QE QE QE QE QE QE QE QE QE QE Q Q Q Q Q Q Q S S S S S S S S S S S S S S E S E S E S E S E S E S E S 990 5 2 9 9 9 1 1 8 4 7 6 2 5 8 0 2 4 8 58995959285 2 0 8 0 5 4 7 9 0 8 0 4 7 2 92 2 2 2 2036292628 5 4 4 6 7 4 7 6 4 6 50 0 0 0 0 0 0 0 0201717171 1 1 1 1 1 1 10 0 0 0 0 0 0 0 0 0 2 2 2727272727 7 7 77 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 727272727 KS R AGQH F I F E YTVD SDR D AHSSAV AVTE GQLP IDAGR M H N P VR I KSYNFE VVS IESLMIAK L GL NSKIGL GH KE R AK P NL S GV R TDKL I LPR L L N RSNIVL QL WY L QN WR L E E VL LDNIM R L DTIQF VTN QLMRIN GAMF N R R VSY TL GAMMSVVL SE A FI SN GN WKTQFSRSL ACTP VL L CGL AKSF KP DIE GP QF T VFQLAQAFE L KKWE K GH AR L FIL PLASR AQYQE LIL N EPGP 0S5152535455565758571 SMSQVH R L R VLDPA P N L QGIS GR ALS DSIE DTARL KSCP GIYS QTP FIIL ATEIE VVR 22 2 2 2 2 2 2 2 5IKKWS F N VER :: : : : PGLSAVE DL TE KIPG O O O O O:O:O:O:O:L O AGPHI FMDPQH F DQL DD QIY AGN A NN N N N N N N N NL D TP M I DIDIDIDIDIDIDIDIDITL KESL SFTT K L R G G KAAVDGVQYL WFKAL KKQ L Y NAILIAKL E VPQE Q Q Q Q Q Q Q Q Q N DNS E S E S E S E S E S E S E S E S E S MSN ADT VH SKSE P L CVR DDFVYMPVKLL KAFD DL L DS Q F G DN TIL D D M K APDE F 0654 7 4 5 7 5 2 1 75453 8 2 2 6 1 6P 116 5 6 5 5 6 5Y 72717171717171717C572727272727272727 vD B Agcaaacc attcgt acttaactg aattt attcaatc agc ttag tgt ga acaat ctgt tttc ccc gg ga ag aa t ttcc tcaa g gg cata ttcgagaacg ac caac aaagacagga cctctgcatttttagtaacatctgta gtctacct cttcat ttacgt gttctcgata gtta tagtgtacttaaaagtca gtg c ga gccg gttctaatatgg gact acacactca ccgtt gtagta gttcata tttagc tgatcgaggctctagcttcaggtttag caa gta tcatct ctccaatataacct cc agc gttacatt attt cttcgtatgctaaag g a gtgac t taag ttaaa aa ttaa cggtt cacga caa cgc gtg aa ggat ta agtttaggggggaa ga cttatata tttcaaa cactg tccaaac aacagcact gccaa aa ggtagactgt tt ttc gcacaga ata ac actgt atgag cttgcta tcttacgtatct ttc ttcgct gt attca ta tc aagtg gtccagg gcataacaa gttccaa ta tt gtat cag a acttg gcgctacttc gcaccgctgatcaagttacggtttagaaa ctta acact tttc gagg caaact atacagacaagtgaaacgaccatgatt ca ctaagccgga gc tctgagg ttg agatcgcccgatga a tttcggtg cac agcagt ttgttctgttg acggacgacaattg ga cta caat accgggacgaaa aaatc a gt ct agag gatt gg gaaacgcaaacttccgtgtt acccagcctcagagttgtt gt gtatggt gaagca cc atttgcctttctcataggttccccaaag ccatcctaggttgtgatg tctacttgtggtcgtatata tatttc ta attat ttc ttt a ttgagattgtaag aaa aatt aca ttt ctt aa tgctta cac ccttatt cttc gta ct agatggt ca ct cgtaatccaggggaagt cc ccatataat g aat ttgt gtcatacgtgcgga gcagctagt cgct gttagagt tttt tcg ttgg gct a cc tc gtt att ct cttctcaca t gatag gg g gc ag c acaca gaattaccaggaatt ctctttact gagaccaac atcgaagtttcga gacgccaataaa tgtggacaaag acg ga atataag aa gcta taatcttataat ccgactgcgagtatgtact agtccg a caccgacttgtaattatagacgccacaaagagtgc gaag ccc tgccacc ga a ttgtaa aa tgtccatg cactat atttgtcgttatgt ttccat cgatgg ttcc tgagatgtgctata tt at aga agta gct a tccc actg cct gt caattt tcg cgtct gtgttaggaag attgt ttagggtagcgctc g actag tcaga aaac aggt aa ac ggtcaactatg ctgttaaccaagtcgg ggtacggatg ataggtag gtattttcgat gcctt ga tt aa ta cag ac at tg ag acgtc ggcat cggcataagcatgaaa caaa ctcatcaca gtt a gggtt aca caca ct aaatagtgatgttagc acattaaagttctt taatacgg ggg gcgtgttctagaa aatttgg tctgttcgtgttacgtaaatat c cgtgctc tatgtatacgtcga tcaac gtcttcga ggata tta cag cttaggggttcaacaaa tgagc atg ta ttaaatct gtatggccg ggag cttt gtct t cc taa tacgcag aaa tt act tttag ac aa22g gcacaa acttgagg gagtatttatggag c atgggttggt attcgc tc tc ta ttga ga tag tt cg tagttaaa agg acct5 aaa acaactgg tt aat gc taatagt cg c cctt at cg gtac aga tatatg aa gaagcgg ga aa :aag atta ct ac ccaaOatt aac gggttcctaagcaaa cgagaaga a ata tggttagtg gga ca ac cc act aa taN c ggcattca cc gagtt ca aaa g taaca t tgt cc ggcc aag atcagI acttgtt gac tac acga taga gtcaaac a t g ata atcca cat ttttg S YKNARSN L QQ F DKVNP S N KDGQ GASTGYPSQAGQRHFDIDQ P DLGIGID LIMHII DI ITWKYATVKQN YPTLGCQ F GFP SADFR E N RPIAFQGYDIE T L VVCCSSE VVVESL VG H DII IN H L ASGLILAPGL TS R R KVDN NLVQGADTTYDTDGT Y F H H R LCIE KFF F RNAT RP *VPS F AL L YQSVPGDSWV QR YKL DR FNIYL KPGIY L E L AI FKP KA TG H AL E DNFS GNTLKIGIH AGTAIAPFGVFEIMVR L MRES F LIPV AL DFL KGE QA P ATE N DE A AN NEESR GKY KQQGG L L R TYFE K DR R R GPQQE K TTPVSY G PQL DSLSGV YAGH ANIN N L R E DIFV L TSEWK RGI ITAESPQF S YTI I SL LER GSER KQRAFK VEIP QPMQDCVGS PE GKRIVTYYQ CN VDNS IYEMFE CG DDLPYPIE GNL CYTVIL YCL S S GL GYP K S VL D9L R L KP KE F AY H F P VDGIDDWE VY ADL V DQTYSD R WVKLPE YVIL KFLFA1T L Y VLTPW Y GVWH ML NSP GAILITFE5:CN L E L E QD E DKFD WS L AYAHA SGAIN L N D AARLISPQWIE RPKD KMDG O LL E WD VQLTLSK YYL YNFVEFDQMKIH N LSNLINTH GYSE Y N GDE R KR H KKIHDLV PI FQN E DP QL VETRTDLQIQ YLPDEIR L QQF L R Q D TL LPDILE LIK ELS FGQIN GT E SFN D N AR R A L S KQY F H VS N GN NS N TQL VMH KTLPGG F Q LIVDWWA YMA L A DN F D E S MS S G N H Y WG H T M N L E K E C K Y E D S K K D H G WCS1G X Egtt aa ctc c gt gc cc gctcaa aagtcta tttaaaccaagga gacg ttaagtggtg tcg agccggctacc ag cgg c tattttt taacttct gttgtaa ttaaa c gctcttc t cagacat ttgtaaacttctttttgattaaaagacaagt agagaacttactttactagg agttttagcct tagctaaa gttcg acca atgcaagt ttttcaaaga agaccta gatttaccagccaccgc gtttccaatacgaaaaaaggtaaaacaaataaccgtc ttgtccat at ta cat gcgaa c atta aaaaatcatcggttcagtc atataact tacaag ac aca tgccactctcaga agacacctt ga tg ttgtt gc gttttgatcgcggttgacct cttgtt gtctgga attggtt gcatggtcatt ga gtttgatt t ac ga ag catt aca catgtt tt ct g c at gacattggcataaa caaaatcac ctggt gtactaca agaa tcg gcaagattctgtgg ttgtctagtttttaaaaa cgc atct tagaca aaacatga cagaggcacttc ctgtagtttgggac acagttaagag acgg acgcgtcataacgct tttcta acagtac gttt gtaccg tac cacggtctgtttt catcatt a tt ta ctttcacaattcaccccgttatttttctatatcagtccagg tagactgac a ttattac ctccttct ag g atatct ggc tag taagtgtttttaagt aat ggaggtatga cata tccagt gtga c gtaa ag caa cc gt g tat g ttag a gt aat att aa ata aa ccct accaaa gaccc caatga aa tatcaaa cag ctcctcgttatcaacag ccgca tcg ga agaac tgcaagggc tac taatctactacgttgttt aacactt ggt gggtcc gtcct ac aa gtcctttgt gatccaattgctcttgctatt ca ctgttatagctggaaaaaga c tccga atcagt t aca ctac ctgta tggagtc gacataac agt a taagtgatcgg gctg ac tcgatc caaggagagt t aaatt tcgtttagactaaact aggt gttccg gtaccgtcaaaagac gacttgttagtccaag tt gc aactcgg aaaagg aaacactttcctag cta ca aaa agaattattttatctaagcat ca c ggata gcaaaggaaa tgccat tacctc acacgg cgaa agcccactctaa cag c aaagagtaccaagta ac cgaca ta ga gt ca ccgag catatttg atctc caactgagt ataatcggtttt gc attt tag gc ttcaaggcgcagaataaag tacctatata tgctgagt gatgtt cta gtccgattgcgg ccgtaactttcaaagtata tgc ag attt tactg ttactcgagcatggtatcgttcagtcc atgtc cac gaccc agtcatgatgtttactatg a acagagaaaggtggttgggaa tgacccg acgaaacgataaacgattgga cata cgttgg aaatttt ttct acagttcacccc gaaatt ac tcgatccaa tcctttaggtacctc g atttcat6gt taacagtccaccc tt a ttaatgaatgcacca caatattt ga ccag7 ggttta acga at cagcagt cgaactaca tca cat at 2ag 5 ttga :cacc gataatgcagctgt cccccc aa agtttag tagttggta ctgga 2ta 5t:cacg att tccacattctaa cgcttgtcgtcgt at aOtcggatat a aacca ttaaag tgattcgata cattacta taggtc tcttacctOtcagaactcaga aggat caaataatgttaaagtg gg aNtDacccttctgg caac gaa taacaatcgattaagtaagtccag tcgataaag cttNt ct Daccttgagcaa atc a cgttg ag ctaataag aI tga gtQg gagtatat ttgtagc gatgc ct acataaagctct ta aaa aagtccg ca aI taQaggatttc act ccgtc aatgctcgggacgacaE Sgtaccccctg ctt cat gtcgcggcg attagcggagtggtccaE Sgtcaccatg gttcctaaa ctc caatagcaaQ*TAAPAG G P TAAPAN QFDSWISSVHSL AVS P K K VDK DDFIE QYA N AN KT QFSVHSL AVS P KK DV D T S R DH DL CE FFGIF L L S DDMYEPGFFSK QSR DH DL CE FFGIFSDE G FL LHPASGH VQL DN TTVL MP VWPL QQ L LFLHPASGH VQL DKTTS C L KSA VTAVK YS E AL TL E L P N DV TNL LAIL KSA VTAVKE YSMAL TS QEN KIKTF GVIVIE LLMIR TTH NIIDPGF T KKTAGIGVIVIE LLIR TTTPH VTSKY N N R L N R TNKYTIREIDSAD R DL F KFH VTSKY N N R L N R TTK F E L T VPIF QLSWIRI SGLE E K RGIR E T GMEFL PIF QLSWIRLI SYCRSIFI STN R Q VTL GS TE SDMTQIP L L AKTDSIFIVSTN R QTE GSS DWD N GRIITLWIGILNWKFKFPSTL MQ VKLWVL M N GR VT DWGLNWKFKF PDSAIPRSL KAA DA AE VL E WDFL VNDIM R LI IAIPRSKAA AE VALWP32LILLSP PS H R KQS CR N QE KTVE CID42L LLLSP PS H R KQS KRGQGPF5MP ILHVFGITG L E F G DKTLPPLIGALKP5I P ILHVFGITGLE AR L:K O APPDPL TDEIPII FS VH QIF NSIY:MK D O APP PL TDHIP IIMGNL GPGK Q H KWCVS KF GL S QTQL R ARE MDRP NL GGK Q KWCVSKFGEFNT F DIAP IL L KFSAAH YQMMDQH DFL TKL DIE L D TKP G S P GEITP HPIDIAP IL L KFSAAH YQMDQH DFA H L AMDL QSL G AVVTE EPFCIL H L G AV L RED S MKL E L R KA T N K K Q QL YAE NIL DGQK L A AI VIIVR KL Y D R WK Q LEDL AM S MKL ESL R KA T N K K Q QL YAE NIL 31281284244747ttaaagcaaag atga aca gggacc ccggcgatatc gg gc tta at ttttaccgtgttta aaatta aaaagc aag atgagaagtatg ccaattacgttggcacc cacttt tca ccaac attat ctacttctaactaggggt tttaatcagctt gttgta acacgc tcaaagcc a tt cg cactttcaat cta atga gt ctcccag ga aa a tcct g ctatatat tattaa gtt ca gagga cact cttgtttgatct gttgtgtatgg ctttat ta ataa gttgc ctattttgg gg t gctttttacc ttaa ggtt aaaa ca at ctggtg ccgtacatgctgac ag aagaaa ttgcg tg gt gttcttgttcaacat tctctac ggtt ac actttga gg cct cgtaaattaac atac ctggtg ac aacagtt acc ag ag acga gcaac ggccgta tccg tt cttagattgattcaattttccg ag ga cgtaca cggtctcgactatta cacctta cgt ctt ttatcgcc aatt c ctt attcag agcctatagtgcgt aggttc at gggttt gaaatc cgtt at ataatt tg ggagcta t gttcaa ccgtta ataacc gtta aca c cgg tgtcttag aa tcaagacagt agatca ac ctg tgtcga actcatgttataga act a caaaaaatcaataatcaactcctttgg gttccac a cc ctag agtgg gtaaggggtatt tact g caaaaagccaa ag gcct gaagagg ag ctg ata tttt gt att ac gaaac tctgatcact aa c ttt ttcccc cg ag ag ggatcagagagag acg agttt tg att ac ataaagcctgaccgct aggaaaa at t aattt tataaaacag gttgtc cg gtata cccg ca agaa g gcctt ataccct tagaaa ga t aatttaactttagctgcaaa acacgctacg cgtactccgtctttaacagtc agg at c ga ag aa aa gc aa gtct ga a ac ta gatc cg ct aaaa caac acag tc gatc ct aaagaga gaaattgag agctatattgcgttgatcagctga ca gagatgttttt ct tatcaacc gttcgga gattaggtaga at cgag cttttt gg a ataataaatt gatagggt ctc aa tcatttgatat cg actc t ggactatgact aaa gc gg gaga aagata ttaaatt gatag gt cgaatcta ggattatgcgggt ca gcta gtcta acta aatttagtttggt aactggacctga ct ca gtcg ataac ctc gctcctggca agctacctaaact gttcat cttgtaaaacgcttagaatacg ggcattttat attcacacagtcccgcattcctgaagt agc tcaa tgttatag tactgga gt ac ctagcgca gccccaat at attgac aacccact ag ca c att agct gta cg g at ttatc aa ac atgtcagtagca aa ataaatcatac attaa ttctggttatgattcttaagcacc g accacac t agtca ggtgtttct tagtgccgaattgcgg ccgtagagtt atta gaaag ctgcac ggcacaca agtca agcca atgtggaaatatttctcctac atta tt atttt catgccgtattg a a c ggaaa caa gagtaa gcaaccgattg tgtg cgacaaattttttc actca ttc ctgcc cagatc ggtgct gactg aag ttacc t c t a cct ca tatgcaa gttat gatgttgt c82tt c tcaatgactgtccccagt gct gt t t c 4ct gtaac aagt ccgt ctcaaa t5c cgttca at : at aacca ttaaa cggatttcgtc ttaaaaa aa aa ca gt c ctccgt aa t5ctctgat :ct ag ttgtcgacagcta aag tcaatO actt cg aa Ntactcc gttaac gaaaat atca tta c tatagctagtcgcact aaatg tcaatOtac cca N ttatgtctaaagtatc gaatgcg ggat gc tD cIctagggttt aag tgcca gcgctgctcaata agacgttaagatc c gaagggat gc tD cI ctccccgc gttga gttggacaacg gtgatQgcgaagE Sgatccctacatg gt ttattccaaa ct gccag gttga gttgtaaaaggacaacg gtgcg ataaQ g EtSgt ctac gcgttDFIKA E QG P AG K TAFAHPSAVP KVDFKAG P AG P KD VIVDML YLNAN PGFT Q K QSV L S K R DH L C DDIE QY AN T E FFD L LNPFSMR KV YE MP VWFPSQQSFHAD FGGH QLI SDTVMYEGSKVMP WFQQIAFSL L L L L LPSVVKDCTL L V P L L VQNL E DA LAL KSAA S E ATL E DAL LAPGH P N NIIT DNPL GTIKIKVT Y VTIE LMIL TH P N NIIT DNPL TIE R GNSNIREIDSADF AG L FFGVITSKYL R TNN N R TIERIDADGF AG L F KI EIGSGL KR D KHV N R L LR TLSKR D KIL R E EGR MEFE TPF QWI I SG EGR ME A RMTQIRPITMQL AGL KTDSILIVIM F NSTN QSTL GR R VTE GSS METQIRPIPDTMQL AGL KTD AMM MSS WL KLWVLWGLNWKFKL L KLWVL L L VE VFLDMDI INISAAFDAE VFL MD E L WD KVTNIERIL R D5APL LKPH AE V Q L KR N WD KVTNDIRIL D9 DIAM QE VSKF G A2LFTLPPLIGIL SL S R KS QE VE2MAVIILKP5MP ILHVLGITGLE N KF G TLPPLICALKP5SVC L SS VH QF NSIY:K O APPDPT KL QDEIP IIMS VH QGINSIY:O TSSEGIQTQL R AR DE MDRP NL GPG H KWCVS KFGL S QTQL R AFR MDRP N SSYLL TKILKP GP GEIT P D AP ILFSAA Y QH DQFL TKIL D KE GP GEIPD SAVL DE TPSIIL KMD H L DE TPPII SSAVTE E FCIL L H L L G AV TE E SCLSAIDGQKVL A AII IVR K Y D R WK Q LED A S MKL MESL R KA T N K K Q QL YAE NIV L DGQKVL A AII IFYI IR KL D R WK Q L E S NSS M AT T 7128R 24T 4A7tA aaggta tggacc tctacttgtgttgatctactgtctcc ct tact atagaatga a c gg atcgc gt cgagt at ga catatt cctt tcgac a tagagaattttccgttgaattgctgtgaagcaacgatgctattta aagcgctcct ttg tagta ttgat ca at cccatgc gcta acaagtccgt cc tctttggt ttctg actcctgaatacg ggg gattaaaatt gttaccataattggtcctttaaccacggt aaca g gatgctt ct gaaga ttgagt gt agt agtagca tgcact acga tcagacgaga attagataa atctaaatcgag tttca gt tccaga cttaa gcct aca aaa attcggc aagacgaacgata ggtaact ttgag gcaa acgcaac a tatg gccgtc gtcgtacttga gacaccg a cgct atg gatgt ctcacc gtcgac aggac ggg gatac gttagacaaaac aaagcaa aatc gcg gcta aatgcc gaagcctctt a gttaggga atcatgttgtgta gttg gcattc ggta ctgaggttttca gttc ctcta tttcgc gg ctgt acac tcatatga gggatcata agaattggtaagaggt c aagc a cagtgaacacttggtac g tccatccggag atgaccataagtaatgctt a aactgaa agag acacccttaatcctt atatctg cccggataacga ag atggtaaagatt g acggtgtcacgt gtc g ac a tgtagtgtc gagg ctaa cggaa ggaa a aaaaa tact agatc gagt aaag ccaa ag aga acccgcgag atc a acaa gggag g ttg cgct ggaa ctgga ttagaat ct t tcgac aagtt agcgcgtt gtaaacc cacggtct cgt tt aggtttcaaa attag agga tcccggt cc at catgattgt ag a atagctcc aaacgtac ct ctgta aggtcatcccct gcatcc ccagtcggg agtaagg atcca tgca agtt ac ca gtagtat cata tg a gaagcgg a agtactacta agg ca aa atgtttgaacgttgtggta gttccaagg gg gcagtaa atct agaggtt gga ccaaacttgtcgacactaacgcgtataggt agc g ac at tg ct atga ttga gtctgt caaca attttgaa a tcca a g agtagagtttt agc agcacaact ccaaa gttcaagg aatat agtttttg ga gtt gtc aa tc ca ctacct ggattc cgatag caac gcttataa aactac gttaagtac cactaatgac ag ga ctt aagt g tgggta ct at tgtt cag ta gc ag gg caat gacaggg aga atata ga gggtg ata tttcgtcacagct aaacctt ttatctc ttgccgaat cgtaa ac gtct tc ccaggg tag caactt ttaccga ac aa gg gcatcagtatc gcgagct caaccatt caccttaatcttcattggag ttt tggagaaaacactaa gtctgc ggctttaatcctacgtaa cac g gata aaa gc ggc t ca ccc gact gggt acctgttcat g gttaaagcaactc tcat gt cttag cttc ggatt atac c ca ct tt ac aa ac tt gtgccgtaatagcttta tcgagcg cttgt t tataa aacaaca cga c tgccacgcgt aaaacgctacc aggtaa gcgtgcaggacttc ttgta tagt ccag ccgag tcta taca tgtg gga tcata tt tactatt cg gt cgg aattt atccaa cta tt acgttc aagccggttgcattaaattg cctaagttgt tt caca agcc gg gtagagt tttat gctatc agtcac ggaaa gagattccatc c agattcatttgttgaaaatg ccg atacg a gggtacaactta aacccgg tc caataa ac tt acgctgagg gtgaatgagaagt gaaca atttat cttccaaga t ggaggca ag gagtagttaag attg gcgtacatgtg74 c5ccgaatttact cctgatt tgatt agagtt ca gaagcaag gacgaacgta ggt ctccaaag cacg cccgttcctt tag tgtgaag atta gatat :aOct aacc gttcttttgcttacttca cctccgg aa agaagtgtatgtgtttacaaa g ctctagaaga acgtagcgttgaa g agg ctcc tctctgaagctct tc agcta N ta gt tac ctaa atDaca gt ttttac ca gttaggc tctc gggtatca tg actttc ag tg gg acga Igctc t ctcactag gatcgttac t aag g aatgagc gtaagt t ctg cat ttgc at tttaa g g ag c g t a g tgggagca c cSa c g g a g g cITKF R DNVE S N AVVVME M E P V A VPKGFFF FDVD N KDGFKAYMCP H VGL E YIILFRPE V MF MGG N DE TE KYL P STHSLRITAGNE F DE AVTL DL P A AWAA F CPVVF R KKE TE E A S TAF VPLHS PIA RTKV DETH GL RLDN E AGFL K S LPS F TV VAKGH SSQ A K D D Q K S KPMFS KSR SVE EKFEIS K R P AYV N E L DTIPDTKQR YK YGT GL P VE GHIDVE VGS GFATT V RKR KWQV DYQDHPAIAL L ES ADL KS P R P L EE YE CD DLKT DAS TT VSVK S R AR AL KR LIHDSKGPTML A VMPFTDPV A KYVES FDSSE WKLYIKYSSITIENN EDAKEFN L PDE R GR VQ AE VIKGK TPKAAAITF R FTPL G*W F LQP SS DLPYT KAIE E L WR YA QL YDL HET GPPSS KSCN E S QDGY AQ GQL E V GSFN DNSN KVRE GE L E AGDNFAAEF I SSP PVGE L VTCS L DS E L AF L ESSVQL ME GR F R R R G S QQDM AF ARPV NMFDS F P VVA L VKGRERA D QR V N L ASKVGFSIL LP FE S L R L KPKD DTG P YE WAYR DK H GDCE CKMISHIFI RFN R AITY03AKDVTS V VTH LKIAFAE KVLAATNSE L AA YL VYFRPP CVMH R S N LG 5: FL AL W QDA N AE E TLAVGA YGL NIT DF YGP VH R E GLR E L R GASAL GFLWS RSO T STSSDKETLRS PL E DP ADGKDDPTN T AH VSF TL ALPTPS CGFEIDH QNP QTS PTDS L N S K AEDSKTD L VDL GL YTWVEIA VML H E DYTAE TTSQ P R L MN TL A QR KEGVSLSVL D AADNIY DEQ EASE QPDIE ADDS E DEP TD E KCNIR P E SPP KR K S VKIL KL KPE Q VA L G A QA T D KG TD P R L D S S E A Y KGIGGSD A V E S M NIIP L N D V GVI4N C Gttgaatttttatagacatagggt aaactcaga gt gta acta aagatcc a gctacatc ag ccgga atc at ggatataatc cacc ta at aagaaacacggatacacaatt g ca g ga ac gacatt atccgtgtacatg tgtgtctcc acttac gtt cactaaga tttt ctta acag ccga gataga ga atatagagtaact taggttaaga atgtag a ctataag ccgcttccgag ac gg g ctata ac ggccgc ctatacctccc ca ttggg gttcagta caggta cagcgtatct aaataa gcgttcttagtcg acactcgttt c aa gg tc gctcagacttatcaccaaca tcgctgt ctcaatccgaccataatagttaacgg a gataacgagt c ccttc atc caagtatcctt gtggtt tttc ccgtggacctgtcaaaagac gtatt ag tt catgg gtttgt cgt a t ccatctcaggt gtc cc ttc tata aatatgg ccgatacgtaaagta gttat a ttcgaatttc att tttc tagg g ga tct t ctta c aa accatttaggttc at a t aac cctt ctgg gag ac ata ag a g ca agta atatgata cga a tat a ctcagac atcagcgttcatatttca taaggc ata gg taatccgtc gagtataga gatgac taa agcgccatcgcacg acgata gtcacaaa cctcgtaccttttctaaat gtgttctgc g tgaaattaaataagtg gaa aagttgtgttctggtacacag taagt gagt g g ttaggcgt ac aaatacagaatat gag aagtg tctaaaaa tcaacgc tatgtaac ttgtt at gt gccaggattc cca ctatttgatttgacgtaagacc gaaaacgttctgaca ata ccgtgtttcccagt atacata ct gatag gtattc gggcttacgatac gtgatt ctc ttta gatagac ct acga cctcga ct cgt gc gaacatg ggtc cttaa gat aggcacgttaa gtcgtttcttttctta attt cagtcgagg cttgtcttttttgatacg agc ggtctactaaaa cact g tcacatg gtgtagc gtcg aaatccc caatt c gtgaaaa ataccaaagcagcgtacctttcttg atgccca g cctgcaaag a ga g ccca ctctactacaagcaatacgttctcaagagtgagtcgcaatga cc acct tttgatc cac attaagccccta actctgagaacggtgtatagttc atggact gt aga cc atatattgaca ttagctagga aaattttctagtcaaa tacaggaactttagtat aggagtaggagatagatt a a atttt atggac ac ggat caaaaaagtgggtatcaaagt gactcagtgt acc ctttagaataattaatgt g tcagtacgagcttagt gaagt ctattagctaataaagttact agagtt a ctcggcacgaaggtatag acc a tccggaat agata tccagcgtt atagag aaag aaa ggagatacacactctccg caagt agaaattgaaaatccag cta at a ttca gaggataag gc a taccatcgact cccgagaagtattataacagcgttgttt cccttaatggcaa aaga aacc ataa aacaacacctacaccta gc ag ttaggt actataa ctcataaatta 0a 5ataa tcactttt a ttagg ctacgagcaacaa 1a5c caccaaaag gc aagcacc cttaaagagatgttgcga tcccac cgaaaaaacaaag5t:ctcOtt acaa gN aa a a c ttagtattctctc g5tc acgta ctataat :ggg ctgga gtt cct atgatt cc agaccgct ataggatgt caa cgtata gggagaO gNttttaaa tt t c ttgt ac cg cag gtacg aa aa aI g c ct ccDIa cact t at acg c aacQa a a gtQctaataggE Sgtaaacggcaca atttggttga tcttcE Sgta gttaat gctagtaatgaa ata at acctgttagcc caatacccgaggA C S L TLIIMETDESE V IQ L VCTGL QV VKHE LFIGP QFGS IFFTQGGIVP PN P TYDQN DR VPSL R R N D N L R E H TN YTTINSASN YQEFE DVE N V SIWRQE KTGL HMN K F V L VYGF LYF FE H P GDTF PAPL L NS IGVYPL L FH ACLS QYL N TMN VV VD R AC KKPFTTHKIDKL VAQFE L C EHN QN AY NKPSKPHIGDIHDQ SIDLGSTT AKL M QKIF S H QAKQFN GH R GNK VP I DYDLRSLIYSYDS N N N E VV E L RLGR FSR V H KPD QCDGYP PN VQAE QVL VP R LF E VL ATDR R VPAGDYLIHDGHIG R D P RI WY F N VYR YDE V TR VG Q TL NIRPVFHIL YVR YD AE K GMKSL VGK R TSHPKDFAP R T MR DGIS KLSNF IYE NSF R F M DPTH NS ML TPS YP P R GDVNE QFIDSE K NGIR MVVAGWFQDYV S DNIL N L L V TPR DGQIAH DQGA K1DSEIKTGKR VHIE S2E R Q QP ASDTD R DGAIYQ GFAARI IYPLDR35EQIDSKKFQ QITIVT L K35N TIN N GAN LSN KVQAD AATSTNEL E:V Q R O DARKN S KTR:KE VFECI SGYNFLK N TT APQYPNYSAKQG DKVLN K VFEIYAMAIHEEH O N QPR DKVT QI SEWSWE VSFFQ F KWQMK DIISNIN I EVR K P LILN TFMN VLSQL D GENNFTIDWPM VWEIP V KQLKDHGL KPDCYIQ T FIL KIP H DGDN L R QKTY L N TARSN YPPQQL QE QCN F N L DDGDR D D QSN ADTG VN KHIYTN GLFF AAA Q LIK L R S M K G A V V H H Q F E S M GL S V T G Q A H K N D F N L Y P YAPG 5 O1R AT A Ctataaag t cacatttata gggga ttt gttag t ggaggat ct aaaaa aa agttaga gagtatt cttt tta atttagatattggtatcagtcattcgtctcaaaggctagg ataa ata ttt gaaag ggta a at ga ct gt aa t c acg aaat gt tcat atga aac aagtgcatcg tcacg acgttgt c cgaaaac gtac c aatttgagataacgcta aag ga aag tcacca ctgc acgtt aag a c gtgaacggaagtg accatc ataaatacatgggataacgagtt aga acagctttttcgtgattgatcccaa gc agtttttgaaactat gtaaacccgctc gg ggc gt ggtagaaacaaacgtacgattcgag aacagt gatctca cc aa gc ttaa tggg gta aatgtaa atctacag a cacgtatag ca ca atatgacccaccgtcgtgtg atatagctgacat tcgt att caaa gg acaggt ag atga gac accgttgac gagat agtgagaaa ggagag tgaatcactcaatgtctg tat ttaccggct ggt gactggtagcc ataaccaatacgcgtg ga ctca ac c cactataacacgccctacc ggtattcg cct cggtatagaataatagag ggttat at at aa ag ca tggc gaaact gttg gt aag tag atc ctgaac ag ggtttcccttatg ataacgccaatttccttgccaa tca aggtcaaacctatgctt gta tata atc aa caccc ctcatatt ctctaa caagtcgt ta aatcaataa cgtgatcg gaattat attt ttt aaaaacgactagatagactc taacgttagttgtgacagccgcttg agtataac tgggggtct gccat cttgtgattc at gaaaat gtcatt gt tccaaccaaagtgt t tggaaca agaa g acc tact gcaac cggagaaagagcatg caaa aataaca cc tttcgcacga atgtgaa aaaaatgaacccccccag ttatag aac aact ga attctgcta atttggc taagca acctcaataa agggc gt gtcttataac acga gatgaattta cgtttttatagta atttggta at ccgaaaaaca a aaattaacac agcctcatccc gt atttta a g ca gtattt a a agagcgacg cc t cagagcgcaatgtg gaaa agttaaaag tttc aatca catagt ttg gta caaac g a tt g tt agag atc c gtttg aga ct aa agccgaacacc aa c tactt ctgt tcgc aata g at ctct gta g taggtc tttc ggt caaacctc gtc ca gaatc tctaacca aagtaccggctgtttcaa g cgata gtggtgggttctattc aaactaggt gggagat gtttcttagatgaa attct gaagcta gattatgtg caacatgata gttaat acc aa c atta aa acg gaa ac tttaaga ttgtgcgtaa2 gt5tatt gtggacca gg5ccagactattt actca ttccccctcgaattatactgaagt cg ga3c aatgatttttg tatt ataaggaaact:ga cggOaNt t tc atagcga aagac tt cataatagt atgtctgagttacattaatcattt5c5:gaacacgagtgaa ggagtctcgta aggctaag gtcttaa tctt tctgcgtccg at agcaaacggta gccccgtgg tta ataOcgccttagagct gttagttac gt tctDa aIa agg aa tatttg tagcac agcacgcc cgg catgcgccgctggtttga aNaagcagatDcc cttt ctgc cggttcggaa gt atgQtEg cagagatc tc a ggacca attcgg tca gaaaa gct ctg tattttaa t ggctaagIt gQccgga c tga gattaaa agat ggtatSgtaattt actcc gtaacgaattgataacag gtaag ata gtattg atctacE SgtagccaaatgcagggagaTLLRN E R I QIYKAII E N L AVDL ADKL R HLSN AI GR TIR WYGIR RK WPN D E L TK R MN L KQ S KQE LP TE L VE P KH KCML KPDSGVFVE GTGT L N R AWGE P RRGG L Y E TTP E GSR KVFIQKV YDDYIRIML DS L T R P LPIWL LDTIMPGG F S PTSS PTE L VE DFKAITAKIH QGE H L S F VL K D QATL F GAW QN P F LFIE DKTTDSFMKNAS DPIG N N TNIVAVS SH R E P S VN E D LKP A SEFDH AWPN LPLFIMFQ ATP AKTVVGAFD LIS KHRS SE AITR F DID W TYPGQ H K*TLDIL QG I HL R R TQ H K DS AM C KG PPIS YADE YNIG MN R YF VEEIE WTMRMA DGK S VATL K EIF E MRMYPDL T DL E LRIP L R MGINTVSTSV VA A YVIY YMV KSQGWEELTIDAREDMFGSGPTTAR VL GH TGTG FIR CVMDVKL QEPD MDIQFAKPDES33L E DA DIH A L N T YN L V S EPL D5A L:TLPVYLFERN A E WLLF P4D DEIKAKIE L TDMITL D R R H VN NL AQIKYK35NKIE YDVAR KF FO N DSAA GN N PLFISKGGSN VKCIL E CAKA:TE A O TQ ATMGL CNDL KQ V L QL QR APL R S P G R NPADSMRS TA ASPNS P K N MTFNIDA ADI SITL NWAGSISIYP H L E VR MLSY LTL QVE L K KIIDSFFDKL DL DSR TN P VYIDPEFM GRIH H AAT P VL E PTAFIEI AGKDQAL RQE VAN DL MDDYS M V A N M N K L DP IF QE CTAE H HGG D YP L N N A VIATVKD QPP TKCQN AG L VN T GL D A K N Y E S M R Q Y KD L K G7L1AHDPGtgcgctct ggt aa g g ga gagtttctactatcgtttta g ttaaaaatcattagtgttatgt cg atttacag attgttg a aaataccgtct ccttaccccaa gtaaag ag attaccgatttc gccgtac gatga tcta acac ga ggg c taattgct taaa cac atccata tacagaact caccat c atttt agcaac atcccta gagagtagcacaactaaaaca cccaa a aat act ga atttt aa gatac gttt ggttatct tttga tttaaac cgcta a aca gagccagcg a cggtagtc aaggggactccctg tggctat ggc ca att ctat ataaagattatccgtaagcgtg g gc tc gagaag ct c tggtcagcacct atttcaaggaa ct ggggcttaaaa cgttt gtagatt tgc gaacgatcta atatcgt ac cc ctata aa ag at ct agaat aagt atcgcaaagatatcaatctc gcatgaaaggata tcaggc actaaaagacc gttaggta accatcccc tgtatattattactt ctcaaacg aagagaac cagaa tca gacg tc attgttgacaa gaagcg acagacctgtacctt ccgt gc tcc tgtga tc cc catagacgctt caacca ga aaaaaaacagt g ctcgtggaaatcat g tcgatttca ctt a caaga aca ggtgat gttaccaa tt gatgacg aagt ggcac taa aa ga acattga atgtc gcgt gttaaagaatt aagt cc aaatg acac tgtgaggatagt ata g tg gg ta attt tac aaggt ctca aggtgtccc ataga atag aat gt cga g gtaagg acttgca t aaatgg caatgt gt ctgaaaatatccac ccgtgaat ag atta tccaacta ggga gacg acctg tctgaaa gacttgaccactctttgctga ctcgccc a accac tc aca ga aaat aattt g tgc gg ataaatt tg ctttta ag agatagctg catg c gtc gtgaga aaaaacagagcagtatacgagtcttgatatacgcctcg cgatat gt g g ga tcatgacg atta ag at tatataaga agagcc caacga gtt atgtgatctgatgaggat gtctctgaagcagtc ctgacgggtt ccgatttg a acgcag ct gaa at ctttaact ag ta ctatatt ctggtcctcg tt ggcttgcca ctttt c gc ttga gt a ga g attcaacttcgtagaca taaaaga g tatc tgta gca cctgcgccaatacgg gct gttagcgga caagagt tagaactttc ctcta ga a ggttcgatttagg gtag gc cgcc a ctgtttt tat tt ct aactaaaa cg gc gta t ct cta aa cc g ccagctgatt ttg gg gttgat cgaaggacg c c gagg aa atat aa tgct attaatggaaggt ct ttcc a ag aa cgg ct ttc tgaa g t ttgag t gt ca tctg gtcaaagctgttaatc g acatga at taagagtg a aacggtaata ttggaga aa gttt ttatgtactcaactaat tgg gagactaa c agcacc caacaat atggtg tcctacctttcg gt aggt tg acatattttcgagtcacacataactatc gaaacacatgcgtctagg a atc a aact cgcatgta catt tatggtttcta gacactaa actacatcgatacttctccttcat ctggtggtgc tattggaa ggga ccggg gcgttctct gaccg ctggt ga a agaagaatatgga gtaaccacaagact tcga a tttgtttt gtcatattt tgccg taagtacaa aa tt agcagt cta cg ttccatta ca gtttt tttcgat aaactgggt acactat ctaatt acgga a g ctgggtgtttggattcttatgtagttat aaagcttag4 gc gcaccga ttcccc aa accccgtattgttatcactgtattt cc cgg cggcgt ctcgca aatatt aaaccct tcc gg ta agaggtga atg aaa55 ctcc: c cctttcatat cgaagt ga agtggaa tag aaggcaa g gtgttaaaagagtattgctaaaattgt aa g gagtgctgaa cggtaggttt cggt agggaOggN gacgcgctg cgcatagtattagaggacaaa acaacacaac a gtgaacaacg cgtt gacgtttgtac atgatt g tatgatt gtt at catattcaa ct c a gcDaIgtgttttgtctacattccta acaagtgatggcga attcagatg aattgtca at gtttgtaca agaa tac gat t act gtgcag aactcg aagtctaggg agg ccg caat gtg acaataggQggEaSg attctac ctacgg tag ct attgggct gtgtgN TT YL I VIINNS KSI EKQTGSKKDQKE F GAK VAFHRSV GN DK N L DL KIL VMNPS R DL DQD KSK R S TL DL F H YN G GGNF F IRL R ATPL NVFL F V E QA GQVKIN YNSE DVD L VS K S AADRLVGHLEPN N VF DR L KL V T TTL DKKSE KDR EIE L DTGIQP P L F L YDESF DF AD PP IWPYPKLVSDN KIKAGE HKE DGEF PKR R FNIPVDDPVDAYF P IH H PIE ESVSRFH GGFIL E Y DYDH L H TDGFDS KGGL DWLP VYFKVKYE AA MFA AYK HG VETIY E QE N TVSGG AN AK THPE AVDLILETYAFVLF IKI IN YVTVHPL AGSTYVEEVGVE S N AG TAAL EVKAKLL R Y VSGDKK KG N N AN YEYSV* FP K VDKDFR E LTKQYYFA TL TTIAQIHPKL AF F P L LGN QVVMPLL TARPS T VPSEL VSIL L YRIGFL R SE CAWW KVAD KATL QAHSLRNSEIGL H DE FFDVS PE VYHN GPGHPN PGVR AAWVD DMFQIMKKIE Q T LSVE GDI PI IEFQL ERIKK QGQRDSE V GDKV N E VIAL QY QDKL Q ALIQTK TL ANFMG GE S TV L GN SSVKL N53KRFR YD S VYNKVGIWL QQPFEL EFFRKWMN L A D L TLFIND IIESEIL WWI5:EF LSKVN VKQE R Q E DQ EIR D DYS SL YY T O KGL ARQAN WL AKT WP L R L K N AGL S YE D F MSSLFIR Q L VMGEIS NVSR L LWVNTIS E N S P TL VDR VYIYQL YIKVIPDIIGN L DS I NGVGR SN VY DIPL D AE KFKKEIE QR E AN N EPV DE H E N YIRPF SQE GPEFFAE S V R R H Y L KK QNIEILE GE E WRGFAE YVAMLF DH YNEE I Q S FTMQ K E KASYWPTN S Y GKSL TIEIS AN TT P K N V K C KVFVL S KH F C E S M KS L VEIVA L 1FW Z ac at acaaagga ggtgc gtgataa gcaacat ctc aattcctgttg tgtggctaag a tcaa acga cttgttagaa cg tcgtag gtgattcact gatcagaaacgt gtgtcgt tgg gctgtttaccgt gaacat gacggtctac tttttggactt gaat cgtc caatctctatttat agcccccccat tgtgatggactt t g cggacccgggt a tc gtatttgagtagaacg cgat tc acat g ct caggca at aga caaa ac c gggcaaga cactcc g cct acgact ca at tc cct tag caaggcagat catttcag actaaagctggttggt ggatt ctactaccg acggag cc agta ga actgatgagacg gtaatttacaaaa agg gag agctag aa gttc c tag ccat tt aaagaacagtg cca tgctgtaccttagatc tatc atta tatctatttttaacgac ctttt tcattgtctccactacta ataaccaat ga aattt gacttgag gaaaccgt agctgcg gca taggttgt attac agcctg g ta tt ggc gt aatgtccgactacggtatgaacgagcaacctatta acaagttt gatt ggaagtgg tg atagtag ac gga gcaggt ggt g cacgaaacaatgta c tgcctacggc accttgg ct c tatttc gtactccagggggtaagtt atgaataattatgctgt ctacaa ca tatacccat ggagt t tc att aa gc aatatg gaccact gtgg gaacgc gt aagaatgtttt gtcgtgtgaga aagggggtaatctg ca tgctgt ctgaa cag ggtgc tat ga aaaac acg ttg gc aattgctccc acgcgtggagcgag tc aggaaact acgc aatattttcttaaaac acac aaggggatttaca accac ctaagtagtttaatcg tt tt ccagggagaa gtt aga c caggt gg cc acactactggag ac ctaact gt ccagtagat ttgtggttatttcacctaa aa a at ga ggcaat a t tccagggttcca tcgagctct tttcg ggta agtgggttagaagactaaccagtatctatgtgacacg gt gcct acgt tt g ggcatttctgaaagc gacagagatggagtg acccacatacc ggccc acaa aggcctcacagatacaggcgct tcggg tgt gg atcgcgacg ctgtac gg tcgc gac g atatcagagtacta gtgtcatgttg gaac aacagtggacactc actt ttccatatatt tt cc cgct a ta at gc tcgaac gatt aatt atgagattgtgcactt gggta ggaat c aat t gag agtttac taac ca agc gtc a cg atag atg ac gagca aatt cc t tctt ccaca gt caaat ttag ca aa tc at cccat a a cattt ca actgt cg ggatgcca gtactcacgtggctccatatattggtt aggc agga aa c gaaaagt agaa gtt g cggtt at ac a gg gtctaaacctaggtgtcg gcttctt g catgcaga accaccaccgcgtcgtattt c cttctt atgt cacgct ctgg actaagac gaagtgtgggtgc gtgat cc cggacccgccgcac atggt aaactaggt ac agctcggct gtt cg cgattagcgtgctg agtac g gacat gtgta gtgacaatgtctacttaaaacaaaaagagaataagt gtaaccatacggg atgcaa 5g5tt gtaa aacgtatgtttcgctctgtga65 acg gagagttaagctcgt ggcattgtcaacca att c ta gtcta ctggtatac cc c a aaatgggc5: cttgtctt aactgcaag atagc gaaa 5 tact: ta ga gcaggtcga a ga ta gg tacttgtccag t cc aagat gagc c gtac cgcgatcc c ccOa tatcagg ct gtNat ag a caag tcagtacOccaaaNtg taga cgcggg ttaaag ccttgactcgacga tt atct agc gcacataaca gcgattDagI tacaggca gc gcctaaggctatctgaDaaaI cc ctttcaaacatataagtctgaagccaag gcg gtcctgaa taQg acaatctgtcc cctcQa cacgtgtgatag ggagaaccggtggtga gattgE Sgtaccacactgag ttcgcaaE Sgtaccac gtacgacgaaacgNDD RRIS S KAERIDTL R K LEIH L KD R VVKK KVA I N E A P Y KGKICL CE VL RESLSRISAN VV KLSDE NHIAK N S R QR S DNIWGE G I P YFL L A QDH E KQ SDQTAE TRL MNVI SN DE E T L DSGLEVE TWQSGH L L VAVNS G VDE VMRST P CLSFVKN AIL DSGHDAGA YSGI IEDMADFS GL CGN L Y P N VP E KTKIY DTF FE YGKDYLG F G GQL GY ALFY KF ANL YVPLKA VSRIS T L EFIKD S QL AS ICVE EPIR VHIVG R Q KVNKG ASIF GQGR D D E DKMKGY L AGGEPKYTGR S RLIEL TLLFVT N E KG NPHFVL DN R MD F PGG TDMIVTEPWKPKSGAAESVVA AESGHSLVIQL DT AL V KYGSFE T V K L DITPGAISIGT V NPPK G L H VAL AD QVD AVIDVAGL LFFTGR TLPDVL G GSWDR ANF L SPL KCIYGLGNL GTKDSL VL Q VVP IF TAKAD QNSFVDE VFKDE W F VAIQQ DGA6N VN VGRGIDA7VDEENPDFKSL K VL RML EIAD VWAL Q YDYPY35GE QWL E AGL K D35KW KGTSLLIN QAF A NNKQL K R KY L YE YVR RYI PH:O GVAKAFVWKKFVSIL H VASKN:TR CYWLID DESIK P N QASVFEKN VFN E G VAKV DVPAFTR O SNTYKFGSKDL LPIQN KK EIL A R AYNPTEPD FPITG VTL ELVN H D L QLGL V N QTE R L ELEVQVSNKSMKE GF IE DP TSH P MIT RSVDK DTYFIKAKAII TS PTV Y F EISSYFGQIV DDTVQL G E M K VN D L GDV Q AATQP Y E S M NPKKIAGVRNQIFA VIS SD Q TF A TH DS V T GV FESM A A YGAMVFE V G VIE 711ID P U T Bctaagcaagc ttg cgttgaagttcttga tg tgt gctaaatg t cgtttt ac gcaatctagatat gatattg a t ataa aacctta gta tt gtatgtc tg aatttcaggtgtc cgat agcat gtttag cacta at caca ga agtataat ag taatata at aag ctg taa gccttttatccttg ctgaataagt t tttt cgggcagttg cctatgctt cctcacatattta at gaggagtcc gcttatt gcagtgt gtggtgc ag tt tatgtggtgtccc tctg c a gt gtcagtcttcga tt ag ggctct cg gtg ggct gtcttga gta ga taggcgttcggatctgatga gacactttggtcccatgctttc ca attactag gat a gtgggaga tta ga catttccctc agttgggttttgag gacgc gtgaactttg aa at cgagacatctg ttcctaga cg cgaa tagactcca agaggaaatgttca ta aaaggtgtatgcgtatagggcaacg ta tt ttgaatg gttta tc ct tc tcata agtgtggt agtcgttcaga gtcacata t acaaatc gttt ggctg ag aa gta g cttg ata caataa cggtatacgtaaaaca aat ga tt cc tctc ttggaatcgta t ta gtcgt gagg tcgtgttttaatta c c gt a ggagtaaggcctcta tactgaa atc a acgttat gtacaa tttaaagt acacgaggatgcacact caaaa ggta ttcacc gggtgc attgtc aaaatgactt cctaaa cttttcctttttct cat c ctcacaggggt ttgtg atacaagga catt a at ctag c a agg tatggtga gtctctta tatcgtccg ag ag ctacg tacaattcaaagtgttcaaag cacacg tcg a cgagtgc cag gtgttttttctaacata tc gt c ac ctg ac tgt a gttta g ttc gtgtt aaactgat aga att gttca c agct g atctt cttacctttgacaatct cg ataagattg cctttttccaggaaaatatt aggtt gaca gtgatttga tacatga at tatt gg tt gtgttcttgggtccagg aa c a ga c cccacgcgtaac gttga ttaacatca taatttt catgcaa ttgtgacgt ag gtgcttttatat ggtg gtagt gt taaa tgaactgttttaagtaatcatgg a ggttgtgtt ccttgatagct ccaa ctt ttgtcg ga ggtattagtgttgagt ctgattcgtgtgttaacctt aacaaacagtacatggttgctagtagattc aggaccgc ccataaaacatt att gtgcaatgtaa aactggcgcttattcaattgg cagagcaca ggc ccgtataaaggttt a ttggatgcggttgaagtaag gagggaaagtgtggtcagcgt at aaa t gt tg gtat cca gttctt atgttgcgg at gaaggaagtt gtatggttcta tcaata ccgtcggtaa cacataa atcacggcgta ct a tc ttaatg ta gt acgaattattaatacacg 75ctcttc tcaggtaatcctg tttg tt gt a tatcttacatgttgtgtccacg8 t5c accgttataaactcagc actttctt aaacga ggttt5c:agcga caattgt at ac ac ag tg tcaactg aattggtatgttcatttct agact5: ggt tattgcgataaattt tactgaaggtttg ca cOgtat tN tg gt aacgga gttgtttaa atagtt ct cggtga cggtgga gtttttcgtOcg Ngaatca ccacaaggacaagc atcgta cc caaa cDIat ct tttgttg atcaca atg gcggct aa agtagaac gaaagaatcaagtcgDI ttc a ggccaacaaaggaacagtat gacta atcat aQ ctEag cSgt aaaatg attctg act gaaatgca tt attggtcccggc a gtctc tttgactgcca ttctgtg gtcgttacgtgcaa tattQtct g g gcgttE Sgt atatatacagaaaa tctgctagctgcgaaaacgag tctV E I I L E S IQLR G WSICTT D A R KN AN KNIE S S VYKS LSPN ETVR L K TL KP DKVL LTIE EE GF WE CYFGP IIIML KCL HTQIL QE DL DL T CFAPCN L L NNE AG GKE G S V W MDAGTQIV QAF HIWVK E T YSHF IL T QNNAIS L SPL DG QTVI ST GEIL TVA ML YRFI SDWL L PIMAE TYWI FLR N RSS L FADL A D TDASAKFASIMAAGTL F SLKLPH QH GE R EIY DL TGWYAS KGN K K GDKE AADML YPFIGMS P E KVWLVIQDIN VPAE DVDAL L AVVIN QKGE E N VMGSKSGN ML KQH E R YCIELGITKI PL YC DG TEAGTMN T R AAV YDFE KVGKQ WTIGIV DKVYFLLSSDTTIKIL RNAQKIMLPGVSD DIPKGAKRPKDE AKL T E VVKYNLILL KVTGIV G YS AL TIPTPKFSN GGIYFL KGIR GS YQE DYILVFLSL P KVS GPDE LL ARFVGG N APVVG LSVDIVTL GV EIPWR W TYKWGPI PL R GI 83E Q AVR L GAVIE HSKIYTK P F G TFPA93AE E RILTSMA L ES5:AKD TN E GKVWP PN TSACIE N R KSVK5 E AIL Y KQIELIL VGLQPIT TRIKVSQTIALRV: PY T Y TAIO DMGKIG EMFS E OYN L Q VMTCN L DNFFTE AR N DQLIV CGTK GGLITYVSTEDTNPPSR TTVEIVVRR LR DQ DIH K L NSP DAG F A S DL YCVAAGN YDGVT EFY D WVWMAG CLL MTRIDYK KNQAAVNPIL L KAFK QDVIDAIN HSFV YAHFFI MTI YIGTLIQE TIV F E TE AGGGKELFIKFQGP GGSYY QE L NSYLS ILI FL L K D S M L C AISAIPM VRIT G A R V F G T V S M E T W WFSG N W F 61D C L D A Y taacgaagatcacaat ac a cactt ggca cag cta gt tgcaaacgt cttcg a gata aaaa gtaatatgtgc t aattt ga attggcattcaaag taa cga gtgtttaatggtatttttat agag t aactaaaaagacccg atctact gaag caactctcga gtttttt aagtagtttaccct aaagaagtg tttaa a gaa ag atcaaaagtgattaa gtaattttaat aaggg ttttttggtgccttt ctata accattcctactgtaggtc g catg ag atcctcaaaaca aa ta cca cgtgt a acggtttc gtgtaatac gttacc t cgat tcccgt cgacaattaatggaggagtata gggcagt attgtttgtt aagtggt tcag g ta tgtctcagttctcgatggt gagagttt cggagc ata gagagagtttttgtgcaata aaag ctg ga acaccaaaaa ttta atgca taatgagcttcaggtaaca cattac aga gctcagta tg agt ct tg tg ctctgggttatctatgta aaacatccagat ttgggagt acattg ct tta gtaaa agaag aaccgat ca ct ttttat ga gataaaggt gttcgagaaca gg tt ctc atcta tgaaagtta ct cta taa aaattaa ca aa atcgac tacaagat gattcg aaaggt gtc acg tt tttcggtcaaaaaaacatacccctatac cgtaggatc ag gct cgcccgt g tt ac attctctattacagc ggcat ttgttta acttttag taac cttct aa gc tttgaaaggt gtct taagtta ga gttgtatgcagcg gaaactctgt aa g aggagacac ttaact c gcgatacttgca a aaacggcga agaactga t tactgatat tgtacatg aggag aac acaatccc cg aaagaaacg ctactcag aa g t a ct gttgtt ca cttatagaggcc tac ccaa agtaatcgacccatc catgttgggttctaa cg ag cta aaaga aa a ca gt cc ttggatt ctaattc ggctgatattt agttcaaacgaa aat gg gtta ac gctc ag ag gtaaagat cacagagtaccttagagagact ca aaggcc g gtttgt at agta gt aga a gtgt cctgttttagatcgtcca ggt aa gagttttgatcaggagttta aaaggt aac acaa aa acc aag agttt tagttt gc ga tatagatcagcgccaaaagaag caatcagtttaagcaatctgt gt aagttgccta g gactaaagtgtatt aac agac gtctcct att aa gggtt tcagcatttatggag gt ca agagtaaa tcca gc ta ac g tattttgagacctgg ata ga a agccaaata acctagttcca ttg ca agtc ggttca gtttcg t tggtgaggctatgtttcaa cgcgccaaagttctaat ggagtattttcat cttga ttct gttct gattccaa aga ggatg ag ta acgt atacag tt gc g aggagaggaa acgtgaagtct ttg ttgcatca gaact ctaaat a ca g tttagga g aga cag gtta aaat ggtcatct at aggaat ctt ag gcc at gtcgg agctat aat gtt ga a aaacaa a5t: gc ggc ca cggOaagaN aa aaaatgc aaagataaccactcataaag agt atggat :g Ott a a a gtt cN g gtagcagacgaaggtOa cNgaca ctttctta c a ataaDIgcg gcac gaatggggtgtatatgaa catcg gg DI tgctgcggag cc tcgttctgaaaatcDI cgaaaaactttgtgaataaacQaa ctaaE Sgt ctttagcagtgatgagaa tc tta gtcttcaagaca gataacgQagcaaaagaaagcgtccE Sgtagtacaac g agt cat caaa atttact ccac atQtct cttaagtgcatac ataE SgtaacaacaF L E E I R Y AD L GKQSND Q L RYS D F I E YNDN E E DKSN QAP LSK M NSE RFL M L L QVIVPLIDM S FGFYQL E VIL WL S L E LID L TGLIGMQ R E E K L E C KKVE ALSLRL GPIQA E AIIYNGYKAD S TP N VKS N DDE NNEDIKKKT VE G NESAL YR E D AVI SGM KSSVQPP HFH AKQY TQ LYH GH T KMTF SKNMT N TE VE EF PAS FILIGID P E E DKME DKL ELSR N D N FPD EGQIKGL AA H E N EFLFTL DE E A P DAR Y T L WE S MSE L A LFR L N KTS D YKH KK VS KSQIDPWFL GN LLESL KCL Q TGN L E E V KL L D TTQI PDTVGSFDEYP IKD KLYKN DEVGQSE K P L LSEP SL V HSH K DPNNL R D VK L N DN QSRAH E S N Q AKKL KEIKWL EVQSEKSE D MH E A YN G TTESPVQKLSR H KFYYL T DYE EIVEST AL F KIGL R S E NDEVEMN E K N DS N Q DE KR S K YH DSVP D0F F4D D5FS SN GQKKGME KR : N GEIP14DCPAKAAF Q GRII24YN KN N N QFTGSQGL N EPD5:QDDI VINNICVD5:WG QVGI FYGV O DK AANHPGPE D S N E ALEYOSASL TN E KN L G ODPDLVSVGWQTNYQVKVNAVIKQIDG N GD N KIWFGALEE PE E GN QQM I AESTR N D EGWVTIFIIN VQMKSE DVL AGLSM QTIF WVLIE E DIVQR N QSTS D R Q DIP PNIP Q NDGN N T AVIE QL VAV KDIFASE PSLIFE RTLL KG K L GSMPA ESF E E VDD T VL D DE L D F VL M Q T E K S MFE AD Y QFN E G G Q S Y LE DA G EVE KDFN E S MQPWYP91 4X X2ESPR G D Lttggca ttattga ac g agtagtt cta tttatat ttcttt ac tta agt g ttaa caaa a acccg agttgagga gcgtt gc atg aag tg ata g ttg gggcatt cgttca gg ttagcaatggataaa ct ttc aa cac gagtaaacattatttggcgt attctgtaatgttgc gcccgct ct aaaaact tctttt att ct cc atgt gc gtggg tt ggta gc ca c cattagatcact g t gaaga a gcatgtcgt ttaatg aaaattaaa ag gc g ca gagtaaac ta atatgtta at atcgtt ggtcct atcaattt aa acc aggt acgtaaa tagtga tgc g aa aactg tag gt aatc atcagt accagtgtccaggcc ataa gggttct tat ttt tt tttcgatataa aga gcgt aga gt gatg caatcgt c aatagaaaaatgtttaat aggt c agcc gattg g g attaccaagaaatccatttcctcgaa tg gttat gatatag attgaaaa gaag aaacaatcaac attacagc tgatataacgttc at ca cacagaattgtttta acagccaaata agt g ttagggattgtg ccc ca ttaag cgagatttacgct a a tag cg aag cggtgt gg aagc ga cc ga aaaaac ataggtatc ct gtttgtggt g ct ttttccctccacattca cgct gctatgatcacaatga gg a ag cagga a aa aaatt ctattattgttat gaacgaatataa tt gc ga gtgtcgtat aaacctcgtcgtttgtgca act gc aa acctt acgataatccgtt aagcttactcgta atcagtcga gaac aa actt atgtt acctt ccttgatgtata tctcccccgtgcctcctaa gttttagctattggat ctttct tagtagtcttaaaat c cccggatagggtg at ttgtatttaatg gcatttaattgtt g ga tc tg tga tt agt gtctccaacaaat cta ttaata taaact aaga ttgtagga ttgttttcttttc gtgcggc gtctac aactatacg cttgtt ttcac atcgg tcggtt a ttcaagc t tctat aactttctgttgtt g tatt aagaaaaat aa aaaggtag tgccct gctt ga ctataactagacggtat taatt tcttgtcaag tcaaat cttaa aaag aggccga gctt catacaaa agtac ctt ag gaacaatg tttt tacg a caacctaatatcacgat tc gga ga tacacaa tatccactta aacgaggtt cgttatcc cgaa atcact ta aa ta aacggta atct gt ca ta c aa aag cgtgg ctt tt at at gacgatgaaaaa ct cata tg aaaat aagattaat gcctctc ca ttactttaat atgtgaat aact gtaacggtca ct aacatccaaa gtt g ag cgtc at a cttggggt accca acccgagt ccct aca aa agtggtgatgtgagatctcc gtgtggat aa gtggttccgtagctattactcggcggat gct tgt ata taactatacgccc ct ctctgaa gta ccga acctga ga ga ttcgggcttct gttaagtaattac tc agcc at ctga ttagacatct tctggcttgtaatc gcgact ctctat tttgacta ctcaa g aag gct ataacc aagtag tccatt ga tgctactaggt gtgagaagagct ccttaattgca gt cc aag ca cg acttga g a ttggctggttg c cc gttgg ccatat a ttacggaa ag tttt ct 2attcttg ctc actgttttttttg a a cg a gat g tac6tggttc cgcta 5tc : g cttac ccaaOct aagata c atatct tc ga ataacta tt att ta ctgcgtat gg ttagOaatctgtactcactttgc ttc ta attcttgacNaa actt gcDag gttacg tc agctaatgtat gtgatcc tccccact cc aaagc atcagaa NttaDgt cataatctcttgatgctga tttgtgtcactaccggaIac tcccQaEa gttagt ct cag cagcca tta ttccgtttaac taca caatatagt attctaag a g tctt a gcataatc gtc tt cgt aaIttactQtccEtcgaactt a attat c aSa gctat a c a accaaaaattctc ggctcStagcL GI TAFF L F F PFF I PKL GPPPA H YH H MPIFI KIKE KF S EVS P ES DIL LS SE KGELVTFLSL GVPGTL CLVPVTLFNIPSSFTPFR CTF IQF VN N AQSKSGFFFMLLIANIN TAKN E WD E VF R G DSFTIQP TPNIKPF PHSTKL P RSIC D L QG L N TRSPIQH AQINPT R N R YTWE L L N AIH Y I VPI FYKGH VGSPIL GE L CSIS P DE D RIS ME YKS EP L KD R KH R NIE H G LFIH QVWSV N TSYKIVAVL GL H LL DQ KL L Y NCIYQKFETL L YITFDV NEIVFNS GKGQ P MCMESYVILGKIQIL CQE E E S NIKH D H L QFVPT VTL ALPGLL QFTSKTVSLF PVSEPR RSL EFGIGQITQ QAL NL E R VDSIPE L AE F YSDTWYWA DQS CL TLKSLLVF SK YVIA QN R VTP DL Y QL AYVYL H E L DCEF RFNNFG GGF V VPKIFWTGF LYL WSVALTYGS SCIISE S TK KGN YE GR AIG N L YNATKL LL LPLLG3PV YL N L G S YK KL R P EQIL M P QKL R L GKDML AE L4VTI SIR GSLGFEFWSVT45A QL QE H KS R GKFIIFV N DN KR DHGCIGA45 TY TIF TAFLMYKA GP:N DD L N E RNEWSDQTRSYL DSKFF MN LIAS KK: PVHP HFAYFAF VEE O N KEVTPQKF P MDYPMIKE DMH KR YV NYIO NSEAVMVIYGS IFGGAPE DDSCW YR L E G LLYR VE TCKPR N AGDDFKDK ATS C DDID RIYMKN YTA IIE GDTSILIP H KRF M CKIWDE N C MDSCLILL MFL AIR Y GYGPQ N M R S P L L YQGFNSPPDIVAK HPLSIRL VPE VEE Q S V L L P T VW FPSVIFP S E S M R E V D K Y V T V G Q L Q W A K E G L E S M K 11FT M A G Pgtttggtga atga gtt t ga aga aa caa cggtgt tcgtt tcgatcactttga g cactccta ct at acacgat cg ccg ttaggatatcgagaaagctgtt cgatgggg gg agt a tctt cgaggaa ctgggattcgta aatttatc ctttttgtagt gttg cgag tcaag tcaa caatctaaca aaagaagacgt ttt ct ttggac gtag ctg cc ata ccg tggaagca ccgaccccgaaaactca ttgctgtttgcacgattacaa at agcgcc cata acac t tccccc ttt t caaatatgtttaacgcca ac aattat cag ggacag aaatcacgttttagcccga ctgtct aa tggga tgataatg cttca ccgtt cgtgggtaa cccattgtcgtc taataatt cttagatag ct gcgct ct ttg accagtttggctcttttt agcggtgatcacaca aaa aga ga tataccgcttgatgtg tactcataaaaag acggtatccctata actgaat tcc ta gtgt cataa ttgtgttccgcttt tc ga aggtt g g acccaa gt agtgacct ctgtacttacaagaat aaagg gaaa g tatat at gcg ga gtaactagtgc ctt a gc ga cag cgttagagcctatc tcct agatt ata gat cttctt at a gggagtgtgatcttc actcacg tttttgctat atcc ccagctgtct atag gtataatatt atta ac at ggccttgt c gc gttcgt at acgc cattttatgcttagagttaa gataa agatgga agccatctcata aggt agaagtacacaaaa ag tt atattatgtatgcatggtt caattt ta aa g tcg gggcttctg a gttgtgt ggcttttagggatccttatta aagag attcttcacgt aag aggttgatac ctattgt atg a g c tac aaactctct a ttc gt aaacgaataatcg ttct tttg gagg t ctt atcagttg ca tt acgg g cagg gg cc aag aata a g aata aat agtatg aga tat atagc cccggatacgttgtcgaa aattg gaa tat ga tc t aacac ttc ac cctgtttcgc tct tc aa ct agac gtcagg ctttctc atctcctacatagaagggggcg tttgtc tgagagcta cttactatacaa gtg gggaagccgaaaactctgttacac gttattttagatc gatgtacct at aatggtagctt aatcacacaagcattgtt cgggctagtcaaattcgctc gt cgct gtatcttataa gtctttaaagatacctgc g atgtaaga gg aaactcatctccatgcgaatt cccttttctatggcttagaagga cgttg ggaaatactt taa ca agct atgtcgt caataaa cgtcctc tcct gt ccc tgg gt t tcggct ataattgtgaaaacactca tat a agagc tttaata cc ag ctaatc c tcttgtc ggtgg ca gtaggaatgttata gtgttta atg tt attc g g aat ggatgct ct aa at gcataacc gttaaatac caa gt ga gt atcga attgt gtccat c actatag aat g atggtt cc tcggagaa gt gt g gtta aa ga ccg acat g at at cgtaagacttaaacaccta t ta cattctgtttgt cgataag gacttga aca cgatgtttg caa taatt tctcgattcacga agacatc aggcca acgta aacataa cc cgtcgcat cttcc gacgg agacccg acctgtattcctctttacaac cacat actca ctacgccgcttcccagctga ga t taagcttttaaaatc gc atatgatatatgcg agccgtac atat tgt acttc cggtgttcaga aaagc taacaat gg 4g gc at65 aagacacac acaataga ct attcg gta gt cgtgc gtactaggaagatttctaag gatc cgtgagttgt tta att gtta a agt gggta gta c at tcgt :c Oacccaaatgtatc cg gttt gagact aattatcttaaa acct tgctcattacttccca aact cctaacaaa gaaaatca gga aggagctattgatc agat acaa aacN ttcctccactcttctg aaccctggagccca acga gg cccgtaaa tg caa caagggt gaacgt cagtttgt ag gtt cga ttca ca ccctatgg cD aIga Qataaccattttgttcaa ca cggtt aacc cgctacc aa ctgctgga at tcttcttcga atttgggtttatga ct tctat at tctttaa tgttg acaaaa gtaE Sgtcaaaggac aaatcagtaagca ctgacaa acctg agattaggggtAEIIPA DGRPGAF T SVL N L VIIL E N K D TIKCLTR L TDRSTCSANNE N L NGYYYIIKFR E L D GEPKIS IN R S VD R GS AV V YNAIYL H VSEIMFFKH K E DTVTARKIIHAIGTD VQDNPDAA AL L G YF TT E YL QPSR GGILSMSP S KLPLAQI SN V VLIHL L L KVFIDPGY K E VKWE SSFRL GEKN AF SVM NITL Q DKFL H DHIVMKSDKLNKPA D LFAH S AR AN L YDIG KL AIIDIAIDIWL D GVFN T L N LFG P AQFSIEAKIR RIYQERGSY AQTQISN AESGS FAF ACKE FFKGVGAPQDGIQMIAPP AE YKGGAAA IYGGVSL WE V DVDTKLKIE CAPLIVR KIQPKYLE R R R YVTDSG WK QLP F F S STALIG L TE CGQKVNDKS E KPIQDAIYK KYL VD YL YN HN L GPIYL N ANDKFG TDIPALID KGPPFSFFDITE T KKALSTFF YRPIR VK PIL MPYRVPDANIPL V NLGL K QL NESAFG N DGP ESKEIQS KKL S LPKTP SN GDVR GHSTGLFIN H RVR AWRI SAE E DVE F K5KL N TF GSSQE W L CS KF N QTL TVGQAVTSKE L KS WD VFL GH E CEAFL V YVI4T Q 5 VALKE LSSE N L L GKG YTLDGILGVI EPNLL DNAGTQRPYPN KIHPFGLS :L ATFII IVKL YL EFDV H CGKGLI F FGAN QL L DGIGVS GEPEHQ NRINIO LS NNIT S N E TQ GVIY E KSIN DFGVKGPL GKVL VVY E L GQYTN YST DGEAVPNS SN LKFGEIIE H KE L E QGFYSVR VGGPYKEE TYIKCGFR R YCSI GK DI KSHTPPFFN S NNP PTIAK IDSAIDL TFAWT ARAR S R VS SL QAP S E NKL QE GCNN KG AM T N KPL K A KP L Y NFL H GS FITA GEL D Y GE EYIT F N P D G V E S M K MN L GITLIVS IS N G CT S T P K L R N 1T U P gaac tt ct gaaagctc t aggatt ggatt cagtc ccctt gg gact cg cggtcaagtcttta ccttaaggcaggaaaactagaagtttct cc ta at a ctgtgttt ctgact ctataattagggtta ttctt cagt c gcctaattcaca ctgacaggggtgga cta ctaca cac a gaa aaaaccg aag gccac ca ctc c tatggtcgtga ggctcc ct gct gag g g cataaactag catctc gactgtgt ac aga tcaagcttaac aa tg tccgaaagctcgaatttgtt ttttcca ct caacacctttatc gcgcaa aa gggaatttg ag gt caa aatc g cag gtat cc ga acg tatt cgccagacgc gcatg cat gttcta cct taagtctgcat tttgataagtaaa aata cac tcataatgaggggtacaa aa cact ct g aac cgta gtcgcttcac cta aaggttgcg ag ctcacttttatc aaatccagtacaaacact aatcgtt aa cgggat cttcacactctaaaccacatccct gcggctg gct tcagcgac gtat ctctttcatcgactta tactctg tt caggcaggatt aacta a aggaacgaaagaatctc tcgtatagtta ca ccc ga gttcataggaagaattgc gtgccagacagaaaacacgtgtgtaa cactctctaaaggttcccgatgccagc gtcatacgatagcacc ctcact tgagg tta tttagaagt ga taccgga aa cc c cgc ctaattagttagccatgct tgtgtca atgta acaa at agcggacaag gggtccag caac ctataagttgtcgt cttgtccagcgcttccag cc g atcc ccgtt gtccgta gataaaatgggtacg gtcgtaagg tga aaaccctaaactgtgacaactttg cca tcacac ggact agca tcggc agcactatctctacaagtcctagccacacaa t ccaaa gttcaagga atctat ag ca t tgcctttt ccgacct agt tttc a at caca ccc g caaaagagcgctcaacatagt agcct ttaggta ac cactaactcag tactcgc gt agca gttatc ttatcatgcgatct a gacgatt tt aagc gga tata tcgaacctg gag aaat tcaggtgac ccat acgtctaa g ccaacgtt accata aataggacag cat ct tcataagagatt gggttaagcggttatta gtagtccaatgttctct aaaggcga ccc caac caat ct ccg t gtacggta gtctacgaaaa tagtaatac ctttttca gtgatc gaaagaaat attacgcaggtca cc gtatc cacct gccagctc ga at tac tataagcaacggctag a agatca ggccgttgatgccttc aaaggagttt agaca agc tcaatg gtc gtctat gt accccttaa ttccaggattaatttaa gctacaactctttaagtgtc a tgagcggctcggattagagtacct ctt cacaac ctatggt catatagtatgca tttgc cgca aga ct t gt ctct gt ccacc taga ggcac a gtcacactccaggctgc gcagcg agggt at tgttcgagaa ttt aa atatgcattt ac agtag tcc gata tgaggaa a cagctgtt cgctcattt ccgtgca aggt gggta a cactg tatgtgaac tt gctcac gtacg gattac ac gt ccagatatgag gta ccgcat ggatagc gt gtgaccccta gtaga aataagtcaagatttaatca 8cccggcataa ac ttaacgctaagttccg cagttc c t aaa cgggcc tcctttcaaa tgtatcacactagttaagc4ccgaattt ct ca ctttgatt aagggt9 tt4 gagta ctaag tctccacgt cctcggctttg66tcaaaa caagaatgg 5ga :act ac agtgtataOtctttgcatt gta cccaa 5ac Natc : aacgcatc cataga acgaacgagccgata 5: taagcgt tgaactacgtttattcc ctctacata gt gaOgagtN agcgccttttcc ctag gccacccc aggtcO Naatatgttt gacgacca atDIgc atgtt tttcac cca acgtta tagtgcDI caaagcc ctgaa gaagacgtcacc taagtg DIga gt ttaggacaccQct cttc tccaaa ag gtcttga acataatcgaQccagggtaca agcttcaaagattaattgtgQaagt taacaaccgE Sgtaacagggacatgag ctccgatgEaSgt cagttgcaagga tctcggg ataagE Sgtaaaa tttacaVDA LTP ARNDKI FR K TA QVYTAEKR NQDIMLIL T DIQEGPPLPKIWYCL G HLEL W HPMQWPG K KASDGG NL VDLIS YI PS L YEVIY KRIDKNIM V LSDLSIL N A PKP FEKKD0 5DKD H EAAG3 6GEI IVYGN*5 5H VTKS L H E: :NIDKN G N Q O O V Y CADTL VN NN YE H LQIR R D D TQE NTL R KP I IGVPS DLIQ Q KWFAKYL S N L T Y K E SESMG E VG P -o44 dketA t D N NcC Co esO sDjG GnKnwaC Mcaaa gtgctac actttc cat cagc t gggcttaa catggg tga ccgt ccctgtttata gt cttgtc tccacgtgctagg cgccacaaccgatccgttt ct cc actgcgatttt ctcaaacc taccctactc atc ttaactctatagt c gtgagtcagttaaat ag ggaccaagagcctttacct cactgtgata catc ttg gcg ctgag gttt tt cgctctt aagttgga caaaagttccc aat c a agg gagagtgaaa tatg ttctcgcctttgcttt agaagggctata gcc aatc tgcc tgcttt ttaaact gac cc gagc atc tagg c agtg aggagtacc aga caagaaatttcatttgcatgacgtcttaaccgcttgttc gcggcgt a aggctctagttg aagt ga agggagag ttaat c ctttt gc aa a aagac gt ggt cctaggttaacatg gt cta ctgg cgg ac ctttcaaaac ggt gagttc aag gt gaaatttgtgt ggatataagc ggttgacttctaaagattt ctcgttg ca tccata gctcgctttactacttctatgt atgt tc aatg ga ccgg caattcaaa a acg gtgagtaacg cctttt ttttgttttggttaaaagagt ca ttcatg tcacgtagggg a agt gtgg cattaaatac ag ctca gt ggggaataaacacacctc taatattcc agccggtcac ttccta caaagattacg a ag gctctca a cc ct atcacaa caataact acgtgtgt g aggcggcgg cggg gta gtta c atggatgaagcttgaaaaa gc acattacacc actcc gatatagagta aaaggtttac aa tatg aaaggatttaagatttac ctctg t cagtcgcctcaca cc t ac c cttcttaaagt aca at ctcatca ct actcgacgcctcta acca gcctattaatggct aggaagtcc c c atggg gacgacaagca tcg caaaaaacatat aattcctcacc gattcgacgtaaa tgacataggg ggtgtcactagtg tct tttcctaaa atgagaactcttagtcgaa atga cagaaatgt g acatatcatctgttt aatcc tcgg tgagac actattgatt ct agg caga g ttg ggactctcagataa cgaatctgaaggttcactca ccatttccctctttaggt aat tctgtttagact cac a ca aa aagtttg ggaaaaccttcc ccttgccgcggccaccttaggatccg cgacaaa aacttt tgactga cggtttt ct attg gtgttcga ggcctgggtgatct accttacattcccttaacaggaa ctaagtggcgacgctagttacgt gctaagtata gggact at cc taacgaa atctt c ggct a a ttt aagagggatacttcaaggccctattata c gagctgctccca aggcccgtctcttcgttata cg ccgtaagttgagacaa gcca aa ggtgctg ctga gctggtaaat ttcgtattttgtataatttat86aac 5a t gagtatca ctgaatcaa gt aatgcaga gaattcttt ta caa cgtt0 agc75ac c ggacataa ttgttgttgcaagatttag :Oattatcctt ccc a ctcgtatg ata actgga gggat gggtatgaataga aacaaa : tcOca tc cacgttatgagtttc gat ttaccgatttN accgtttc tgcgatcgttcata aa tctt a ag ga att gac ctt gtatgcatatc ggN ca gac ac agggatgcaaagt ggagactgtDIgc ccgaat caatc ttctgacga ggcc tttcga ag gggagataga tatgDaaI tggttattca at ccgagccatgtcgga caaaacta gggtQ a EaSg gtttc c cacccaacacgaccgaggggc gcc tt at gac aga gttgtgtg ct c ataagaacaaggaaga atgcQ g EgSgt ctcacagtgaa gt gga tt tcgtaQS I I N K A S RVGSIN E L Q*GN TSSILFTP YF GFKGD QRIVH AKA RDILS KLP E DWLIDW D QL TGS S SVKTQSIAPT K L F TT APNS VYE VEPL SG LE E NIL L AM INPKPKMTTFPHD H ALWTESFSWM RFGAGKK F V MMGL A AN VCIGPAAN QTFL LFIQ L LIG GPF D DIE H QILFE GAL E MESSHSE AWE TK QWKKTPPILTE VS V CTESE Y VL P KEFISP L G G A WG H ES AFAN LPG AKATMILI IR V VLPTFQ DGVSPSVSEGE WR N GK ALP NFFMCAELPVFAFNIV HIL P VDD ANADSSEPH G N L AL KLE*LFPTFS FDQPYSL GN G H SGP R VSCI PE S Q P F EAN Y QSL YL L LLIME GKLMANPVLFTIN AFFKCDATVSTR SS TAPG TY N R WP E KL GWEPVE EESF IV TEN VFS Y E K L GYYKSFSQLFGGILAEP L VA GVNPR N E VTIE AL CFMGHEL VPYHGE L S G F H DH VH R P HFG SSL ARQPE GE VL V H KMGINGPPHN TRLP FV76G H TR DL L KWIWLE MGR L MLIAK D96L V GQARFFYDGSYG5:N M N TAHE SIKDQMPL QME L E KSE M A KQ5:DR TE MTV WH DSL L H N O N L LLIYAN GDSRSKVFMNYE D L E E L P M O AATA QKLTAHAI PL E ANME L HPR V QWIRQ R TE QIDVISLVIK KVNTAFN E VL PIH GH A A VDQ DI KI FRPL L DSFL Y N AT L PFKN YR GA D S K I H L R LFN DGWP LHVVKQGS GKK D TKTN N FD TEL KGLP SA R Q TR F G L GHPYHPRIGWL VM E E K WSH S M H A N DW L G S NLTS TFP QGN L E F S N N A K C YKE F Q GAE V DSMIKCL GSPGHE A QIEDEIG QA T P O T DT cjGG5M5AbDgttagagagtgcgtaga atg tcaga attg cagacggctaccttcacaa gt cacat gaatattataattaa ga gc ata gat ct gtatg gg ctagaaggg c gaaagaagtt tgggaaga cggcttg gc tttctt attcgtgaaa agtcccta taagccgcct cggagcgctattctt gcacatacgaattttt g a aag ggtttaa aaattt taga aaa gatt gactg taa acaac tcgc gg ta cc act cc gtg ctaa aa gagt atg gtaa aag gtgctcttaa ac accgccg aatgcc acgaagag ttggacca ccctaaaggtcagt cccaaag cctaggtatgggcg g aggatga gggagaa ac c gaggtgtt gaaaa c aataca ca ggcc aag gg a gt ac tggg gaaaatttt tgga cc taac c ttcttt t g taacgta agtgca cctgggtgaccgaac ta c c g a aac ataattt gtagcacgtgggtaa ga gtgtcc c agtcagacaaggctttt gttt gccggtacg aggtttatatccaa gg acg ga tacacc agg gaggaag tacaat aa at cc gagcgc aggtgttagagttgcat gt ctaagggttggggtta cg tgttgcaacag ccacctcac tgtcgtatg tt cgct ga agaccg ccagaccaaa acggagca cgtagt tttgagcacgtctcggg aga aagatcgttcaatacgat gagggggt acggtga g ga ca tg ct ttgc ccctct g aaccggcggc ggggtcgaaag a tatatgtggga gaaa gtttta ata gcggagc g tg cc a ttgtaggggtcttgtgcgt atttctaaaatccactc gtt gccttggatt ggtaa atgttagggtgcggtgttaa aatgc aag tgttggacgtcag g cggctgttaccc tt ttcccatggaggtgct tagt gacc a aagactatctgga atg gtaagg aa ggt ag gagcgtgag gt ccgatg g aag tagg t ctga cgct cccag c atcaatg acgggtagccg gttt aag gcgcgttccacgatcg aaggaca ttaaggcaaa ttcgtgtacta aggatt ct aggtg ctc c gtccctta gt cta gt ggaacca acgactg ga atggg ca actgtggcaggagggcac aaa g ttt gt gatt tcca gcg aagaaattta ac cgct c tcccgtta gc cc gaagg tga ag ttgtaggtatgg gttgggt agttggtttatttacgatc ggcatt a gagagc gt ttg gaaaaca ct actcg ag aatttcatcttttgctaa aacgaca attt gaagag tttgcttgaga taa ga aa t tt cg gttac c attagaa gac agagc aaa gcg ca ag g ataatctca cac c gcct aaggggaaggctag ctaaggg taacag aa tctgctcaaggggaag acaa c ca ct cttcgga tata gagca ctta g ggaa ac tcc g gctattt cata ggtt ttcgggg g gagaacgctatttc aaaccta a tctgtggcaagtgag gtt ctagaaccc actcgctgttctcgctg gtct ctcag ac gctggt g taaag ggga acagggtcttatac cgtagaaggtgttgtatta gtagatcacaacca aacg aggtactct tt a gagggtgcct cggg gggtg agatgtagcggg gtcctctaagat gataccacg gtacacgagg aggaaaatgc ttatccttttgattt agggtttatggtct gtgtaat tgaaataagga tcaagt cg tttctaa cagaggtcaaaaa27a c5actcatctcttgctgatcgag gtcgtttttaaccgt aagact gg gttgga agatg ga cggcggcagttc gttcagaag ga : acOatact ctaccaa cgt cctttg cctatgg aaata aggtggttttctaccatt gagcgtagaccaccgaggataStatcacctcgcaagacggagcctatagagggtaaRTR R IS H DGL QTDE H L E S P F R TL R L L CWQKEQPE R GVCME G L L TGTGRIIA E S L AKY L G P L N YANQNIPNL AP D L KVL MMKSKE E QVRKRSR GVL GN L R N QKWEIKK KL L APPD R VSN L RSS WE F WGE E H L VN WISKR ME DE E L V VKIFEIR GFAK V E A DSRKTL G L VVE EH RP E L R F QCIWIGGN CH DA REIGN GH L L H P AVKIF CMNR VVSMSGIVFL TDAYIF QEL H FIR L Q AP DEL WYR QP N R AQIPFDL N MK VE NF R D KAKVQR TQSR L EPRASL T F TTSS GA GDQFFEE TFMWKSWV ADPLTYDESGH K E FAL E L P L TTLE F SFVPFV QKE VGGG TFQCN E KMSFDIDSGFEDL L VGF RF PYKKAF HPSPY TTGSL S P A GS DN P KHK KVTEL R KAE GGTP WEY IIL L HDY G N E FFIAAWL DQRIKESA K L QV VE ETE E NKSLPPAWKE GSS H QFIILIL CGS E PEDSKGVMFE E MESSDSGYCSKFSLN A S L TL E T A H VKSVG17QPTNKIVGF DSIKF WMGAG AE WG*IWE EMGMGE5:E L L NIS PTE E PNE GESCILR GTL L GKAVR NVPW KEE LI PVVEO QSLITDFDDIS STYFPE E AP G RCSYD DEAMSVIGL HSL VAEIENL VR A*NKLFS HCIDAFNML VIKFE WTGGKKE VIH CL N VG QGQAGVR E D TR N L L GGR CLILSS KH G RLLE EEISYP G E P KI SH DKHTVL P DEEIK KP V WD QPSIVAWSASSN FPLP V KKKYSEAGA KKAE Q E DH WGN E LIR Q AIG S E L QTR GR R GIE L DVADWG Y L K R D L H W ELIEIM T S M H R N T V H H S G F G W L G V L A R P O DT cqGC5A acg gtt tacaa a tg g gttg cttc ca tttggggaa gt at gta taac acaa gt tca agt tgat gtaag ca ca aagttcaag gt cg gagag ttta acttggtgtttaaccg gcgga cgggtctgagca actacaagtcctgct g ttc ga ttttca aagggagat a agtggt gaaatgt gta ggttat cttt gattccgcttgaaatca atgtga g a ata aaaaca ccc gt gg ctcaaagtg cgt ttgcaccgat tggc atcgtac ttt cgttaggtaagacg gtgggtaggg gttgcttgtc t atagt gtgtatact aacac attattag ccagtagg cttaaga gggggtctctcctagcttt gtctgcctt tt agc tgttagggt gaatct c ga gt tg g tattctcgct tcc tacg gtagaaggtgttctc caattaatac tccttttaa tcggga gc tacg aa a a acg aaaa ag gcgcaagta agatatacgcgagaac aaatgggagtaattcc cc acctcgctagcaaggcgtcg a gtatgtt tcg gggtagt atttgt ggagaaggcctctgctcctgtacaattcaa c ttacag gagt aa agg acgt gaccacattggcgt tagtg tt acctgagcagaag gaagttaggtag agaggaattgg cc aa gtga ga gttcatgatcct accgctacggtcggctacacacgacgtttctattactctcga aca gg gaattacggtaagggtt gagcct gta atc g a ggtcgatgctaa agctta gttcgagcaattaacgg tg gtgtc aa acct gggagataac ggcttataggat agttaagaaatcaggga a ta cgaaact tttcg aga ctggta gctt agcaa gaccaaaattacccggtaaacatctactaatca ctggaa cgt attttg a ctc ga tgc gaga a tg cgggttaaaa attgtgt tatctaag agtttttcgtgcacttttcg a cggatc atgaaa aatggcttgtagtgacctta gg gaggtag aggg ag cc tcaggata att cagcttgtgaat at tag tat agagcgtttaagatacataggcgttt gtgtgta ccaattgcttagataataaatatacatat gtaagatgttg gcggag tagatgga c tt gc atttatcaagccg ggaaag tgcacgggga gaaacctgt atcaaccccagtt agtttttaaagg ccagtgaaaa caaaag g gg g at aa cctctg gatg cta tg g taagctcgtgccataaagctacaacc aagaatcatttatgat ag agatgaggtta aagg acg gtgataag atggatc gtgtaactgc ct tc gt ggctcactcctct aa gag ttgaccatgca ccgtttt cgctgtaaagt acgatcattgtttaaa actg agaaatctttccagatct aca gg acac gaa aaga ttt ac gtcc aaaagttttgg tctaccgatgt attcagatacga acgtag a g gagt cc cttac cg cccttttctgt tt atca aaa ataact gtgtg taatgtgggaa4 ct ag ta c a a gg ggg c ga ttgtaa a a t ga7 gt5atc:tga gttaaggta a g a t cagaa accgaattaaac tgcgtgctt aatcttcattctttatttatgtac aag67cta ctc ggtttctttagaOtt ctgttc ggagtcac gt tgatag gtcc tgcg gttg tgcagtggt gc ttcccttaaggttc atgaga gg aa5t: acttacgg gt acagagtNc ggttttctggtcgct a tccgacatgga gt tgct atgaacgtgaa c ctacctaaccaga ggga ttgatgO aNaagtc cgaa attttttactgDtI ctcttg aatgaQc cgttcaa cgtcag aataaa gca ctgtgtaga ccctga ccctcgttttaagacggttatccDI ctttc cgcgtaaagcatcEacSgatg ccaca cata g cag tgat atc gt aaact gtg gaa a t aat gt ctgaaa tgctag gtcctacgtt attaa g aggac ggtgcagcaaca acatgtgagQtttgcggccgggagEgSgtctaa taacagcaga gatgaaaaa ttcV S DDGKIE R GI T L L VP I AAKGKP I AWL R F QL E*AL P GDA DSAL E T E E AL R ES VHDE HFE SE R D T P PAL SKE DAY N V GQW LAKTVILF LSTD YA L S K QNAFKWRIELVDL AIL P STSP RPCFN QMG E L E E V QISPL QTKF D ADDVGLYEDIHE PS N LFSV GSF Q R R E Q KVD E R F TESGF F TA TKDKDTPGKSEPITTICVGLL H A ASS KA R GNSF I IL TL N T VVFF AL GWD D Y L E AAE AKKVNSH D R N E DKL MISHIIFRFR CADH Y G KFVVKNE MIL DF GAGL CL WATG NDE KA YKVYRIP PAGMIWL R TG L MKTE LSVYK S VK KVAE YD ADGQ QE A ENFYPASA VE YD AR E E Y AALL R G P TALFPGGFL L E VR E L S QH TAVSKR K E KKAL LFMTDYL D T H VHL E SSTIAVQSG K QGLGL T KA AKIL D DANS TGIS QT S GP R L P C L E GSVADL MR L N GKK GARE3FVST KQDIVDVIE7L LPITVCREGIIV S S E HL V H F TETQKMSRP GHP GSGGKR K K DENSDE Y S E DVG L L AAAY VSQE VL D AV 57LVIKDE VE5:DAMGKFFN KQDKK QGDTYVI IK AL E ME MM EVIPL MGA5SAKVE L D DOSALSLFF V AAEENFD DDE QVTE L C S P A AAAVGFKKE:O VAWIVADNYTPIL T KSATTH DDTAYHGAW LQFS F TPIPDN N H AAEN KIAFDK AGDIL T ASAIL VKEFE E YGKF VTIGPF ASVVV ATS E KL QDS D S SLD N SFDFA VE RT K Y W L L R D K QGL P VGLLPVYE GH N P L E VGSIDYCS S DAKGYQ TLGKR L K TPL L VKN A Q DE CLE DE S M VSR G A KYFR N VKDR E D H CRSKP G VAD S KPPR S MS E E VV P M Y K Y G E S MF SGI IL A TD L1 1R RT TAtAAvB gctcttccgtgtcttaat tattcctaaata actcccctttaaacggatctttgtg t attt cccctaatcgaac ttaggtgttactgta ttt atcccttg c gttgacaa attt cctct gtt ccccggtagctt tcttcg aa ggga atttcggtaatgt attttgtgcagaa gccttc aatatata ag ggc ggggtatcg ata cgg tggctggaaaggtatct g tatgtggt cgattt gatggt ctag agca gcgt gg ac gtttaacgaaagtcggta ag acctgc catctgaggaaa cta aaaaggcaa agacttga gc tcgt ttaagtctt gt gttagc cgagccg cggtc gaatgggttac taatgaagttaa cacgcaaacgt gcac c cacgggccgttcagggc aaagacagatctatctgaca gattagcgtgtt cttgag t ttt cc c c agtggaagggaac ccggc ccgtctgttcaatacctc acaaccgag aagt ctttc acgttgtcatt g a g atctgtgtgttgt gtccataaaag agg ggtaaatat gtcatttgatacttttggtataggta tctg atccagg g tacta cc cgt gtgagttttttcttagaggttgcagaacgtgt atgagg taacc gttg atcattttca atcccgttct ttgctcaatcagaatgtacaacttaggataggagtgtta gaaatagcataac aact ctgttgtg aatcgtgg ggtatt gacctcagctatcact g agagatcatg aagggctcag ctttg tactacgtat ctagtac ggtgtc gtacggacta a gatcaacgata agagcttt ttctcttgcaataa catttc ctcgcctcaga atcttctgcttaaa ttggcggttac ccggtta gagatag gacgggtatctggcgt aaatcg t aga tcctcgtt cgga cggaatac acga cagcgcgta agctagtt ct aggtaatccg tt act ga ggtg g gttgctggtaaagtacaa gt tcccttcttgaaggtg tgtttcaat acagcgt g cgctagt cagg aaaaa gaagtg tctattt cg atcga catg ggg accaagctc aagt ct gcaatatctagt ctt tg caacgcc cgggtaa ccgtgtatgt gga aat gggaattttaacg gtttat cagag cttcg attt ggac ta gtacca c agaa agc g ttgtgtgtgatatta gagggtgtt gacgaaggg ga gatccaagaacg gta tacacct gttaagctgtg tctt gaacttcctgc caca tcg ttg cttacagtaggataggat gataa cta at aggg gaataacatttta g tggaatgctgagaa cc cgg gt tcgg cgaggtgga cact aattggtga gtcttcgatcgcactcgcgctcttt taagtttc tgtaggaa gtatcgctag cagtt gat ca at a gagtg gggattg gccg aaggaggacgaagagggtctt attc at gagtgctgccgagaaa gt taacaaaatac ccacgta gg ac gag aa a cgtc caaag ag tacaat at cattcgttcttgtaggac ttt ttttgcg t8g gg 7t g5c at tat aaccg gt c at ca tcacttaaataaggtgct gattcgagttag gttct tac accc acgtggctggtt gtt ag gt :Oagtttagggttt ctatttt ac ctgtaatgt ac ttt gttgccgagtaaatacggtc gg caaa gtagt tcctaactcaaaa gac ct ta gatga ataggNctt accttaa cggggta ggc agc ctag c tgattattaaacgcgagca gtgtgaccctgta cga g tt caaaac aggtgacgggtcta cgDItgcca tgttg gcagta ccagttgaa tgaaagacaggtt ac gctgc tcgt acaatagaaatgcttatg tccttcag ctaa atcg actaaactcg aga ttggagaaQ c EgSgt gttagata tcgagatc tca tggcttagg ccgctaaa acgatgctgEEK T AVVIK F N P L H IGKIA R DT L QPVF KAQYS AKR V VEV D GC DR E KCH VAAVNSN G VR G VHIFDVQDQ YL P A A QV P WAFCVSG H DSS DQQGSS DAKIE AL L RPRDELKKDDG AAKL GLFALQF TSDE LE VCGGSNSAIEE YA L NGFKWL YEFSHENLFDE V H DDVNGLPP ASYVV H N K KAL DYVM*SPR EL ADDVAAFIAIC GR ESTRE P LL E GLIR MPL AE E KYG GW DR E L DTPGF GE QR AN SFE L L AR G L DSS Y V V L WDAD AGRWY ACS ASAKPWKRI TYQ S E K E TEWEKQGL R E P VEE TSGPKPATFEFDPGGE D L A R L VEAAGLIL AT YNS SYRVPDHFN VLFH D GK QF VAKAAVSNCSQVE GQLL GFPE F YDQ QQSF PMDPE VAE TVPPSSPR VQLF KR QITY S VV G G E L VE DYL DDTSN KR GL L R P VDL E H VPTSSAF PSGR RS NVGF IH R G S GKADL TWL DVNL HA RFL L ESK FFR N AVL E L T AP VET LAGKW TL AVYVCN GL YASIHIF R CVN VTT7TVIS GDL VE KICN QEN E AS DDKMSIP P V R7S VKT R AN RDV GGL DPIH R E CE AL VYR AAG W F L Q VH L5 GIAI PQVMFEAIQDEFQTPYQE KTGDYNE E A DYR E YGTWL GFE DVN:O L S A VTKGL L WAGVF N GKY DDTV A TN S AAV GTR KL R H TAL PPS MCTLGI SALSD AR K VNDS TV TWVFFL A AL ENTFDAK H DDVVDN L ATYPIL E S Q DP VR A D LITF RDNGQE FPN ATV HSR F ANL K DH GQGE MMISS LKSS KE E G D WYLLI SAYLDIDTS H S L DYRPQSRP LSEIGL TE MGGE Q ALIDV K KYKKQGKGR T W E D VWSE G T LDSA A V GMID V M K A E S M A G T R L Y R V DHIC P 2 RT AvB cggatg ta ga aacg gtca tgtgta gt ct gacttccgtgatattag tatcacaa g gtt ggta cggc ggtg attctg gaggg tcgggac attt gtcatttgtg tag attcaagtagga taggg atcgacagcgggcggaca tgga tgtgaagag tgctcag taacataagtt gtt gttct accctc gaag gt gaccgt tttctatttat ccctga acccatgttaacgtgcc agaagcgttc actt ctt gct gg gagt gcatgg cttat gtc gtcag gt ggtat gca atgg ggtgtga tcagact c aggcccatccgt ctagac ttta gtc cg tgcatagcacgagg t aa gac atct agtttt ac acgt aagg aca agtggcttacact gtaa cctt ttga ttgattctactg a gttg cagtaagact aatc gga caa tc acct ggggggg aggtattccta tgacc c tttgcggtaaacggtctgag gg ttggg ga c ttat gttggaacg ctct aaag catcgctcaa ctgagg tgaact acttagatggt gat tc c ggctcat actgcca gttcgc tac cgcagtgac ggt g tg a ctttg ccttc tatgtagatgt atgaat gattt gctttgcacctttg tacttggagacttt cc atagta cgcta cgagcattt cgc ggatta taacaaa t ata ca gag ggt tttc tcataacgcacctcc ct g cca ct agaa ga ttaa cc aaaga at gt ggtggct gcc at ct cagc ca gaaagag gaaggc agaagga gg ggttgct gcttttagcatactatgcgtacagt gt cattcgtc agatctgtgtt atggg tca ct ttt tttctact taagtgcata gtg ca atgtgc t ctcccct cttagttt a ctgcac gg taggggaagagc ga cgatct gtgt cttgtcccgatg atagagat gtaaaaaaaAL P S AGKATF E QDGGE VEE GKE YVIGRPPSASL S CNSLF ME QD RGR P R VAGR RSSS VILE LDPIS AF P TL ESGRIR NF IN Y AL RCSKFF R H GL YLN DLSIH IP VN L G E KMSIRPAC GVWT R DE D G L AKV AL E YG GFL L F EYH MA E YTWT SSVQYDY L R PSLIV LVSH R AL AE S P TCGPAAAD KR KGIR QP N GPG KVSLAL GQG DAH FVDL AGL SPRE QSSR HSV E AP E L E VMIA AVML EIIQ MG VVKKETDL A L THVIVAAP PGFKH AAE S CSCVD QDKYIIQP AWATVSHLSGGALAS FVAP QE VGS YCEGLLPYF H N DKETFA V KAL E E VVGKP L E P L DGV R MPL AYKYL K*KL L P N W K R F Q E A G P AIT Y Q W Attorney Docket No. G0919.70121WO00   It should be appreciated that sequences disclosed in this application may or may not contain secretion signals. The sequences disclosed in this application encompass versions with or without secretion signals. It should also be understood that amino acid sequences disclosed in this application may be depicted with or without a start codon (M). The sequences disclosed in this application encompass versions with or without start codons. Accordingly, in some instances amino acid numbering may correspond to amino acid sequences containing secretion signal and / or a start codon, while in other instances, amino acid numbering may correspond to amino acid sequences that do not contain a secretion signal and / or a start codon. It should also be understood that sequences disclosed in this application may be depicted with or without a stop codon. The sequences disclosed in this application encompass versions with or without stop codons. EQUIVALENTS Those skilled in the art will recognize or be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments of the invention described in the present application. Such equivalents are intended to be encompassed by the following claims. All references, including patent documents, are incorporated by reference in their entirety.

Claims

Attorney Docket No. G0919.70121WO00   CLAIMS What is claimed is:

1. A variant tyrosine hydroxylase, wherein the variant tyrosine hydroxylase comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 1 and wherein the amino acid sequence of the variant tyrosine hydroxylase comprises an amino acid substitution relative to SEQ ID NO: 1 at one or more residues corresponding to position 26, 31, 95, 114, 115, 147, 198, 228, 240, 254, 259, 280, 288, 346, 403, 405, 409, 418, 459 and / or 467 of SEQ ID NO:

1.

2. The variant tyrosine hydroxylase of claim 1, wherein the amino acid sequence of the variant tyrosine hydroxylase comprises: a) the amino acid serine (S) at a residue corresponding to position 13 in the sequence of SEQ ID NO: 1; b) the amino acid serine (S) at the residue corresponding to position 26 in the sequence of SEQ ID NO: 1; c) the amino acid arginine (R) at the residue corresponding to position 26 in the sequence of SEQ ID NO: 1; d) the amino acid threonine (T) at the residue corresponding to position 26 in the sequence of SEQ ID NO: 1; e) the amino acid leucine (L) at the residue corresponding to position 26 in the sequence of SEQ ID NO: 1; f) the amino acid arginine (R) at the residue corresponding to position 31 in the sequence of SEQ ID NO: 1; g) the amino acid alanine (A) at the residue corresponding to position 95 in the sequence of SEQ ID NO: 1; h) the amino acid leucine (L) at the residue corresponding to position 95 in the sequence of SEQ ID NO: 1; i) the amino acid serine (S) at the residue corresponding to position 114 in the sequence of SEQ ID NO: 1; j) the amino acid leucine (L) at the residue corresponding to position 115 in the sequence of SEQ ID NO: 1;Attorney Docket No. G0919.70121WO00   k) the amino acid leucine (L) at the residue corresponding to position 147 in the sequence of SEQ ID NO: 1; l) the amino acid asparagine (N) at the residue corresponding to position 198 in the sequence of SEQ ID NO: 1; m) the amino acid aspartate (D) at the residue corresponding to position 198 in the sequence of SEQ ID NO: 1; n) the amino acid serine (S) at the residue corresponding to position 198 in the sequence of SEQ ID NO: 1; o) the amino acid glutamate (E) at the residue corresponding to position 198 in the sequence of SEQ ID NO: 1; p) the amino acid glycine (G) at the residue corresponding to position 198 in the sequence of SEQ ID NO: 1; q) the amino acid lysine (K) at the residue corresponding to position 228 in the sequence of SEQ ID NO: 1; r) the amino acid serine (S) at the residue corresponding to position 240 in the sequence of SEQ ID NO: 1; s) the amino acid lysine (K) at the residue corresponding to position 240 in the sequence of SEQ ID NO: 1; t) the amino acid asparagine (N) at the residue corresponding to position 240 in the sequence of SEQ ID NO: 1; u) the amino acid aspartate (D) at the residue corresponding to position 254 in the sequence of SEQ ID NO: 1; v) the amino acid glutamate (E) at the residue corresponding to position 254 in the sequence of SEQ ID NO: 1; w) the amino acid glycine (G) at the residue corresponding to position 254 in the sequence of SEQ ID NO: 1; x) the amino acid asparagine (N) at the residue corresponding to position 254 in the sequence of SEQ ID NO: 1; y) the amino acid alanine (A) at the residue corresponding to position 254 in the sequence of SEQ ID NO: 1; z) the amino acid glutamine (Q) at the residue corresponding to position 254 in the sequence of SEQ ID NO: 1; aa) the amino acid arginine (R) at the residue corresponding to position 254 in the sequence of SEQ ID NO: 1;Attorney Docket No. G0919.70121WO00   bb) the amino acid alanine (A) at the residue corresponding to position 259 in the sequence of SEQ ID NO: 1; cc) the amino acid leucine (L) at the residue corresponding to position 259 in the sequence of SEQ ID NO: 1; dd) the amino acid lysine (K) at the residue corresponding to position 259 in the sequence of SEQ ID NO: 1; ee) the amino acid serine (S) at the residue corresponding to position 259 in the sequence of SEQ ID NO: 1; ff) the amino acid valine (V) at the residue corresponding to position 259 in the sequence of SEQ ID NO: 1; gg) the amino acid threonine (T) at the residue corresponding to position 259 in the sequence of SEQ ID NO: 1; hh) the amino acid asparagine (N) at the residue corresponding to position 259 in the sequence of SEQ ID NO: 1; ii) the amino acid methionine (M) at the residue corresponding to position 280 in the sequence of SEQ ID NO: 1; jj) the amino acid tyrosine (Y) at the residue corresponding to position 280 in the sequence of SEQ ID NO: 1; kk) the amino acid aspartate (D) at the residue corresponding to position 288 in the sequence of SEQ ID NO: 1; ll) the amino acid serine (S) at the residue corresponding to position 346 in the sequence of SEQ ID NO: 1; mm) the amino acid valine (V) at the residue corresponding to position 403 in the sequence of SEQ ID NO: 1; nn) the amino acid proline (P) at the residue corresponding to position 405 in the sequence of SEQ ID NO: 1; oo) the amino acid glutamate (E) at the residue corresponding to position 405 in the sequence of SEQ ID NO: 1; pp) the amino acid valine (V) at the residue corresponding to position 409 in the sequence of SEQ ID NO: 1; qq) the amino acid lysine (K) at the residue corresponding to position 409 in the sequence of SEQ ID NO: 1; rr) the amino acid serine (S) at the residue corresponding to position 418 in the sequence of SEQ ID NO: 1;Attorney Docket No. G0919.70121WO00   ss) the amino acid serine (S) at the residue corresponding to position 459 in the sequence of SEQ ID NO: 1; tt) the amino acid glycine (G) at the residue corresponding to position 459 in the sequence of SEQ ID NO: 1; uu) the amino acid glycine (G) at the residue corresponding to position 467 in the sequence of SEQ ID NO: 1; or vv) any combination thereof.

3. The variant tyrosine hydroxylase of claim 1 or 2, wherein the amino acid sequence of the variant tyrosine hydroxylase comprises amino acid substitutions at residues corresponding to the following positions in the amino acid sequence of SEQ ID NO: 1: i. positions 26 and 254; ii. positions 26 and 459; iii. positions 26, 31, and 254; iv. positions 26, 198, and 254; v. positions 26, 147, 254, 259, and 459; vi. positions 26, 147, 198, 254, 280, and 459; vii. positions 26, 198, 254, 259, 403, 409, and 459; viii. positions 26, 114, 198, 240, 254, 259, 403, 405, 409, and 459; ix. positions 95, 254, and 418; x. positions 95, 114, 147, 198, 228, 254, 259, 280, 405, and 459; xi. positions 114, 240, 254, 259, 405, and 459; xii. positions 114, 228, 240, 254, 259, 405, 409, 418, and 459; xiii. positions 147, 254, 459; xiv. positions 198 and 259; xv. positions 198 and 403; xvi. positions 198 and 405; xvii. positions 198, 240, and 254; xviii. positions 198, 254, 259, 459, and 467; xix. positions 198, 228, 240, 254, 403, and 459; xx. positions 198, 240, 254, 409, 418, and 459; xxi. positions 240, 254, and 259; xxii. positions 254 and 259; xxiii. positions 254 and 280;Attorney Docket No. G0919.70121WO00   xxiv. positions 254 and 403; xxv. positions 254 and 459; xxvi. positions 254, 259, and 409; or xxvii. positions 254, 259, 280, 403, 405, 409, and 459.

4. The variant tyrosine hydroxylase of any one of claims 1-3, wherein the amino acid sequence of the variant tyrosine hydroxylase comprises the following amino acid substitutions relative to the sequence of SEQ ID NO: 1: i. Q26R and C254D; ii. Q26L and F459S; iii. Q26S, L31R, and C254N; iv. Q26S, H198S, and C254N; v. Q26S, F147L, C254D, P259K, and F459S; vi. Q26R, F147L, H198N, C254D, F280M, and F459S; vii. Q26R, H198G, C254R, P259L, G288D, I409V, and F459S; viii. Q26S, H198N, C254N, P259L, G288D, I409V, and F459S; ix. Q26S, H198G, C254N, P259L, A403V, I409V, and F459S; x. Q26S, T114S, H198E, C240N, C254D, P259S, A403V, Q405P, I409V, and F459S; xi. P95A, C254N, and C418S; xii. P95L, T114S, F147L, H198E, C228K, C254N, P259L, F280M, Q405P, and F459S; xiii. T114S, C240N, C254D, P259A, Q405P, and F459S; xiv. T114S, C228K, C240K, C254A, P259S, Q405P, I409V, C418S, and F459S; xv. F147L, C254N, and F459S; xvi. H198D and P259N; xvii. H198D and A403V; xviii. H198S and Q405E; xix. H198N , C240S, and C254D; xx. H198N, C254D, and P259L; xxi. H198N , C254D, and P259S; xxii. H198N, C254D, P259L, F459S, and D467G; xxiii. H198G , C228K, C240K, C254A, A403V, and F459S; xxiv. H198G , C240K, C254A, I409K, C418S, and F459G; xxv. C240S, C254D, and P259K; xxvi. C254D and P259V;Attorney Docket No. G0919.70121WO00   xxvii. C254D and P259L; xxviii. C254D and P259K; xxix. C254D and F280Y; xxx. C254D and A403V; xxxi. C254D and F459S; xxxii. C254E, P259T , and I409V; xxxiii. C254E, P259S, and I409V; or xxxiv. C254D, P259A, F280M, A403V, Q405P, I409V, and F459S.

5. The variant tyrosine hydroxylase of any one of claims 1-4, wherein the variant tyrosine hydroxylase is a cytochrome P450 enzyme.

6. The variant tyrosine hydroxylase of claim 5, wherein the cytochrome P450 enzyme is a cytochrome P45076AD1 enzyme (CYP76AD1).

7. The variant tyrosine hydroxylase of any one of claims 1-6, wherein the variant tyrosine hydroxylase comprises an amino acid sequence that is at least 90% identical to any one of SEQ ID NOs: 1-258 and 523-525.

8. The variant tyrosine hydroxylase of any one of claims 1-7, wherein the variant tyrosine hydroxylase comprises the amino acid sequence of any one of: SEQ ID NOs: 2-258 and 523-525.

9. The variant tyrosine hydroxylase of claim 8, wherein the variant tyrosine hydroxylase comprises the amino acid sequence of any one of SEQ ID NOs: 2-258 and 523-525.

10. The variant tyrosine hydroxylase of any one of claims 1-9, wherein the variant tyrosine hydroxylase is capable of indirectly producing more betalain than a tyrosine hydroxylase comprising the amino acid sequence of SEQ ID NO:

1.

11. The variant tyrosine hydroxylase of any one of claims 1-10, wherein the variant tyrosine hydroxylase is capable of indirectly producing at least 1-fold, at least 1.5-fold, at least 2-fold, at least 2.5-fold, at least 3-fold, at least 3.5-fold, at least 4-fold, at least 4.5-fold,Attorney Docket No. G0919.70121WO00   at least 5-fold, at least 6-fold, at least 7-fold, at least 8-fold, at least 9-fold, or at least 10-fold more betalain than a tyrosine hydroxylase comprising the sequence of SEQ ID NO:

1.

12. The variant tyrosine hydroxylase of claim 10 or 11, wherein the betalain is a betacyanin or a betaxanthin.

13. The variant tyrosine hydroxylase of claim 12, wherein the betacyanin is betanin, isobetanin, betanidin, isobetanidin, probetanin, or neobetanin.

14. The variant tyrosine hydroxylase of claim 12, wherein the betaxanthin is vulgaxanthin, miraxanthin, portulaxanthin, or indicaxanthin.

15. A host cell that comprises a heterologous polynucleotide encoding the variant tyrosine hydroxylase of any one of claims 1-14.

16. The host cell of claim 15, wherein the host cell is a bacterial cell, an archaebacterial cell, an algal cell, a fungal cell, a yeast cell, a plant cell, an animal cell, a mammalian cell, or a human cell.

17. The host cell of claim 16, wherein the host cell is a filamentous fungal cell or a yeast cell.

18. The host cell of claim 17, wherein the yeast cell is a Saccharomyces cell, a Yarrowia cell, a Komagataella cell, a Pichia cell, or a Fusarium cell.

19. The host cell of claim 18, wherein the Saccharomyces cell is a Saccharomyces cerevisiae cell.

20. The host cell of claim 18, wherein the Yarrowia cell is a Yarrowia lipolytica cell.

21. The host cell of claim 16, wherein the host cell is a bacterial cell.

22. The host cell of claim 21, wherein the bacterial cell is an Escherichia coli (E. coli) cell, a Bacillus subtilis cell, or a Corynebacterium glutamicum cell.Attorney Docket No. G0919.70121WO00   23. The host cell of claim 16, wherein the plant cell is a sugar beet cell.

24. The host cell of claim 23, wherein the sugar beet cell is a Beta vulgaris cell.

25. The host cell of claim 16, wherein the plant cell is a Solanum lycopersicum cell.

26. The host cell of any one of claims 15-25, wherein the host cell comprises a genetic modification that results in reduced or eliminated expression of the gene CYP76AD5 in the host cell relative to a cell that does not comprise the genetic modification, or wherein the host cell does not comprise a gene encoding a CYP76AD5 enzyme.

27. The host cell of any one of claims 15-26, wherein the host cell comprises a genetic modification that results in increased expression of a polynucleotide encoding ALD6, ATR1, ATR2, LDS2, PEX19, PGM1, TPI1 or ZWF1, or any combination of such genetic modification or increased expression, relative to a cell that does not comprise the genetic modification.

28. The host cell of any one of claims 15-27, wherein the host cell comprises a genetic modification that results in reduced or eliminated expression of a polynucleotide encoding CYP76AD5, ARO5, ATF1, BUD17, CTA1, DAL7, EXG1, GCN4, GPH1, GRX4, MCK1, PUT1 or YDC1, or any combination of such genetic modification or reduced or eliminated expression, relative to a cell that does not comprise the genetic modification.

29. The host cell of any one of claims 15-28, wherein the host cell is capable of producing more betalain than a host cell that expresses a heterologous polynucleotide encoding a tyrosine hydroxylase comprising the amino acid sequence of SEQ ID NO:

1.

30. The host cell of any one of claims 15-29, wherein the host cell is capable of producing at least 1-fold, at least 1.5-fold, at least 2-fold, at least 2.5-fold, at least 3-fold, at least 3.5- fold, at least 4-fold, at least 4.5-fold, at least 5-fold, at least 6-fold, at least 7-fold, at least 8- fold, at least 9-fold, or at least 10-fold more betalain than a host cell that expresses a heterologous polynucleotide encoding a tyrosine hydroxylase comprising the amino acid sequence of SEQ ID NO: 1.Attorney Docket No. G0919.70121WO00   31. The host cell of claim 29 or 30, wherein the betalain is a betacyanin or a betaxanthin.

32. The host cell of claim 31, wherein the betacyanin is betanin, isobetanin, betanidin, isobetanidin, probetanin, or neobetanin.

33. The host cell of claim 31, wherein the betaxanthin is vulgaxanthin, miraxanthin, portulaxanthin, or indicaxanthin.

34. The host cell of any one of claims 15-32, wherein expression of the gene EXG1 in the host cell is increased.

35. The host cell of claim 34, wherein the host cell is capable of producing more betalain than a host cell that expresses a heterologous polynucleotide encoding a tyrosine hydroxylase comprising the amino acid sequence of SEQ ID NO:

1.

36. The host cell of claim 34 or 35, wherein the host cell is capable of producing at least 1-fold, at least 1.5-fold, at least 2-fold, at least 2.5-fold, at least 3-fold, at least 3.5-fold, at least 4-fold, at least 4.5-fold, at least 5-fold, at least 6-fold, at least 7-fold, at least 8-fold, at least 9-fold, or at least 10-fold more betalain than a host cell that expresses a heterologous polynucleotide encoding a tyrosine hydroxylase comprising the amino acid sequence of SEQ ID NO:

1.

37. The host cell of claim 35 or 36, wherein the betalain is betanidin or isobetanidin.

38. The host cell of any one of claims 27-37, which comprises more than one copy of a polynucleotide encoding ALD6, ATR1, ATR2, LDS2, PEX19, PGM1, TPI1 or ZWF1, or any combination thereof, relative to a corresponding wild-type or control host cell.

39. The host cell of any one of claims 28-38, which comprises a deletion in or of a polynucleotide encoding CYP76AD5, ARO5, ATF1, BUD17, CTA1, DAL7, EXG1, GCN4, GPH1, GRX4, MCK1, PUT1 or YDC1, or any combination of such deletion.Attorney Docket No. G0919.70121WO00   40. The host cell of any one of claims 27-38, wherein the ATR1 is AtATR1 and / or the ATR2 is AtATR2.

41. A method of producing a betalain, comprising contacting tyrosine with the variant tyrosine hydroxylase of any one of claims 1-14.

42. A method of producing a betalain, comprising culturing the host cell of any one of claims 15-40.

43. The method of any one of claims 41-42, wherein the betalain is a betacyanin or a betaxanthin.

44. The method of claim 43, wherein the betacyanin is betanin, isobetanin, betanidin, isobetanidin, probetanin, or neobetanin.

45. The method of claim 43, wherein the betaxanthin is vulgaxanthin, miraxanthin, portulaxanthin, or indicaxanthin.

46. The method of claim 43, wherein the betalain is betanidin or isobetanidin.

47. The method of any one of claims 41-46, further comprising isolating the betalain.

48. A host cell that comprises a heterologous polynucleotide encoding a tyrosine hydroxylase, wherein the tyrosine hydroxylase is a tyrosine hydroxylase of Table 2, or wherein the tyrosine hydroxylase comprises an amino acid sequence having at least 70% sequence identity to a tyrosine hydroxylase of Table 2, to CYP76AD1 (SEQ ID NO: 1), or to CYP76AD5 (SEQ ID NO: 517).

49. The host cell of claim 48, wherein the tyrosine hydroxylase comprises an amino acid sequence having at least 80% sequence identity to CYP76AD1, to a tyrosine hydroxylase of Table 2, or to CYP76AD5.

50. The host cell of claim 48, wherein the tyrosine hydroxylase comprises an amino acid sequence having at least 90% sequence identity to CYP76AD1, to a tyrosine hydroxylase ofAttorney Docket No. G0919.70121WO00   Table 2, or to CYP76AD5.

51. The host cell of claim 48, wherein the tyrosine hydroxylase is CYP76AD1, a tyrosine hydroxylase of Table 2, or CYP76AD5.

52. The host cell of any one of claims 48-51, wherein the host cell is a bacterial cell, an archaebacterial cell, an algal cell, a fungal cell, a yeast cell, a plant cell, an animal cell, a mammalian cell, or a human cell.

53. The host cell of claim 52, wherein the host cell is a filamentous fungal cell or a yeast cell.

54. The host cell of claim 53, wherein the yeast cell is a Saccharomyces cell, a Yarrowia cell, a Komagataella cell, a Pichia cell, or a Fusarium cell.

55. The host cell of claim 54, wherein the Saccharomyces cell is a Saccharomyces cerevisiae cell.

56. The host cell of claim 54, wherein the Yarrowia cell is a Yarrowia lipolytica cell.

57. The host cell of claim 52, wherein the host cell is a bacterial cell.

58. The host cell of claim 57, wherein the bacterial cell is an Escherichia coli (E. coli) cell, a Bacillus subtilis cell, or a Corynebacterium glutamicum cell.

59. The host cell of claim 52, wherein the plant cell is a sugar beet cell.

60. The host cell of claim 59, wherein the sugar beet cell is a Beta vulgaris cell.

61. The host cell of claim 52, wherein the plant cell is a Solanum lycopersicum cell.

62. The host cell of any one of claims 48-61, wherein the host cell comprises a genetic modification that results in increased expression of a polynucleotide encoding ALD6, ATR1, ATR2, LDS2, PEX19, PGM1, TPI1 or ZWF1, or any combination of such geneticAttorney Docket No. G0919.70121WO00   modification or increased expression, relative to a cell that does not comprise the genetic modification.

63. The host cell of any one of claims 48-62, wherein the host cell comprises a genetic modification that results in reduced or eliminated expression of a polynucleotide encoding CYP76AD5, ARO5, ATF1, BUD17, CTA1, DAL7, EXG1, GCN4, GPH1, GRX4, MCK1, PUT1 or YDC1, or any combination of such genetic modification or reduced or eliminated expression, relative to a cell that does not comprise the genetic modification.

64. The host cell of claim 63, which does not comprise a polynucleotide encoding CYP76AD5, ARO5, ATF1, BUD17, CTA1, DAL7, EXG1, GCN4, GPH1, GRX4, MCK1, PUT1 or YDC1, or any combination thereof.

65. The host cell of any one of claims 62-64, which comprises more than one copy of a polynucleotide encoding ALD6, ATR1, ATR2, LDS2, PEX19, PGM1, TPI1 or ZWF1, or any combination thereof, relative to a corresponding wild-type or control host cell.

66. The host cell of any one of claims 62-65, which comprises a deletion in or of a polynucleotide encoding CYP76AD5, ARO5, ATF1, BUD17, CTA1, DAL7, EXG1, GCN4, GPH1, GRX4, MCK1, PUT1 or YDC1, or any combination of such deletion.

67. The host cell of any one of claims 62-66, which comprises (a) a first genetic modification that results in increased expression of a polynucleotide(s) encoding ALD6, ATR1, ATR2, LDS2, PEX19, or PGM1, or any combination of such first genetic modification or increased expression, relative to a cell that does not comprise the first genetic modification or such combination; (b) a second genetic modification that results in reduced or eliminated expression of a polynucleotide(s) encoding GCN4, ARO5, ATF1, BUD17, GRX4, YDC1, or EXG1, or any combination of such second genetic modification or reduced or eliminated expression, relative to a cell that does not comprise the second genetic modification or such combination; or (c) any combination of (a) and (b).

68. The host cell of any one of claims 62-67, wherein the ATR1 is AtATR1 and / or the ATR2 is AtATR2.Attorney Docket No. G0919.70121WO00   69. The host cell of any one of claims 62-66, which comprises (a) a first genetic modification that results in increased expression of a polynucleotide(s) encoding TPI1, ZWF1, or TPI1 and ZWF1, relative to a cell that does not comprise the first genetic modification; (b) a second genetic modification that results in reduced or eliminated expression of a polynucleotide(s) encoding GPH1, CTA1, DAL7, PUT1, or MCK1, or any combination of such second genetic modification or reduced or eliminated expression, relative to a cell that does not comprise the second genetic modification or such combination; or (c) any combination of (a) and (b).

70. The host cell of any one of claims 48-69, wherein the tyrosine hydroxylase comprises an amino acid substitution at one or more positions that correspond to one or more positions selected from W13, H18, S25, Q26, T29, L31, R70, K92, H94, P95, T114, M115, F147, Q164, K185, H198, Y219, C228, S232, C240, S241, C254, P259, D260, Q278, F280, T286, G288, I346, A403, Q405, A407, I409, I416, C418, F459, and D467 of SEQ ID NO:

1.

71. The host cell of any one of claims 48-70, wherein the tyrosine hydroxylase comprises an amino acid substitution at one or more positions that correspond to one or more positions selected from W13L, H18L, S25R, Q26D, Q26G, Q26H, Q26I, Q26K, Q26L, Q26N, Q26R, Q26S, Q26T, T29K, T29N, T29S, L31K, L31R, R70K, K92H, H94Q, P95A, P95I, P95L, P95N, P95S, P95V, T114S, C144S, T146A, T146G, T146S, F147I, F147L, Q164K, K185N, H198D, H198E, H198G, H198K, H198N, H198S, Y219L, C228F, C228K, C228Y, S232L, C240A, C240D, C240F, C240G, C240I, C240K, C240N, C240S, C240V, S241Y, C254A, C254D, C254E, C254G, C254N, C254Q, C254R, C254T, A258S, P259A, P259E, P259F, P259K, P259L, P259R, P259S, P259T, P259V, D260S, D270N, Q278D, Q278K, Q278N, F280H, F280I, F280M, F280N, F280S, F280Y, T286S, G288D, I346S, A403V, Q405E, Q405P, Q405S, A407P, I409A, I409E, I409K, I409L, I409S, I409V, I416L, C418S, F459G, F459S, and D467G of SEQ ID NO:

1.

72. The host cell of any one of claims 48-71, wherein the host cell is capable of producing more betalain than a host cell that expresses a heterologous polynucleotide encoding a tyrosine hydroxylase comprising the amino acid sequence of SEQ ID NO:

1.

73. The host cell of any one of claims 48-72, wherein the host cell is capable of producing at least 1-fold, at least 1.5-fold, at least 2-fold, at least 2.5-fold, at least 3-fold, at least 3.5-Attorney Docket No. G0919.70121WO00   fold, at least 4-fold, at least 4.5-fold, at least 5-fold, at least 6-fold, at least 7-fold, at least 8- fold, at least 9-fold, or at least 10-fold more betalain than a host cell that expresses a heterologous polynucleotide encoding a tyrosine hydroxylase comprising the amino acid sequence of SEQ ID NO:

1.

74. The host cell of claim 72 or 73, wherein the betalain is a betacyanin or a betaxanthin.

75. The host cell of claim 74, wherein the betacyanin is betanin, isobetanin, betanidin, isobetanidin, probetanin, or neobetanin.

76. The host cell of claim 74, wherein the betaxanthin is vulgaxanthin, miraxanthin, portulaxanthin, or indicaxanthin.

77. The host cell of any one of claims 48-71, wherein expression of the gene EXG1 in the host cell is increased.

78. The host cell of claim 77, wherein the host cell is capable of producing more betalain than a host cell that expresses a heterologous polynucleotide encoding a tyrosine hydroxylase comprising the amino acid sequence of SEQ ID NO:

1.

79. The host cell of claim 77 or 78, wherein the host cell is capable of producing at least 1-fold, at least 1.5-fold, at least 2-fold, at least 2.5-fold, at least 3-fold, at least 3.5-fold, at least 4-fold, at least 4.5-fold, at least 5-fold, at least 6-fold, at least 7-fold, at least 8-fold, at least 9-fold, or at least 10-fold more betalain than a host cell that expresses a heterologous polynucleotide encoding a tyrosine hydroxylase comprising the amino acid sequence of SEQ ID NO:

1.

80. The host cell of claim 78 or 79, wherein the betalain is betanidin or isobetanidin.

81. A method of producing a betalain using the host cell of any one of claims 48-80, the method comprising culturing the host cell under conditions effective to produce betalain.

82. The method of claim 81, further comprising isolating the betalain from the host cell.Attorney Docket No. G0919.70121WO00   83. The method of any one of claims 81-82, wherein the betalain is a betacyanin or betaxanthin.

84. The method of any one of claims 81-83, wherein the betaxanthin is indicaxanthin.

85. The method of any one of claims 81-83, wherein the betacyanin is betanin, isobetanin, betanidin, isobetanidin, probetanin, or neobetanin.

86. The host cell of any one of claims 27-40 and 62-80, wherein (a) the genetic modification, (b) the polynucleotide encoding ALD6, ATR1, ATR2, LDS2, PEX19, PGM1, TPI1 or ZWF1, or (c) any combination of the genetic modification and polynucleotide encoding ALD6, ATR1, ATR2, LDS2, PEX19, PGM1, TPI1 or ZWF1 comprise a sequence heterologous to the host cell.

87. The host cell of any one of claims 27-40 and 62-80, wherein the polynucleotide encoding ALD6, ATR1, ATR2, LDS2, PEX19, PGM1, TPI1 or ZWF1 or any combination of such polynucleotide comprises a sequence heterologous to the host cell.

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