Resveratrol production from recombinant host

Abstract

The present disclosure relates to methods and materials for the production of resveratrol in yeasts (e.g., yeast of the Saccharomyces genus such as S. cerevisiae) by increasing expression of genes of the pentose phosphate or Shikimate pathway and others, such genes, for example, encoding acetyl-CoA synthase, transketolase, transaldolase, enolase, aromatic aminotransferase, prephenate dehydratase, ribose-5-phosphate isomerase, or a monocarboxylate permease.

Description

[0001] RESVERATROL PRODUCTION FROM RECOMBINANT HOST

[0002] RELATED APPLICATION

[0003] This application claims the benefit under 35 U.S.C. § 119(e) to U.S. Provisional Application No. 63 / 517,229 filed on August 2, 2023, entitled “RESVERATROL PRODUCTION FROM RECOMBINANT HOST”, the entire contents of which are incorporated herein by reference.

[0004] REFERENCE TO AN ELECTRONIC SEQUENCE LISTING

[0005] The contents of the electronic sequence listing (C149770097WO00-SEQ-VLJ.xml; Size: 125,171 bytes; and Date of Creation: August 1, 2024) is herein incorporated by reference in its entirety.

[0006] FIELD OF THE INVENTION

[0007] The present disclosure generally relates to methods and materials for the production of resveratrol in yeasts of the Saccharomyces genus such as S. cerevisiae. The present invention relates to the discovery of several transgenic strains capable of producing resveratrol.

[0008] BACKGROUND OF THE INVENTION

[0009] Resveratrol (or 3,4,5-trihydroxystilbene) is a phytophenol belonging to the group of stilbene phytoalexins. Stilbene phytoalexins are low-molecular-mass secondary metabolites constituting the active defense mechanism in plants in response to infections or other stress- related events. Stilbene phytoalexins contain the stilbene skeleton (trans- 1,2-diphenylethylene) as their common basic structure that may be supplemented by addition of other groups as well. Stilbenes have been found in certain tree species (angiosperms, gymnosperms), but also in some herbaceous plants (in species of the Myrtaceae, Vitaceae and Leguminosae families). Said compounds are toxic to pests, especially to fungi, bacteria and insects. Only a few plants have the ability to synthesize stilbenes or to produce them in an amount that imparts sufficient resistance to pests.

[0010] The synthesis of the basic stilbene skeleton is pursued by stilbene synthases. Substrates that are used by known stilbene synthases include malonyl-CoA, cinnamoyl-CoA or coumaroyl-CoA. These substances occur in every plant because they are used in the biosynthesis of other important plant constituents as well such as flavonoids, flower pigments, and lipids. Resveratrol (FIG. 1, trans isomer) consists of two closely connected phenol rings and belongs to the polyphenols class. While present in other plants, such as eucalyptus, spruce, and lily, and in other foods such as mulberries and peanuts, resveratrol's most abundant natural sources are Vitis vinifera, labrusca and muscadine (rotundifolid) grapes, which are used to make wines. The compound occurs in the vines, roots, seeds, and stalks, but its highest concentration is in the skin, which contains about 50-100 micrograms per gram (pg / g). During red wine vinification the grape skins are included in the must, in contrast to white wine vinification, and therefore resveratrol is found in small quantities in red wine only. Resveratrol has, besides its antifungal properties, been recognized for its cardioprotective and cancer chemopreventive activities acting as a phytoestrogen, an inhibitor of platelet aggregation, and an antioxidant. Recently it has been shown that resveratrol can also activate the SIR2 gene in yeast and the analogous human gene SIRT1, which both play a key role in extending life span. Therefore, much interest has been focused on the life-span extending properties of resveratrol.

[0011] Traditional production processes rely mostly upon extraction of resveratrol, either from the skin of grape berries, or from knotweed. This is a labor-intensive process and generates low yield which, therefore, prompts an incentive for the development of novel, more efficient and high-yielding production processes.

[0012] In plants, the phenylpropanoid pathway is responsible for the synthesis of a wide variety of secondary metabolic compounds, including lignins, salicylates, coumarins, hydroxycinnamic amides, pigments, flavonoids and phytoalexins. Indeed, formation of resveratrol in plants proceeds through the phenylpropanoid pathway. The amino acid L- phenylalanine is converted into trans-cinnamic acid through the non-oxidative deamination by L-phenylalanine ammonia lyase (PAL) (FIG. 2). Next, trans-cinnamic acid is hydroxylated at the para-position to 4-coumaric acid (4-hydroxycinnamic acid, also commonly known as p- coumaric acid) by cinnamate-4-hydroxylase (C4H), a cytochrome P450 monooxygenase enzyme, in conjunction with NADPH: cytochrome P450 reductase (CPR). The 4-coumaric acid is subsequently activated to 4-coumaroyl-CoA by the action of 4-coumarate:CoA ligase (4CL). Finally, resveratrol synthase (VST) catalyzes the condensation of a phenylpropane unit of 4- coumaroyl-CoA with malonyl CoA, resulting in formation of resveratrol.

[0013] A yeast was disclosed that was able to produce resveratrol from 4-coumaric acid that is found in small quantities in grape must. The production of 4-coumaroyl-CoA, and concomitant resveratrol, in laboratory strains of S. cerevisiae, was achieved by co-expressing a heterologous coenzyme-A ligase gene, from hybrid poplar, together with the grapevine resveratrol synthase gene (vstl). The other substrate for resveratrol synthase, malonyl-CoA, is already endogenously produced in yeast and is involved in de novo fatty-acid biosynthesis. The study showed that cells of S. cerevisiae could produce minute amounts of resveratrol, either in the free form or in the glucoside-bound form, when cultured in synthetic medium that was supplemented with 4-coumaric acid.

[0014] However, said yeast would not be suitable for a commercial application because it suffers from low resveratrol yield. There have been considerable efforts to harness various microorganisms to produce resveratrol using metabolic engineering technologies. The first attempt was made by Becker et al (2003) by expressing coumaroyl CoA ligase and Vitis vinifera stilbene synthase in Saccharomyces cerevisiae. After this study, other methods for the producing of resveratrol were by expressing phenylalanine ammonia lyase or tyrosine ammonia lyase, cinnamic 4-hydroxylase, coumaroyl CoA ligase, malonyl coA synthase, and stilbene synthase (e.g., Ibrahim, 2021) in various organisms including Saccharomyces cerevisiae, E. coli, and Yarrowia lipolytica. Other studies reported engineering the shikimate pathway by disrupting ARO4 and ARO7 to prevent feedback inhibition by phenylalanine or tyrosine (Li et al 2015, Liu et al 2022, Saez-Saez et al 2020). However, there still exists the need for the development of micro-organisms capable of higher levels of resveratrol production.

[0015] SUMMARY OF THE INVENTION

[0016] In a first embodiment is a method of increasing resveratrol production using a recombinant Saccharomyces cell comprising cultivating a recombinant Saccharomyces cell in a medium, adding 4-coumaric acid to the medium to initiate the bioconversion of 4-coumaric acid to resveratrol, and extracting resveratrol from at least one of the recombinant cell and medium, wherein the recombinant Saccharomyces cell has been transformed to overexpress a gene encoding an acetyl-coA synthase enzyme.

[0017] In a second embodiment is a method of increasing resveratrol production using a recombinant Saccharomyces cell comprising cultivating a recombinant Saccharomyces cell in a medium, adding 4-coumaric acid to the medium to initiate the bioconversion of 4-coumaric acid to resveratrol, and extracting resveratrol from at least one of the recombinant cell and medium, wherein the recombinant Saccharomyces cell has been transformed to overexpress one or more of the group consisting of a gene encoding a transketolase enzyme, a gene encoding a ribose-5-phosphate ketol isomerase enzyme, a gene encoding a transaldolase enzyme, a gene encoding an enolase 2 enzyme, a gene encoding an aromatic aminotransferase I enzyme, and a gene encoding a prephenate dehydratase enzyme.

[0018] In a third embodiment is a method of increasing resveratrol production using a recombinant Saccharomyces cell comprising cultivating a recombinant Saccharomyces cell in a medium, adding 4-coumaric acid to the medium to initiate the bioconversion of 4-coumaric acid to resveratrol, and extracting resveratrol from at least one of the recombinant cell and medium, wherein the recombinant Saccharomyces cell has been transformed to overexpress one or more of the group consisting of a gene encoding a monocarboxylate permease enzyme.

[0019] Resveratrol produced using the methods and / or the isolated recombinant host cells described herein can be collected and incorporated into a consumer product. For example, the resveratrol can be admixed with a consumer product. In some embodiments, the resveratrol can be incorporated into the consumer product in an amount sufficient to impart, modify, boost or enhance a health boosting benefit.

[0020] Other features and advantages of the present invention will become apparent in the following detailed description, taken with reference to the accompanying drawings.

[0021] BRIEF DESCRIPTION OF THE DRAWINGS

[0022] FIG. 1 illustrates the molecular structure of resveratrol.

[0023] FIG. 2 illustrates a biosynthesis of resveratrol from L-phenylalanine

[0024] FIG. 3 is a bar graph illustrating the generation of CFNS153 strain increasing resveratrol production compared to parent strain CNFS134

[0025] FIG. 4 is a bar graph illustrating increased resveratrol production from CNFS153 strain, repeating experiment shown in figure 1

[0026] FIG. 5 is a bar graph illustrating resveratrol and phloretic acid production from different generations of strains, CNFS153, CNFS173, CNFS204 and CNFS226.

[0027] FIG. 6 is a bar graph illustrating increased resveratrol and phloretic acid production by overexpressing genes in pentose phosphate pathway and shikimate pathway

[0028] FIG. 7 is a bar graph illustrating further strain engineering generating CNFS364

[0029] FIG. 8 is a bar graph illustrating the effectiveness of overexpression of putative transporter, ESBP6

[0030] FIG 9. illustrates pentose phosphate, shikimate and resveratrol biosynthetic pathways and the enzymes that overexpressed. The enzymes overexpressed are shown in grey boxes. Abbreviation; G6P: Glucose 6-phosphate, 6PGL; 6-Phosphoglucono-delta-lactone, 6PGC;6- Phosphoclugonate, RU5P; Ribulose 5-phosphate, X5P;Xylulose 5-phosphate, R5P; Ribose 5- phosphate, G3P; Glyceraldehyde 3-phosphate, S7P; Sedoheptulose 7-phosphate, E4P; Erythrose 4-phosphate, F6P; Fructose 6-phosphate, DHAP; Dihydroxyacetone-phosphate, PEP; Phosphoenolpyruvate, DAHP; 3-deoxy-D-arabino heptulosonate-7-phosphate, DHQ;3- dehydroquinate, DHShiki; 3-Dehydroshikimate, S3P; Shikimate 3-phosphate, 5EPS3P; 5- Endopyruvylshikimate 3-phosphate, 2PGA; 2-phosphoglycerate, RKIl;Ribose-5-phosphate ketol isomerase, TALI; Transaldolase, TKL1; Transketolase, AR01; Pentafunctional aromatic protein, AR02; Bifunctional chorismite synthase and flavin reductase, AR04; 3-deoxy-D- arabino-heptulosonate-7-phosphate synthase, AR07; Chorismate mutase, AR08; Aromatic aminotransferase I, PHA2; Prephenate dehydratase, PAL; Phenylalanine ammonia lyase, C4H; Cinnamic acid 4-hydroxylase, 4CL- 4-coumaric acid CoA ligase, STS; Stilbene synthase, EN02; Enolase II, ACS1; Acetyl-CoA synthase, ACC1; Acetyl-CoA carboxylase

[0031] DETAILED DESCRIPTION

[0032] As used herein, the singular forms “a,” “an” and “the” include plural references unless the content clearly dictates otherwise.

[0033] To the extent that the term “include,” “have,” or the like is used in the description or the claims, such term is intended to be inclusive in a manner similar to the term “comprise” as “comprise” is interpreted when employed as a transitional word in a claim.

[0034] The word “exemplary” is used herein to mean serving as an example, instance, or illustration. Any embodiment described herein as “exemplary” is not necessarily to be construed as preferred or advantageous over other embodiments.

[0035] “Cellular system” is any cell or population of cells that provide for the expression of proteins. It includes bacteria, yeast, plant cells and animal cells. It includes both prokaryotic and eukaryotic cells. It also includes the in vitro expression of proteins based on cellular components, such as ribosomes.

[0036] “Coding sequence” is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is used without limitation to refer to a DNA sequence that encodes a specific amino acid sequence.

[0037] “Growing” or “cultivating” a cellular system includes providing an appropriate medium that would allow cells to multiply and divide. It also includes providing resources so that cells or cellular components can translate and make recombinant proteins. The terms “microorganism,” “microorganism host,” “microorganism host cell,” “recombinant host,” “host cell,” and “recombinant host cell” can be used interchangeably. As used herein, the term “recombinant host” is intended to refer to a host, the genome of which has been augmented by at least one DNA sequence. Such DNA sequences include but are not limited to genes or DNA sequences that are not naturally present, that are not normally transcribed into RNA, nor translated into protein (“expressed”) natively in the cell, and other genes or DNA sequences one desires to introduce into a host. It will be appreciated that typically the genome of a recombinant host described herein is augmented through stable introduction of one or more recombinant genes. Generally, introduced DNA is not originally resident in the host that is the recipient of the DNA, but it is within the scope of this disclosure to isolate a DNA segment from a given host, and to subsequently introduce one or more additional copies of that DNA into the same host, e.g., to enhance production of the product of a gene or alter the expression pattern of a gene. In some instances, the introduced DNA will modify or even replace an endogenous gene or DNA sequence by, e.g., homologous recombination or site-directed mutagenesis. Suitable recombinant hosts include microorganisms

[0038] “Yeasts” are eukaryotic, single-celled microorganisms classified as members of the fungus kingdom. Yeasts are unicellular organisms which evolved from multicellular ancestors but with some species useful for the current invention being those that have the ability to develop multicellular characteristics by forming strings of connected budding cells known as pseudo hyphae or false hyphae.

[0039] The term “complementary” is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is used without limitation to describe the relationship between nucleotide bases that are capable to hybridizing to one another. For example, with respect to DNA, adenosine is complementary to thymine and cytosine is complementary to guanine. Accordingly, the subjection technology also includes isolated nucleic acid fragments that are complementary to the complete sequences as reported in the accompanying Sequence Listing as well as those substantially similar nucleic acid sequences.

[0040] The terms "nucleic acid" and "nucleotide" are to be given their respective ordinary and customary meanings to a person of ordinary skill in the art and are used without limitation to refer to deoxyribonucleotides or ribonucleotides and polymers thereof in either single- or double-stranded form. Unless specifically limited, the term encompasses nucleic acids containing known analogues of natural nucleotides that have similar binding properties as the reference nucleic acid and are metabolized in a manner similar to naturally-occurring nucleotides. In any one embodiment provided herein, a particular nucleic acid sequence can also encompass conservatively modified or degenerate variants thereof (e.g., degenerate codon substitutions) and complementary sequences, as well as the sequence explicitly indicated. As used herein, the terms “polynucleotide”, “nucleotide”, “oligonucleotide”, and “nucleic acid” can be used interchangeably to refer to nucleic acid comprising DNA, RNA, derivatives thereof, or combinations thereof.

[0041] As used herein, the term “gene” refers to a polynucleotide unit comprised of at least one of the DNA sequences disclosed herein, or any DNA sequences encoding the amino acid sequences disclosed herein, or any DNA sequence that hybridizes to the complement of the coding sequence disclosed herein. Preferably, the term includes coding and non-coding regions, and preferably all sequences necessary for normal gene expression including promoters, enhancers, and other regulatory sequences.

[0042] As used herein, the term “recombinant gene” refers to a gene or DNA sequence that is introduced into a recipient host, regardless of whether the same or a similar gene or DNA sequence may already be present in such a host. “Introduced,” or “augmented” in this context, is known in the art to mean introduced or augmented by the hand of man. Thus, a recombinant gene can be a DNA sequence from another species, or can be a DNA sequence that originated from or is present in the same species, but has been incorporated into a host by recombinant methods to form a recombinant host. It will be appreciated that a recombinant gene that is introduced into a host can be identical to a DNA sequence that is normally present in the host being transformed, and is introduced to provide one or more additional copies of the DNA to thereby permit overexpression or modified expression of the gene product of that DNA. The recombinant genes are particularly encoded by cDNA.

[0043] A recombinant gene encoding a polypeptide described herein comprises the coding sequence for that polypeptide, operably linked in sense orientation to one or more regulatory regions suitable for expressing the polypeptide. Because many microorganisms can be capable of expressing multiple gene products from a polycistronic mRNA, multiple polypeptides are optionally expressed under the control of a single regulatory region for those microorganisms, if desired. A coding sequence and a regulatory region are operably linked when the regulatory region and coding sequence are positioned so that the regulatory region is effective for regulating transcription or translation of the sequence. Typically, the translation initiation site of the translational reading frame of the coding sequence is positioned between one and about fifty nucleotides downstream of the regulatory region for a monocistronic gene. In many cases, the coding sequence for a polypeptide described herein is identified in a species other than the recombinant microorganism, i.e., is a heterologous nucleic acid. Thus, the coding sequence can be from other prokaryotic or eukaryotic microorganisms, from plants or from animals. In some cases, however, the coding sequence is a sequence that is native to the microorganism and is being reintroduced into that organism.

[0044] As used herein, the term “engineered biosynthetic pathway” refers to a biosynthetic pathway that occurs in a recombinant host, as described herein, and does not naturally occur in the host. In some embodiments, the engineered biosynthetic pathway comprises enzymes naturally produced by the host, wherein in certain embodiments the extent and amount of expression of the genes encoding these enzymes are altered in the recombinant host; in some embodiments these enzymes are overexpressed in the recombinant host.

[0045] As used herein, the term “endogenous” gene refers to a gene that originates from and is produced or synthesized within a particular organism, tissue, or cell.

[0046] The term "isolated" is to be given its ordinary and customary meaning to a person of ordinary skill in the art, and when used in the context of an isolated nucleic acid or an isolated polypeptide, is used without limitation to refer to a nucleic acid or polypeptide that, by the hand of man, exists apart from its native environment and is therefore not a product of nature. An isolated nucleic acid or polypeptide can exist in a purified form or can exist in a non-native environment such as, for example, in a transgenic host cell.

[0047] The terms "incubating" and "incubation" as used herein means a process of mixing two or more chemical or biological entities (such as a chemical compound and an enzyme) and allowing them to interact under conditions favorable for producing resveratrol.

[0048] The term "degenerate variant" refers to a nucleic acid sequence having a residue sequence that differs from a reference nucleic acid sequence by one or more degenerate codon substitutions. Degenerate codon substitutions can be achieved by generating sequences in which the third position of one or more selected (or all) codons is substituted with mixed base and / or deoxyinosine residues. A nucleic acid sequence and all of its degenerate variants will express the same amino acid or polypeptide.

[0049] The terms "polypeptide," "protein”, and "peptide" are to be given their respective ordinary' and customary meanings to a person of ordinary skill in the art; the three terms are sometimes used interchangeably and are used without limitation to refer to a polymer of amino acids, or amino acid analogs, regardless of its size or function. Although "protein" is often used in reference to relatively large polypeptides, and "peptide" is often used in reference to small polypeptides, usage of these terms in the art overlaps and varies. The term “polypeptide” as used herein refers to peptides, polypeptides, and proteins, unless otherwise noted. The terms "protein," "polypeptide," and "peptide" are used interchangeably herein when referring to a polynucleotide product. Thus, exemplary polypeptides include polynucleotide products, naturally occurring proteins, homologs, orthologs, paralogs, fragments and other equivalents, variants, and analogs of the foregoing.

[0050] The terms "polypeptide fragment" and "fragment," when used in reference to a reference polypeptide, are to be given their ordinary and customary meanings to a person of ordinary skill in the art and are used without limitation to refer to a polypeptide in which amino acid residues are deleted as compared to the reference polypeptide itself, but where the remaining amino acid sequence is usually identical to the corresponding positions in the reference polypeptide. Such deletions can occur at the amino-terminus or carboxy -terminus of the reference polypeptide, or alternatively both.

[0051] The term "functional fragment" of a polypeptide or protein refers to a peptide fragment that is a portion of the full-length polypeptide or protein, and has substantially the same biological activity, or carries out substantially the same function as the full-length polypeptide or protein (e.g., carrying out the same enzymatic reaction). In any one embodiment, the AghSHCl polypeptide may be a functional fragment.

[0052] The terms "variant polypeptide," "modified amino acid sequence" or "modified polypeptide," which are used interchangeably, refer to an amino acid sequence that is different from the reference polypeptide by one or more amino acids, e.g., by one or more amino acid substitutions, deletions, and / or additions. In an aspect, a variant is a "functional variant" which retains some or all of the ability of the reference polypeptide. In any one embodiment, the AghSHCl polypeptide may be a functional variant.

[0053] The term "functional variant" further includes conservatively substituted variants. The term "conservatively substituted variant" refers to a peptide having an amino acid sequence that differs from a reference peptide by one or more conservative amino acid substitutions and maintains some or all of the activity of the reference peptide. A "conservative amino acid substitution" is a substitution of an amino acid residue with a functionally similar residue. Examples of conservative substitutions include the substitution of one non-polar (hydrophobic) residue such as isoleucine, valine, leucine or methionine for another; the substitution of one charged or polar (hydrophilic) residue for another such as between arginine and lysine, between glutamine and asparagine, between threonine and serine; the substitution of one basic residue such as lysine or arginine for another; or the substitution of one acidic residue, such as aspartic acid or glutamic acid for another; or the substitution of one aromatic residue, such as phenylalanine, tyrosine, or tryptophan for another. Such substitutions are expected to have little or no effect on the apparent molecular weight or isoelectric point of the protein or polypeptide. The phrase "conservatively substituted variant" also includes peptides wherein a residue is replaced with a chemically-derivatized residue, provided that the resulting peptide maintains some or all of the activity of the reference peptide as described herein.

[0054] The term "variant," in connection with the polypeptides of the subject technology, further includes a functionally active polypeptide having an amino acid sequence 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%, and even 100% identical to the amino acid sequence of a reference polypeptide. In any one embodiment, the AghSHCl polypeptide may be a variant with any one of the foregoing percentage identities. Preferably such a AghSHCl polypeptide is functional in the conversion of 4-coumaric acid to resveratrol.

[0055] The term "homologous" in all its grammatical forms and spelling variations refers to the relationship between polynucleotides or polypeptides that possess a "common evolutionary origin," including polynucleotides or polypeptides from super families and homologous polynucleotides or proteins from different species (Reeck et al., CELL 50:667, 1987). Such polynucleotides or polypeptides have sequence homology, as reflected by their sequence similarity, whether in terms of percent identity or the presence of specific amino acids or motifs at conserved positions. For example, two homologous polypeptides can have amino acid sequences that are 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 900 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%, and even 100% identical.

[0056] The term “Regulatory region” refers to a nucleic acid having nucleotide sequences that influence transcription or translation initiation and rate, and stability and / or mobility of a transcription or translation product. Regulatory regions include, without limitation, promoter sequences, enhancer sequences, response elements, protein recognition sites, inducible elements, protein binding sequences, 5' and 3' untranslated regions (UTRs), transcriptional start sites, termination sequences, polyadenylation sequences, introns, and combinations thereof. A regulatory region typically comprises at least a core (basal) promoter. A regulatory region also may include at least one control element, such as an enhancer sequence, an upstream element or an upstream activation region (UAR). A regulatory region is operably linked to a coding sequence by positioning the regulatory region and the coding sequence so that the regulatory region is effective for regulating transcription or translation of the sequence. For example, to operably link a coding sequence and a promoter sequence, the translation initiation site of the translational reading frame of the coding sequence is typically positioned between one and about fifty nucleotides downstream of the promoter. A regulatory region can, however, be positioned at further distance, for example as much as about 5,000 nucleotides upstream of the translation initiation site, or about 2,000 nucleotides upstream of the transcription start site.

[0057] "Suitable regulatory sequences" is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is used without limitation to refer to nucleotide sequences located upstream (5' non-coding sequences), within, or downstream (3' non-coding sequences) of a coding sequence, and which influence the transcription, RNA processing or stability, or translation of the associated coding sequence. Regulatory sequences may include promoters, translation leader sequences, introns, and polyadenylation recognition sequences.

[0058] The choice of regulatory regions to be included depends upon several factors, including, but not limited to, efficiency, selectability, inducibility, desired expression level, and preferential expression during certain culture stages. It is a routine matter for one of skill in the art to modulate the expression of a coding sequence by appropriately selecting and positioning regulatory regions relative to the coding sequence. It will be understood that more than one regulatory region may be present, e.g., introns, enhancers, upstream activation regions, transcription terminators, and inducible elements. One or more genes can be combined in a recombinant nucleic acid construct in “modules” useful for a discrete aspect of compound production. Combining a plurality of genes in a module, particularly a polycistronic module, facilitates the use of the module in a variety of species. In addition to genes useful for compound production, a recombinant construct typically also contains an origin of replication, and one or more selectable markers for maintenance of the construct in appropriate species.

[0059] "Promoter" is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is used without limitation to refer to a DNA sequence capable of controlling the expression of a coding sequence or functional RNA. In general, a coding sequence is located 3' to a promoter sequence. Promoters may be derived in their entirety from a native gene or be composed of different elements derived from different promoters found in nature, or even comprise synthetic DNA segments. It is understood by those skilled in the art that different promoters may direct the expression of a gene in different tissues or cell types, or at different stages of development, or in response to different environmental conditions. Promoters, which cause a gene to be expressed in most cell types at most times, are commonly referred to as "constitutive promoters." It is further recognized that since in most cases the exact boundaries of regulatory sequences have not been completely defined, DNA fragments of different lengths may have identical promoter activity.

[0060] The term "operably linked" refers to the association of nucleic acid sequences on a single nucleic acid fragment so that the function of one is affected by the other. For example, a promoter is operably linked with a coding sequence when it is capable of affecting the expression of that coding sequence (i.e., that the coding sequence is under the transcriptional control of the promoter). Coding sequences can be operably linked to regulatory sequences in sense or antisense orientation.

[0061] The term "expression" as used herein, is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is used without limitation to refer to the transcription and stable accumulation of sense (mRNA) or antisense RNA derived from the nucleic acid fragment of the subject technology or production of a gene product in transgenic, transformed or recombinant organisms.

[0062] "Transformation" is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is used without limitation to refer to the transfer of a polynucleotide into a target cell. The transferred polynucleotide can be incorporated into the genome or chromosomal DNA of a target cell, resulting in genetically stable inheritance, or it can replicate independent of the host chromosomal. Host organisms containing the transformed nucleic acid fragments are referred to as "transgenic" or “transformed” or “recombinant”.

[0063] The terms "transformed," "transgenic," and "recombinant," when used herein in connection with host cells, are to be given their respective ordinary and customary meanings to a person of ordinary skill in the art and are used without limitation to refer to a cell of a host organism, such as a plant or microbial cell, into which a heterologous nucleic acid molecule has been introduced. The nucleic acid molecule can be stably integrated into the genome of the host cell, or the nucleic acid molecule can be present as an extrachromosomal molecule. Such an extrachromosomal molecule can be auto-replicating. Transformed cells, tissues, or subjects are understood to encompass not only the end product of a transformation process, but also transgenic progeny thereof.

[0064] The terms "recombinant," "heterologous," and "exogenous," when used herein in connection with polynucleotides, are to be given their ordinary and customary meanings to a person of ordinary skill in the art and are used without limitation to refer to a polynucleotide (e.g., a DNA sequence or a gene) that originates from a source foreign to the particular host cell or, if from the same source, is modified from its original form. Thus, a heterologous gene in a host cell includes a gene that is endogenous to the particular host cell but has been modified through, for example, the use of site-directed mutagenesis or other recombinant techniques. The terms also include non-naturally occurring multiple copies of a naturally occurring DNA sequence. Thus, the terms refer to a DNA segment that is foreign or heterologous to the cell, or homologous to the cell but in a position or form within the host cell in which the element is not ordinarily found.

[0065] Similarly, the terms "recombinant," "heterologous," and "exogenous," when used herein in connection with a polypeptide or amino acid sequence, means a polypeptide or amino acid sequence that originates from a source foreign to the particular host cell or, if from the same source, is modified from its original form. Thus, recombinant DNA segments can be expressed in a host cell to produce a recombinant polypeptide.

[0066] “Protein expression” refers to protein production that occurs after gene expression. It consists of the stages after DNA has been transcribed to messenger RNA (mRNA). The mRNA is then translated into polypeptide chains, which are ultimately folded into proteins. DNA is present in the cells through transfection - a process of deliberately introducing nucleic acids into cells. The term is often used for non-viral methods in eukaryotic cells. It may also refer to other methods and cell types, although other terms are preferred: "transformation" is more often used to describe non-viral DNA transfer in bacteria and non-animal eukaryotic cells, including plant cells. In animal cells, transfection is the preferred term as transformation is also used to refer to progression to a cancerous state (carcinogenesis) in these cells. Transduction is often used to describe virus-mediated DNA transfer. Transformation, transduction, and viral infection are included under the definition of transfection for this application.

[0067] The terms "plasmid," "vector," and "cassette" are to be given their respective ordinary and customary meanings to a person of ordinary skill in the art and are used without limitation to refer to an extra chromosomal element often carrying genes which are not part of the central metabolism of the cell, and usually in the form of circular double-stranded DNA molecules. Such elements may be autonomously replicating sequences, genome integrating sequences, phage or nucleotide sequences, linear or circular, of a single- or double-stranded DNA or RNA, derived from any source, in which a number of nucleotide sequences have been joined or recombined into a unique construction which is capable of introducing a promoter fragment and DNA sequence for a selected gene product along with appropriate 3' untranslated sequence into a cell. "Transformation cassette" refers to a specific vector containing a foreign gene and having elements in addition to the foreign gene that facilitate transformation of a particular host cell. "Expression cassette" refers to a specific vector containing a foreign gene and having elements in addition to the foreign gene that allow for enhanced expression of that gene in a foreign host.

[0068] As used herein "sequence identity" refers to the extent to which two optimally aligned polynucleotide or peptide sequences are invariant throughout a window of alignment of components, e.g., nucleotides or amino acids. An "identity fraction" for aligned segments of a test sequence and a reference sequence is the number of identical components which are shared by the two aligned sequences divided by the total number of components in reference sequence segment, i.e., the entire reference sequence or a smaller defined part of the reference sequence.

[0069] As used herein, the term "percent sequence identity" or "percent identity" refers to the percentage of identical nucleotides in a linear polynucleotide sequence of a reference ("query") polynucleotide molecule (or its complementary strand) as compared to a test ("subject") polynucleotide molecule (or its complementary strand) when the two sequences are optimally aligned (with appropriate nucleotide insertions, deletions, or gaps totaling less than 20 percent of the reference sequence over the window of comparison). Optimal alignment of sequences for aligning a comparison window are well known to those skilled in the art and may be conducted by tools such as the local homology algorithm of Smith and Waterman, the homology alignment algorithm of Needleman and Wunsch, the search for similarity method of Pearson and Lipman, and preferably by computerized implementations of these algorithms such as GAP, BESTFIT, FASTA, and TFASTA available as part of the GCG® Wisconsin Package® (Accelrys Inc., Burlington, MA). An "identity fraction" for aligned segments of a test sequence and a reference sequence is the number of identical components which are shared by the two aligned sequences divided by the total number of components in the reference sequence segment, i.e., the entire reference sequence or a smaller defined part of the reference sequence. Percent sequence identity is represented as the identity fraction multiplied by 100. The comparison of one or more polynucleotide sequences may be to a full-length polynucleotide sequence or a portion thereof, or to a longer polynucleotide sequence. For purposes of this invention "percent identity" may also be determined using BLASTX version 2.0 for translated nucleotide sequences and BLASTN version 2.0 for polynucleotide sequences.

[0070] The percent of sequence identity is preferably determined using the "Best Fit" or "Gap" program of the Sequence Analysis Software Package™ (Version 10; Genetics Computer Group, Inc., Madison, WI). "Gap" utilizes the algorithm of Needleman and Wunsch (Needleman and Wunsch, JOURNAL OF MOLECULAR BIOLOGY 48:443-453, 1970) to find the alignment of two sequences that maximizes the number of matches and minimizes the number of gaps. "BestFit" performs an optimal alignment of the best segment of similarity between two sequences and inserts gaps to maximize the number of matches using the local homology algorithm of Smith and Waterman (Smith and Waterman, ADVANCES IN APPLIED MATHEMATICS, 2:482-489, 1981, Smith et al., NUCLEIC ACIDS RESEARCH 11 :2205-2220, 1983). The percent identity is most preferably determined using the "Best Fit" program.

[0071] Useful methods for determining sequence identity are also disclosed in the Basic Local Alignment Search Tool (BLAST) programs which are publicly available from National Center Biotechnology Information (NCBI) at the National Library of Medicine, National Institute of Health, Bethesda, Md. 20894; see BLAST Manual, Altschul el al., NCBI, NLM, NIH; Altschul etal., J. MOL. BIOL. 215:403-410 (1990); version 2.0 or higher of BLAST programs allows the introduction of gaps (deletions and insertions) into alignments; for peptide sequence BLASTX can be used to determine sequence identity; and, for polynucleotide sequence BLASTN can be used to determine sequence identity.

[0072] As used herein, the term "substantial percent sequence identity" refers to a percent sequence identity of at least about 70% sequence identity, at least about 80% sequence identity, at least about 85% identity, at least about 90% sequence identity, or even greater sequence identity, such as about 98% or about 99% sequence identity. Thus, one embodiment of the invention is a polynucleotide molecule that has at least about 70% sequence identity, at least about 80% sequence identity, at least about 85% identity, at least about 90% sequence identity, or even greater sequence identity, such as about 98% or about 99% sequence identity with a polynucleotide sequence described herein. Polynucleotide molecules that have the activity genes of the current invention are useful in the production of resveratrol as provided herein and have a substantial percent sequence identity to the polynucleotide sequences provided herein and are encompassed within the scope of this invention.

[0073] Identity is the fraction of amino acids that are the same between a pair of sequences after an alignment of the sequences (which can be done using only sequence information or structural information or some other information, but usually it is based on sequence information alone), and similarity is the score assigned based on an alignment using some similarity matrix. The similarity index can be any one of the following BLOSUM62, PAM250, or GONNET, or any matrix used by one skilled in the art for the sequence alignment of proteins.

[0074] Identity is the degree of correspondence between two sub-sequences (no gaps between the sequences). An identity of 25% or higher implies similarity of function, while 18-25% implies similarity of structure or function. Keep in mind that two completely unrelated or random sequences (that are greater than 100 residues) can have higher than 20% identity. Similarity is the degree of resemblance between two sequences when they are compared. This is dependent on their identity.

[0075] As used herein, the term “disrupted gene” refers to a gene containing one or more mutations (e.g., insertion, deletion, or nucleotide substitution, etc.) relative to the wild-type counterpart so as to substantially reduce or completely eliminate the activity of the encoded gene product. The one or more mutations may be located in a non-coding region, for example, a promoter region, a regulatory region that regulates transcription or translation; or an intron region. Alternatively, the one or more mutations may be located in a coding region (e.g., in an exon). In some instances, the disrupted gene does not express or expresses a substantially reduced level of the encoded protein. In other instances, the disrupted gene expresses the encoded protein in a mutated form, which is either not functional or has substantially reduced activity. In some embodiments, a disrupted gene is a gene that does not encode functional protein. In some embodiments, a cell that comprises a disrupted gene does not express a detectable level (e.g., by enzymatic activity) of the protein encoded by the gene. A cell that does not express a detectable level of the protein may be referred to as a knockout cell. For a non-limiting example, a cell having an arolO gene edit may be considered a knockout cell if enzymatic activity associated with the protein cannot be detected using a substrate specific for the arolO enzyme.

[0076] It is noted that terms like “preferably,” “commonly,” and “typically” are not utilized herein to limit the scope of the claimed invention or to imply that certain features are critical, essential, or even important to the structure or function of the claimed invention. Rather, these terms are merely intended to highlight alternative or additional features that can or cannot be utilized in a particular embodiment of this invention. For the purposes of describing and defining this invention it is noted that the term “substantially” is utilized herein to represent the inherent degree of uncertainty that can be attributed to any quantitative comparison, value, measurement, or other representation. The term “substantially” is also utilized herein to represent the degree by which a quantitative representation can vary from a stated reference without resulting in a change in the basic function of the subject matter at issue.

[0077] Constructs According to the Present Invention

[0078] In some aspects, the present invention relates to constructs like expression vectors for expressing a transgenic polypeptide. In an embodiment, the expression vector includes those genetic elements for expression of a recombinant polypeptide described herein (e.g., a 4-coumaric acid:Coenzyme A ligase) in various host cells. The elements for transcription and translation in the host cell can include a promoter, a coding region for the protein complex, and a transcriptional terminator.

[0079] Methods well known to those skilled in the art can be used to construct the genetic expression constructs and recombinant cells disclosed herein. These methods include in vitro recombinant DNA techniques, synthetic techniques, in vivo recombination techniques, and polymerase chain reaction (PCR) techniques. See, for example, techniques as described in Maniatis et al., 1989, MOLECULAR CLONING: A LABORATORY MANUAL, Cold Spring Harbor Laboratory, New York; Ausubel et al., 1989, CURRENT PROTOCOLS IN MOLECULAR BIOLOGY, Greene Publishing Associates and Wiley Interscience, New York, and PCR Protocols: A Guide to Methods and Applications (Innis et al., 1990, Academic Press, San Diego, Calif.). A person of ordinary skill in the art will be aware of the molecular biology techniques available for the preparation of expression vectors. The polynucleotide used for incorporation into the expression vector of the subject technology, as described above, can be prepared by routine techniques such as polymerase chain reaction (PCR). In molecular cloning, a vector is a DNA molecule used as a vehicle to artificially carry foreign genetic material into another cell, where it can be replicated and / or expressed (e.g., plasmid, cosmid, Lambda phages). A vector containing foreign DNA is considered recombinant DNA. The four major types of traditional vectors are plasmids, viral vectors, cosmids, and artificial chromosomes. Of these, the most commonly used vectors are plasmids. Common to all engineered vectors are an origin of replication, a multicloning site, and a selectable marker.

[0080] A number of molecular biology techniques have been developed to operably link DNA to vectors via complementary cohesive termini. In one embodiment, complementary homopolymer tracts can be added to the nucleic acid molecule to be inserted into the vector DNA. The vector and nucleic acid molecule are then joined by hydrogen bonding between the complementary homopolymeric tails to form recombinant DNA molecules.

[0081] In an alternative embodiment, synthetic linkers containing one or more restriction sites provide are used to operably link the polynucleotide of the subject technology to the expression vector. In an embodiment, the polynucleotide is generated by restriction endonuclease digestion. In an embodiment, the nucleic acid molecule is treated with bacteriophage T4 DNA polymerase or E. coli DNA polymerase I, enzymes that remove protruding, 3 '-single-stranded termini with their 3'-5'-exonucleolytic activities, and fill in recessed 3'-ends with their polymerizing activities, thereby generating blunt-ended DNA segments. The blunt-ended segments are then incubated with a large molar excess of linker molecules in the presence of an enzyme that is able to catalyze the ligation of blunt-ended DNA molecules, such as bacteriophage T4 DNA ligase. Thus, the product of the reaction is a polynucleotide carrying polymeric linker sequences at its ends. These polynucleotides are then cleaved with the appropriate restriction enzyme and ligated to an expression vector that has been cleaved with an enzyme that produces termini compatible with those of the polynucleotide.

[0082] Alternatively, a vector having ligation-independent cloning (LIC) sites can be employed. The required PCR amplified polynucleotide can then be cloned into the LIC vector without restriction digest or ligation (Aslanidis and de Jong, NUCL. ACID. RES. 18 6069-74, (1990), Haun et al, BIOTECHNIQUES 13, 515-18 (1992), each of which are incorporated herein by reference).

[0083] In an embodiment, in order to isolate and / or modify the polynucleotide of interest for insertion into the chosen plasmid, it is suitable to use PCR. Appropriate primers for use in PCR preparation of the sequence can be designed to isolate the required coding region of the nucleic acid molecule, add restriction endonuclease or LIC sites, place the coding region in the desired reading frame.

[0084] In an embodiment, a polynucleotide for incorporation into an expression vector of the subject technology is prepared using PCR appropriate oligonucleotide primers. The coding region is amplified, whilst the primers themselves become incorporated into the amplified sequence product. In an embodiment, the amplification primers contain restriction endonuclease recognition sites, which allow the amplified sequence product to be cloned into an appropriate vector.

[0085] The expression vectors can be introduced into host cells by conventional transformation or transfection techniques. Transformation of appropriate cells with an expression vector of the subject technology is accomplished by methods known in the art and typically depends on both the type of vector and cell. Suitable techniques include calcium phosphate or calcium chloride co-precipitation, DEAE-dextran mediated transfection, lipofection, chemoporation or electroporation.

[0086] Successfully transformed cells, that is, those cells containing the expression vector, can be identified by techniques well known in the art. For example, cells transfected with an expression vector of the subject technology can be cultured to produce polypeptides described herein. Cells can be examined for the presence of the expression vector DNA by techniques well known in the art. The host cells can contain a single copy of the expression vector described previously, or alternatively, multiple copies of the expression vector.

[0087] In some embodiments, the transformed cell is a plant cell, an algal cell, a fungal cell, or a yeast cell of the Saccharomyces genus, e.g., Saccharomyces cerevisiae.

[0088] Microbial host cell expression systems and expression vectors containing regulatory sequences that direct high-level expression of foreign proteins that are well-known to those skilled in the art. Any of these could be used to construct vectors for expression of the recombinant polypeptide of the subjection technology in a microbial host cell. These vectors could then be introduced into appropriate microorganisms via transformation to allow for high level expression of the recombinant polypeptide of the subject technology.

[0089] Vectors or cassettes useful for the transformation of suitable microbial host cells are well known in the art. Typically, the vector or cassette contains sequences directing transcription and translation of the relevant polynucleotide, a selectable marker, and sequences allowing autonomous replication or chromosomal integration. Suitable vectors comprise a region 5' of the polynucleotide which harbors transcriptional initiation controls and a region 3' of the DNA fragment which controls transcriptional termination. It is preferred for both control regions to be derived from genes homologous to the transformed host cell, although it is to be understood that such control regions need not be derived from the genes native to the specific species chosen as a host.

[0090] Termination control regions may also be derived from various genes native to the microbial hosts. A termination site optionally may be included for the microbial hosts described herein.

[0091] Preferred host cells include those known to have the ability to produce resveratrol from 4-coumaric acid. For example, preferred host cells can include yeast of the species Saccharomyces cerevisiae.

[0092] As used herein, the term “substituted,” whether preceded by the term “optionally” or not, means that at least one hydrogen present on a group (e.g., a carbon or nitrogen atom) is replaced with a permissible substituent, e.g., a substituent which upon substitution results in a stable compound, e.g., a compound which does not spontaneously undergo transformation such as by rearrangement, cyclization, elimination, or other reaction. Unless otherwise indicated, a “substituted” group has a substituent at one or more substitutable positions of the group, and when more than one position in any given structure is substituted, the substituent is either the same or different at each position. The term “substituted” is contemplated to include substitution with all permissible substituents of organic compounds, any of the substituents described herein that results in the formation of a stable compound. The present disclosure contemplates any and all such combinations in order to arrive at a stable compound. For purposes of this disclosure, heteroatoms such as nitrogen may have hydrogen substituents and / or any suitable substituent as described herein which satisfy the valencies of the heteroatoms and results in the formation of a stable moiety.

[0093] As used herein, the terms “chaicone” and “chaiconoid” are interchangeable and refer to derivatives the compound of formula (I):

[0094] (I) wherein formula (I) may be substituted at one or more suitable positions. Exemplary substituents include, but are not limited to, halogen, cyano, nitro, Ci-Ce alkyl, Ci-Ce haloalkyl, Ci-Ce hydroxyalkyl, hydroxy, Ci-Ce alkoxy, thiol, Ci-Ce alkylthio, amino, Ci-Ce alkyl amino, di-Ci-Ce alkyl amino, carboxyl, Ci-Ce alkoxycarbonyl, amido, and glycosyl.

[0095] As used herein, the terms “stilbene” and “stilbenoid” are interchangeable and refer to compounds based on the compound of formula (II):

[0096] (II) wherein formula (II) may be substituted at one or more suitable positions. Exemplary substituents include, but are not limited to, halogen, cyano, nitro, Ci-Ce alkyl, Ci-Ce haloalkyl, Ci-Ce hydroxyalkyl, hydroxy, Ci-Ce alkoxy, thiol, Ci-Ce alkylthio, amino, Ci-Ce alkyl amino, di-Ci-Ce alkyl amino, carboxyl, Ci-Ce alkoxycarbonyl, amido, and glycosyl.

[0097] As used herein, the terms “dihydrochalcone” and “dihydrochalconoid” are interchangeable and refer to derivatives the compound of formula (III): wherein formula (III) may be substituted at one or more suitable positions. Exemplary substituents include, but are not limited to, halogen, cyano, nitro, Ci-Ce alkyl, Ci-Ce haloalkyl, Ci-Ce hydroxyalkyl, hydroxy, Ci-Ce alkoxy, thiol, Ci-Ce alkylthio, amino, Ci-Ce alkyl amino, di-Ci-Ce alkyl amino, carboxyl, Ci-Ce alkoxycarbonyl, amido, and glycosyl.

[0098] As used herein, the terms “dihydrostilbene” and “dihydrostilbenoid” are interchangeable and refer to compounds based on the compound of formula (IV): wherein formula (IV) may be substituted at one or more suitable positions. Exemplary substituents include, but are not limited to, halogen, cyano, nitro, Ci-Ce alkyl, Ci-Ce haloalkyl, Ci-Ce hydroxyalkyl, hydroxy, Ci-Ce alkoxy, thiol, Ci-Ce alkylthio, amino, Ci-Ce alkyl amino, di-Ci-Ce alkyl amino, carboxyl, Ci-Ce alkoxycarbonyl, amido, and glycosyl.

[0099] As used herein, the term “phenylpropanoid” refers to compounds based on a 3- phenylprop-2-enoate backbone. Examples of such compounds include, but are not limited to, cinnamic acid, coumaric acid, caffeic acid, ferulic acid, 5-hydroxyferulic acid, sinapinic acid, cinnamoyl-CoA, / ?-coumaroyl-CoA, and the like.

[0100] As used herein, the terms “phenylpropanoid derivative” and “phenylpropanoid derivative compound” are interchangeable and refer to any compound derived from, synthesized from, or biosynthesized from a phenylpropanoid; z.e., a phenylpropanoid derivative includes any compound for which a phenylpropanoid compound is a precursor or intermediate. Examples of phenylpropanoid derivatives include, but are not limited to, stilbene compounds and chaicone compounds. Specific examples of phenylpropanoid derivatives include, but are not limited to, naringenin, resveratrol, pinosylvin, pinocembrin chaicone, and pinocembrin.

[0101] As used herein, the term “dihydrophenylpropanoid” refers to compounds based on a phenylpropanoate backbone. Examples of such compounds include, but are not limited to, dihydrocinnamic acid, phloretic acid, 3,4-dihydroxyhydrocinnamic acid, hydroferulic acid, dihydrocoumaroyl-CoA, dihydrocinnamoyl-CoA, and the like.

[0102] As used herein, the terms “dihydrophenylpropanoid derivative” and “dihydrophenylpropanoid derivative compound” are interchangeable and refer to any compound derived from, synthesized from, or biosynthesized from a dihydrophenylpropanoid; i.e. a dihydrophenylpropanoid derivative includes any compound for which a dihydrophenylpropanoid compound is a precursor or intermediate. Examples of dihydrophenylpropanoid derivatives include, but are not limited to, dihydrostilbenoid compounds and dihydrochalcone compounds. Specific examples of dihydrophenylpropanoid derivatives include, but are not limited to, phloretin, phlorizin, dihydropinosylvin, 3-0- methyldihydropinosylvin, 2-isoprenyl-3-O-methyldihydropinosylvin (amorfrutin 2; IUPAC: 3 -methoxy-2-(3 -methylbut-2-en- 1 -y 1 )- 5 -phenethylphenol), and dihydroresveratrol .

[0103] As used herein, the terms “phenylpropanoid pathway,” “phenylpropanoid derivative pathway,” “phenylpropanoid derivative synthesis pathway,” and “phenylpropanoid derivative biosynthesis pathway” are interchangeable and refer to any biosynthesis pathway in which a phenylpropanoid is a precursor or intermediate and in which a phenylpropanoid derivative compound is a product. Phenylpropanoid derivatives, such as chaicones and stilbenes, are biosynthesized according to phenylpropanoid derivative biosynthesis pathways.

[0104] As used herein, the terms “dihydrophenylpropanoid pathway,” “dihydrophenylpropanoid derivative pathway,” “dihydrophenylpropanoid derivative synthesis pathway,” and “dihydrophenylpropanoid derivative biosynthesis pathway” are interchangeable and refer to any biosynthesis pathway in which a phenylpropanoid or dihydrophenylpropanoid is a precursor or intermediate and in which a dihydrophenylpropanoid derivative compound is a product. Dihydrophenylpropanoid derivatives, such as dihydrochalcones and dihydrostilbenes, are biosynthesized according to dihydrophenylpropanoid derivative biosynthesis pathways.

[0105] As used herein, the term “alkyl” means a straight or branched chain hydrocarbon containing from 1 to 20 carbon atoms unless otherwise specified. The term “Cm-Cn alkyl” means an alkyl group having from m to n carbon atoms. For example, “Ci-Ce alkyl” is an alkyl group having from one to six carbon atoms. Representative examples of alkyl include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, iso-butyl, tertbutyl, n-pentyl, isopentyl, neopentyl, n-hexyl, 3 -methylhexyl, 2,2-dimethylpentyl, 2,3- dimethylpentyl, n-heptyl, n-octyl, n-nonyl, and n-decyl.

[0106] The term “alkenyl” as used herein, means a straight or branched chain hydrocarbon containing from 2 to 20 carbons, unless otherwise specified, and containing at least one carbon-carbon double bond. The term “Cm-Cn alkenyl” means an alkenyl group having from m to n carbon atoms. For example, “C2-C6 alkenyl” is an alkenyl group having from one to six carbon atoms. Representative examples of alkenyl include, but are not limited to, ethenyl, 2-propenyl, 2-methyl-2-propenyl, 3-butenyl, 4-pentenyl, 5-hexenyl, 2-heptenyl, 2-methyl-l- heptenyl, 3-decenyl, and 3, 7-dimethylocta-2, 6-dienyl, and 2-propyl-2-heptenyl.

[0107] The term “alkoxy” as used herein, means an alkyl group, as defined herein, appended to the parent molecular moiety through an oxygen atom. Representative examples of alkoxy include, but are not limited to, methoxy, ethoxy, propoxy, 2-propoxy, butoxy, tert-butoxy, pentyloxy, and hexyloxy.

[0108] The terms “cyano” and “nitrile” as used herein, mean a — CN group.

[0109] The term “halogen” as used herein, means — Cl, — Br, — I or — F.

[0110] The term “haloalkyl” refers to an alkyl group, which is substituted with one or more halogen atoms.

[0111] The term “heterocyclyl” as used herein, means a monocyclic heterocycle or a bicyclic heterocycle. The monocyclic heterocycle is a 3, 4, 5, 6 or 7 membered ring containing at least one heteroatom independently selected from the group consisting of O, N, and S where the ring is saturated or unsaturated, but not aromatic. The 3 or 4 membered ring contains 1 heteroatom selected from the group consisting of O, N and S. The 5 membered ring can contain zero or one double bond and one, two or three heteroatoms selected from the group consisting of O, N and S. The 6 or 7 membered ring contains zero, one or two double bonds and one, two or three heteroatoms selected from the group consisting of O, N and S. The bicyclic heterocycle is a monocyclic heterocycle fused to either a phenyl, a monocyclic cycloalkyl, a monocyclic cycloalkenyl, a monocyclic heterocycle, or a monocyclic heteroaryl. The bicyclic heterocycle may be attached through either cyclic moiety (e.g., either through heterocycle or through phenyl.) Representative examples of heterocycle include, but are not limited to, aziridinyl, diazepanyl, 1,3-dioxanyl, 1,3-dioxolanyl, 1,3-dithiolanyl, 1,3-dithianyl, imidazolinyl, imidazolidinyl, isothiazolinyl, isothiazolidinyl, isoxazolinyl, isoxazolidinyl, morpholinyl, oxadiazolinyl, oxadiazolidinyl, oxazolinyl, oxazolidinyl, piperazinyl, piperidinyl, pyranyl, pyrazolinyl, pyrazolidinyl, pyrrolinyl, pyrrolidinyl, tetrahydrofuranyl, tetrahydrothienyl, thiadiazolinyl, thiadiazolidinyl, thiazolinyl, thiazolidinyl, thiomorpholinyl, 1,1-dioxidothiomorpholinyl (thiomorpholine sulfone), thiopyranyl, trithianyl, 2,3- dihydrobenzofuran-2-yl, and indolinyl.

[0112] The term “hydroxyalkyl” refers to an alkyl group, which is substituted with one or more — OH groups.

[0113] As used herein, the term “glycosyl” means is a univalent radical obtained by removing the hemiacetal hydroxyl group from the cyclic form of a monosaccharide or disaccharide. The monosaccharide or monosaccharides units can be selected from any 5-9 carbon atom containing sugars consisting of aldoses (e.g. D-glucose, D-galactose, D-mannose, D-ribose, D-arabinose, L-arabinose, D-xylose, etc.), ketoses (e.g. D-fructose, D-sorbose, D-tagatose, etc.), deoxysugars (e.g. L-rhamnose, L-fucose, etc.), deoxy-aminosugars (e.g. N- acetylglycosamine, N-acetylmannosamine, N-acetylgalactosamine, etc.), uronic acids, ketoaldonic acids (e.g. sialic acid) and like.

[0114] The term “nitro” as used herein, means a — NCh group.

[0115] The phrase “one or more” substituents, as used herein, refers to a number of substituents that equals from one to the maximum number of substituents possible based on the number of available bonding sites, provided that the above conditions of stability and chemical feasibility are met. Unless otherwise indicated, an optionally substituted group may have a substituent at each substitutable position of the group, and the substituents may be either the same or different. As used herein, the term “independently selected” means that the same or different values may be selected for multiple instances of a given variable in a single compound.

[0116] “Optional” or “optionally” means that the subsequently described event or circumstance may or may not occur, and that the description includes instances where said event or circumstance occurs and instances in which it does not. One of ordinary skill in the art would understand that with respect to any molecule described as containing one or more optional substituents, only sterically practical and / or synthetically feasible compounds are meant to be included. “Optionally substituted” refers to all subsequent modifiers in a term, unless stated otherwise.

[0117] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the disclosure belongs. Although any methods and materials similar to or equivalent to those described herein may be used in the practice or testing of the present disclosure, the preferred materials and methods are described below.

[0118] In accordance with the present disclosure, biosynthetic methods for synthesizing dihydrochalcones and / or dihydrostilbenoids are disclosed. Also in accordance with the present disclosure nucleic acid constructs and recombinant cells which find use in the biosynthetic methods are provided.

[0119] Recombinant Saccharomyces Strains

[0120] Producing resveratrol in recombinant hosts requires multiple reaction steps including the ligation of Coenzyme A to 4-coumaric acid and the condensation of one part coumaroyl- CoA to three parts malonyl-CoA. Here is disclosed engineered Saccharomyces strains producing resveratrol by integrating expression cassettes of a 4-coumaroyl-CoA (4CL) ligase from Arabidopsis thaliana and expression cassettes of a stilbene synthase from Vitis vinifera (VvSTS). To increase malonyl-CoA supply, overexpression cassettes of feedback inhibition-resistant mutant acetyl-CoA carboxylase (ACC1) is utilized. Engineering a host cell as provided herein and cultivating the engineered host strain in a mixture including 4-coumaric acid achieved high levels of resveratrol production.

[0121] The Saccharomyces strains of the present disclosure have been transformed to disrupt one or more genes encoding native enzymes that are involved in the degradation of phenylpyruvate. This transformation improves resveratrol production by eliminating competing pathways for the precursor phenylpyruvate. One such gene codes for AROIO, a phenylpyruvate decarboxylase that catalyzes the decarboxylation of phenylpyruvate to phenylacetaldehyde. PDC5 is another phenylpyruvate decarboxylase native to Saccharomyces. In a representative embodiment, either or both genes AROIO (SEQ ID NO: 3 and 4) and PDC5 (SEQ ID NO: 26 and 27) may be disrupted by any of the methods outlined above. In an exemplary embodiment, both genes are disrupted by total sequence deletion. Four At4CL genes have been identified in Arabidopsis thaliana (At4CLl-At4CL4), any of which may be transformed into a Saccharomyces species such as S. cerevisiae. In a nonlimiting embodiment, the Saccharomyces strain is transformed to express a gene coding for At4CLl (SEQ ID NO: 11 and 12), a gene coding for At4CL2 (SEQ ID NO: 13 and 14), or both. The 4CL gene or genes may be codon optimized or harmonized, as is the case for the sequences according to SEQ. ID. NOs: 12 and 14. In one embodiment, the recombinant 4CL gene has at least 90%, 95%, or 99% sequence identity to any one of SEQ. ID. NOs: 12 and 14. In another embodiment, the recombinant 4CL gene has at least 98% or 99% sequence identity to any one of SEQ. ID. NOs: 12 and 14.

[0122] To enhance resveratrol production, the Saccharomyces strain may be transformed to host multiple copies of a gene encoding a stilbene synthase from Vitis vinifera (VvSTS). In representative embodiments, the number of VvSTS genes that are transformed into the host cell may be 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15. Each gene may be selected from a number of differently codon optimized versions of VvSTS, such as those according to sequences SEQ ID NOs: 20, 21, 22, 23, 24, and 25. In one embodiment, each VvSTS gene has at least 90%, 95%, or 99% sequence identity to any one of SEQ. ID. NOs.: 20, 21, 22, 23, 24, and 25. In a further embodiment, each VvSTS gene has at least 98%, or 99% sequence identity to any one of SEQ. ID. NOs.: 20, 21, 22, 23, 24, and 25. In an additional embodiment, each VvSTS gene has a nucleotide sequence selected from the group consisting of SEQ. ID. NOs.: NOs.: 20, 21, 22, 23, 24, and 25.

[0123] Acetyl-CoA carboxylase (ACC) is a biotin-dependent enzyme that catalyzes the carboxylation of acetyl-CoA to produce malonyl-CoA. This enzyme is rate-limiting for the biosynthesis of fatty acids and is known to be inhibited by phosphorylation. Therefore, in embodiments of the present disclosure, the host strain is transformed with a recombinant gene coding for a feedback-inhibition resistant mutant of the S. cerevisiae ACC1 enzyme. In the example mutant of SEQ ID NO: 11, two amino acid substitutions occur at position 659 and 1157, where serine residues have been changed to alanine. In one embodiment, the gene encoding a feedback inhibition-resistant mutant of an acetyl-CoA carboxylase has at least 90%, 95%, or 99% sequence identity to SEQ. ID. NO: 30. In a further embodiment, the gene encoding a feedback inhibition-resistant mutant of an acetyl-CoA carboxylase comprises a nucleotide sequence according to SEQ ID NO: 30. In an additional embodiment, the gene encoding a feedback inhibition-resistant mutant of an acetyl-CoA carboxylase comprises a nucleotide sequence according to SEQ ID NO: 30. Herein is presented the overexpression of the enzymes involved in shikimate pathway e.g., AR01, AR02, AR08. Strains were constructed wherein two main rate-limiting enzymes, AR04 and AR07, were overexpressed to alleviate the feedback inhibition, Overexpression of AR01, AR02 and AR08 were tested in the strain containing the overexpression cassettes of AR04 and AR07 feedback inhibition mutants.

[0124] Herein is presented the overexpression of the enzymes involved in shikimate pathway e.g., AR01, AR02, AR08. Strains were constructed wherein two main rate-limiting enzymes, AR04 and AR07, were overexpressed to alleviate the feedback inhibition, Overexpression of AR01, AR02 and AR08 were tested in the strain containing the overexpression cassettes of AR04 and AR07 feedback inhibition mutants.

[0125] In some embodiments, the host cell has been further transformed with two nucleic acids encoding feedback inhibition mutant of AR04, 3-deoxy-D-arabino-heptulosonate-7-phosphate (DAHP) synthase (SEQ ID NO: 6), and AR07, chorismate mutase (SEQ ID NO:8). Native AR04 can be inhibited by high concentration of tyrosine, phenylalanine and tryptophan. Therefore, a mutation at amino acid position 229 has been introduced to change the lysine residue to leucine, alleviating the feedback inhibition. Similarly, chorismate mutase AR07, is feedback inhibited by high concentrations of phenylalanine, tyrosine and / or tryptophane. The introduction of a feedback inhibition resistant mutant on AR07 amino acid position 141 changing glycine to serine can alleviate the feedback inhibition. In some embodiments of the present invention, the overexpression of these two rate-limiting enzymes increases the carbon flux to the pathway.

[0126] In one non-limiting example, the -deoxy-D-arabino-heptulosonate-7-phosphate (DAHP) synthase, AR04 comprises SEQ ID NO: 5 and SEQ ID NO: 6 and the chorismate mutase AR07 comprises SEQ ID NO: 7 and SEQ ID NO: 8.

[0127] In some embodiments, the host cell has been further transformed with a nucleic acid encoding phenylalanine ammonia lyase SEQ ID NOs: 16 and 47. In more embodiments, the host cell has been further transformed with a nucleic acid construct encoding a cinnamic acid- 4- hydroxylase from Arabidopsis thaliana (SEQ ID NO: 18). In one non-limiting example, the cinnamic acid-4- hydroxylase from Arabidopsis thaliana an amino sequence according to SEQ ID NO: 17.

[0128] Engineering of high titer resveratrol production

[0129] The present disclosure describes the application of metabolic engineering strategies to increase resveratrol production. However, no prior art is identified investigating 1 the effect of overexpression of the enzymes in the other related pathway such as pentose phosphate pathway (FIG. 9) to boost production of major building block for shikimate, erythrose-4-phosphate. The production of another building block for shikimate, phosphoenolpyruvate, derived from glycolysis step before it is converted to pyruvate, can be enhanced by overexpression of EN02 (FIG. 9). Together, enhancing the production of both basic building blocks could result in increased resveratrol production. In some embodiment, to increase the resveratrol production further, several native sequences of Saccharomyces cerevisiae encoding enzymes in pentose phosphate and shikimate pathways were overexpressed under strong promoters such as PDC1, TEF1, TEF2, TDH3, PGK1 and ADH1 (SEQ ID NOs: 49, 50, 51, 52, 53, 54). In more embodiments, the host cell has been further transformed with a nucleic acid construct encoding ribose-5-phosphate ketol isomerase (SEQ ID NO: 56), transaldolase 1 (SEQ ID NO: 10), transketolase (SEQ ID NO:58), pentafunctional aromatic protein (SEQ ID NO: 38), bifunctional chorismite synthase and flavin reductase (SEQ ID NO:40), aromatic aminotransferase I (SEQ ID NO: 36), prephenate dehydratase (SEQ ID NO: 34). In one non-limiting example, the ribose-5-phosphate ketol isomerase (SEQ ID NO: 55), transaldolase 1 (SEQ ID NO:9), transketolase (SEQ ID NO:57), pentafunctional aromatic protein (SEQ ID NO: 37), bifunctional chorismite synthase and flavin reductase (SEQ ID NO:39), aromatic aminotransferase I (SEQ ID NO: 35), prephenate dehydratase (SEQ ID NO: 34) amino sequence according to SEQ ID NOs: 55, 9, 57, 37, 39, 35 and 34.

[0130] ACS1, acetyl CoA synthase, is an enzyme that converts acetate to acetyl CoA. The enzyme is acetylated on amino acid residue 641 by protein acetyltransferase (Starai 2005) when the concentration of acetate is high in cytosol, which makes the enzyme inactive. The inventors introduced a mutant of Salmonella enterica ACS1, SeACS I / .6- / / / J(SEQ ID NO: 1 and 2) to prevent this inhibition mechanism, into the recombinant host which had been used for genetic modifications described above. Together with ACC1 mutant overexpression, this modification will increase the production of malonyl CoA and will increase resveratrol production.

[0131] Transferring endogenously produced resveratrol outside cell

[0132] In some embodiments, to prevent the product inhibition of stilbene synthase by resveratrol, several native sequences of Saccharomyces cerevisiae encoding native transporters were overexpressed under strong promoters such as PDC1, TEF1, TEF2, TDH3, PGK1 and ADH1 (SEQ ID NOs: 49, 50, 51, 52, 53, 54). Another difficulty preventing increased titer of resveratrol producing engineered microorganisms is the product inhibition of resveratrol influencing the activity of stilbene synthase. Therefore, a possible solution is to overexpress native transporters to remove resveratrol from cytosol. In US patent application #2013 / 0209613, it is described that SNQ2 and other ABC transporters increase resveratrol production. Based on the coding sequences presented therein, the authors reported and tested only a limited number of predicted transporters. However, Pereira, et al. (PNAS 2020) conducted adapted laboratory evolution experiments to discover functions or enzymes to make strain resistance to p-coumaric acid. They found ESBP6 and Aro80 are responsible to enhancement of tolerance to p-coumaric acid. Since p-coumaric acid shares a similar molecular structure to resveratrol, provided herein ESBP6 and Aro80 are engineered into a microbial cell to transport resveratrol outside of the microbial cell to alleviate product inhibition by resveratrol through its over expression. In certain embodiments is provided a microbial cell expressing or over-expressing ESBP6 to increase production of resveratrol. In other certain embodiments is provided a Saccharomyces cerevisiae cell expressing or over-expressing ESBP6 to increase production of resveratrol. In other embodiments is provided a microbial cell expressing or over-expressing Aro80 to increase production of resveratrol. In other certain embodiments is provided a Saccharomyces cerevisiae cell expressing or over-expressing Aro80 to increase production of resveratrol. In still other embodiments is provided a microbial cell expressing or over-expressing both Aro80 and ESBP6 to increase production of resveratrol. In still other certain embodiments is provided a Saccharomyces cerevisiae cell expressing or over-expressing both Aro80 and ESBP6 to increase production of resveratrol. In certain embodiments, the host cell has been transformed with a nucleic acid construct encoding putative monocarboxylate permease ESBP6 (SEQ ID NO: 46), zinc finger transcriptional activator ARO 80 (SEQ ID NO:42) and ATP -binding cassette transporter PDR10 (SEQ ID NO: 44). In one non-limiting example, the encoding putative monocarboxyla (SEQ ID NO:41) and ATP-binding cassette transporter PDR10 (SEQ ID NO: 43) amino sequence according to SEQ ID NOs: 45, 41 and 43.

[0133] Cultivation of host cells can be carried out in an aqueous medium in the presence of usual nutrient substances. A suitable culture medium, for example, can contain a carbon source, an organic or inorganic nitrogen source, inorganic salts and growth factors. For the culture medium, glucose can be a preferred carbon source. Phosphates, growth factors and trace elements can be added.

[0134] An illustrative example of a production process is provided in the Examples.

[0135] One skilled in the art will recognize that the resveratrol composition produced by such methods can be further purified and mixed with the ingredients of edible consumer products as described above. The disclosure will be more fully understood upon consideration of the following nonlimiting Examples. It should be understood that these examples, while indicating preferred embodiments of the subject technology, are given by way of illustration only. From the above discussion and these examples, one skilled in the art can ascertain the essential characteristics of the subject technology, and without departing from the spirit and scope thereof, can make various changes and modifications of the subject technology to adapt it to various uses and conditions.

[0136] EXAMPLES

[0137] High titer RSV strain engineering

[0138] Example 1: Construction of Background Strains for de novo resveratrol production strain

[0139] The genome of S. cerevisiae strain BY4741 was modified by deletion of the ARO10 (SEQ ID NOs:3 and 4) open reading frame. ARO10 is phenylpyruvate decarboxylase catalyzing phenylpyruvate degradation to phenylacetaldehyde. The gene was deleted by replacing the coding sequence of ARO10 with the Metl5 marker. Approximately 1000 base pairs of upstream and downstream flanking region of ARO10 coding sequences were amplified producing two PCR products. Complete gene sequence of MET 15 including promoter and terminator was amplified separately. Those three PCR products, ARO10 upstream, MET 15 and ARO10 downstream were stitched together by overlapped PCR to produce ARO 10 knock out DNA fragment. The DNA fragment was transformed directly into BY4741 and selected for methionine prototrophy. The resulting strain was designated as CNFS004 and was used as a background strain for all resveratrol production strains.

[0140] Example 2. Transformation and culture set up

[0141] The integration vector was digested using restriction enzymes to remove vector sequence before transformation. A number of colonies were picked from the transformation plate and inoculated on a 48-well microculture plate. After 48 hours of incubation at 30 °C to make the culture reach saturation, 80 pl of seed culture were inoculated into 48-well plates containing 1 ml of fermentation medium. The medium was composed of synthetic drop out medium without uracil buffered by 50 mM succinate (pH 6.0) with the addition of 40 g / L EnPump (Enpresso GmbH, Berlin, Germany), 0.4% reagent A, 2% vitamin solution (50 mg biotin, 200 mg p-aminobenzoic acid, 1 g nicotinic acid, 1 g Ca-pantothenate, 1 g pyridoxine-HCl, 1 g thiamine-HCl, 25 g myo-inositol per liter). The transformants were cultured in shaking incubator at 250 rpm at a temperature of 30 °C, for a duration of 4 days.

[0142] Example 3. Extraction and analysis of resveratrol from culture

[0143] Resveratrol, dihydroresveratrol, phloretic acid and p-coumaric acid were extracted by adding equal volumes of methanol. The samples were analyzed by high performance liquid chromatography (HPLC) using an Ultra C18 column (100x4.6mm, packed with 3 pm particles). The chromatography was carried out using a Thermo Scientific Vanquish system. Mobile phase A was 50 ppm trifluoroacetic acid in water and mobile phase B was 50 ppm trifluoroacetic acid in 100% methanol. The chromatography was performed according to a linear gradient method with a 1.3 ml / minute flow rate, z.e., initial equilibration was 30% for B, linear gradient for 0 to 6.5 minutes 30% to 75% of B, then the percentage of B was kept stationary for two minutes, and the column was primed with 30% of B for 1 minute. Eluted compounds were detected by diode array illumination at the UV wavelength of 225 nm.

[0144] Example 4. Medium titer resveratrol production strain construction

[0145] The CNFS004 strain was further modified by integrating At4CLl (SEQ ID NOs: l l and 12), one of the resveratrol biosynthetic pathway genes. At4CLl is one of four 4-coumaric acid:Coenzyme A ligase from Arabidopsis thaliana. The open reading frame of At4CLl was codon optimized (SEQ ID NOs: 11 and 12) and integrated into the PDC5 locus (SEQ ID NOs:26 and 27). PDC5 is one of the decarboxylases that degrades phenylpyruvate. The entire open reading frame of PDC5 was replaced with At4CLl flanked by the PGK1 promoter and the SSA1 terminator. The product strain was designated as CNFS007.

[0146] CNFS007 was engineered to produce resveratrol. The engineering was conducted by integrating one copy of gene for each steps including AtPAL2 (SEQ ID NOs: 15 and 16), AtC4H (SEQ ID NOs: 17 and 18), At4CL2(SEQ ID NOs: 13 and 14), and two copies of VvSTS. The sources for genes are described in table 1.

[0147] Table 1. Resveratrol pathway gene cassettes integrated into XII- 1 locus The resulting strain was designated as CNFS76. After curing for uracil marker (cured strain were designated as CNFS 134), the strain was subjected for further modification by integrating AtC4H- ATR2, feedback inhibition mutant Salmonella enterica ACS 1L64 IP (SEQ ID NOs: 3 and 4) and four copies of STS were integrated and the strain was designated as CNFS153 (FIG. 33 and 4). Mutant Aro4K229L (SEQ ID NOs: 5 and 6) and Aro7G141S (SEQ ID NOs: 7 and 8) were integrated into CNFS 173 to relieve feedback resistance by tyrosine or phenylalanine. The strains were designated as CNFS204.

[0148] One more transformation step integrated multiple copies of stilbene synthase VvSTS and one copy of feedback -resistant ACC1S659A, S1157A, (SEQ ID NOs: 29 and 30) to generate a strain designated CNFS226 and cured for markers using a cre-loxP recombination system, yielding a strain designated CNFS273 (FIG. 55).

[0149] Example 5: Impact of overexpression of multiple genes in pentose phosphate and shikimate pathway

[0150] In order to improve resveratrol production further, multiple enzymes that carry out biosynthetic reactions in pentose phosphate pathway and shikimate pathway were overexpressed under strong constitutive promoters. The contents of the integrated plasmids and their promoters are listed in Table 2. Those plasmids were mixed in different combinations to optimized the overexpression of the pathways and integrated into CNFS273 genome.

[0151] 32

[0152] SUBSTITUTE SHEET (RULE 26) Table 2.

[0153] Among all combinations, set 9.02 and 9.06 of Table 2 showed the improvement of RSV production, and negative control for transformation having only the assembler 1 (pYJSS081) also showed production increase (FIG. 66). The transformants received set 9.02, 9.06 and pYJSS081 were designated as CNFS325, 327 and 331 respectively. Set 9.02 contains the

[0154] 33

[0155] SUBSTITUTE SHEET (RULE 26) overexpression cassettes of transaldolase 1 (TALI SEQ ID NOs:9, 10), enolase 2 (ENO2, SEQ ID NOs:31 and 32), aromatic aminotransferase I (ARO8, SEQ ID NOs:35 and 36) and prephenate dehydratase (PHA2, SEQ IDNOs:33 and 34) while set 9.06 and pYJSS081 contains only transaldolase 1 (TALI) and enolase 2 (ENO2).

[0156] The three best strains were subjected for next round of transformation. This round of transformation was to fill uracil auxotrophic marker and add 2 or 6 more copies of VvSTS. Among those transformants, the transformants integrated 6 copies of VvSTS along with uracil marker in CNFS331 was one of the best performers producing 25% more of resveratrol compared to parent strain (FIG. 7). The best producer was designated as CNFS364.

[0157] Example 6: Impact of native transporter overexpression

[0158] Three endogenous transporters or the transcriptional regulator of transporters, ESBP6 (SEQ ID NOs: 45 and 46), PDR10 (SEQ ID NOs: 43 and 44) and Aro80 (SEQ ID NOs: 41 and 42), were tested if the overexpression of these transporters can boost the resveratrol production. All three genes were cloned into integrative vector and transformed into the genome of CNFS364. Transformants were picked and cultures were set up using the protocols described above with minor modification. The culture was set up using the same medium described above, but instead adding 40g / L of Enpump, the culture was fed only with initial 2% glucose, and no further glucose was added. Resveratrol and other products were extracted and analyzed using the protocols described above.

[0159] As a result, the overexpression of ESPB6 increased resveratrol production 20% while overexpression of Aro80 and PDR10 did not make significant difference (FIG. 88). ESBP6 is monocarboxylate permease like protein.

[0160] SEQUENCES

[0161] SEQ ID NO: 1 - Amino acid

[0162] Salmonella enterica acetic co enzyme A synthetase feedback inhibition mutant

[0163] MSQTHKHAIPANIADRCLINPEQYETKYKQSINDPDTFWGEQGKILDWITPYQKVKN TSFAPGNVSIKWYEDGTLNLAANCLDRHLQENGDRTAIIWEGDDTSQSKHISYRELH RDVCRFANTLLDLGIKKGDVVAIYMPMVPEAAVAMLACARIGAVHSVIFGGFSPEA VAGRIIDSSSRLVITADEGVRAGRSIPLKKNVDDALKNPNVTSVEHVIVLKRTGSDID WQEGRDLWWRDLIEKASPEHQPEAMNAEDPLFILYTSGSTGKPKGVLHTTGGYLVY AATTFKYVFDYHPGDIYWCTADVGWVTGHSYLLYGPLACGATTLMFEGVPNWPTP ARMCQVVDKHQVNILYTAPTAIRALMAEGDKAIEGTDRSSLRILGSVGEPINPEAWE

[0164] WYWKKIGKEKCPVVDTWWQTETGGFMITPLPGAIELKAGSATRPFFGVQPALVDNE

[0165] GHPQEGATEGNLVITDSWPGQARTLFGDHERFEQTYFSTFKNMYFSGDGARRDEDG

[0166] YYWITGRVDDVLNVSGHRLGTAEIESALVAHPKIAEAAVVGIPHAIKGQAIYAYVTL

[0167] NHGEEPSPELYAEVRNWVRKEIGPLATPDVLHWTDSLPKTRSGKIMRRILRKIAAGD TSNLGDTSTLADPGVVEKPLEEKQAIAMPS

[0168] SEQ ID N0:2 - Synthetic DNA

[0169] Salmonella enterica acetic co enzyme A synthetase feedback inhibition mutant

[0170] CTATGATGGCATTGCAATGGCTTGCTTCTCTTCGAGCGGTTTTTCCACAACGCCA

[0171] GGATCTGCGAGAGTGGACGTGTCACCTAAATTACTTGTATCTCCGGCGGCGATTT

[0172] TTCGCAGGATTCTCCTCATAATTTTCCCACTCCTTGTTTTTGGTAGAGAGTCTGTC

[0173] CAATGTAAAACATCTGGAGTAGCCAAAGGCCCAATCTCTTTTCGAACCCAGTTCC

[0174] TTACCTCCGCATACAATTCTGGAGAAGGCTCTTCACCATGATTGAGTGTCACATA

[0175] AGCATATATAGCTTGCCCTTTGATAGCATGAGGGATGCCCACAACAGCCGCTTCA

[0176] GCTATCTTAGGATGCGCTACTAGAGCGCTCTCTATTTCAGCCGTCCCCAACCTAT

[0177] GGCCGGAAACGTTTAAGACATCATCAACTCTACCAGTTATCCAGTAATATCCATC

[0178] TTCATCTCTTCTGGCACCATCACCAGAAAAATACATGTTTTTAAAGGTGCTGAAA

[0179] TATGTTTGCTCAAATCTTTCATGATCTCCAAAAAGTGTCCTTGCTTGTCCGGGCCA

[0180] AGAATCTGTTATTACTAAGTTACCTTCTGTCGCGCCCTCTTGTGGATGACCTTCAT

[0181] TATCAACTAAAGCAGGCTGAACCCCGAAAAATGGCCGTGTCGCCGAACCTGCCT

[0182] TCAATTCAATAGCCCCAGGCAGCGGTGTGATCATGAACCCGCCTGTTTCGGTCTG

[0183] CCACCAGGTGTCAACCACTGGGCATTTTTCCTTACCGATTTTCTTCCAATACCACT

[0184] CCCAAGCTTCAGGATTAATTGGTTCGCCCACCGACCCTAAAATCCTTAAGCTAGA

[0185] ACGGTCCGTACCCTCAATGGCTTTATCGCCCTCCGCCATCAATGCTCTGATCGCT

[0186] GTCGGAGCGGTATACAAGATGTTCACTTGATGTTTGTCCACTACTTGACACATTC

[0187] TAGCGGGAGTTGGCCAGTTAGGAACACCCTCAAACATCAATGTAGTAGCACCAC

[0188] ATGCGAGTGGTCCGTATAGTAAGTAAGAGTGACCAGTTACCCAACCCACATCTG

[0189] CTGTACACCAGTAAATGTCACCTGGGTGATAGTCAAATACATACTTAAATGTTGT

[0190] AGCTGCGTACACCAAATAACCGCCGGTTGTATGAAGCACACCTTTTGGCTTGCCG

[0191] GTGGAACCTGAAGTGTACAGAATAAATAGAGGATCTTCAGCATTCATAGCTTCC

[0192] GGTTGATGCTCTGGGGATGCTTTCTCAATCAAATCTCTCCACCACAGATCCCTAC

[0193] CTTCTTGCCAATCTATGTCACTACCGGTTCTTTTCAAAACGATTACGTGTTCAACA

[0194] GAAGTTACATTTGGATTCTTTAACGCATCATCGACATTCTTTTTCAATGGGATAGA

[0195] CCTGCCTGCTCTTACTCCTTCGTCTGCTGTAATAACTAGGCGACTACTACTATCTA

[0196] TGATCCTGCCAGCTACAGCCTCGGGTGAAAAACCACCGAAAATCACGGAATGTA

[0197] CAGCTCCTATCCGAGCGCATGCTAGCATCGCTACGGCGGCCTCTGGAACCATAGG

[0198] CATATAAATAGCAACAACGTCACCCTTTTTAATACCTAAGTCTAGTAATGTGTTT

[0199] GCGAACCTGCACACATCTCTGTGTAGCTCTCTGTACGAGATGTGCTTGGATTGTG

[0200] ATGTATCATCTCCTTCCCATATTATGGCGGTTCTATCTCCGTTCTCTTGTAAATGG

[0201] CGGTCTAGGCAATTTGCAGCCAAATTCAATGTTCCATCTTCATACCATTTAATACT

[0202] GACATTTCCAGGTGCAAATGAGGTGTTTTTAACCTTCTGATAGGGTGTGATCCAA

[0203] TCCAGAATCTTACCCTGCTCTCCCCAAAACGTGTCAGGATCATTGATAGATTGCT TATATTTTGTCTCATATTGTTCGGGATTAATTAAGCACCGATCTGCTATATTAGCA

[0204] GGAATTGCATGTTTGTGGGTCTGGCTCAT

[0205] SEQ ID NO: 3 - Amino acid

[0206] AROIO

[0207] MAPVTIEKFVNQEERHLVSNRSATIPFGEYIFKRLLSIDTKSVFGVPGDFNLSLLEYLY

[0208] SPSVESAGLRWVGTCNELNAAYAADGYSRYSNKIGCLITTYGVGELSALNGIAGSFA

[0209] ENVKVLHIVGVAKSIDSRSSNFSDRNLHHLVPQLHDSNFKGPNHKVYHDMVKDRVA

[0210] CSVAYLEDIETACDQVDNVIRDIYKYSKPGYIFVPADFADMSVTCDNLVNVPRISQQ

[0211] DCIVYPSENQLSDIINKITSWIYSSKTPAILGDVLTDRYGVSNFLNKLICKTGIWNFSTV

[0212] MGKSVIDESNPTYMGQYNGKEGLKQVYEHFELCDLVLHFGVDINEINNGHYTFTYK

[0213] PNAKIIQFHPNYIRLVDTRQGNEQMFKGINFAPILKELYKRIDVSKLSLQYDSNVTQY

[0214] TNETMRLEDPTNGQSSIITQVHLQKTMPKFLNPGDVVVCETGSFQFSVRDFAFPSQLK

[0215] YISQGFFLSIGMALPAALGVGIAMQDHSNAHINGGNVKEDYKPRLILFEGDGAAQMT

[0216] IQELSTILKCNIPLEVIIWNNNGYTIERAIMGPTRSYNDVMSWKWTKLFEAFGDFDGK

[0217] YTNSTLIQCPSKLALKLEELKNSNKRSGIELLEVKLGELDFPEQLKCMVEAAALKRN

[0218] KK

[0219] SEQ ID NO:4 - Native DNA

[0220] AROIO

[0221] ATGGCACCTGTTACAATTGAAAAGTTCGTAAATCAAGAAGAACGACACCTTGTTT

[0222] CCAACCGATCAGCAACAATTCCGTTTGGTGAATACATATTTAAAAGATTGTTGTC

[0223] CATCGATACGAAATCAGTTTTCGGTGTTCCTGGTGACTTCAACTTATCTCTATTAG

[0224] AATATCTCTATTCACCTAGTGTTGAATCAGCTGGCCTAAGATGGGTCGGCACGTG

[0225] TAATGAACTGAACGCCGCTTATGCGGCCGACGGATATTCCCGTTACTCTAATAAG

[0226] ATTGGCTGTTTAATAACCACGTATGGCGTTGGTGAATTAAGCGCCTTGAACGGTA

[0227] TAGCCGGTTCGTTCGCTGAAAATGTCAAAGTTTTGCACATTGTTGGTGTGGCCAA

[0228] GTCCATAGATTCGCGTTCAAGTAACTTTAGTGATCGGAACCTACATCATTTGGTC

[0229] CCACAGCTACATGATTCAAATTTTAAAGGGCCAAATCATAAAGTATATCATGATA

[0230] TGGTAAAAGATAGAGTCGCTTGCTCGGTAGCCTACTTGGAGGATATTGAAACTGC

[0231] ATGTGACCAAGTCGATAATGTTATCCGCGATATTTACAAGTATTCTAAACCTGGT

[0232] TATATTTTTGTTCCTGCAGATTTTGCGGATATGTCTGTTACATGTGATAATTTGGT

[0233] TAATGTTCCACGTATATCTCAACAAGATTGTATAGTATACCCTTCTGAAAACCAA

[0234] TTGTCTGACATAATCAACAAGATTACTAGTTGGATATATTCCAGTAAAACACCTG

[0235] CGATCCTTGGAGACGTACTGACTGATAGGTATGGTGTGAGTAACTTTTTGAACAA

[0236] GCTTATCTGCAAAACTGGGATTTGGAATTTTTCCACTGTTATGGGAAAATCTGTA

[0237] ATTGATGAGTCAAACCCAACTTATATGGGTCAATATAATGGTAAAGAAGGTTTAA

[0238] AACAAGTCTATGAACATTTTGAACTGTGCGACTTGGTCTTGCATTTTGGAGTCGA

[0239] CATCAATGAAATTAATAATGGGCATTATACTTTTACTTATAAACCAAATGCTAAA

[0240] ATCATTCAATTTCATCCGAATTATATTCGCCTTGTGGACACTAGGCAGGGCAATG

[0241] AGCAAATGTTCAAAGGAATCAATTTTGCCCCTATTTTAAAAGAACTATACAAGCG

[0242] CATTGACGTTTCTAAACTTTCTTTGCAATATGATTCAAATGTAACTCAATATACGA

[0243] ACGAAACAATGCGGTTAGAAGATCCTACCAATGGACAATCAAGCATTATTACAC

[0244] AAGTTCACTTACAAAAGACGATGCCTAAATTTTTGAACCCTGGTGATGTTGTCGT TTGTGAAACAGGCTCTTTTCAATTCTCTGTTCGTGATTTCGCGTTTCCTTCGCAAT

[0245] TAAAATATATATCGCAAGGATTTTTCCTTTCCATTGGCATGGCCCTTCCTGCCGCC

[0246] CTAGGTGTTGGAATTGCCATGCAAGACCACTCAAACGCTCACATCAATGGTGGC

[0247] AACGTAAAAGAGGACTATAAGCCAAGATTAATTTTGTTTGAAGGTGACGGTGCA

[0248] GCACAGATGACAATCCAAGAACTGAGCACCATTCTGAAGTGCAATATTCCACTA

[0249] GAAGTTATCATTTGGAACAATAACGGCTACACTATTGAAAGAGCCATCATGGGC

[0250] CCTACCAGGTCGTATAACGACGTTATGTCTTGGAAATGGACCAAACTATTTGAAG

[0251] CATTCGGAGACTTCGACGGAAAGTATACTAATAGCACTCTCATTCAATGTCCCTC

[0252] TAAATTAGCACTGAAATTGGAGGAGCTTAAGAATTCAAACAAAAGAAGCGGGAT

[0253] AGAACTTTTAGAAGTCAAATTAGGCGAATTGGATTTCCCCGAACAGCTAAAGTG

[0254] CATGGTTGAAGCAGCGGCACTTAAAAGAAATAAAAAATAG

[0255] SEQ ID NO: 5 - Amino acids

[0256] ARO4

[0257] MSESPMFAANGMPKVNQGAEEDVRILGYDPLASPALLQVQIPATPTSLETAKRGRRE

[0258] AIDIITGKDDRVLVIVGPCSIHDLEAAQEYALRLKKLSDELKGDLSIIMRAYLEKPRTT

[0259] VGWKGLINDPDVNNTFNINKGLQSARQLFVNLTNIGLPIGSEMLDTISPQYLADLVSF

[0260] GAIGARTTESQLHRELASGLSFPVGFKNGTDGTLNVAVDACQAAAHSHHFMGVTLH

[0261] GVAAITTTKGNEHCFVILRGGKKGTNYDAKSVAEAKAQLPAGSNGLMIDYSHGNSN

[0262] KDFRNQPKVNDVVCEQIANGENAITGVMIESNINEGNQGIPAEGKAGLKYGVSITDA

[0263] CTGWETTEDVLRI<LAAAVRQRREVNI<I<

[0264] SEQ ID NO: 6 - Synthetic DNA

[0265] ARO4

[0266] ATGAGTGAATCTCCAATGTTCGCTGCCAACGGCATGCCAAAGGTAAATCAAGGT

[0267] GCTGAAGAAGATGTCAGAATTTTAGGTTACGACCCATTAGCTTCTCCAGCTCTCC

[0268] TTCAAGTGCAAATCCCAGCCACACCAACTTCTTTGGAAACTGCCAAGAGAGGTA

[0269] GAAGAGAAGCTATAGATATTATTACCGGTAAAGACGACAGAGTTCTTGTCATTGT

[0270] CGGTCCTTGTTCCATCCATGATCTAGAAGCCGCTCAAGAATACGCTTTGAGATTA

[0271] AAGAAATTGTCAGATGAATTAAAAGGTGATTTATCCATCATTATGAGAGCATACT

[0272] TGGAGAAGCCAAGAACAACCGTCGGCTGGAAAGGTCTAATTAATGACCCTGATG

[0273] TTAACAACACTTTCAACATCAACAAGGGTTTGCAATCCGCTAGACAATTGTTTGT

[0274] CAACTTGACAAATATCGGTTTGCCAATTGGTTCTGAAATGCTTGATACCATTTCTC

[0275] CTCAATACTTGGCTGATTTGGTCTCCTTCGGTGCCATTGGTGCCAGAACCACCGA

[0276] ATCTCAACTGCACAGAGAATTGGCCTCCGGTTTGTCTTTCCCAGTTGGTTTCAAG

[0277] AACGGTACCGATGGTACCTTAAATGTTGCTGTGGATGCTTGTCAAGCCGCTGCTC

[0278] ATTCTCACCATTTCATGGGTGTTACTTTGCATGGTGTTGCTGCTATCACCACTACT

[0279] AAGGGTAACGAACACTGCTTCGTTATTCTAAGAGGTGGTAAAAAGGGTACCAAC

[0280] TACGACGCTAAGTCCGTTGCAGAAGCTAAGGCTCAATTGCCTGCCGGTTCCAACG

[0281] GTCTAATGATTGACTACTCTCACGGTAACTCCAATAAGGATTTCAGAAACCAACC

[0282] AAAGGTCAATGACGTTGTTTGTGAGCAAATCGCTAACGGTGAAAACGCCATTAC

[0283] CGGTGTCATGATTGAATCAAACATCAACGAAGGTAACCAAGGCATCCCAGCCGA AGGTAAAGCCGGCTTGAAATATGGTGTTTCCATCACTGATGCTTGTATAGGTTGG

[0284] GAAACTACTGAAGACGTCTTGAGGAAATTGGCTGCTGCTGTCAGACAAAGAAGA

[0285] GAAGTTAACAAGAAATAG

[0286] SEQ ID NO: 7 - Amino acids

[0287] ARO7

[0288] MDFTKPETVLNLQNIRDELVRMEDSIIFKFIERSHFATCPSVYEANHPGLEIPNFKGSF

[0289] LDWALSNLEIAHSRIRRFESPDETPFFPDKIQKSFLPSINYPQILAPYAPEVNYNDKIKK

[0290] VYIEKIIPLISKRDGDDKNNFSSVATRDIECLQSLSRRIHFGKFVAEAKFQSDIPLYTKLI

[0291] KSKDVEGIMKNITNSAVEEKILERLTKKAEVYGVDPTNESGERRITPEYLVKIYKEIVI

[0292] PITKEVEVEYLLRRLEE

[0293] SEQ ID NO: 8 - Synthetic DNA

[0294] ARO7

[0295] ATGGATTTCACAAAACCAGAAACTGTTTTAAATCTACAAAATATTAGAGATGAAT

[0296] TAGTTAGAATGGAGGATTCGATCATCTTCAAATTTATTGAGAGGTCGCATTTCGC

[0297] CACATGTCCTTCAGTTTATGAGGCAAACCATCCAGGTTTAGAAATTCCGAATTTT

[0298] AAAGGATCTTTCTTGGATTGGGCTCTTTCAAATCTTGAAATTGCGCATTCTCGCAT

[0299] CAGAAGATTCGAATCACCTGATGAAACTCCCTTCTTTCCTGACAAGATTCAGAAA

[0300] TCATTCTTACCGAGCATTAACTACCCACAAATTTTGGCGCCTTATGCCCCAGAAG

[0301] TTAATTACAATGATAAAATAAAAAAAGTTTATATTGAAAAGATTATACCATTAAT

[0302] TTCGAAAAGAGATGGTGATGATAAGAATAACTTCTCTTCTGTTGCCACTAGAGAT

[0303] ATAGAATGTTTGCAAAGCTTGAGTAGGAGAATCCACTTTGGCAAGTTTGTTGCTG

[0304] AAGCCAAGTTCCAATCGGATATCCCGCTATACACAAAGCTGATCAAAAGTAAAG

[0305] ATGTCGAGGGGATAATGAAGAATATCACCAATTCTGCCGTTGAAGAAAAGATTC

[0306] TAGAAAGATTAACTAAGAAGGCTGAAGTCTATGGTGTGGACCCTACCAACGAGT

[0307] CAGGTGAAAGAAGGATTACTCCAGAATATTTGGTAAAAATTTATAAGGAAATTG

[0308] TTATACCTATCACTAAGGAAGTTGAGGTGGAATACTTGCTAAGAAGGTTGGAAG AGTAA

[0309] SEQ ID NO: 9 - Amino acids

[0310] TALI

[0311] MSEPAQKKQKVANNSLEQLKASGTVVVADTGDFGSIAKFQPQDSTTNPSLILAAAK

[0312] QPTYAKLIDVAVEYGKKHGKTTEEQVENAVDRLLVEFGKEILKIVPGRVSTEVDARL

[0313] SFDTQATIEKARHIIKLFEQEGVSKERVLIKIASTWEGIQAAKELEEKDGIHCNLTLLFS

[0314] FVQAVACAEAQVTLISPFVGRILDWYKSSTGKDYKGEADPGVISVKKIYNYYKKYG

[0315] YKTIVMGASFRSTDEIKNLAGVDYLTISPALLDKLMNSTEPFPRVLDPVSAKKEAGD KISYISDESKFRFDLNEDAMATEKLSEGIRKFSADIVTLFDLIEKKVTA SEQ ID NO: 10 - Native DNA

[0316] TALI

[0317] ATGTCTGAACCAGCTCAAAAGAAACAAAAGGTTGCTAACAACTCTCTAGAACAA

[0318] TTGAAAGCCTCCGGCACTGTCGTTGTTGCCGACACTGGTGATTTCGGCTCTATTG

[0319] CCAAGTTTCAACCTCAAGACTCCACAACTAACCCATCATTGATCTTGGCTGCTGC

[0320] CAAGCAACCAACTTACGCCAAGTTGATCGATGTTGCCGTGGAATACGGTAAGAA

[0321] GCATGGTAAGACCACCGAAGAACAAGTCGAAAATGCTGTGGACAGATTGTTAGT

[0322] CGAATTCGGTAAGGAGATCTTAAAGATTGTTCCAGGCAGAGTCTCCACCGAAGTT

[0323] GATGCTAGATTGTCTTTTGACACTCAAGCTACCATTGAAAAGGCTAGACATATCA

[0324] TTAAATTGTTTGAACAAGAAGGTGTCTCCAAGGAAAGAGTCCTTATTAAAATTGC

[0325] TTCCACTTGGGAAGGTATTCAAGCTGCCAAAGAATTGGAAGAAAAGGACGGTAT

[0326] CCACTGTAATTTGACTCTATTATTCTCCTTCGTTCAAGCAGTTGCCTGTGCCGAGG

[0327] CCCAAGTTACTTTGATTTCCCCATTTGTTGGTAGAATTCTAGACTGGTACAAATCC

[0328] AGCACTGGTAAAGATTACAAGGGTGAAGCCGACCCAGGTGTTATTTCCGTCAAG

[0329] AAAATCTACAACTACTACAAGAAGTACGGTTACAAGACTATTGTTATGGGTGCTT

[0330] CTTTCAGAAGCACTGACGAAATCAAAAACTTGGCTGGTGTTGACTATCTAACAAT

[0331] TTCTCCAGCTTTATTGGACAAGTTGATGAACAGTACTGAACCTTTCCCAAGAGTT

[0332] TTGGACCCTGTCTCCGCTAAGAAGGAAGCCGGCGACAAGATTTCTTACATCAGCG

[0333] ACGAATCTAAATTCAGATTCGACTTGAATGAAGACGCTATGGCCACTGAAAAAT

[0334] TGTCCGAAGGTATCAGAAAATTCTCTGCCGATATTGTTACTCTATTCGACTTGATT

[0335] GAAAAGAAAGTTACCGCTTAA

[0336] SEQ ID NO: 11 - Amino acid

[0337] Arabidopsis thaliana coumaroyl CoA ligase 1

[0338] MAPQEQAVSQVMEKQSNNNNSDVIFRSKLPDIYIPNHLSLHDYIFQNISEFATKPCLIN GPTGHVYTYSDVHVISRQIAANFHKLGVNQNDVVMLLLPNCPEFVLSFLAASFRGAT ATAANPFFTPAEIAKQAKASNTKLIITEARYVDKIKPLQNDDGVVIVCIDDNESVPIPE GCLRFTELTQSTTEASEVIDSVEISPDDVVALPYSSGTTGLPKGVMLTHKGLVTSVAQ QVDGENPNLYFHSDDVILCVLPMFHIYALNSIMLCGLRVGAAILIMPKFEINLLWELI QRCKVTVAPMVPPIVLAIAKSSETEKYDLSSIRVVKSGAAPLGKELEDAVNAKFPNA KLGQGYGMTEAGPVLAMSLGFAKEPFPVKSGACGTVVRNAEMKIVDPDTGDSLSR NQPGEICIRGHQIMKGYLNNPAATAETIDKDGWLHTGDIGLIDDDDELFIVDRLKELI KYKGFQVAPAELEALLIGHPDITDVAVVAMKEEAAGEVPVAFVVKSKDSELSEDDV KQFVSKQVVFYKRINKVFFTESIPKAPSGKILRKDLRAKLANGL

[0339] SEQ ID NO: 12 - Synthetic DNA

[0340] Codon optimized Arabidopsis thaliana coumaroyl CoA ligase 1

[0341] ATGGCGCCACAAGAACAAGCAGTTTCTCAGGTGATGGAGAAACAGAGCAACAAC

[0342] AACAACAGTGACGTCATTTTCCGATCAAAGTTACCGGATATTTACATCCCGAACC

[0343] ACCTATCTCTCCACGACTACATCTTCCAAAACATCTCCGAATTCGCCACTAAGCC TTGCCTAATCAACGGACCAACCGGCCACGTGTACACTTACTCCGACGTCCACGTC

[0344] ATCTCCCGCCAAATCGCCGCCAATTTTCACAAACTCGGCGTTAACCAAAACGACG

[0345] TCGTCATGCTCCTCCTCCCAAACTGTCCCGAATTCGTCCTCTCTTTCCTCGCCGCC

[0346] TCCTTCCGCGGCGCAACCGCCACCGCCGCAAACCCTTTCTTCACTCCGGCGGAGA

[0347] TAGCTAAACAAGCCAAAGCCTCCAACACCAAACTCATAATCACCGAAGCTCGTT

[0348] ACGTCGACAAAATCAAACCACTTCAAAACGACGACGGAGTAGTCATCGTCTGCA

[0349] TCGACGACAACGAATCCGTGCCAATCCCTGAAGGCTGCCTCCGCTTCACCGAGTT

[0350] GACTCAGTCGACAACCGAGGCATCAGAAGTCATCGACTCGGTGGAGATTTCACC

[0351] GGACGACGTGGTGGCACTACCTTACTCCTCTGGCACGACGGGATTACCAAAAGG

[0352] AGTGATGCTGACTCACAAGGGACTAGTCACGAGCGTTGCTCAGCAAGTCGACGG

[0353] CGAGAACCCGAATCTTTATTTCCACAGCGATGACGTCATACTCTGTGTTTTGCCC

[0354] ATGTTTCATATCTACGCTTTGAACTCGATCATGTTGTGTGGTCTTAGAGTTGGTGC

[0355] GGCGATTCTGATAATGCCGAAGTTTGAGATCAATCTGCTATGGGAGCTGATCCAG

[0356] AGGTGTAAAGTGACGGTGGCTCCGATGGTTCCGCCGATTGTGTTGGCCATTGCGA

[0357] AGTCTTCGGAAACGGAGAAGTATGATTTGAGCTCGATAAGAGTGGTGAAATCTG

[0358] GTGCTGCTCCTCTTGGTAAAGAACTTGAAGATGCCGTTAATGCCAAGTTTCCTAA

[0359] TGCCAAACTCGGTCAGGGATACGGAATGACGGAAGCAGGTCCAGTGCTAGCAAT

[0360] GTCGTTAGGTTTTGCAAAGGAACCTTTTCCGGTTAAGTCAGGAGCTTGTGGTACT

[0361] GTTGTAAGAAATGCTGAGATGAAAATAGTTGATCCAGACACCGGAGATTCTCTTT

[0362] CGAGGAATCAACCCGGTGAGATTTGTATTCGTGGTCACCAGATCATGAAAGGTT

[0363] ACCTCAACAATCCGGCAGCTACAGCAGAAACCATTGATAAAGACGGTTGGCTTC

[0364] ATACTGGAGATATTGGATTGATCGATGACGATGACGAGCTTTTCATCGTTGATCG

[0365] ATTGAAAGAACTTATCAAGTATAAAGGTTTTCAGGTAGCTCCGGCTGAGCTAGAG

[0366] GCTTTGCTCATCGGTCATCCTGACATTACTGATGTTGCTGTTGTCGCAATGAAAG

[0367] AAGAAGCAGCTGGTGAAGTTCCTGTTGCATTTGTGGTGAAATCGAAGGATTCGG

[0368] AGTTATCAGAAGATGATGTGAAGCAATTCGTGTCGAAACAGGTTGTGTTTTACAA

[0369] GAGAATCAACAAAGTGTTCTTCACTGAATCCATTCCTAAAGCTCCATCAGGGAAG

[0370] ATATTGAGGAAAGATCTGAGGGCAAAACTAGCAAATGGATTGTGA

[0371] SEQ ID NO: 13 - Amino acid

[0372] Arabidopsis thaliana coumaroyl CoA ligase 2

[0373] MTTQDVIVNDQNDQKQCSNDVIFRSRLPDIYIPNHLPLHDYIFENISEFAAKPCLINGP TGEVYTYADVHVTSRKLAAGLHNLGVKQHDVVMILLPNSPEVVLTFLAASFIGAITT SANPFFTPAEISKQAKASAAKLIVTQSRYVDKIKNLQNDGVLIVTTDSDAIPENCLRFS ELTQSEEPRVDSIPEKISPEDVVALPFSSGTTGLPKGVMLTHKGLVTSVAQQVDGENP NLYFNRDDVILCVLPMFHIYALNSIMLCSLRVGATILIMPKFEITLLLEQIQRCKVTVA MVVPPIVLAIAKSPETEKYDLSSVRMVKSGAAPLGKELEDAISAKFPNAKLGQGYGM TEAGPVLAMSLGFAKEPFPVKSGACGTVVRNAEMKILDPDTGDSLPRNKPGEICIRG NQIMKGYLNDPLATASTIDKDGWLHTGDVGFIDDDDELFIVDRLKELIKYKGFQVAP AELESLLIGHPEINDVAVVAMKEEDAGEVPVAFVVRSKDSNISEDEIKQFVSKQVVFY KRINKVFFTDSIPKAPSGKILRKDLRARLANGLMN

[0374] SEQ ID NO: 14 - Synthetic DNA Codon optimized Arabidopsis thaliana coumaroyl CoA ligase 2

[0375] ATGACTACGCAGGATGTTATTGTCAATGATCAAAATGACCAAAAGCAATGTTCG

[0376] AATGATGTTATCTTTCGTAGTAGACTCCCTGATATATACATACCTAACCATCTACC

[0377] ATTGCATGATTACATATTTGAAAATATATCGGAATTTGCTGCTAAGCCATGCCTA

[0378] ATCAATGGTCCAACAGGTGAAGTGTATACCTATGCTGATGTTCATGTTACTTCCA

[0379] GGAAGCTCGCTGCTGGTTTGCACAACTTGGGCGTTAAACAGCATGACGTCGTTAT

[0380] GATATTGCTGCCAAATAGCCCAGAAGTGGTACTTACTTTCTTGGCCGCCTCGTTT

[0381] ATTGGCGCCATTACGACATCCGCAAATCCCTTCTTCACGCCCGCTGAAATTTCTA

[0382] AACAAGCTAAAGCATCTGCTGCTAAATTAATCGTCACACAAAGTAGATATGTTG

[0383] ATAAGATTAAGAACTTACAAAACGATGGGGTCTTAATTGTCACAACCGATTCTGA

[0384] TGCTATCCCTGAAAATTGTCTGAGATTCTCTGAGTTAACTCAATCCGAAGAGCCT

[0385] AGAGTAGACAGTATACCTGAGAAGATCTCTCCAGAAGATGTGGTGGCTTTGCCA

[0386] TTTTCCTCAGGTACTACCGGTCTGCCAAAGGGTGTGATGTTGACTCACAAGGGTT

[0387] TGGTGACGTCAGTAGCTCAGCAAGTAGATGGGGAGAACCCTAATCTGTATTTCA

[0388] ATAGAGATGACGTCATTTTGTGCGTATTACCTATGTTCCATATTTATGCATTAAAC

[0389] TCGATTATGCTATGCTCTCTGCGAGTTGGAGCAACTATATTAATCATGCCAAAGT

[0390] TTGAGATAACTCTCTTGTTAGAACAAATTCAGAGGTGCAAGGTCACTGTTGCTAT

[0391] GGTAGTACCACCAATAGTCCTGGCAATCGCAAAGAGTCCTGAAACCGAGAAGTA

[0392] TGATTTAAGTAGTGTGCGGATGGTTAAATCAGGCGCTGCCCCTCTAGGTAAAGAA

[0393] TTAGAAGATGCCATTTCCGCTAAATTTCCGAATGCAAAATTAGGCCAAGGATATG

[0394] GCATGACGGAAGCTGGTCCAGTTCTAGCAATGTCTTTGGGGTTTGCTAAAGAGCC

[0395] TTTTCCCGTAAAGAGCGGTGCCTGTGGCACTGTTGTGCGTAATGCTGAGATGAAA

[0396] ATACTGGATCCAGACACGGGCGATTCACTACCACGCAATAAACCAGGCGAGATA

[0397] TGTATAAGGGGAAACCAGATTATGAAGGGGTATTTGAACGATCCCCTGGCCACC

[0398] GCCTCAACTATCGATAAGGACGGATGGTTACACACTGGTGACGTTGGGTTTATTG

[0399] ACGATGATGATGAATTATTCATCGTTGACAGATTAAAGGAATTGATCAAATACAA

[0400] AGGTTTTCAAGTAGCTCCAGCAGAACTCGAAAGCCTTTTGATTGGACATCCAGAG

[0401] ATAAATGACGTCGCAGTGGTCGCTATGAAAGAAGAGGATGCTGGTGAAGTTCCC

[0402] GTTGCATTTGTAGTTAGATCGAAGGATTCCAACATTAGCGAGGACGAAATTAAAC

[0403] AATTTGTAAGCAAACAGGTTGTCTTTTATAAAAGAATCAATAAAGTTTTCTTCAC

[0404] TGACTCAATTCCAAAGGCCCCTTCTGGTAAAATCCTGCGTAAGGACTTGAGGGCA

[0405] CGATTGGCTAATGGCCTCATGAATTGA

[0406] SEQ ID NO: 15 - Amino acids

[0407] Ammonia phenylalanine lyase from Arabidopsis thaliana

[0408] MDQIEAMLCGGGEKTKVAVTTKTLADPLNWGLAADQMKGSHLDEVKKMVEEYRR PVVNLGGETLTIGQVAAISTVGGSVKVELAETSRAGVKASSDWVMESMNKGTDSYG VTTGFGATSHRRTKNGTALQTELIRFLNAGIFGNTKETCHTLPQSATRAAMLVRVNT LLQGYSGIRFEILEAITSLLNHNISPSLPLRGTITASGDLVPLSYIAGLLTGRPNSKATGP DGESLTAKEAFEKAGISTGFFDLQPKEGLALVNGTAVGSGMASMVLFEANVQAVLA EVLSAIFAEVMSGKPEFTDHLTHRLKHHPGQIEAAAIMEHILDGSSYMKLAQKVHEM

[0409] DPLQKPKQDRYALRTSPQWLGPQIEVIRQATKSIEREINSVNDNPLIDVSRNKAIHGG NFQGTPIGVSMDNTRLAIAAIGKLMFAQFSELVNDFYNNGLPSNLTASSNPSLDYGFK GAEIAMASYCSELQYLANPVTSHVQSAEQHNQDVNSLGLISSRKTSEAVDILKLMST TFLVGICQAVDLRHLEENLRQTVKNTVSQVAKKVLTTGINGELHPSRFCEKDLLKVV DREQVFTYVDDPCSATYPLMQRLRQVIVDHALSNGETEKNAVTSIFQKIGAFEEELK AVLPKEVEAARAAYGNGTAPIPNRIKECRSYPLYRFVREELGTKLLTGEKVVSPGEEF DKVFTAMCEGKLIDPLMDCLKEWNGAPIPIC

[0410] SEQ ID NO: 16 - Synthetic DNA

[0411] Codon optimized Arabidopsis thaliana phenylalanine ammonia lyase ctaacaaatcggtattggagcaccgttccattcctttaagcaatccatcaacgggtctattagtttaccctcacacattgcagtaaagacttt atcaaattcttccccgggagaaactaccttttcacctgtaagtaactttgtgccaagctcttctctaacaaatctgtataaggggtaggatct acactcctttatacgattaggtattggggcagttccgttaccataggcagctcttgcagcttccacctcttttggtagtacggcttttagctct tcttcaaatgcaccaattttctggaaaatagaagtgacggcattcttctcggtttctccatttgataaggcatggtctacaattacttgacgta atctctgcattaagggatacgtagctgaacagggatcatcaacataagtgaaaacttgttccctgtcaacaacctttagcaaatccttttca caaaacctggaggggtgtaattcgccgttaattccggttgttaagaccttcttggcaacctgacttacagtattcttaacagtctgtctcag gttctcttcaagatgtctaaggtcaacagcctggcagattccaactagaaatgttgtagacatcaacttgagtatgtctactgcttcggaag tctttctcgatgaaattaaaccgagagagttcacgtcctgattatgttgttctgcggattgcacatgagatgttacaggattggctaaatatt ggagctccgaacagtaacttgccatggctatttctgctcctttgaaaccgtaatctaaggatgggttactggaagcggttaaattggacg gtagtccattgttatagaaatcgttcaccaattctgaaaattgagcgaacattaatttaccaatcgccgcgatagctagtctcgtgttgtcca ttgacacaccaataggtgtcccttggaagttaccaccatgaatggctttattgcggctgacgtcaattagaggattatcattcacggaatta atctccctttcgatgctcttagtggcttgtcttattacttcaatttgtgggcccagccattgtggtgaggttctcaaagcatacctatcttgttta ggcttttgtagtggatccatttcatgcaccttttgagcgagtttcatataggagctcccatccaaaatgtgttccattatagcagctgcctca atttgacctggatgatgcttcaatctatgagtcaaatgatcagtaaactctggttttcctgacatcacttccgcaaatatagccgacagcac ctcagccaacactgcttgaacattggcctcgaaaagaaccatactggccatacccgaaccaactgctgtcccattaacaagcgctagg ccttccttgggttgaagatcaaagaatccagtcgatatgcctgccttttcgaatgcctcctttgccgtaagagattccccatctgggccggt tgctttagaattaggtctacctgttaataatcctgcaatataagacagtggtacaagatcaccactggccgttatagtgccccttaatggta gtgaagggctgatattatggttcagaagggacgttatagcttcaaggatttcgaacctaatacccgaataaccctgcaaaagagtatttac ccttaccaacattgcagctctggtagctgattgaggtaaagtatgacatgtctctttggtattgccaaagattccagcgttcaagaagcgg attagttcagtttgaagagcagtaccattctttgtcctcctatgcgaggttgccccgaaaccggtagtcacaccgtatgaatccgtgccttt gttcatactttccattacccaatctgaagaagcttttacgccagccctagatgtttccgctaattcaactttgacgctgccaccaacggtact aatagccgctacttgtcctatcgtcaaagtttcacctcctagattcaccacgggcctacggtactcttcgaccattttcttaacttcatcaag atggcttcctttcatctggtctgcggccagtccccagtttaaaggatcagccaatgtcttagtagtaacggccactttagtcttttcgccacc tccacagagcattgcttcgatttgatccat

[0412] SEQ ID NO: 17 - Amino acids

[0413] Cinnamic acid 4- hydroxylase from Arabidopsis thaliana

[0414] MDLLLLEKSLIAVFVAVILATVISKLRGKKLKLPPGPIPIPIFGNWLQVGDDLNHRNLV DYAKKFGDLFLLRMGQRNLVVVSSPDLTKEVLLTQGVEFGSRTRNVVFDIFTGKGQ DMVFTVYGEHWRKMRRIMTVPFFTNKVVQQNREGWEFEAASVVEDVKKNPDSAT KGIVLRKRLQLMMYNNMFRIMFDRRFESEDDPLFLRLKALNGERSRLAQSFEYNYG DFIPILRPFLRGYLKICQDVKDRRIALFKKYFVDERKQIASSKPTGSEGLKCAIDHILEA EQKGEINEDNVLYIVENINVAAIETTLWSIEWGIAELVNHPEIQSKLRNELDTVLGPGV QVTEPDLHKLPYLQAVVKETLRLRMAIPLLVPHMNLHDAKLAGYDIPAESKILVNA

[0415] WWLANNPNSWKKPEEFRPERFFEEESHVEANGNDFRYVPFGVGRRSCPGIILALPILG

[0416] ITIGRMVQNFELLPPPGQSKVDTSEKGGQFSLHILNHSIIVMKPRNC

[0417] SEQ ID NO: 18 - Synthetic DNA

[0418] Codon optimized Cinnamic acid 4- hydroxylase from Arabidopsis thaliana atggacttgttgttgttggaaaagtctttgatcgctgttttcgttgctgttatcttggctactgttatctctaagttgagaggtaagaagttgaag ttgccaccaggtccaatcccaatcccaatcttcggtaactggttgcaagttggtgacgacttgaaccacagaaacttggttgactacgct aagaagttcggtgacttgttcttgttgagaatgggtcaaagaaacttggttgttgtttcttctccagacttgactaaggaagttttgttgactc aaggtgttgaatttggttcaagaactagaaacgttgttttcgacatcttcactggtaagggtcaagacatggttttcactgtttacggtgaac actggagaaagatgagaagaatcatgactgttccattcttcactaacaaggttgttcaacaaaacagagaaggttgggaatttgaagctg cttctgttgttgaagatgttaagaagaacccagactctgctactaagggtatcgttttgagaaagagattgcaattgatgatgtacaacaac atgttcagaatcatgttcgacagaagattcgaatctgaagatgacccattgttcttgagattgaaggctttgaacggtgaaagatcaagatt ggctcaatctttcgaatacaactacggtgacttcatcccaatcttaagaccattcttgagaggttacttgaagatctgtcaagacgttaagg acagaagaatcgctttgttcaagaagtacttcgttgacgaaagaaagcaaatcgcttcttctaagccaactggttctgaaggtttgaagtg tgctatcgaccacatcttggaagctgaacaaaagggtgaaatcaacgaagataacgttttgtacatcgttgaaaacatcaacgttgctgc tatcgaaactactttgtggtctatcgaatggggtatcgctgaattggttaaccacccagaaatccaatctaagttgagaaacgaattggac actgttttgggtccaggtgttcaagttactgaaccagacttgcacaagttgccatacttgcaagctgttgttaaggaaactttgagattgag aatggctatcccattgttggttccacacatgaacttgcacgacgctaagttggctggttacgacatcccagctgaatctaagatcttggtta acgcttggtggttggctaacaacccaaactcttggaagaagccagaagaatttagaccagaaagattcttcgaagaagaatctcacgtt gaagctaacggtaacgacttcagatacgttccattcggtgttggtagaagatcttgtccaggtatcatcttggctttgccaatcttgggtatc actatcggtagaatggttcaaaacttcgaattgttgccaccaccaggtcaatctaaggttgacacttctgaaaagggtggtcaattctcttt gcacatcttgaaccactctatcatcgttatgaagccaagaaactgttaa

[0419] SEQ ID NO: 19 - Amino acid

[0420] Vitis vinifera stilbene synthase

[0421] MASVEEFRNAQRAKGPATILAIGTATPDHCVYQSDYADYYFKVTKSEHMTALKKKF NRICDKSMIKKRYIHLTEEMLEEHPNIGAYMAPSLNIRQEIITAEVPKLGKEAALKAL KEWGQPKSKITHLVFCTTSGVEMPGADYKLANLLGLEPSVRRVMLYHQGCYAGGT VLRTAKDLAENNAGARVLVVCSEITVVTFRGPSEDALDSLVGQALFGDGSAAVIVGS DPDISIERPLFQLVSAAQTFIPNSAGAIAGNLREVGLTFHLWPNVPTLISENVEKCLTQ AFDPLGISDWNSLFWIAHPGGPAILDAVEAKLNLDKKKLEATRHVLSEYGNMSSAC VLFILDEMRKKSLKGERATTGEGLDWGVLFGFGPGLTIETVVLHSIPMVTN

[0422] SEQ ID NO:20 - Synthetic DNA

[0423] Codon optimized Vitis vinifera stilbene synthase optl

[0424] ATGGCTTCTGTTGAGGAATTTAGGAATGCTCAACGTGCCAAGGGACCCGCCACTA TTCTGGCTATAGGTACTGCCACCCCAGATCATTGCGTATATCAATCGGATTACGC TGACTACTACTTCAAGGTTACCAAAAGTGAGCACATGACAGCCTTGAAGAAGAA GTTTAACCGTATATGCGATAAGTCAATGATCAAGAAAAGATACATTCACTTGACA GAAGAAATGTTAGAGGAACATCCAAATATAGGCGCTTACATGGCTCCATCGTTA

[0425] AACATCCGTCAGGAAATCATTACAGCTGAAGTACCCAAATTAGGTAAAGAGGCT

[0426] GCATTGAAAGCCCTAAAAGAATGGGGCCAACCTAAATCCAAAATTACTCATTTG

[0427] GTATTCTGTACCACAAGCGGCGTTGAAATGCCTGGAGCTGACTATAAACTTGCCA

[0428] ACCTACTGGGCTTGGAACCTTCCGTCCGTAGGGTAATGCTTTACCACCAAGGTTG

[0429] TTATGCTGGTGGGACAGTCTTGAGGACGGCTAAGGACTTAGCCGAAAATAATGC

[0430] TGGGGCACGGGTTCTAGTTGTATGTTCGGAAATTACGGTTGTAACTTTTCGTGGT

[0431] CCATCAGAAGATGCATTAGATTCGTTGGTCGGTCAGGCATTATTTGGCGATGGCT

[0432] CCGCAGCAGTCATCGTCGGTTCGGATCCAGATATTAGTATAGAGCGCCCCTTGTT

[0433] CCAACTCGTATCCGCAGCTCAAACATTTATTCCAAACTCCGCGGGTGCGATTGCC

[0434] GGGAACTTACGGGAAGTGGGTTTAACCTTTCACCTCTGGCCAAATGTTCCTACCC

[0435] TTATTTCCGAAAACGTTGAGAAATGCCTAACACAAGCTTTCGATCCTCTAGGAAT

[0436] CTCGGATTGGAATAGCTTGTTCTGGATTGCCCATCCAGGTGGTCCTGCCATTCTTG

[0437] ATGCGGTTGAGGCTAAATTGAACCTAGACAAGAAGAAGTTGGAAGCCACAAGAC

[0438] ATGTACTGTCAGAATATGGAAATATGAGTTCTGCCTGTGTCTTATTCATACTCGA

[0439] CGAAATGAGAAAGAAGTCCTTAAAGGGCGAAAGAGCTACTACCGGCGAAGGAC

[0440] TAGATTGGGGAGTTTTGTTTGGTTTCGGTCCTGGATTGACAATTGAAACAGTTGTT

[0441] TTGCATAGTATTCCCATGGTTACCAATTAA

[0442] SEQ ID NO: 21 - Synthetic DNA

[0443] Codon optimized Vitis vinifera stilbene synthase opt2

[0444] ATGGCTAGCGTGGAGGAATTTAGGAATGCACAGAGAGCGAAAGGGCCTGCTACC

[0445] ATTTTAGCAATCGGTACTGCGACTCCAGATCATTGTGTATACCAAAGTGATTATG

[0446] CAGACTATTATTTCAAGGTCACCAAGTCTGAACACATGACCGCATTAAAGAAGA

[0447] AGTTTAATAGAATATGCGATAAGAGCATGATCAAGAAACGTTATATTCACTTGAC

[0448] GGAAGAAATGTTGGAAGAACATCCTAATATAGGTGCTTACATGGCACCCTCTTTG

[0449] AATATCAGACAGGAAATAATTACGGCAGAAGTTCCCAAATTGGGAAAAGAGGCT

[0450] GCCTTGAAGGCTTTAAAAGAATGGGGTCAGCCCAAATCTAAAATTACCCACTTA

[0451] GTATTTTGTACGACATCAGGCGTCGAAATGCCAGGTGCGGATTACAAATTAGCCA

[0452] ATTTGTTAGGTTTGGAACCGTCAGTTAGACGTGTTATGTTGTACCATCAAGGATG

[0453] CTATGCCGGTGGGACGGTTCTGAGAACAGCGAAAGATCTAGCTGAGAATAACGC

[0454] AGGCGCAAGAGTATTGGTAGTCTGTTCCGAAATAACTGTTGTCACTTTCAGAGGC

[0455] CCAAGTGAGGACGCGTTGGACTCATTAGTTGGTCAGGCACTGTTTGGCGATGGTT

[0456] CTGCCGCTGTAATTGTCGGTAGCGACCCTGATATAAGTATTGAAAGACCCCTGTT

[0457] CCAATTGGTTTCAGCAGCACAAACTTTTATTCCTAATAGTGCTGGTGCTATCGCT

[0458] GGTAATTTAAGAGAAGTTGGCTTAACATTTCATTTGTGGCCTAATGTTCCAACCC

[0459] TGATAAGCGAAAACGTAGAGAAATGTCTTACCCAAGCGTTCGACCCATTAGGAA

[0460] TTAGTGATTGGAACTCTCTTTTCTGGATCGCACACCCAGGAGGCCCAGCTATATT

[0461] AGACGCAGTTGAAGCTAAGTTAAATTTAGATAAGAAGAAATTGGAGGCAACAAG

[0462] ACATGTGTTATCCGAGTACGGAAATATGTCATCAGCATGTGTGTTGTTTATATTG

[0463] GACGAGATGAGAAAGAAGAGTCTTAAGGGAGAGAGAGCTACCACAGGAGAGGG

[0464] ATTGGATTGGGGTGTCTTATTTGGTTTTGGTCCAGGTCTAACAATTGAAACAGTA

[0465] GTGTTACACTCTATTCCAATGGTCACAAATTAA SEQ ID NO:22 - Synthetic DNA

[0466] Codon optimized Vitis vinifera stilbene synthase opt3

[0467] ATGGCATCCGTGGAAGAATTTAGAAACGCACAGAGGGCAAAAGGTCCAGCAACC

[0468] ATACTAGCTATCGGCACAGCTACCCCTGATCATTGCGTCTATCAGTCGGACTACG

[0469] CTGATTATTATTTTAAGGTTACCAAATCAGAACACATGACCGCATTGAAGAAGAA

[0470] GTTTAACAGAATATGTGACAAATCAATGATTAAGAAGCGCTATATTCATCTAACT

[0471] GAGGAGATGCTGGAGGAACATCCAAATATTGGTGCGTACATGGCACCATCCCTA

[0472] AACATTCGCCAAGAGATTATTACGGCTGAAGTTCCCAAGTTAGGCAAGGAAGCA

[0473] GCTCTGAAGGCATTAAAGGAGTGGGGCCAGCCTAAGAGCAAAATCACTCATCTT

[0474] GTATTTTGTACGACCTCTGGTGTGGAAATGCCTGGAGCTGACTATAAATTAGCGA

[0475] ACTTGTTGGGCCTAGAGCCAAGTGTTAGAAGGGTGATGCTGTATCATCAGGGTTG

[0476] TTATGCAGGTGGTACTGTCTTGAGGACAGCCAAGGATCTGGCTGAAAATAATGCT

[0477] GGCGCCAGAGTACTCGTAGTATGCAGTGAGATCACCGTCGTCACATTTAGGGGA

[0478] CCATCTGAAGATGCTTTGGATTCTCTCGTTGGCCAGGCTTTATTCGGCGATGGTTC

[0479] CGCTGCTGTGATAGTCGGCTCGGATCCTGACATATCCATCGAACGCCCCTTGTTT

[0480] CAATTAGTTAGCGCAGCGCAGACCTTTATACCTAACTCGGCCGGGGCAATAGCA

[0481] GGTAATTTGCGTGAAGTCGGATTGACTTTTCATTTGTGGCCTAACGTCCCCACGTT

[0482] GATTTCAGAAAATGTCGAAAAGTGTTTAACGCAAGCATTCGATCCTCTAGGTATA

[0483] TCTGATTGGAATAGCCTCTTCTGGATTGCACATCCTGGCGGGCCTGCTATTCTGG

[0484] ACGCGGTCGAGGCTAAGTTAAATTTGGATAAGAAGAAGCTGGAAGCCACCAGAC

[0485] ATGTCCTGTCTGAGTACGGGAATATGTCAAGTGCATGTGTGCTCTTTATACTGGA

[0486] CGAGATGAGGAAGAAATCGTTAAAGGGTGAGAGAGCTACTACGGGTGAAGGATT

[0487] AGATTGGGGCGTATTATTCGGCTTCGGTCCGGGGCTCACTATCGAAACAGTAGTC

[0488] CTGCATAGTATCCCCATGGTCACCAATTGA

[0489] SEQ ID NO:23 - Synthetic DNA

[0490] Codon optimized Vitis vinifera stilbene synthase opt4

[0491] ATGGCCTCAGTAGAAGAGTTTCGTAATGCTCAAAGAGCCAAGGGCCCAGCTACA

[0492] ATTTTAGCTATAGGCACCGCTACGCCAGATCATTGTGTTTACCAATCCGATTACG

[0493] CAGATTACTATTTCAAGGTCACAAAGAGCGAACACATGACTGCCTTAAAGAAGA

[0494] AATTTAACCGTATCTGTGACAAATCTATGATCAAGAAGCGTTACATACATTTGAC

[0495] TGAAGAGATGTTAGAGGAGCACCCTAACATTGGTGCCTACATGGCACCGTCGTT

[0496] AAATATCCGTCAAGAAATTATTACAGCTGAGGTCCCAAAGTTAGGTAAGGAAGC

[0497] TGCTCTTAAAGCCTTGAAGGAATGGGGTCAACCTAAGAGTAAAATTACACATTTG

[0498] GTCTTTTGTACCACTTCCGGCGTTGAAATGCCTGGCGCCGATTACAAGTTAGCTA

[0499] ACCTATTAGGTCTGGAACCAAGCGTTCGTCGCGTAATGTTATACCATCAGGGATG

[0500] TTATGCAGGTGGTACTGTATTAAGGACCGCAAAAGACTTGGCAGAAAATAACGC

[0501] GGGCGCCAGAGTATTGGTCGTGTGTAGCGAAATTACGGTTGTAACATTCAGGGGT

[0502] CCATCAGAGGACGCACTGGACAGTCTCGTAGGGCAAGCACTATTTGGTGATGGA

[0503] AGCGCTGCGGTCATTGTTGGTAGCGACCCAGACATATCAATTGAAAGACCTCTTT

[0504] TCCAACTTGTCTCTGCTGCCCAAACTTTTATTCCGAATAGCGCCGGGGCTATCGC

[0505] GGGTAATCTTAGAGAAGTGGGACTGACGTTTCATTTATGGCCAAATGTGCCCACA

[0506] CTTATAAGCGAAAATGTCGAAAAATGTCTTACGCAGGCATTCGATCCTCTTGGTA

[0507] TATCGGATTGGAACTCTCTCTTTTGGATCGCCCATCCAGGTGGTCCTGCAATTCTG

[0508] GATGCTGTAGAAGCAAAACTAAACCTGGACAAGAAGAAACTGGAAGCTACAAG ACATGTCTTGTCGGAATACGGGAACATGAGTTCGGCATGTGTACTTTTTATTTTA

[0509] GATGAGATGCGTAAAAAGTCTCTGAAAGGTGAGCGTGCAACAACCGGTGAAGGT

[0510] TTGGACTGGGGTGTCTTGTTCGGATTCGGTCCCGGCTTAACCATCGAAACTGTAG

[0511] TTCTACATTCTATTCCAATGGTTACTAATTAA

[0512] SEQ ID NO:24 - Synthetic DNA

[0513] Codon optimized Vitis vinifera stilbene synthase opt5

[0514] ATGGCTTCAGTCGAGGAGTTTAGAAATGCTCAGAGGGCCAAGGGTCCTGCCACA

[0515] ATATTAGCTATAGGTACTGCCACCCCAGATCACTGTGTCTATCAAAGTGACTATG

[0516] CTGACTATTATTTTAAAGTCACAAAAAGTGAGCACATGACTGCATTGAAAAAGA

[0517] AATTCAATAGGATATGTGATAAATCAATGATCAAAAAGAGATACATTCATCTAA

[0518] CTGAGGAAATGTTAGAAGAGCATCCAAATATTGGTGCATATATGGCTCCATCCTT

[0519] AAATATCAGACAGGAAATAATAACCGCTGAGGTGCCTAAACTGGGTAAAGAAGC

[0520] TGCATTAAAAGCATTAAAAGAATGGGGTCAGCCTAAATCAAAGATTACGCATCT

[0521] AGTATTTTGCACAACGTCTGGTGTCGAAATGCCTGGAGCCGATTACAAACTAGCA

[0522] AATTTACTAGGTCTTGAACCTTCTGTCCGTCGAGTAATGTTATACCACCAAGGTT

[0523] GCTACGCAGGCGGAACCGTTCTAAGGACTGCCAAGGACTTGGCAGAAAATAACG

[0524] CTGGTGCAAGGGTTTTAGTGGTTTGTTCTGAAATCACTGTAGTCACATTTAGGGG

[0525] TCCCTCTGAAGATGCATTAGACTCTTTAGTTGGGCAAGCACTGTTCGGGGATGGG

[0526] TCTGCGGCCGTTATAGTAGGTTCAGATCCTGACATTTCTATCGAAAGGCCTCTGT

[0527] TTCAACTGGTATCTGCTGCCCAAACTTTTATTCCTAACAGCGCTGGTGCAATCGC

[0528] CGGGAACCTCCGAGAAGTAGGTCTTACATTTCATCTATGGCCTAATGTCCCTACT

[0529] TTGATTTCCGAGAATGTAGAGAAATGCCTGACTCAGGCCTTTGATCCTTTGGGCA

[0530] TATCTGATTGGAACTCACTATTTTGGATTGCACACCCCGGAGGTCCCGCAATTTT

[0531] GGATGCCGTGGAGGCTAAATTAAATTTAGATAAGAAGAAACTCGAAGCAACTAG

[0532] ACATGTATTATCAGAGTACGGCAATATGTCTAGTGCTTGTGTTTTATTTATTTTAG

[0533] ACGAAATGCGTAAAAAGTCTTTAAAGGGAGAGAGGGCTACTACAGGAGAAGGA

[0534] TTAGATTGGGGTGTTTTGTTTGGTTTCGGACCCGGTTTAACGATCGAAACAGTTGT

[0535] TCTGCATAGTATCCCTATGGTGACCAATTGA

[0536] SEQ ID NO:25 - Synthetic DNA

[0537] Codon optimized Vitis vinifera stilbene synthase opt6

[0538] ATGGCATCGGTAGAAGAGTTCAGAAATGCACAGAGGGCTAAAGGCCCTGCCACA

[0539] ATCCTAGCAATTGGTACTGCAACTCCCGATCATTGCGTTTATCAAAGTGATTATG

[0540] CCGACTATTATTTTAAAGTTACGAAATCAGAACACATGACTGCTCTTAAAAAGAA

[0541] ATTCAACAGAATATGTGACAAGAGTATGATTAAAAAGAGATACATTCACTTGAC

[0542] AGAAGAGATGTTGGAGGAGCATCCTAATATCGGCGCTTACATGGCACCTTCATTG

[0543] AACATTCGTCAAGAAATAATTACTGCCGAGGTTCCTAAACTCGGCAAAGAAGCA

[0544] GCACTTAAGGCACTTAAGGAATGGGGTCAGCCAAAGTCAAAGATCACACATTTG

[0545] GTCTTTTGTACAACCTCTGGAGTTGAGATGCCAGGCGCTGATTATAAATTGGCTA

[0546] ATCTTTTAGGATTAGAGCCAAGTGTTAGGCGGGTGATGCTATATCACCAAGGTTG

[0547] TTATGCAGGTGGTACTGTTTTGAGGACAGCCAAGGATCTGGCCGAAAATAATGCT GGGGCCAGAGTCCTGGTTGTTTGCTCCGAGATAACTGTTGTTACATTTCGCGGGC

[0548] CTTCAGAAGATGCACTGGATTCTCTTGTGGGACAGGCGCTGTTTGGTGATGGGTC

[0549] CGCTGCCGTGATCGTAGGCTCTGATCCAGATATATCAATTGAGAGGCCTTTATTT

[0550] CAGTTGGTGTCTGCCGCTCAGACATTCATCCCTAATTCCGCGGGAGCGATAGCTG

[0551] GTAATCTAAGAGAGGTTGGCTTGACATTTCACTTATGGCCTAATGTGCCAACATT

[0552] GATCTCTGAGAACGTCGAAAAGTGCCTAACCCAAGCATTTGACCCATTAGGAATT

[0553] AGCGACTGGAATAGTTTATTTTGGATAGCACACCCTGGAGGTCCGGCTATATTGG

[0554] ATGCTGTGGAAGCAAAGCTAAATCTGGATAAGAAGAAGCTAGAAGCAACAAGA

[0555] CACGTACTATCTGAATACGGAAATATGAGCAGTGCTTGTGTTCTATTTATTCTTGA

[0556] TGAGATGCGTAAAAAGAGTTTAAAtGGAGAAAGAGCCACCACAGGTGAAGGGCT

[0557] AGACTGGGGCGTTTTATTTGGCTTCGGTCCAGGTCTGACAATCGAAACGGTCGTC

[0558] TTACACTCAATTCCAATGGTTACAAATTGA

[0559] SEQ ID NO:26 - Amino acids

[0560] PDC5

[0561] MSEITLGKYLFERLSQVNCNTVFGLPGDFNLSLLDKLYEVKGMRWAGNANELNAA

[0562] YAADGYARIKGMSCIITTFGVGELSALNGIAGSYAEHVGVLHVVGVPSISSQAKQLLL

[0563] HHTLGNGDFTVFHRMSANISETTAMITDIANAPAEIDRCIRTTYTTQRPVYLGLPANL

[0564] VDLNVPAI<LLETPIDLSLI<PNDAEAEAEVVRTVVELII<DAI<NPVILADACASRHDVI<

[0565] AETKKLMDLTQFPVYVTPMGKGAIDEQHPRYGGVYVGTLSRPEVKKAVESADLILSI

[0566] GALLSDFNTGSFSYSYKTKNIVEFHSDHIKIRNATFPGVQMKFALQKLLDAIPEVVKD

[0567] YKPVAVPARVPITKSTPANTPMKQEWMWNHLGNFLREGDIVIAETGTSAFGINQTTF

[0568] PTDVYAIVQVLWGSIGFTVGALLGATMAAEELDPKKRVILFIGDGSLQLTVQEISTMI

[0569] RWGLKPYIFVLNNNGYTIEKLIHGPHAEYNEIQGWDHLALLPTFGARNYETHRVATT

[0570] GEWEKLTQDKDFQDNSKIRMIEVMLPVFDAPQNLVKQAQLTAATNAKQ

[0571] SEQ ID NO:27 - DNA

[0572] PDC5

[0573] ATGTCTGAAATAACCTTAGGTAAATATTTATTTGAAAGATTGAGCCAAGTCAACT

[0574] GTAACACCGTCTTCGGTTTGCCAGGTGACTTTAACTTGTCTCTTTTGGATAAGCTT

[0575] TATGAAGTCAAAGGTATGAGATGGGCTGGTAACGCTAACGAATTGAACGCTGCC

[0576] TATGCTGCTGATGGTTACGCTCGTATCAAGGGTATGTCCTGTATTATTACCACCTT

[0577] CGGTGTTGGTGAATTGTCTGCTTTGAATGGTATTGCCGGTTCTTACGCTGAACATG

[0578] TCGGTGTTTTGCACGTTGTTGGTGTTCCATCCATCTCTTCTCAAGCTAAGCAATTG

[0579] TTGTTGCATCATACCTTGGGTAACGGTGACTTCACTGTTTTCCACAGAATGTCTGC

[0580] CAACATTTCTGAAACCACTGCCATGATCACTGATATTGCTAACGCTCCAGCTGAA

[0581] ATTGACAGATGTATCAGAACCACCTACACTACCCAAAGACCAGTCTACTTGGGTT

[0582] TGCCAGCTAACTTGGTTGACTTGAACGTCCCAGCCAAGTTATTGGAAACTCCAAT

[0583] TGACTTGTCTTTGAAGCCAAACGACGCTGAAGCTGAAGCTGAAGTTGTTAGAACT

[0584] GTTGTTGAATTGATCAAGGATGCTAAGAACCCAGTTATCTTGGCTGATGCTTGTG

[0585] CTTCTAGACATGATGTCAAGGCTGAAACTAAGAAGTTGATGGACTTGACTCAATT

[0586] CCCAGTTTACGTCACCCCAATGGGTAAGGGTGCTATTGACGAACAACACCCAAG ATACGGTGGTGTTTACGTTGGTACCTTGTCTAGACCAGAAGTTAAGAAGGCTGTA

[0587] GAATCTGCTGATTTGATATTGTCTATCGGTGCTTTGTTGTCTGATTTCAATACCGG

[0588] TTCTTTCTCTTACTCCTACAAGACCAAAAATATCGTTGAATTCCACTCTGACCACA

[0589] TCAAGATCAGAAACGCCACCTTCCCAGGTGTTCAAATGAAATTTGCCTTGCAAAA

[0590] ATTGTTGGATGCTATTCCAGAAGTCGTCAAGGACTACAAACCTGTTGCTGTCCCA

[0591] GCTAGAGTTCCAATTACCAAGTCTACTCCAGCTAACACTCCAATGAAGCAAGAAT

[0592] GGATGTGGAACCATTTGGGTAACTTCTTGAGAGAAGGTGATATTGTTATTGCTGA

[0593] AACCGGTACTTCCGCCTTCGGTATTAACCAAACTACTTTCCCAACAGATGTATAC

[0594] GCTATCGTCCAAGTCTTGTGGGGTTCCATTGGTTTCACAGTCGGCGCTCTATTGG

[0595] GTGCTACTATGGCCGCTGAAGAACTTGATCCAAAGAAGAGAGTTATTTTATTCAT

[0596] TGGTGACGGTTCTCTACAATTGACTGTTCAAGAAATCTCTACCATGATTAGATGG

[0597] GGTTTGAAGCCATACATTTTTGTCTTGAATAACAACGGTTACACCATTGAAAAAT

[0598] TGATTCACGGTCCTCATGCCGAATATAATGAAATTCAAGGTTGGGACCACTTGGC

[0599] CTTATTGCCAACTTTTGGTGCTAGAAACTACGAAACCCACAGAGTTGCTACCACT

[0600] GGTGAATGGGAAAAGTTGACTCAAGACAAGGACTTCCAAGACAACTCTAAGATT

[0601] AGAATGATTGAAGTTATGTTGCCAGTCTTTGATGCTCCACAAAACTTGGTTAAAC

[0602] AAGCTCAATTGACTGCCGCTACTAACGCTAAACAATAA

[0603] SEQ ID NO:28 - DNA

[0604] TDH3 promoter tcattatcaatactgccatttcaaagaatacgtaaataattaatagtagtgattttcctaactttatttagtcaaaaaattagccttttaattctgct gtaacccgtacatgcccaaaatagggggcgggttacacagaatatataacatcgtaggtgtctgggtgaacagtttattcctggcatcca ctaaatataatggagcccgctttttaagctggcatccagaaaaaaaaagaatcccagcaccaaaatattgttttcttcaccaaccatcagtt cataggtccattctcttagcgcaactacagagaacaggggcacaaacaggcaaaaaacgggcacaacctcaatggagtgatgcaac ctgcctggagtaaatgatgacacaaggcaattgacccacgcatgtatctatctcattttcttacaccttctattaccttctgctctctctgattt ggaaaaagctgaaaaaaaaggttgaaaccagttccctgaaattattcccctacttgactaataagtatataaagacggtaggtattgattg taattctgtaaatctatttcttaaacttcttaaattctacttttatagttagtcttttttttagttttaaaacaccaagaacttagtttcgaataaacac acataaacaaacaaa

[0605] SEQ ID NO:29 - Amino acid

[0606] Modified Saccharomyces cerevisiae acetyl CoA carboxylase 1

[0607] MSEESLFESSPQKMEYEITNYSERHTELPGHFIGLNTVDKLEESPLRDFVKSHGGHTVI SKILIANNGIAAVKEIRSVRKWAYETFGDDRTVQFVAMATPEDLEANAEYIRMADQ YIEVPGGTNNNNYANVDLIVDIAERADVDAVWAGWGHASENPLLPEKLSQSKRKVI FIGPPGNAMRSLGDKISSTIVAQSAKVPCIPWSGTGVDTVHVDEKTGLVSVDDDIYQ KGCCTSPEDGLQKAKRIGFPVMIKASEGGGGKGIRQVEREEDFIALYHQAANEIPGSP IFIMKLAGRARHLEVQLLADQYGTNISLFGRDCSVQRRHQKIIEEAPVTIAKAETFHE MEKAAVRLGKLVGYVSAGTVEYLYSHDDGKFYFLELNPRLQVEHPTTEMVSGVNL PAAQLQIAMGIPMHRISDIRTLYGMNPHSASEIDFEFKTQDATKKQRRPIPKGHCTAC RIT SEDPNDGFKP SGGTLHELNFRS S SN VWGYF S VGNNGNIHSF SD SQFGHIF AFGEN RQASRKHMVVALKELSIRGDFRTTVEYLIKLLETEDFEDNTITTGWLDDLITHKMTA EKPDPTLAVICGAATKAFLASEEARHKYIESLQKGQVLSKDLLQTMFPVDFIHEGKR YKFTVAKSGNDRYTLFINGSKCDIILRQLADGGLLIAIGGKSHTIYWKEEVAATRLSV DSMTTLLEVENDPTQLRTPSPGKLVKFLVENGEHIIKGQPYAEIEVMKMQMPLVSQE NGIVQLLKQPGSTIVAGDIMAIMTLDDPSKVKHALPFEGMLPDFGSPVIEGTKPAYKF KSLVSTLENILKGYDNQVIMNASLQQLIEVLRNPKLPYSEWKLHISALHSRLPAKLDE QMEELVARSLRRGAVFPARQLSKLIDMAVKNPEYNPDKLLGAVVEPLADIAHKYSN GLEAHEHSIFVHFLEEYYEVEKLFNGPNVREENIILKLRDENPKDLDKVALTVLSHSK VSAKNNLILAILKHYQPLCKLSSKVSAIFSTPLQHIVELESKATAKVALQAREILIQGA LPSVKERTEQIEHILKSSVVKVAYGSSNPKRSEPDLNILKDLIDSNYVVFDVLLQFLTH QDPVVTAAAAQVYIRRAYRAYTIGDIRVHEGVTVPIVEWKFQLPSAAFSTFPTVKSK MGMNRAVAVSDLSYVANSQSSPLREGILMAVDHLDDVDEILSQSLEVIPRHQSSSNG PAPDRSGSSASLSNVANVCVASTEGFESEEEILVRLREILDLNKQELINASIRRITFMFG FKDGSYPKYYTFNGPNYNENETIRHIEPALAFQLELGRLSNFNIKPIFTDNRNIHVYEA VSKTSPLDKRFFTRGIIRTGHIRDDISIQEYLTSEANRLMSDILDNLEVTDTSNSDLNHI FINFIAVFDISPEDVEAAFGGFLERFGKRLLRLRVSSAEIRIIIKDPQTGAPVPLRALINN VSGYVIKTEMYTEVKNAKGEWVFKSLGKPGSMHLRPIATPYPVKEWLQPKRYKAH LMGTTYVYDFPELFRQASSSQWKNFSADVKLTDDFFISNELIEDENGELTEVEREPGA NAIGMVAFKITVKTPEYPRGRQFVVVANDITFKIGSFGPQEDEFFNKVTEYARKRGIP RIYLAANSGARIGMAEEIVPLFQVAWNDAANPDKGFQYLYLTSEGMETLKKFDKEN SVLTERTVINGEERFVIKTIIGSEDGLGVECLRGSGLIAGATSRAYHDIFTITLVTCRSV

[0608] GIGAYLVRLGQRAIQVEGQPIILTGAPAINKMLGREVYTSNLQLGGTQIMYNNGVSH LTAVDDLAGVEKIVEWMSYVPAKRNMPVPILETKDTWDRPVDFTPTNDETYDVRW MIEGRETESGFEYGLFDKGSFFETLSGWAKGVVVGRARLGGIPLGVIGVETRTVENLI PADPANPNSAETLIQEPGQVWHPNSAFKTAQAINDFNNGEQLPMMILANWRGFSGG QRDMFNEVLKYGSFIVDALVDYKQPIIIYIPPTGELRGGSWVVVDPTINADQMEMYA DVNARAGVLEPQGMVGIKFRREKLLDTMNRLDDKYRELRSQLSNKSLAPEVHQQIS KQLADRERELLPIYGQISLQFADLHDRSSRMVAKGVISKELEWTEARRFFFWRLRRR LNEEYLIKRLSHQVGEASRLEKIARIRSWYPASVDHEDDRQVATWIEENYKTLDDKL KGLKLESFAQDLAKKIRSDHDNAIDGLSEVIKMLSTDDKEKLLKTLK

[0609] SEQ ID NO:30 - DNA

[0610] Modified Saccharomyces cerevisiae acetyl CoA carboxylase 1

[0611] ATGAGCGAAGAAAGCTTATTCGAGTCTTCTCCACAGAAGATGGAGTACGAAATT

[0612] ACAAACTACTCAGAAAGACATACAGAACTTCCAGGTCATTTCATTGGCCTCAATA

[0613] CAGTAGATAAACTAGAGGAGTCCCCGTTAAGGGACTTTGTTAAGAGTCACGGTG

[0614] GTCACACGGTCATATCCAAGATCCTGATAGCAAATAATGGTATTGCCGCCGTGAA

[0615] AGAAATTAGATCCGTCAGAAAATGGGCATACGAGACGTTCGGCGATGACAGAAC

[0616] CGTCCAATTCGTCGCCATGGCCACCCCAGAAGATCTGGAGGCCAACGCAGAATA

[0617] TATCCGTATGGCCGATCAATACATTGAAGTGCCAGGTGGTACTAATAATAACAAC

[0618] TACGCTAACGTAGACTTGATCGTAGACATCGCCGAAAGAGCAGACGTAGACGCC

[0619] GTATGGGCTGGCTGGGGTCACGCCTCCGAGAATCCACTATTGCCTGAAAAATTGT

[0620] CCCAGTCTAAGAGGAAAGTCATCTTTATTGGGCCTCCAGGTAACGCCATGAGGTC

[0621] TTTAGGTGATAAAATCTCCTCTACCATTGTCGCTCAAAGTGCTAAAGTCCCATGT

[0622] ATTCCATGGTCTGGTACCGGTGTTGACACCGTTCACGTGGACGAGAAAACCGGTC TGGTCTCTGTCGACGATGACATCTATCAAAAGGGTTGTTGTACCTCTCCTGAAGA

[0623] TGGTTTACAAAAGGCCAAGCGTATTGGTTTTCCTGTCATGATTAAGGCATCCGAA

[0624] GGTGGTGGTGGTAAAGGTATCAGACAAGTTGAACGTGAAGAAGATTTCATCGCT

[0625] TTATACCACCAGGCAGCCAACGAAATTCCAGGCTCCCCCATTTTCATCATGAAGT

[0626] TGGCCGGTAGAGCGCGTCACTTGGAAGTTCAACTGCTAGCAGATCAGTACGGTA

[0627] CAAATATTTCCTTGTTCGGTAGAGACTGTTCCGTTCAGAGACGTCATCAAAAAAT

[0628] TATCGAAGAAGCACCAGTTACAATTGCCAAGGCTGAAACATTTCACGAGATGGA

[0629] AAAGGCTGCCGTCAGACTGGGGAAACTAGTCGGTTATGTCTCTGCCGGTACCGTG

[0630] GAGTATCTATATTCTCATGATGATGGAAAATTCTACTTTTTAGAATTGAACCCAA

[0631] GATTACAAGTCGAGCATCCAACAACGGAAATGGTCTCCGGTGTTAACTTACCTGC

[0632] AGCTCAATTACAAATCGCTATGGGTATCCCTATGCATAGAATAAGTGACATTAGA

[0633] ACTTTATATGGTATGAATCCTCATTCTGCCTCAGAAATCGATTTCGAATTCAAAA

[0634] CTCAAGATGCCACCAAGAAACAAAGAAGACCTATTCCAAAGGGTCATTGTACCG

[0635] CTTGTCGTATCACATCAGAAGATCCAAACGATGGATTCAAGCCATCGGGTGGTAC

[0636] TTTGCATGAACTAAACTTCCGTTCTTCCTCTAATGTTTGGGGTTACTTCTCCGTGG

[0637] GTAACAATGGTAATATTCACTCCTTTTCGGACTCTCAGTTCGGCCATATTTTTGCT

[0638] TTTGGTGAAAATAGACAAGCTTCCAGGAAACACATGGTTGTTGCCCTGAAGGAA

[0639] TTGTCCATTAGGGGTGATTTCAGAACTACTGTGGAATACTTGATCAAACTTTTGG

[0640] AAACTGAAGATTTCGAGGATAACACTATTACCACCGGTTGGTTGGACGATTTGAT

[0641] TACTCATAAAATGACCGCTGAAAAGCCTGATCCAACTCTTGCCGTCATTTGCGGT

[0642] GCCGCTACAAAGGCTTTCTTAGCATCTGAAGAAGCCCGCCACAAGTATATCGAAT

[0643] CCTTACAAAAGGGACAAGTTCTATCTAAAGACCTACTGCAAACTATGTTCCCTGT

[0644] AGATTTTATCCATGAGGGTAAAAGATACAAGTTCACCGTAGCTAAATCCGGTAAT

[0645] GACCGTTACACATTATTTATCAATGGTTCTAAATGTGATATCATACTGCGTCAACT

[0646] AGCTGATGGTGGTCTTTTGATTGCCATAGGCGGTAAATCGCATACCATCTATTGG

[0647] AAAGAAGAAGTTGCTGCTACAAGATTATCCGTTGACTCTATGACTACTTTGTTGG

[0648] AAGTTGAAAACGATCCAACCCAGTTGCGTACTCCATCCCCTGGTAAATTGGTTAA

[0649] ATTCTTGGTGGAAAATGGTGAACACATTATCAAGGGCCAACCATATGCAGAAAT

[0650] TGAAGTTATGAAAATGCAAATGCCTTTGGTTTCTCAAGAAAATGGTATCGTCCAG

[0651] TTATTAAAGCAACCTGGTTCTACCATTGTTGCAGGTGATATCATGGCTATTATGA

[0652] CTCTTGACGATCCATCCAAGGTCAAGCACGCTCTACCATTTGAAGGTATGCTGCC

[0653] AGATTTTGGTTCTCCAGTTATCGAAGGAACCAAACCTGCCTATAAATTCAAGTCA

[0654] TTAGTGTCTACTTTGGAAAACATTTTGAAGGGTTATGACAACCAAGTTATTATGA

[0655] ACGCTTCCTTGCAACAATTGATAGAGGTTTTGAGAAATCCAAAACTGCCTTACTC

[0656] AGAATGGAAACTACACATCTCTGCTTTACATTCAAGATTGCCTGCTAAGCTAGAT

[0657] GAACAAATGGAAGAGTTAGTTGCACGTTCTTTGAGACGTGGTGCTGTTTTCCCAG

[0658] CTAGACAATTAAGTAAATTGATTGATATGGCCGTGAAGAATCCTGAATACAACC

[0659] CCGACAAATTGCTGGGCGCCGTCGTGGAACCATTGGCGGATATTGCTCATAAGTA

[0660] CTCTAACGGGTTAGAAGCCCATGAACATTCTATATTTGTCCATTTCTTGGAAGAA

[0661] TATTACGAAGTTGAAAAGTTATTCAATGGTCCAAATGTTCGTGAGGAAAATATCA

[0662] TTCTGAAATTGCGTGATGAAAACCCTAAAGATCTAGATAAAGTTGCGCTAACTGT

[0663] TTTGTCTCATTCGAAAGTTTCAGCGAAGAATAACCTGATCCTAGCTATCTTGAAA

[0664] CATTATCAACCATTGTGCAAGTTATCTTCTAAAGTTTCTGCCATTTTCTCTACTCC

[0665] TCTACAACATATTGTTGAACTAGAATCTAAGGCTACCGCTAAGGTCGCTCTACAA

[0666] GCAAGAGAAATTTTGATTCAAGGCGCTTTACCTTCGGTCAAGGAAAGAACTGAA

[0667] CAAATTGAACATATCTTAAAATCCTCTGTTGTGAAGGTTGCCTATGGCTCATCCA ATCCAAAGCGCTCTGAACCAGATTTGAATATCTTGAAGGACTTGATCGATTCTAA

[0668] TTACGTTGTGTTCGATGTTTTACTTCAATTCCTAACCCATCAAGACCCAGTTGTGA

[0669] CTGCTGCAGCTGCTCAAGTCTATATTCGTCGTGCTTATCGTGCTTACACCATAGG

[0670] AGATATTAGAGTTCACGAAGGTGTCACAGTTCCAATTGTTGAATGGAAATTCCAA

[0671] CTACCTTCAGCTGCGTTCTCCACCTTTCCAACTGTTAAATCTAAAATGGGTATGA

[0672] ACAGGGCTGTTGCTGTTTCAGATTTGTCATATGTTGCAAACAGTCAGTCATCTCC

[0673] GTTAAGAGAAGGTATTTTGATGGCTGTGGATCATTTAGATGATGTTGATGAAATT

[0674] TTGTCACAAAGTTTGGAAGTTATTCCTCGTCACCAATCTTCTTCTAACGGACCTGC

[0675] TCCTGATCGTTCTGGTAGCTCCGCATCGTTGAGTAATGTTGCTAATGTTTGTGTTG

[0676] CTTCTACAGAAGGTTTCGAATCTGAAGAGGAAATTTTGGTAAGGTTGAGAGAAA

[0677] TTTTGGATTTGAATAAGCAGGAATTAATCAATGCTTCTATCCGTCGTATCACATTT

[0678] ATGTTCGGTTTTAAAGATGGGTCTTATCCAAAGTATTATACTTTTAACGGTCCAA

[0679] ATTATAACGAAAATGAAACAATTCGTCACATTGAGCCGGCTTTGGCCTTCCAACT

[0680] GGAATTAGGAAGATTGTCCAACTTCAACATTAAACCAATTTTCACTGATAATAGA

[0681] AACATCCATGTCTACGAAGCTGTTAGTAAGACTTCTCCATTGGATAAGAGATTCT

[0682] TTACAAGAGGTATTATTAGAACGGGTCATATCCGTGATGACATTTCTATTCAAGA

[0683] ATATCTGACTTCTGAAGCTAACAGATTGATGAGTGATATATTGGATAATTTAGAA

[0684] GTCACCGACACTTCAAATTCTGATTTGAATCATATCTTCATCAACTTCATTGCGGT

[0685] GTTTGATATCTCTCCAGAAGATGTCGAAGCCGCCTTCGGTGGTTTCTTAGAAAGA

[0686] TTTGGTAAGAGATTGTTGAGATTGCGTGTTTCTTCTGCCGAAATTAGAATCATCAT

[0687] CAAAGATCCTCAAACAGGTGCCCCAGTACCATTGCGTGCCTTGATCAATAACGTT

[0688] TCTGGTTATGTTATCAAAACAGAAATGTACACCGAAGTCAAGAACGCAAAAGGT

[0689] GAATGGGTATTTAAGTCTTTGGGTAAACCTGGATCCATGCATTTAAGACCTATTG

[0690] CTACTCCTTACCCTGTTAAGGAATGGTTGCAACCAAAACGTTATAAGGCACACTT

[0691] GATGGGTACCACATATGTCTATGACTTCCCAGAATTATTCCGCCAAGCATCGTCA

[0692] TCCCAATGGAAAAATTTCTCTGCAGATGTTAAGTTAACAGATGATTTCTTTATTTC

[0693] CAACGAGTTGATTGAAGATGAAAACGGCGAATTAACTGAGGTGGAAAGAGAAC

[0694] CTGGTGCCAACGCTATTGGTATGGTTGCCTTTAAGATTACTGTAAAGACTCCTGA

[0695] ATATCCAAGAGGCCGTCAATTTGTTGTTGTTGCTAACGATATCACATTCAAGATC

[0696] GGTTCCTTTGGTCCACAAGAAGACGAATTCTTCAATAAGGTTACTGAATATGCTA

[0697] GAAAGCGTGGTATCCCAAGAATTTACTTGGCTGCAAACTCAGGTGCCAGAATTG

[0698] GTATGGCTGAAGAGATTGTTCCACTATTTCAAGTTGCATGGAATGATGCTGCCAA

[0699] TCCGGACAAGGGCTTCCAATACTTATACTTAACAAGTGAAGGTATGGAAACTTTA

[0700] AAGAAATTTGACAAAGAAAATTCTGTTCTCACTGAACGTACTGTTATAAACGGTG

[0701] AAGAAAGATTTGTCATCAAGACAATTATTGGTTCTGAAGATGGGTTAGGTGTCGA

[0702] ATGTCTACGTGGATCTGGTTTAATTGCTGGTGCAACGTCAAGGGCTTACCACGAT

[0703] ATCTTCACTATCACCTTAGTCACTTGTAGATCCGTCGGTATCGGTGCTTATTTGGT

[0704] TCGTTTGGGTCAAAGAGCTATTCAGGTCGAAGGCCAGCCAATTATTTTAACTGGT

[0705] GCTCCTGCAATCAACAAAATGCTGGGTAGAGAAGTTTATACTTCTAACTTACAAT

[0706] TGGGTGGTACTCAAATCATGTATAACAACGGTGTTTCACATTTGACTGCTGTTGA

[0707] CGATTTAGCTGGTGTAGAGAAGATTGTTGAATGGATGTCTTATGTTCCAGCCAAG

[0708] CGTAATATGCCAGTTCCTATCTTGGAAACTAAAGACACATGGGATAGACCAGTTG

[0709] ATTTCACTCCAACTAATGATGAAACTTACGATGTAAGATGGATGATTGAAGGTCG

[0710] TGAGACTGAAAGTGGATTTGAATATGGTTTGTTTGATAAAGGGTCTTTCTTTGAA

[0711] ACTTTGTCAGGATGGGCCAAAGGTGTTGTCGTTGGTAGAGCCCGTCTTGGTGGTA

[0712] TTCCACTGGGTGTTATTGGTGTTGAAACAAGAACTGTCGAGAACTTGATTCCTGC TGATCCAGCTAATCCAAATAGTGCTGAAACATTAATTCAAGAACCTGGTCAAGTT

[0713] TGGCATCCAAACTCCGCCTTCAAGACTGCTCAAGCTATCAATGACTTTAACAACG

[0714] GTGAACAATTGCCAATGATGATTTTGGCCAACTGGAGAGGTTTCTCTGGTGGTCA

[0715] ACGTGATATGTTCAACGAAGTCTTGAAGTATGGTTCGTTTATTGTTGACGCATTG

[0716] GTGGATTACAAACAACCAATTATTATCTATATCCCACCTACCGGTGAACTAAGAG

[0717] GTGGTTCATGGGTTGTTGTCGATCCAACTATCAACGCTGACCAAATGGAAATGTA

[0718] TGCCGACGTCAACGCTAGAGCTGGTGTTTTGGAACCACAAGGTATGGTTGGTATC

[0719] AAGTTCCGTAGAGAAAAATTGCTGGACACCATGAACAGATTGGATGACAAGTAC

[0720] AGAGAATTGAGATCTCAATTATCCAACAAGAGTTTGGCTCCAGAAGTACATCAG

[0721] CAAATATCCAAGCAATTAGCTGATCGTGAGAGAGAACTATTGCCAATTTACGGA

[0722] CAAATCAGTCTTCAATTTGCTGATTTGCACGATAGGTCTTCACGTATGGTGGCCA

[0723] AGGGTGTTATTTCTAAGGAACTGGAATGGACCGAGGCACGTCGTTTCTTCTTCTG

[0724] GAGATTGAGAAGAAGATTGAACGAAGAATATTTGATTAAAAGGTTGAGCCATCA

[0725] GGTAGGCGAAGCATCAAGATTAGAAAAGATCGCAAGAATTAGATCGTGGTACCC

[0726] TGCTTCAGTGGACCATGAAGATGATAGGCAAGTCGCAACATGGATTGAAGAAAA

[0727] CTACAAAACTTTGGACGATAAACTAAAGGGTTTGAAATTAGAGTCATTCGCTCAA

[0728] GACTTAGCTAAAAAGATCAGAAGCGACCATGACAATGCTATTGATGGATTATCT

[0729] GAAGTTATCAAGATGTTATCTACCGATGATAAAGAAAAATTGTTGAAGACTTTGA

[0730] AATAA

[0731] SEQ ID NO: 31 - Amino acids

[0732] ENO2

[0733] MAVSKVYARSVYDSRGNPTVEVELTTEKGVFRSIVPSGASTGVHEALEMRDEDKSK

[0734] WMGKGVMNAVNNVNNVIAAAFVKANLDVKDQKAVDDFLLSLDGTANKSKLGAN

[0735] AILGVSMAAARAAAAEKNVPLYQHLADLSKSKTSPYVLPVPFLNVLNGGSHAGGAL

[0736] ALQEFMIAPTGAKTFAEAMRIGSEVYHNLKSLTKKRYGASAGNVGDEGGVAPNIQT

[0737] AEEALDLIVDAIKAAGHDGKVKIGLDCASSEFFKDGKYDLDFKNPESDKSKWLTGV

[0738] ELADMYHSLMKRYPIVSIEDPFAEDDWEAWSHFFKTAGIQIVADDLTVTNP ARIATAI

[0739] EKKAADALLLKVNQIGTLSESIKAAQDSFAANWGVMVSHRSGETEDTFIADLVVGL

[0740] RTGQIKTGAPARSERLAKLNQLLRIEEELGDKAVYAGENFHHGDKL

[0741] SEQ ID NO:32 - Native DNA

[0742] ENO2

[0743] ATGGCTGTCTCTAAAGTTTACGCTAGATCCGTCTACGACTCCCGTGGTAACCCAA

[0744] CCGTCGAAGTCGAATTAACCACCGAAAAGGGTGTTTTCAGATCCATTGTTCCATC

[0745] TGGTGCCTCCACCGGTGTCCACGAAGCTTTGGAAATGAGAGATGAAGACAAATC

[0746] CAAGTGGATGGGTAAGGGTGTTATGAACGCTGTCAACAACGTCAACAACGTCAT

[0747] TGCTGCTGCTTTCGTCAAGGCCAACCTAGATGTTAAGGACCAAAAGGCCGTCGAT

[0748] GACTTCTTGTTGTCTTTGGATGGTACCGCCAACAAGTCCAAGTTGGGTGCTAACG

[0749] CTATCTTGGGTGTCTCCATGGCCGCTGCTAGAGCCGCTGCTGCTGAAAAGAACGT

[0750] CCCATTGTACCAACATTTGGCTGACTTGTCTAAGTCCAAGACCTCTCCATACGTTT

[0751] TGCCAGTTCCATTCTTGAACGTTTTGAACGGTGGTTCCCACGCTGGTGGTGCTTTG GCTTTGCAAGAATTCATGATTGCTCCAACTGGTGCTAAGACCTTCGCTGAAGCCA

[0752] TGAGAATTGGTTCCGAAGTTTACCACAACTTGAAGTCTTTGACCAAGAAGAGATA

[0753] CGGTGCTTCTGCCGGTAACGTCGGTGACGAAGGTGGTGTTGCTCCAAACATTCAA

[0754] ACCGCTGAAGAAGCTTTGGACTTGATTGTTGACGCTATCAAGGCTGCTGGTCACG

[0755] ACGGTAAGGTCAAGATCGGTTTGGACTGTGCTTCCTCTGAATTCTTCAAGGACGG

[0756] TAAGTACGACTTGGACTTCAAGAACCCAGAATCTGACAAATCCAAGTGGTTGAC

[0757] TGGTGTCGAATTAGCTGACATGTACCACTCCTTGATGAAGAGATACCCAATTGTC

[0758] TCCATCGAAGATCCATTTGCTGAAGATGACTGGGAAGCTTGGTCTCACTTCTTCA

[0759] AGACCGCTGGTATCCAAATTGTTGCTGATGACTTGACTGTCACCAACCCAGCTAG

[0760] AATTGCTACCGCCATCGAAAAGAAGGCTGCTGACGCTTTGTTGTTGAAGGTTAAC

[0761] CAAATCGGTACCTTGTCTGAATCCATCAAGGCTGCTCAAGACTCTTTCGCTGCCA

[0762] ACTGGGGTGTTATGGTTTCCCACAGATCTGGTGAAACTGAAGACACTTTCATTGC

[0763] TGACTTGGTTGTCGGTTTGAGAACTGGTCAAATCAAGACTGGTGCTCCAGCTAGA

[0764] TCCGAAAGATTGGCTAAGTTGAACCAATTGTTGAGAATCGAAGAAGAATTGGGT

[0765] GACAAGGCTGTCTACGCCGGTGAAAACTTCCACCACGGTGACAAGTTGTAA

[0766] SEQ ID NO: 33 - Amino acids

[0767] PHA2

[0768] MASKTLRVLFLGPKGTYSHQAALQQFQSTSDVEYLPAASIPQCFNQLENDTSIDYSV

[0769] VPLENSTNGQVVFSYDLLRDRMIKKALSLPAPADTNRITPDIEVIAEQYVPITHCLISPI

[0770] QLPNGIASLGNFEEVIIHSHPQVWGQVECYLRSMAEKFPQVTFIRLDCSSTSESVNQCI

[0771] RSSTADCDNILHLAIASETAAQLHKAYIIEHSINDKLGNTTRFLVLKRRENAGDNEVE

[0772] DTGLLRVNLLTFTTRQDDPGSLVDVLNILKIHSLNMCSINSRPFHLDEHDRNWRYLFF

[0773] IEYYTEKNTPKNKEKFYEDISDKSKQWCLWGTFPRNERYYHK

[0774] SEQ ID NO: 34 - Native DNA

[0775] PHA2

[0776] ATGGCCAGCAAGACTTTGAGGGTTCTTTTTCTGGGTCCCAAAGGTACGTATTCCC

[0777] ATCAAGCTGCATTACAACAATTTCAATCAACATCTGATGTTGAGTACCTCCCAGC

[0778] AGCCTCTATCCCCCAATGTTTTAACCAATTGGAGAACGACACTAGTATAGATTAT

[0779] TCAGTGGTACCGTTGGAAAATTCCACCAATGGACAAGTAGTTTTTTCCTATGATC

[0780] TCTTGCGTGATAGGATGATCAAAAAAGCCCTATCCTTACCTGCTCCAGCAGATAC

[0781] TAATAGAATTACACCAGATATAGAAGTTATAGCGGAGCAATATGTACCCATTAC

[0782] CCATTGTCTAATCAGCCCAATCCAACTACCAAATGGTATTGCATCCCTTGGAAAT

[0783] TTTGAAGAAGTCATAATACACTCACATCCGCAAGTATGGGGCCAGGTTGAATGTT

[0784] ACTTAAGGTCCATGGCAGAAAAATTTCCGCAGGTCACCTTTATAAGATTGGATTG

[0785] TTCTTCCACATCTGAATCAGTGAACCAATGCATTCGGTCATCAACGGCCGATTGC

[0786] GACAACATTCTGCATTTAGCCATTGCTAGTGAAACAGCTGCCCAATTGCATAAGG

[0787] CGTACATCATTGAACATTCGATAAATGATAAGCTAGGAAATACAACAAGATTTTT

[0788] AGTATTGAAGAGAAGGGAGAACGCAGGCGACAATGAAGTAGAAGACACTGGAT

[0789] TACTACGGGTTAACCTACTCACCTTTACTACTCGTCAAGATGACCCTGGTTCTTTG

[0790] GTAGATGTTTTGAACATACTAAAAATCCATTCACTCAACATGTGTTCTATAAACT CTAGACCATTCCATTTGGACGAACATGATAGAAACTGGCGATATTTATTTTTCAT

[0791] TGAATATTACACCGAGAAGAATACCCCAAAGAATAAAGAAAAATTCTATGAAGA

[0792] TATCAGCGACAAAAGTAAACAGTGGTGCCTGTGGGGTACATTCCCCAGAAATGA

[0793] GAGATATTATCACAAATAA

[0794] SEQ ID NO: 35 - Amino acids

[0795] ARO8

[0796] MTLPESKDFSYLFSDETNARKPSPLKTCIHLFQDPNIIFLGGGLPLKDYFPWDNLSVDS PKPPFPQGIGAPIDEQNCIKYTVNKDYADKSANPSNDIPLSRALQYGFSAGQPELLNFI RDHTI<IIHDLI<YI<DWD VLAT AGNTNAWESTLRVFCNRGD VILVEAHSF S S SL AS AEA QGVITFPVPIDADGIIPEKLAKVMENWTPGAPKPKLLYTIPTGQNPTGTSIADHRKEAI YKIAQKYDFLIVEDEPYYFLQMNPYIKDLKEREKAQSSPKQDHDEFLKSLANTFLSLD TEGRVIRMDSFSKVLAPGTRLGWITGSSKILKPYLSLHEMTIQAPAGFTQVLVNATLS RWGQKGYLDWLLGLRHEYTLKRDCAIDALYKYLPQSDAFVINPPIAGMFFTVNIDAS VHPEFKTKYNSDPYQLEQSLYHKVVERGVLVVPGSWFKSEGETEPPQPAESKEVSNP

[0797] NIIFFRGTYAAVSPEKLTEGLKRLGDTLYEEFGISK

[0798] SEQ ID NO: 36 - Native DNA

[0799] ARO8

[0800] ATGACTTTACCTGAATCAAAAGACTTTTCTTACTTGTTTTCGGATGAAACCAATGC

[0801] TCGTAAACCATCCCCATTGAAAACCTGCATCCATCTTTTCCAAGATCCTAACATT

[0802] ATCTTTTTGGGTGGTGGCCTGCCATTAAAAGATTATTTCCCATGGGATAATCTATC

[0803] TGTAGATTCACCCAAGCCTCCTTTTCCCCAGGGTATTGGAGCTCCAATTGACGAG

[0804] CAGAATTGCATAAAATACACCGTCAACAAAGATTACGCTGATAAAAGTGCCAAT

[0805] CCTTCCAACGATATTCCTTTGTCAAGAGCTTTGCAATACGGGTTCAGTGCTGGTC

[0806] AACCTGAACTATTAAACTTCATTAGAGATCATACCAAGATTATCCACGATTTGAA

[0807] GTATAAGGACTGGGACGTTTTAGCCACTGCAGGTAACACAAATGCCTGGGAATC

[0808] TACTTTAAGAGTCTTTTGTAACCGAGGTGATGTCATCTTAGTTGAGGCACATTCTT

[0809] TTTCCTCTTCATTGGCTTCTGCAGAGGCTCAAGGTGTCATTACCTTCCCCGTGCCA

[0810] ATTGACGCTGATGGTATCATTCCTGAAAAATTAGCTAAAGTCATGGAAAACTGGA

[0811] CACCTGGTGCTCCTAAACCAAAGTTGTTATACACTATTCCAACGGGCCAAAATCC

[0812] AACTGGTACTTCCATTGCAGACCATAGAAAGGAGGCAATTTACAAGATCGCTCA

[0813] AAAGTACGACTTCCTAATTGTGGAAGATGAACCTTATTATTTCTTACAAATGAAT

[0814] CCCTACATCAAAGACTTGAAGGAAAGAGAGAAGGCACAAAGTTCTCCAAAGCAG

[0815] GACCATGACGAATTTTTGAAGTCCTTGGCAAACACTTTCCTTTCCTTGGATACAG

[0816] AAGGCCGTGTTATTAGAATGGATTCCTTTTCAAAAGTTTTGGCCCCAGGGACAAG

[0817] ATTGGGTTGGATTACTGGTTCATCCAAAATCTTGAAGCCTTACTTGAGTTTGCATG

[0818] AAATGACGATTCAAGCCCCAGCAGGTTTTACACAAGTTTTGGTCAACGCTACGCT

[0819] ATCCAGGTGGGGTCAAAAGGGTTACTTGGACTGGTTGCTTGGCCTGCGTCATGAA

[0820] TACACTTTGAAACGTGACTGTGCCATCGATGCCCTTTACAAGTATCTACCACAAT

[0821] CTGATGCTTTCGTGATCAATCCTCCAATTGCAGGTATGTTTTTCACCGTGAACATT

[0822] GACGCATCTGTCCACCCTGAGTTTAAAACAAAATACAACTCAGACCCTTACCAGC TAGAACAGAGTCTTTACCACAAAGTGGTTGAACGTGGTGTTTTAGTGGTTCCCGG

[0823] TTCTTGGTTCAAGAGTGAGGGTGAGACGGAACCTCCTCAACCCGCTGAATCTAAA

[0824] GAAGTCAGTAATCCAAACATAATTTTCTTCAGAGGTACCTATGCAGCTGTCTCTC

[0825] CTGAGAAACTGACTGAAGGTCTGAAGAGATTAGGTGATACTTTATACGAAGAAT

[0826] TTGGTATTTCCAAATAG

[0827] SEQ ID NO: 37 - Amino acids

[0828] ARO1

[0829] MVQLAKVPILGNDIIHVGYNIHDHLVETIIKHCPSSTYVICNDTNLSKVPYYQQLVLEF KASLPEGSRLLTYVVKPGETSKSRETKAQLEDYLLVEGCTRDTVMVAIGGGVIGDMI GFVASTFMRGVRVVQVPTSLLAMVDSSIGGKTAIDTPLGKNFIGAFWQPKFVLVDIK WLETLAKREFINGMAEVIKTACIWNADEFTRLESNASLFLNVVNGAKNVKVTNQLT NEIDEISNTDIE AMLDHT YKLVLESIK VK AE V VS SDERES SLRNLLNFGHSIGHAYEAI LTPQALHGECVSIGMVKEAELSRYFGILSPTQVARLSKILVAYGLPVSPDEKWFKELT LHKKTPLDILLKKMSIDKKNEGSKKKVVILESIGKCYGDSAQFVSDEDLRFILTDETL VYPFKDIPADQQKVVIPPGSKSISNRALILAALGEGQCKIKNLLHSDDTKHMLTAVHE LKGATISWEDNGETVVVEGHGGSTLSACADPLYLGNAGTASRFLTSLAALVNSTSSQ KYIVLTGNARMQQRPIAPLVDSLRANGTKIEYLNNEGSLPIKVYTDSVFKGGRIELAA TVSSQYVSSILMCAPYAEEPVTLALVGGKPISKLYVDMTIKMMEKFGINVETSTTEPY TYYIPKGHYINPSEYVIESDASSATYPLAFAAMTGTTVTVPNIGFESLQGDARFARDV LKPMGCKITQTATSTTVSGPPVGTLKPLKHVDMEPMTDAFLTACVVAAISHDSDPNS ANTTTIEGIANQRVKECNRILAMATELAKFGVKTTELPDGIQVHGLNSIKDLKVPSDS SGPVGVCTYDDHRVAMSFSLLAGMVNSQNERDEVANPVRILERHCTGKTWPGWW DVLHSELGAKLDGAEPLECTSKKNSKKSVVIIGMRAAGKTTISKWCASALGYKLVD LDELFEQQHNNQSVKQFVVENGWEKFREEETRIFKEVIQNYGDDGYVFSTGGGIVES AESRKALKDFASSGGYVLHLHRDIEETIVFLQSDPSRPAYVEEIREVWNRREGWYKE CSNFSFFAPHCSAEAEFQALRRSFSKYIATITGVREIEIPSGRSAFVCLTFDDLTEQTEN LTPICYGCEAVEVRVDHLANYSADFVSKQLSILRKATDSIPIIFTVRTMKQGGNFPDEE FKTLRELYDIALKNGVEFLDLELTLPTDIQYEVINKRGNTKIIGSHHDFQGLYSWDDA EWENRFNQALTLDVDVVKFVGTAVNFEDNLRLEHFRDTHKNKPLIAVNMTSKGSIS RVLNNVLTPVTSDLLPNSAAPGQLTVAQINKMYTSMGGIEPKELFVVGKPIGHSRSPI LHNTGYEILGLPHKFDKFETESAQLVKEKLLDGNKNFGGAAVTIPLKLDIMQYMDEL TDAAKVIGAVNTVIPLGNKKFKGDNTDWLGIRNALINNGVPEYVGHTAGLVIGAGG

[0830] TSRAALYALHSLGCKKIFIINRTTSKLKPLIESLPSEFNIIGIESTKSIEEIKEHVGVAVSC VPADKPLDDELLSKLERFLVKGAHAAFVPTLLEAAYKPSVTPVMTISQDKYQWHVV PGSQMLVHQGVAQFEKWTGFKGPFKAIFDAVTKE

[0831] SEQ ID NO: 38 - Native DNA

[0832] ARO1

[0833] ATGGTGCAGTTAGCCAAAGTCCCAATTCTAGGAAATGATATTATCCACGTTGGGT

[0834] ATAACATTCATGACCATTTGGTTGAAACCATAATTAAACATTGTCCTTCTTCGAC

[0835] ATACGTTATTTGCAATGATACGAACTTGAGTAAAGTTCCATACTACCAGCAATTA GTCCTGGAATTCAAGGCTTCTTTGCCAGAAGGCTCTCGTTTACTTACTTATGTTGT

[0836] TAAACCAGGTGAGACAAGTAAAAGTAGAGAAACCAAAGCGCAGCTAGAAGATT

[0837] ATCTTTTAGTGGAAGGATGTACTCGTGATACGGTTATGGTAGCGATCGGTGGTGG

[0838] TGTTATTGGTGACATGATTGGGTTCGTTGCATCTACATTTATGAGAGGTGTTCGTG

[0839] TTGTCCAAGTACCAACATCCTTATTGGCAATGGTCGATTCCTCCATTGGTGGTAA

[0840] AACTGCTATTGACACTCCTCTAGGTAAAAACTTTATTGGTGCATTTTGGCAACCA

[0841] AAATTTGTCCTTGTAGATATTAAATGGCTAGAAACGTTAGCCAAGAGAGAGTTTA

[0842] TCAATGGGATGGCAGAAGTTATCAAGACTGCTTGTATTTGGAACGCTGACGAATT

[0843] TACTAGATTAGAATCAAACGCTTCGTTGTTCTTAAATGTTGTTAATGGGGCAAAA

[0844] AATGTCAAGGTTACCAATCAATTGACAAACGAGATTGACGAGATATCGAATACA

[0845] GATATTGAAGCTATGTTGGATCATACATATAAGTTAGTTCTTGAGAGTATTAAGG

[0846] TCAAAGCGGAAGTTGTCTCTTCGGATGAACGTGAATCCAGTCTAAGAAACCTTTT

[0847] GAACTTCGGACATTCTATTGGTCATGCTTATGAAGCTATACTAACCCCACAAGCA

[0848] TTACATGGTGAATGTGTGTCCATTGGTATGGTTAAAGAGGCGGAATTATCCCGTT

[0849] ATTTCGGTATTCTCTCCCCTACCCAAGTTGCACGTCTATCCAAGATTTTGGTTGCC

[0850] TACGGGTTGCCTGTTTCGCCTGATGAGAAATGGTTTAAAGAGCTAACCTTACATA

[0851] AGAAAACACCATTGGATATCTTATTGAAGAAAATGAGTATTGACAAGAAAAACG

[0852] AGGGTTCCAAAAAGAAGGTGGTCATTTTAGAAAGTATTGGTAAGTGCTATGGTG

[0853] ACTCCGCTCAATTTGTTAGCGATGAAGACCTGAGATTTATTCTAACAGATGAAAC

[0854] CCTCGTTTACCCCTTCAAGGACATCCCTGCTGATCAACAGAAAGTTGTTATCCCC

[0855] CCTGGTTCTAAGTCCATCTCCAATCGTGCTTTAATTCTTGCTGCCCTCGGTGAAGG

[0856] TCAATGTAAAATCAAGAACTTATTACATTCTGATGATACTAAACATATGTTAACC

[0857] GCTGTTCATGAATTGAAAGGTGCTACGATATCATGGGAAGATAATGGTGAGACG

[0858] GTAGTGGTGGAAGGACATGGTGGTTCCACATTGTCAGCTTGTGCTGACCCCTTAT

[0859] ATCTAGGTAATGCAGGTACTGCATCTAGATTTTTGACTTCCTTGGCTGCCTTGGTC

[0860] AATTCTACTTCAAGCCAAAAGTATATCGTTTTAACTGGTAACGCAAGAATGCAAC

[0861] AAAGACCAATTGCTCCTTTGGTCGATTCTTTGCGTGCTAATGGTACTAAAATTGA

[0862] GTACTTGAATAATGAAGGTTCCCTGCCAATCAAAGTTTATACTGATTCGGTATTC

[0863] AAAGGTGGTAGAATTGAATTAGCTGCTACAGTTTCTTCTCAGTACGTATCCTCTA

[0864] TCTTGATGTGTGCCCCATACGCTGAAGAACCTGTAACTTTGGCTCTTGTTGGTGGT

[0865] AAGCCAATCTCTAAATTGTACGTCGATATGACAATAAAAATGATGGAAAAATTC

[0866] GGTATCAATGTTGAAACTTCTACTACAGAACCTTACACTTATTATATTCCAAAGG

[0867] GACATTATATTAACCCATCAGAATACGTCATTGAAAGTGATGCCTCAAGTGCTAC

[0868] ATACCCATTGGCCTTCGCCGCAATGACTGGTACTACCGTAACGGTTCCAAACATT

[0869] GGTTTTGAGTCGTTACAAGGTGATGCCAGATTTGCAAGAGATGTCTTGAAACCTA

[0870] TGGGTTGTAAAATAACTCAAACGGCAACTTCAACTACTGTTTCGGGTCCTCCTGT

[0871] AGGTACTTTAAAGCCATTAAAACATGTTGATATGGAGCCAATGACTGATGCGTTC

[0872] TTAACTGCATGTGTTGTTGCCGCTATTTCGCACGACAGTGATCCAAATTCTGCAA

[0873] ATACAACCACCATTGAAGGTATTGCAAACCAGCGTGTCAAAGAGTGTAACAGAA

[0874] TTTTGGCCATGGCTACAGAGCTCGCCAAATTTGGCGTCAAAACTACAGAATTACC

[0875] AGATGGTATTCAAGTCCATGGTTTAAACTCGATAAAAGATTTGAAGGTTCCTTCC

[0876] GACTCTTCTGGACCTGTCGGTGTATGCACATATGATGATCATCGTGTGGCCATGA

[0877] GTTTCTCGCTTCTTGCAGGAATGGTAAATTCTCAAAATGAACGTGACGAAGTTGC

[0878] TAATCCTGTAAGAATACTTGAAAGACATTGTACTGGTAAAACCTGGCCTGGCTGG

[0879] TGGGATGTGTTACATTCCGAACTAGGTGCCAAATTAGATGGTGCAGAACCTTTAG

[0880] AGTGCACATCCAAAAAGAACTCAAAGAAAAGCGTTGTCATTATTGGCATGAGAG CAGCTGGCAAAACTACTATAAGTAAATGGTGCGCATCCGCTCTGGGTTACAAATT

[0881] AGTTGACCTAGACGAGCTGTTTGAGCAACAGCATAACAATCAAAGTGTTAAACA

[0882] ATTTGTTGTGGAGAACGGTTGGGAGAAGTTCCGTGAGGAAGAAACAAGAATTTT

[0883] CAAGGAAGTTATTCAAAATTACGGCGATGATGGATATGTTTTCTCAACAGGTGGC

[0884] GGTATTGTTGAAAGCGCTGAGTCTAGAAAAGCCTTAAAAGATTTTGCCTCATCAG

[0885] GTGGATACGTTTTACACTTACATAGGGATATTGAGGAGACAATTGTCTTTTTACA

[0886] AAGTGATCCTTCAAGACCTGCCTATGTGGAAGAAATTCGTGAAGTTTGGAACAG

[0887] AAGGGAGGGGTGGTATAAAGAATGCTCAAATTTCTCTTTCTTTGCTCCTCATTGC

[0888] TCCGCAGAAGCTGAGTTCCAAGCTCTAAGAAGATCGTTTAGTAAGTACATTGCAA

[0889] CCATTACAGGTGTCAGAGAAATAGAAATTCCAAGCGGAAGATCTGCCTTTGTGT

[0890] GTTTAACCTTTGATGACTTAACTGAACAAACTGAGAATTTGACTCCAATCTGTTA

[0891] TGGTTGTGAGGCTGTAGAGGTCAGAGTAGACCATTTGGCTAATTACTCTGCTGAT

[0892] TTCGTGAGTAAACAGTTATCTATATTGCGTAAAGCCACTGACAGTATTCCTATCA

[0893] TTTTTACTGTGCGAACCATGAAGCAAGGTGGCAACTTTCCTGATGAAGAGTTCAA

[0894] AACCTTGAGAGAGCTATACGATATTGCCTTGAAGAATGGTGTTGAATTCCTTGAC

[0895] TTAGAACTAACTTTACCTACTGATATCCAATATGAGGTTATTAACAAAAGGGGCA

[0896] ACACCAAGATCATTGGTTCCCATCATGACTTCCAAGGATTATACTCCTGGGACGA

[0897] CGCTGAATGGGAAAACAGATTCAATCAAGCGTTAACTCTTGATGTGGATGTTGTA

[0898] AAATTTGTGGGTACGGCTGTTAATTTCGAAGATAATTTGAGACTGGAACACTTTA

[0899] GGGATACACACAAGAATAAGCCTTTAATTGCAGTTAATATGACTTCTAAAGGTAG

[0900] CATTTCTCGTGTTTTGAATAATGTTTTAACACCTGTGACATCAGATTTATTGCCTA

[0901] ACTCCGCTGCCCCTGGCCAATTGACAGTAGCACAAATTAACAAGATGTATACATC

[0902] TATGGGAGGTATCGAGCCTAAGGAACTGTTTGTTGTTGGAAAGCCAATTGGCCAC

[0903] TCTAGATCGCCAATTTTACATAACACTGGCTATGAAATTTTAGGTTTACCTCACA

[0904] AGTTCGATAAATTTGAAACTGAATCCGCACAATTGGTGAAAGAAAAACTTTTGG

[0905] ACGGAAACAAGAACTTTGGCGGTGCTGCAGTCACAATTCCTCTGAAATTAGATAT

[0906] AATGCAGTACATGGATGAATTGACTGATGCTGCTAAAGTTATTGGTGCTGTAAAC

[0907] ACAGTTATACCATTGGGTAACAAGAAGTTTAAGGGTGATAATACCGACTGGTTA

[0908] GGTATCCGTAATGCCTTAATTAACAATGGCGTTCCCGAATATGTTGGTCATACCG

[0909] CTGGTTTGGTTATCGGTGCAGGTGGCACTTCTAGAGCCGCCCTTTACGCCTTGCA

[0910] CAGTTTAGGTTGCAAAAAGATCTTCATAATCAACAGGACAACTTCGAAATTGAA

[0911] GCCATTAATAGAGTCACTTCCATCTGAATTCAACATTATTGGAATAGAGTCCACT

[0912] AAATCTATAGAAGAGATTAAGGAACACGTTGGCGTTGCTGTCAGCTGTGTACCA

[0913] GCCGACAAACCATTAGATGACGAACTTTTAAGTAAGCTGGAGAGATTCCTTGTG

[0914] AAAGGTGCCCATGCTGCTTTTGTACCAACCTTATTGGAAGCCGCATACAAACCAA

[0915] GCGTTACTCCCGTTATGACAATTTCACAAGACAAATATCAATGGCACGTTGTCCC

[0916] TGGATCACAAATGTTAGTACACCAAGGTGTAGCTCAGTTTGAAAAGTGGACAGG

[0917] ATTCAAGGGCCCTTTCAAGGCCATTTTTGATGCCGTTACGAAAGAGTAG

[0918] SEQ ID NO: 39 - Amino acids

[0919] ARO2

[0920] MSTFGKLFRVTTYGESHCKSVGCIVDGVPPGMSLTEADIQPQLTRRRPGQSKLSTPRD

[0921] EKDRVEIQSGTEFGKTLGTPIAMMIKNEDQRPHDYSDMDKFPRPSHADFTYSEKYGI

[0922] KASSGGGRASARETIGRVASGAIAEKFLAQNSNVEIVAFVTQIGEIKMNRDSFDPEFQ HLLNTITREKVDSMGPIRCPDASVAGLMVKEIEKYRGNKDSIGGVVTCVVRNLPTGL GEPCFDKLEAMLAHAMLSIPASKGFEIGSGFQGVSVPGSKHNDPFYFEKETNRLRTK TNNSGGVQGGISNGENIYFSVPFKSVATISQEQKTATYDGEEGILAAKGRHDPAVTPR

[0923] A I PI VE AMT AL VLAD ALLIQKARDF SRS VVH

[0924] SEQ ID NO: 40 - Native DNA

[0925] ARO2

[0926] ATGTCAACGTTTGGGAAACTGTTCCGCGTCACCACATATGGTGAATCGCATTGTA

[0927] AGTCTGTCGGTTGCATTGTCGACGGTGTTCCTCCAGGAATGTCATTAACCGAAGC

[0928] TGACATTCAGCCACAATTGACCAGAAGAAGACCGGGTCAATCTAAGCTATCGAC

[0929] CCCTAGAGACGAAAAGGATAGAGTGGAAATCCAGTCCGGTACCGAGTTCGGCAA

[0930] GACTCTAGGTACACCCATCGCCATGATGATCAAAAACGAGGACCAAAGACCTCA

[0931] CGACTACTCCGACATGGACAAGTTCCCTAGACCTTCCCATGCGGACTTCACGTAC

[0932] TCGGAAAAGTACGGTATCAAGGCCTCCTCTGGTGGTGGCAGAGCTTCTGCTAGA

[0933] GAAACGATTGGCCGTGTCGCTTCAGGTGCCATTGCTGAGAAGTTCTTAGCTCAGA

[0934] ACTCTAATGTCGAGATCGTAGCCTTTGTGACACAAATCGGGGAAATCAAGATGA

[0935] ACAGAGACTCTTTCGATCCTGAATTTCAGCATCTGTTGAACACCATCACCAGGGA

[0936] AAAAGTGGACTCAATGGGTCCTATCAGATGTCCAGACGCCTCCGTTGCTGGTTTG

[0937] ATGGTCAAGGAAATCGAAAAGTACAGAGGCAACAAGGACTCTATCGGTGGTGTC

[0938] GTCACTTGTGTCGTGAGAAACTTGCCTACCGGTCTCGGTGAGCCATGCTTTGACA

[0939] AGTTGGAAGCCATGTTGGCTCATGCTATGTTGTCCATTCCAGCATCCAAGGGTTT

[0940] CGAAATTGGCTCAGGTTTTCAGGGTGTCTCTGTTCCAGGGTCCAAGCACAATGAC

[0941] CCATTTTACTTTGAAAAAGAAACAAACAGATTAAGAACAAAGACCAACAATTCA

[0942] GGTGGTGTACAAGGTGGTATCTCTAATGGTGAGAACATCTATTTCTCTGTCCCAT

[0943] TCAAGTCAGTGGCCACTATCTCTCAAGAACAAAAAACCGCCACTTACGATGGTG

[0944] AAGAAGGTATCTTAGCCGCTAAGGGTAGACATGACCCTGCTGTCACTCCAAGAG

[0945] CTATTCCTATTGTGGAAGCCATGACCGCTCTGGTGTTGGCTGACGCGCTTTTGATC

[0946] CAAAAGGCAAGAGATTTCTCCAGATCCGTGGTTCATTAA

[0947] SEQ ID NO:41 - Amino acids

[0948] ARO80

[0949] MSAKKRPSGNAAFELPKRRRTYQACISCRSRKVKCDLGPVDNPHDPPCARCKRELK

[0950] KCIFSSNKGTSNDLPPNSINAISLPSLGKSKQEIQNDSTSPILSDVPLSRKGISSEKSFKSE

[0951] GMKWKLELSSMQNALEFLAQAAGTVAKEGAKEIIKEKSTTPKPLKSSLDATNKSAT

[0952] DEGLKRLSKSDSTNTLYENTADMLNHTLNTNRKTSQLMEEIGKVRPPPTRKIDDFDY

[0953] IGPDSLLTKEEAIELIEAFFLTMHPFFPNIPLQLHDPKELAEYPILFCAILTVSARYHPFD

[0954] TLGLDNGEDGMRHIEVHDKLWVYCQKLISQTIWAEASTRSIGTVLAFIIFTEWNPRSI

[0955] HYKWSDYANDPELNNVNARGSKNISTRKDEEGLTGVGAIRRSDRMSWMLTGSAVR

[0956] LAQDMGFIENSSKVFIVTHISETTSAMNMNQRSLLAESFSVLNLNLGKIENDGNESNE

[0957] DYLGNEI<FYLNEILPDEESI<LRWI<RVFENSENDHDNEI<NFLTDWEREFLNDEYVLY

[0958] YSNKKDDTNLAQNHIPPFPLRFSFAQRAKIEIIRILSIAYETIYCEKNKRKLATTDQRHN

[0959] LSVLSVFSPLIEGWLSNYRELLVPLSDVPFSLADRKNKKQIFDNIDRINGESIITDFNYC QLYIFSLALQVDGKTSRLNMNEIVTSARYVELAYRSAKEILSSAKRVSRQGMLKYMP VRWVIRIIRSIAFIVKCYLTLTGSELATNPDARNILKLSAISVDETFDIIRDTAVTLKEAT PDELHLCQRYAAILMYLCTEMKLRKKSYLERPPLLRDGTTPLESNRESSLEGQDLTK KPIFSKRIGYNKTETTFEPSERPLTEEINSNSQNSNDTSSKGIVDPFVEQNNDITTALLN NELFQGPSLSDEVTDWFGASEDIGLEFVEPWTELIEQRYMQCGDGDNNNFENLYNLF VNSNNINNDINNSRPITRK

[0960] SEQ ID NO:42 - Native DNA

[0961] ARO80

[0962] ATGTCTGCTAAGAAAAGGCCTTCGGGAAACGCAGCATTTGAACTTCCAAAACGG

[0963] AGAAGAACCTACCAAGCTTGCATCAGCTGCAGATCAAGGAAGGTGAAATGTGAT

[0964] CTTGGTCCGGTTGATAACCCACACGACCCACCGTGTGCACGTTGCAAAAGGGAG

[0965] CTAAAAAAATGTATTTTTAGCTCTAATAAGGGAACTTCGAACGACTTGCCTCCTA

[0966] ATTCGATTAATGCAATAAGTCTGCCATCTCTAGGTAAGAGTAAGCAAGAGATAC

[0967] AAAATGACTCAACGAGCCCAATTTTATCGGATGTACCTTTGTCAAGAAAAGGGA

[0968] TTAGCAGTGAAAAATCATTTAAATCAGAAGGGATGAAGTGGAAGCTTGAACTTT

[0969] CCTCCATGCAGAACGCCCTAGAGTTTCTGGCCCAAGCTGCTGGAACTGTAGCAAA

[0970] AGAAGGCGCAAAAGAAATCATAAAAGAGAAGTCCACAACACCGAAACCACTGA

[0971] AAAGTTCTTTGGATGCGACAAATAAATCTGCTACGGACGAGGGGTTGAAACGAC

[0972] TTTCAAAAAGTGACAGTACTAACACACTTTACGAAAATACAGCAGATATGCTTA

[0973] ACCACACGCTGAATACGAATAGGAAAACATCACAATTAATGGAAGAAATCGGGA

[0974] AAGTGAGACCTCCACCTACCCGGAAAATTGACGACTTCGATTACATCGGTCCAG

[0975] ATAGCTTGCTTACTAAAGAGGAGGCGATTGAACTCATAGAGGCATTTTTTCTCAC

[0976] GATGCACCCATTCTTTCCCAATATCCCACTTCAATTGCATGATCCGAAAGAATTA

[0977] GCAGAATATCCAATTTTGTTTTGTGCAATTTTGACTGTTTCTGCTCGCTATCATCC

[0978] TTTCGATACTTTAGGATTAGACAATGGAGAAGATGGGATGAGACACATTGAAGT

[0979] TCACGATAAATTATGGGTGTATTGCCAGAAGCTTATATCTCAAACAATTTGGGCA

[0980] GAGGCTAGTACTAGGTCAATTGGCACCGTGCTTGCTTTCATAATTTTCACGGAAT

[0981] GGAACCCAAGGAGTATCCACTATAAATGGTCTGACTATGCAAATGATCCTGAGTT

[0982] AAATAATGTCAACGCTAGAGGAAGTAAGAATATTAGTACGAGGAAGGACGAAG

[0983] AAGGATTGACCGGTGTCGGCGCAATCCGTAGAAGCGACCGAATGTCATGGATGC

[0984] TGACAGGGTCTGCAGTAAGGCTGGCGCAAGATATGGGATTCATTGAAAACAGCT

[0985] CAAAAGTATTCATTGTCACTCATATATCTGAGACTACCAGTGCTATGAATATGAA

[0986] TCAAAGATCCTTATTAGCAGAATCATTCAGCGTTTTAAACTTGAATTTAGGAAAA

[0987] ATTGAAAACGATGGAAATGAAAGCAATGAGGATTACCTTGGGAATGAAAAATTT

[0988] TATCTGAATGAGATTTTGCCTGATGAAGAAAGTAAACTAAGGTGGAAGAGAGTT

[0989] TTTGAAAACTCAGAAAATGACCACGACAACGAGAAAAATTTTTTGACTGATTGG

[0990] GAGAGGGAGTTTTTAAACGATGAGTATGTTCTATATTATTCTAATAAAAAAGATG

[0991] ATACTAATCTAGCACAGAATCACATACCACCATTTCCACTAAGATTCTCATTCGC

[0992] CCAAAGAGCAAAAATAGAGATCATTCGAATCCTATCCATAGCATATGAGACGAT

[0993] TTACTGTGAGAAGAATAAGAGGAAATTGGCAACGACAGATCAGAGACACAACCT

[0994] CTCTGTCCTAAGTGTTTTTTCTCCCTTGATAGAGGGCTGGCTCAGTAACTACAGA

[0995] GAGCTTCTTGTACCCCTTTCTGATGTCCCTTTCTCACTAGCAGATAGGAAGAACA

[0996] AAAAACAAATATTTGATAACATCGATAGAATAAATGGTGAAAGTATTATCACAG ATTTCAATTATTGTCAACTTTATATCTTTTCCCTCGCACTGCAAGTGGATGGGAAA

[0997] ACAAGCAGATTGAATATGAATGAAATTGTGACAAGCGCGAGGTATGTGGAATTA

[0998] GCATACAGATCTGCAAAAGAAATATTGAGTTCTGCAAAGCGAGTTTCAAGGCAA

[0999] GGAATGCTAAAATACATGCCCGTAAGATGGGTAATACGAATAATTAGATCCATT

[1000] GCGTTCATAGTAAAATGCTACCTAACACTTACTGGTAGTGAACTGGCAACAAATC

[1001] CAGATGCCAGAAACATTTTAAAATTAAGTGCAATATCGGTTGACGAAACATTCG

[1002] ATATCATCCGTGACACTGCGGTTACTTTGAAAGAAGCTACACCAGATGAATTACA

[1003] TCTATGTCAAAGATACGCAGCCATATTAATGTACTTATGTACAGAGATGAAACTT

[1004] CGAAAAAAATCTTACTTAGAACGACCACCCTTATTAAGAGATGGCACCACTCCTC

[1005] TAGAGAGCAATCGCGAATCCTCACTGGAGGGACAAGACTTAACTAAGAAGCCAA

[1006] TATTCTCTAAACGTATTGGATATAATAAAACCGAGACTACTTTTGAACCCTCGGA

[1007] AAGGCCTTTGACGGAGGAAATTAATAGCAATTCTCAGAATTCAAATGATACATCT

[1008] TCTAAAGGTATCGTTGATCCTTTTGTTGAACAAAACAACGATATCACAACAGCGT

[1009] TACTGAACAATGAACTCTTCCAAGGTCCATCTCTATCTGACGAGGTTACAGATTG

[1010] GTTCGGTGCTAGTGAAGATATCGGGCTTGAATTTGTAGAACCATGGACAGAACTT

[1011] ATTGAGCAACGATATATGCAATGTGGAGATGGTGATAATAATAATTTCGAAAATT

[1012] TATACAACTTGTTCGTGAATAGTAATAACATCAATAATGATATTAATAACTCAAG

[1013] GCCAATAACGCGTAAATAA

[1014] SEQ ID NO:43 - Amino acids

[1015] PDR10

[1016] MLQAPSSSNSGLNQGNAAPDGPPNETQPYEGLDAAAQEEIKELARTLTSQSSLLSQE KRITGTGDPNTLT AAS S S SL SRSIF ASDIKGVNPILLD VNDPD YDETLDPRSENF S S VR WVRNMAQICENDSDFYKPFSLGCAWKDLSASGDSADITYQGTFGNMPIKYLKMSW RCISRRLFHRTHGKSEDNDSGFQILKPMDGCINPGELLVVLGRPGAGCTTLLKSISVN THGFKISPDTIITYNGFSNKEIKNHYRGEVVYNAESDIHIPHLTVFQTLYTVARLKTPR NRIKGVDRDTFAKHMTEVAMATYGLSHTADTKVGNDFVRGVSGGERKRVSIAEVSI CGSKFQCWDNATRGLDSATALEFIKALKTQATITKSAATVAIYQCSKDAYDLFDKVC VLYDGYQIFFGPSKQAKKYFQRMGYVCPERQTTADYLTSITSPSERIKDKDMVKHGI MIPQTAYEMNQYWIQSEEYKQLQVQVNKHLDTDSSQQREQIKNAHIAKQSKRARPS SPYTVSFFLQVKYILIRDIWRIKNDPSIQLFTVLSHAAMALILGSMFYEVMLSTTTTTF YYRGAAIFF AILFNAF S SLLEIF SL YETRPITEKHKT YSL YRP S AD AF ASTF SD VPTKL A TAVTFNIPYYFLINLKRDAGAFFFYFLINIITVFAMSHLFRCIGSVSKTLPQAMVPASVL LLAFAMYTGFAIPRVQMLGWSKWISYINPLSYLFESLMINEFHGRNFPCAQYIPSGPN YVNATGDEVTCSALGSIPGNNYVSGDDFIQTNYGYRHKNKWRSVGIGLAYIIFFLFL YLFFCEYNEGAKQNGEMLVFPHSVVKKMKKKGIVSEKKKKNQPTLSTSDAEKDVE MNNNSSATDSRFLRDSDAAIMGNDKTVAKEHYSSPSSSASQSNSFSKSDDIELSKSQA IFHWKNLCYDIPIKNGKRRILDNVDGWVKPGTLTALIGASGAGKTTLLDCLAERTTM GLITGDVFVDGRPRDQSFPRSIGYCQQQDLHLKTATVRESLRFSAYLRQADDVSIEEK DKYVEEVIEVLEMKLYADAIVGVPGEGLNVEQRKRLTIGVELAAKPKLLVFLDEPTS GLDSQTAWSTCQLMKKLASRGQAILCTIHQPSALLMQEFDRLLFLQEGGQTVYFGEL GKGCKTMINYFEAHGAHKCPPDANPAEWMLEIVGAAPGTHASQDYFAIWRDSEEY REMQKELDWMERELPKRTEGSSNEEQKEFATSTLYQIKLVSYRLFHQYWRTPFYLW SKFFSTIVSELFIGFTFFKANTSLQGLQNQMLAIFMFTVVFNPILQQYLPLFVQQRELY EARERPSRTFSWKAFIVSQILVEIPWNLLAGTIAFFVYYYPVGFYRNASYANQLHERG ALFWLFACAFYVYISSMGVLVISCIEIAENAANLASLFFIMSLSFCGVLATPNILPRFWI

[1017] FMYRVSPLTYLIDALLSVGLANASVVCSSNELLKIVPPSGMTCSEYMEPYMQSTGTG YLLDGS SETECHFCQF S STND YL AT VS S S YSRRWMNYGIF S AYIVFD YC AAIFL YWL VRVPKKSKKLKK

[1018] SEQ ID NO:44 - Native DNA

[1019] PDR10

[1020] ATGTTGCAAGCGCCCTCAAGTTCAAACTCGGGTTTGAATCAAGGAAATGCTGCGC

[1021] CGGACGGCCCACCTAACGAAACACAGCCGTACGAAGGCCTCGACGCGGCAGCTC

[1022] AAGAAGAAATAAAAGAATTGGCAAGAACGCTGACGAGCCAATCTTCCCTTTTAT

[1023] CGCAAGAAAAGCGTATTACCGGCACTGGCGACCCGAATACACTAACTGCTGCTT

[1024] CTTCATCGTCATTGAGCCGGTCAATTTTCGCTAGTGATATCAAGGGAGTTAACCC

[1025] AATCCTTTTGGACGTCAATGATCCAGACTACGATGAGACATTGGATCCTCGATCA

[1026] GAAAATTTCTCGAGTGTCAGATGGGTACGAAATATGGCACAAATATGCGAGAAT

[1027] GATTCGGATTTCTATAAACCGTTTTCATTAGGTTGCGCCTGGAAAGATTTGAGTG

[1028] CCTCCGGTGATTCTGCCGATATAACATATCAGGGAACATTTGGTAATATGCCCAT

[1029] CAAATACTTGAAAATGAGTTGGAGGTGCATATCCCGACGTCTTTTCCACCGGACA

[1030] CATGGCAAGAGTGAAGATAATGACTCCGGTTTCCAAATTTTGAAGCCGATGGAC

[1031] GGATGCATCAATCCGGGGGAACTACTTGTTGTGCTTGGACGACCCGGTGCAGGA

[1032] TGTACTACGCTGCTGAAATCTATATCTGTAAATACACACGGATTCAAGATTTCTC

[1033] CGGACACAATCATCACGTACAATGGATTCTCCAACAAAGAGATCAAAAACCATT

[1034] ACCGTGGTGAAGTGGTCTACAATGCAGAATCAGACATTCACATCCCGCACTTGAC

[1035] AGTATTCCAAACTTTATACACAGTGGCAAGACTGAAGACACCAAGGAACCGAAT

[1036] CAAGGGTGTCGATAGGGACACATTTGCCAAACACATGACTGAAGTGGCAATGGC

[1037] AACTTACGGACTGAGCCACACTGCAGATACAAAAGTGGGTAATGATTTTGTTCGT

[1038] GGTGTATCCGGGGGAGAAAGGAAAAGAGTTTCCATTGCTGAAGTGTCTATATGT

[1039] GGCTCGAAGTTTCAGTGCTGGGATAATGCCACGAGGGGCTTAGATTCTGCTACCG

[1040] CGCTGGAGTTCATCAAGGCCTTGAAAACGCAAGCCACTATCACAAAGTCTGCAG

[1041] CCACTGTGGCCATTTACCAATGTTCTAAAGATGCCTATGATTTGTTCGATAAAGT

[1042] CTGTGTTCTTTACGATGGTTACCAAATCTTCTTTGGCCCAAGTAAGCAGGCCAAA

[1043] AAGTACTTTCAAAGAATGGGATATGTGTGTCCCGAAAGGCAGACCACAGCAGAT

[1044] TATTTGACCTCTATTACTAGTCCTTCTGAAAGAATTAAGGACAAAGACATGGTCA

[1045] AACATGGAATTATGATCCCACAAACGGCCTATGAAATGAACCAGTACTGGATTC

[1046] AATCAGAGGAATACAAACAATTACAGGTGCAGGTGAACAAACATTTAGATACAG

[1047] ACTCTTCCCAGCAAAGAGAACAAATAAAAAATGCACATATTGCCAAACAATCTA

[1048] AGAGAGCACGGCCCTCCTCTCCTTATACAGTAAGTTTCTTTTTGCAAGTTAAGTA

[1049] TATTCTAATCAGGGATATATGGAGGATTAAGAATGACCCAAGTATTCAACTTTTC

[1050] ACGGTTTTGAGTCATGCAGCAATGGCTCTTATCTTGGGATCAATGTTTTATGAAG

[1051] TCATGCTTTCCACTACCACAACAACCTTTTATTACCGAGGCGCGGCTATTTTTTTT

[1052] GCTATTCTGTTCAATGCGTTCTCATCACTTTTAGAGATCTTTTCACTCTATGAGAC

[1053] GAGGCCCATTACCGAAAAGCACAAGACTTACTCGTTATATCGCCCAAGTGCTGAT

[1054] GCCTTCGCCTCTACATTTTCTGATGTTCCAACAAAATTAGCCACGGCAGTAACTTT

[1055] CAACATACCATATTATTTTTTAATCAATCTAAAAAGAGATGCCGGTGCTTTTTTCT TTTACTTTTTAATAAACATTATAACAGTTTTTGCTATGTCGCATTTGTTCAGATGC

[1056] ATTGGCTCAGTGTCGAAAACTTTACCTCAGGCAATGGTTCCCGCATCTGTTCTTCT

[1057] GTTAGCTTTTGCAATGTACACTGGGTTTGCCATCCCAAGAGTCCAAATGCTTGGC

[1058] TGGTCAAAATGGATTTCTTATATCAACCCATTGTCTTACCTTTTTGAATCGCTAAT

[1059] GATTAACGAATTTCATGGTAGAAATTTCCCATGTGCTCAGTATATACCTAGTGGG

[1060] CCAAATTATGTCAACGCAACAGGTGACGAAGTCACCTGCTCCGCCCTCGGTTCTA

[1061] TCCCAGGAAATAATTATGTAAGTGGTGATGATTTCATTCAAACGAACTACGGCTA

[1062] TCGACATAAGAACAAATGGCGGTCTGTTGGTATTGGTTTAGCATACATTATTTTTT

[1063] TCTTATTTCTGTATTTATTCTTTTGTGAATACAATGAAGGAGCAAAGCAAAATGG

[1064] TGAGATGTTAGTATTTCCCCATAGTGTGGTTAAAAAGATGAAGAAGAAGGGTATT

[1065] GTCTCTGAGAAGAAAAAGAAAAACCAACCAACGTTGTCAACATCTGATGCTGAG

[1066] AAAGATGTAGAGATGAACAACAATTCAAGTGCGACTGATTCAAGATTTTTACGC

[1067] GATTCTGATGCAGCTATAATGGGTAACGATAAAACTGTCGCCAAGGAGCATTATT

[1068] CATCTCCTTCATCTTCTGCGTCTCAAAGCAATAGTTTTAGTAAAAGTGATGACATT

[1069] GAATTGTCCAAATCACAAGCGATTTTTCATTGGAAAAACTTATGCTACGATATCC

[1070] CGATTAAGAATGGGAAGAGGAGAATTTTGGATAATGTTGATGGTTGGGTCAAGC

[1071] CTGGTACACTAACTGCCTTGATTGGCGCATCTGGTGCAGGAAAAACAACGTTATT

[1072] AGATTGTCTTGCCGAGAGAACCACGATGGGTTTAATCACTGGTGATGTATTCGTA

[1073] GATGGTAGACCGCGGGACCAGTCTTTCCCCAGATCAATTGGTTATTGTCAGCAGC

[1074] AGGATTTGCATTTGAAAACCGCAACTGTGAGAGAGTCATTAAGGTTTTCCGCGTA

[1075] CCTGCGTCAAGCCGATGATGTATCCATCGAGGAGAAAGATAAATACGTTGAAGA

[1076] AGTCATTGAGGTATTGGAGATGAAACTTTATGCTGATGCCATAGTAGGCGTTCCT

[1077] GGTGAAGGTTTAAATGTGGAACAAAGAAAAAGGTTAACCATAGGTGTGGAGTTA

[1078] GCTGCCAAACCAAAACTGTTGGTATTTTTAGATGAGCCCACGTCTGGGCTTGATT

[1079] CCCAAACTGCATGGTCAACTTGTCAATTAATGAAGAAATTGGCTAGTCGCGGAC

[1080] AAGCAATTTTATGTACCATTCATCAACCTTCTGCTCTCTTAATGCAAGAGTTTGAT

[1081] AGGTTACTATTTTTGCAAGAGGGCGGACAAACTGTATATTTTGGAGAGCTAGGGA

[1082] AAGGTTGCAAAACAATGATTAACTATTTCGAAGCTCATGGTGCCCATAAATGCCC

[1083] ACCAGATGCCAATCCAGCCGAATGGATGTTAGAAATAGTAGGTGCTGCACCAGG

[1084] AACTCACGCTAGTCAAGATTATTTTGCCATTTGGAGAGATTCTGAAGAATATAGG

[1085] GAAATGCAGAAAGAGTTGGACTGGATGGAACGAGAATTGCCTAAACGGACGGA

[1086] AGGTTCGTCAAATGAGGAGCAGAAGGAGTTCGCTACGTCAACTTTGTACCAGAT

[1087] CAAATTGGTGAGTTATCGATTATTCCATCAATATTGGAGAACACCATTTTACTTAT

[1088] GGTCAAAATTTTTTTCAACAATTGTGTCTGAACTCTTCATAGGCTTCACTTTTTTC

[1089] AAGGCGAATACATCATTACAGGGCCTACAGAATCAAATGCTGGCCATTTTTATGT

[1090] TTACAGTGGTATTCAACCCAATATTGCAACAATATTTACCACTTTTCGTTCAGCA

[1091] GAGGGAACTTTATGAAGCTAGAGAAAGGCCATCAAGAACCTTTTCGTGGAAAGC

[1092] ATTTATTGTATCGCAGATTCTCGTGGAAATCCCTTGGAATTTACTGGCCGGTACTA

[1093] TAGCTTTTTTCGTCTATTATTATCCTGTTGGATTTTACAGAAATGCTTCTTATGCA

[1094] AATCAACTTCATGAACGAGGAGCTTTATTTTGGTTATTTGCGTGCGCGTTTTACGT

[1095] CTACATCAGTTCAATGGGGGTATTAGTGATTTCATGCATTGAAATTGCAGAAAAT

[1096] GCTGCGAATCTCGCTTCACTTTTCTTTATAATGTCATTATCTTTCTGCGGTGTTCTG

[1097] GCTACGCCAAATATTCTACCAAGATTCTGGATTTTTATGTATAGAGTATCGCCAC

[1098] TGACATACCTCATTGATGCTCTGCTATCGGTAGGACTGGCCAATGCTAGTGTCGT

[1099] TTGTTCCAGCAACGAACTTTTAAAAATTGTTCCTCCAAGCGGTATGACATGCTCG

[1100] GAATATATGGAACCTTATATGCAATCCACCGGGACGGGTTATCTGCTCGATGGGA GTTCCGAAACTGAATGTCACTTTTGTCAATTCAGTTCTACCAATGATTATCTGGCG

[1101] ACTGTGAGTTCTTCGTATTCACGTAGATGGATGAACTATGGCATTTTTAGTGCAT

[1102] ATATTGTCTTTGACTATTGTGCAGCAATATTTTTATACTGGCTGGTGCGGGTTCCA

[1103] AAGAAAAGCAAAAAATTAAAGAAATAA

[1104] SEQ ID NO:45 - Amino acids

[1105] ESBP6

[1106] MSTHSNDYFSASSGMVSETSSEVSSINSSQPVSFSKASIAAPVPCSDLHSTKSNDASRK LSISRTLTNRLNDIKKAVDDDNLQTEENSADVNKILESRFDVADAIRLQHNESVQSKL NIP VTHTTT AGASL S APS S S AF S AS SIQNDTTEHK ASMD SKLMRNRL YP ASTKHSGKD LEAQGITEFEPDEPTVKKVFTNKSTGQLELPPDGGYGWVVTFCVFLTMFSTWGCNAS FGVDLAYYLNHDTYPGASKYDYALIAGLTVFLGQLLSPLVMALMRIIGLRTTMLFGD AVMLAAYLLASFTTKLWQLYVTQGFMVGCSISLIFVPATTVLPGWFLKKRAVAMGV SLLGTGAGGVVYGLATNKMLSDFGNTRWCLRIIGISCSISVLVAIALLKERNPTPAIGL KSPRAMFEQLKAMF SLKVITKPF VVLIALWFMF ALF AYNMMVFTLS S YAISKGLS SH DASTLTAILNGSQSIGRPLMGLAGDKFGRANVTIVLTTLLTIYMFAFWIPAHTFVQLIF FSILVGSCVGVANVMNTVLIADMVKPEEFLPAWAFVNYCGAPFLLVCEVIAQALTVE KDKSNPYLHAQIFCGCCFIAALILISILREYSIRMKLTERQAMTNEKLKEWKASEYDT

[1107] DSADEDWGKLKERKTKYDLLLGPGIKKYFLRMVYPMKV

[1108] SEQ ID NO:46 - DNA

[1109] ESBP6

[1110] ATGTCAACGCACTCAAACGACTACTTTTCTGCTTCTTCCGGAATGGTCTCTGAGA CATCGTCCGAGGTTTCTTCGATAAACTCTTCACAGCCTGTATCATTCTCTAAGGCT

[1111] TCTATTGCTGCTCCGGTTCCATGCTCTGATCTACACAGCACCAAGTCGAACGATG CATCGAGAAAATTGTCTATTAGTAGGACGTTAACTAATCGGCTCAACGACATTAA

[1112] AAAGGCTGTCGATGACGACAACTTGCAGACGGAAGAAAATTCCGCAGACGTTAA TAAAATATTAGAATCTAGATTTGACGTGGCCGATGCCATTAGGCTACAGCACAAT GAGTCAGTCCAGTCAAAGTTAAACATCCCAGTCACACACACCACGACTGCAGGC GCCTCGTTGTCGGCACCATCTTCCTCTGCTTTCTCTGCTTCTTCTATTCAAAATGA TACTACAGAACATAAAGCTTCCATGGACTCCAAACTCATGAGGAATAGACTATA TCCGGCTTCCACGAAACACTCCGGTAAGGATCTTGAGGCCCAAGGAATAACCGA ATTCGAGCCTGATGAACCGACTGTAAAAAAAGTATTCACCAACAAGTCTACCGG GCAGCTGGAACTGCCCCCCGACGGTGGTTATGGCTGGGTCGTGACATTCTGTGTG TTCTTGACCATGTTTTCCACGTGGGGCTGCAACGCATCCTTCGGTGTCGACCTTGC

[1113] CTACTACTTAAACCATGATACTTACCCTGGTGCTTCGAAGTACGATTATGCCTTA ATTGCTGGCCTAACTGTCTTTCTCGGTCAACTCTTATCCCCCCTTGTGATGGCACT

[1114] GATGAGAATAATTGGTCTGCGGACCACCATGCTTTTTGGTGATGCTGTAATGCTT GCCGCATATCTCTTGGCCTCCTTTACTACCAAGTTATGGCAATTGTATGTCACCCA

[1115] AGGTTTTATGGTCGGTTGTTCAATATCACTGATTTTCGTTCCAGCAACAACCGTCT TACCAGGATGGTTCTTGAAAAAAAGAGCTGTCGCAATGGGTGTCTCATTATTGGG TACCGGTGCTGGTGGTGTCGTTTACGGTTTGGCTACAAACAAAATGCTTTCTGAC TTTGGAAATACCCGGTGGTGCCTTCGTATCATAGGCATATCGTGTAGCATAAGTG

[1116] TTCTAGTTGCTATTGCGCTCTTAAAAGAAAGAAACCCTACACCTGCCATAGGATT

[1117] GAAATCGCCTCGGGCCATGTTTGAACAGCTCAAAGCAATGTTTTCATTAAAGGTT

[1118] ATAACTAAGCCATTTGTGGTACTTATTGCATTATGGTTCATGTTCGCATTATTTGC

[1119] CTACAATATGATGGTTTTTACTTTATCTTCATACGCAATCTCGAAAGGATTATCAT

[1120] CGCACGACGCTTCCACATTGACTGCCATTTTGAACGGCTCGCAATCCATCGGAAG

[1121] ACCTCTGATGGGTTTAGCGGGAGATAAGTTTGGTAGGGCAAACGTAACGATCGT

[1122] ATTAACCACTTTGTTAACAATATATATGTTTGCGTTCTGGATCCCCGCTCATACGT

[1123] TTGTTCAACTCATCTTTTTTTCAATTCTAGTTGGCTCATGCGTTGGTGTCGCCAAC

[1124] GTCATGAATACCGTTCTGATTGCCGATATGGTTAAACCAGAAGAGTTTTTGCCCG

[1125] CTTGGGCCTTCGTCAACTACTGTGGTGCGCCTTTCTTATTGGTTTGTGAGGTGATT

[1126] GCCCAGGCATTGACGGTGGAGAAAGATAAGAGCAATCCTTACTTACATGCACAA

[1127] ATTTTTTGCGGTTGCTGCTTTATTGCCGCACTAATTTTAATTTCTATCCTTCGTGAA

[1128] TATTCTATCAGGATGAAATTAACGGAAAGACAAGCTATGACAAACGAGAAGTTA

[1129] AAAGAATGGAAGGCAAGCGAATACGATACCGATTCTGCCGATGAAGATTGGGGT

[1130] AAATTAAAAGAAAGAAAGACTAAATATGACCTTCTTTTAGGTCCGGGCATTAAA

[1131] AAATACTTCCTAAGAATGGTATATCC AATGAAGGTCTAG Native DNA

[1132] SEQ ID NO: 47 - Amino acid

[1133] Phenylalanine ammonia lyase from Arabidopsis thaliana

[1134] MEINGAHI<SNGGGVDAMLCGGDII<TI<NMVINAEDPLNWGAAAEQMI<GSHLDEVI<

[1135] RMVAEFRKPVVNLGGETLTIGQVAAISTIGNSVKVELSETARAGVNASSDWVMESM

[1136] NKGTDSYGVTTGFGATSHRRTKNGVALQKELIRFLNAGIFGSTKETSHTLPHSATRA

[1137] AMLVRINTLLQGFSGIRFEILEAITSFLNNNITPSLPLRGTITASGDLVPLSYIAGLLTGR

[1138] PNSKATGPNGEALTAEEAFKLAGISSGFFDLQPKEGLALVNGTAVGSGMASMVLFET

[1139] NVLSVLAEILSAVFAEVMSGKPEFTDHLTHRLKHHPGQIEAAAIMEHILDGSSYMKL

[1140] AQKLHEMDPLQKPKQDRYALRTSPQWLGPQIEVIRYATKSIEREINSVNDNPLIDVSR

[1141] NKAIHGGNFQGTPIGVSMDNTRLAIAAIGKLMFAQFSELVNDFYNNGLPSNLTASRN

[1142] PSLDYGFKGAEIAMASYCSELQYLANPVTSHVQSAEQHNQDVNSLGLISSRKTSEAV

[1143] DILKLMSTTFLVAICQAVDLRHLEENLRQTVKNTVSQVAKKVLTTGVNGELHPSRFC

[1144] EKDLLKVVDREQVYTYADDPCSATYPLIQKLRQVIVDHALINGESEKNAVTSIFHKIG

[1145] AFEEELKAVLPKEVEAARAAYDNGTSAIPNRIKECRSYPLYRFVREELGTELLTGEKV

[1146] TSPGEEFDKVFTAICEGKIIDPMMECLNEWNGAPIPIC

[1147] SEQ ID NO: 48 - DNA

[1148] Codon optimized phenylalanine ammonia lyase from Arabidopsis thaliana

[1149] ATGGAGATTAACGGGGCACACAAGAGCAACGGAGGAGGAGTGGACGCTATGTT

[1150] ATGCGGCGGAGACATCAAGACAAAGAACATGGTGATCAACGCGGAGGATCCTCT

[1151] CAACTGGGGAGCAGCAGCGGAGCAAATGAAAGGTAGCCATTTGGATGAAGTGA

[1152] AGAGAATGGTTGCTGAGTTTAGGAAGCCAGTTGTGAATCTTGGTGGTGAGACTCT

[1153] GACCATTGGACAAGTGGCTGCGATCTCAACTATTGGTAACAGTGTGAAGGTGGA

[1154] GCTATCGGAGACAGCTAGAGCCGGTGTGAATGCTAGTAGTGATTGGGTTATGGA GAGTATGAACAAAGGCACTGATAGTTATGGTGTTACTACTGGTTTTGGTGCTACT

[1155] TCTCATCGGAGAACCAAGAACGGTGTCGCACTTCAGAAGGAACTTATTAGATTCC

[1156] TTAACGCCGGAATATTCGGAAGCACGAAAGAAACAAGCCACACATTGCCACACT

[1157] CCGCCACAAGAGCCGCCATGCTTGTACGAATCAACACTCTCCTCCAAGGATTTTC

[1158] CGGTATCCGATTTGAGATTCTCGAAGCAATTACCAGTTTCCTCAACAACAACATC

[1159] ACTCCATCTCTCCCGCTCCGTGGTACAATCACCGCCTCCGGAGATCTCGTTCCTCT

[1160] CTCCTACATCGCCGGACTTCTCACCGGTCGTCCCAATTCCAAAGCTACTGGTCCC

[1161] AACGGTGAAGCTTTAACAGCAGAGGAAGCTTTCAAATTAGCAGGAATCAGCTCC

[1162] GGATTCTTTGATCTCCAGCCTAAGGAAGGTCTGGCGCTAGTCAATGGCACGGCGG

[1163] TTGGATCTGGAATGGCGTCAATGGTGTTATTCGAAACGAATGTTCTCTCTGTTTTG

[1164] GCTGAGATTTTGTCGGCGGTTTTCGCAGAGGTGATGAGTGGTAAGCCTGAGTTCA

[1165] CCGATCATCTCACTCACAGACTTAAACATCATCCCGGTCAAATCGAAGCGGCGGC

[1166] GATAATGGAGCATATCCTCGACGGAAGCTCGTACATGAAATTAGCTCAGAAGCT

[1167] TCACGAGATGGATCCGTTACAGAAACCTAAACAAGATCGTTACGCTCTTCGTACT

[1168] TCTCCTCAATGGTTAGGTCCTCAAATCGAAGTGATCCGTTACGCAACGAAATCGA

[1169] TCGAGCGTGAGATTAACTCCGTCAACGATAATCCGTTGATCGATGTTTCGAGGAA

[1170] CAAGGCGATTCACGGTGGTAACTTCCAAGGAACACCAATCGGAGTTTCAATGGA

[1171] TAACACGAGATTGGCGATAGCAGCGATTGGTAAACTCATGTTTGCTCAATTCTCA

[1172] GAGCTTGTGAATGATTTCTACAACAATGGTTTACCCTCGAATCTAACCGCTTCGA

[1173] GGAATCCAAGTTTGGATTATGGATTCAAGGGAGCTGAGATTGCAATGGCTTCTTA

[1174] TTGTTCAGAGCTTCAATACTTAGCTAATCCTGTGACTAGCCATGTTCAATCAGCA

[1175] GAGCAACATAACCAAGATGTCAACTCTTTGGGACTAATCAGCTCTCGCAAAACTT

[1176] CTGAAGCTGTTGATATTCTCAAGCTTATGTCAACAACGTTCCTCGTTGCGATTTGT

[1177] CAAGCTGTGGATTTGAGACATTTGGAGGAGAATTTGAGACAGACTGTGAAGAAC

[1178] ACTGTCTCTCAAGTGGCGAAGAAAGTTCTTACTACTGGAGTCAATGGTGAGCTTC

[1179] ATCCTTCTCGCTTCTGCGAAAAGGATTTACTCAAAGTTGTAGACCGTGAACAAGT

[1180] CTACACATACGCGGATGATCCTTGTAGCGCAACGTACCCGTTGATTCAGAAGCTG

[1181] AGACAAGTTATTGTTGACCATGCTTTGATCAATGGTGAGAGTGAGAAGAATGCA

[1182] GTGACTTCAATCTTCCATAAGATTGGAGCTTTCGAGGAGGAGCTTAAGGCAGTGC

[1183] TACCGAAAGAAGTGGAAGCAGCAAGAGCAGCCTACGATAACGGAACATCGGCT

[1184] ATCCCGAACAGGATCAAGGAATGTAGGTCGTATCCATTGTATAGATTCGTGAGG

[1185] GAAGAGCTTGGAACAGAGCTTTTGACCGGAGAGAAAGTGACGTCGCCTGGAGAA

[1186] GAGTTCGACAAGGTTTTCACGGCGATTTGTGAAGGTAAAATCATTGATCCGATGA

[1187] TGGAATGTCTCAACGAGTGGAACGGAGCTCCCATTCCAATATGTTAA

[1188] SEQ ID NO: 49 - DNA

[1189] PDC1 promoter

[1190] ACACACCCCGCGTTTATTTACCTATCTCTAAACTTCAACACCTTATATCATAACTA

[1191] ATATTTCTTGAGATAAGCACACTGCACCCATACCTTCCTTAAAAACGTAGCTTCC

[1192] AGTTTTTGGTGGTTCCGGCTTCCTTCCCGATTCCGCCCGCTAAACGCATATTTTTG

[1193] TTGCCTGGTGGCATTTGCAAAATGCATAACCTATGCATTTAAAAGATTATGTATG

[1194] CTCTTCTGACTTTTCGTGTGATGAGGCTCGTGGAAAAAATGAATAATTTATGAAT

[1195] TTGAGAACAATTTTGTGTTGTTACGGTATTTTACTATGGAATAATCAATCAATTGA

[1196] GGATTTTATGCAAATATCGTTTGAATATTTTTCCGACCCTTTGAGTACTTTTCTTC ATAATTGCATAATATTGTCCGCTGCCCCTTTTTCTGTTAGACGGTGTCTTGATCTA

[1197] CTTGCTATCGTTCAACACCACCTTATTTTCTAACTATTTTTTTTTTAGCTCATTTGA

[1198] ATCAGCTTATGGTGATGGCACATTTTTGCATAAACCTAGCTGTCCTCGTTGAACA

[1199] TAGGAAAAAAAAATATATAAACAAGGCTCTTTCACTCTCCTTGCAATCAGATTTG

[1200] GGTTTGTTCCCTTTATTTTCATATTTCTTGTCATATTCCTTTCTCAATTATTATTTTC

[1201] TACTCATAACCTCACGCAAAATAACACAGTCAAATCAATCAAA

[1202] SEQ ID NO:50 - DNA

[1203] TEF1 promoter

[1204] CCTTGCCAACAGGGAGTTCTTCAGAGACATGGAGGCTCAAAACGAAATTATTGA

[1205] CAGCCTAGACATCAATAGTCATACAACAGAAAGCGACCACCCAACTTTGGCTGA

[1206] TAATAGCGTATAAACAATGCATACTTTGTACGTTCAAAATACAATGCAGTAGATA

[1207] TATTTATGCATATTACATATAATACATATCACATAGGAAGCAACAGGCGCGTTGG

[1208] ACTTTTAATTTTCGAGGACCGCGAATCCTTACATCACACCCAATCCCCCACAAGT

[1209] GATCCCCCACACACCATAGCTTCAAAATGTTTCTACTCCTTTTTTACTCTTCCAGA

[1210] TTTTCTCGGACTCCGCGCATCGCCGTACCACTTCAAAACACCCAAGCACAGCATA

[1211] CTAAATTTCCCCTCTTTCTTCCTCTAGGGTGTCGTTAATTACCCGTACTAAAGGTT

[1212] TGGAAAAGAAAAAAGACACCGCCTCGTTTCTTTTTCTTCGTCGAAAAAGGCAATA

[1213] AAAATTTTTATCACGTTTCTTTTTCTTGAAAATTTTTTTTTTTGATTTTTTTCTCTTT

[1214] CGATGACCTCCCATTGATATTTAAGTTAATAAACGGTCATCAATTTCTCAAGTTTC

[1215] AGTTTCATTTTTCTTGTTCTATTACAACTTTTTTTACTTCTTGCTCATTAGAAAGAA

[1216] AGCATAGCAATCTAATCTAAGTTTTAATTACAAA

[1217] SEQ ID NO:51 - DNA

[1218] TEF2 promoter

[1219] TTGATAGGTCAAGATCAATGTAAACAATTACTTTGTTATGTAGAGTTTTTTTAGCT

[1220] ACCTATATTCCACCATAACATCAATCATGCGGTTGCTGGTGTATTTACCAATAAT

[1221] GTTTAATGTATATATATATATATATATATGGGGCCGTATACTTACATATAGTAGA

[1222] TGTCAAGCGTAGGCGCTTCCCCTGCCGGCTGTGAGGGCGCCATAACCAAGGTATC

[1223] TATAGACCGCCAATCAGCAAACTACCTCCGTACATTCATGTTGCACCCACACATT

[1224] TATACACCCAGACCGCGACAAATTACCCATAAGGTTGTTTGTGACGGCGTCGTAC

[1225] AAGAGAACGTGGGAACTTTTTAGGCTCACCAAAAAAGAAAGAAAAAATACGAG

[1226] TTGCTGACAGAAGCCTCAAGAAAAAAAAAATTCTTCTTCGACTATGCTGGAGGC

[1227] AGAGATGATCGAGCCGGTAGTTAACTATATATAGCTAAATTGGTTCCATCACCTT

[1228] ACTTTTTTTTCTTCGTTGTTCGTTCCTGCCTTTCTCCTTTACATTAAGTTAGTCATAAATTTTTCCTTCGTGTCGTCTATTTTCTCTTCATTATTTTTTTTTTTCTTTCTTTCCTC

[1229] ATCTATTCTACTTGTTTATTCCCTTCAAGGTTTTTTTTTAAGGAGTACTTGTTTTTA

[1230] GAATATACGGTCAACGAACTATAATTAACTAAAC

[1231] SEQ ID NO: 52 - DNA

[1232] TDH3 promoter CAGTTCGAGTTTATCATTATCAATACTGCCATTTCAAAGAATACGTAAATAATTA ATAGTAGTGATTTTCCTAACTTTATTTAGTCAAAAAATTAGCCTTTTAATTCTGCT GTAACCCGTACATGCCCAAAATAGGGGGCGGGTTACACAGAATATATAACATCG TAGGTGTCTGGGTGAACAGTTTATTCCTGGCATCCACTAAATATAATGGAGCCCG

[1233] CTTTTTAAGCTGGCATCCAGAAAAAAAAAGAATCCCAGCACCAAAATATTGTTTT

[1234] CTTCACCAACCATCAGTTCATAGGTCCATTCTCTTAGCGCAACTACAGAGAACAG GGGCACAAACAGGCAAAAAACGGGCACAACCTCAATGGAGTGATGCAACCTGC CTGGAGTAAATGATGACACAAGGCAATTGACCCACGCATGTATCTATCTCATTTT CTTACACCTTCTATTACCTTCTGCTCTCTCTGATTTGGAAAAAGCTGAAAAAAAA

[1235] GGTTGAAACCAGTTCCCTGAAATTATTCCCCTACTTGACTAATAAGTATATAAAG ACGGTAGGTATTGATTGTAATTCTGTAAATCTATTTCTTAAACTTCTTAAATTCTA CTTTTATAGTTAGTCTTTTTTTTAGTTTTAAAACACCAAGAACTTAGTTTCGAATA AACACACATAAACAAACAAA

[1236] SEQ ID NO:53 - DNA

[1237] PGK1 promoter

[1238] GTGAGTAAGGAAAGAGTGAGGAACTATCGCATACCTGCATTTAAAGATGCCGAT

[1239] TTGGGCGCGAATCCTTTATTTTGGCTTCACCCTCATACTATTATCAGGGCCAGAA

[1240] AAAGGAAGTGTTTCCCTCCTTCTTGAATTGATGTTACCCTCATAAAGCACGTGGC

[1241] CTCTTATCGAGAAAGAAATTACCGTCGCTCGTGATTTGTTTGCAAAAAGAACAAA

[1242] ACTGAAAAAACCCAGACACGCTCGACTTCCTGTCATCCTATTGATTGCAGCTTCC

[1243] AATTTCGTCACACAACAAGGTCCTAGCGACGGCTCACAGGTTTTGTAACAAGCA

[1244] ATCGAAGGTTCTGGAATGGCGGGAAAGGGTTTAGTACCACATGCTATGATGCCC

[1245] ACTGTGATCTCCAGAGCAAAGTTCGTTCGATCGTACTGTTACTCTCTCTCTTTCAA

[1246] ACAGAATTGTCCGAATCGTGTGACAACAACAGCCTGTTCTCACACACTCTTTTCT

[1247] TCTAACCAAGGGGGTGGTTTAGTTTAGTAGAACCTCGTGAAACTTACATTTACAT

[1248] ATATATAAACTTGCATAAATTGGTCAATGCAAGAAATACATATTTGGTCTTTTCT

[1249] AATTCGTAGTTTTTCAAGTTCTTAGATGCTTTCTTTTTCTCTTTTTTACAGATCATC

[1250] AAGGAAGTAATTATCTACTTTTTACAACAAATATAAAACA

[1251] SEQ ID NO: 54 - DNA

[1252] ADH1 promoter

[1253] TTGCTCTCCCTAACATGTAGGTGGCGGAGGGGAGATATACAATAGAACAGATAC

[1254] CAGACAAGACATAATGGGCTAAACAAGACTACACCAATTACACTGCCTCATTGA

[1255] TGGTGGTACATAACGAACTAATACTGTAGCCCTAGACTTGATAGCCATCATCATA

[1256] TCGAAGTTTCACTACCCTTTTTCCATTTGCCATCTATTGAAGTAATAATAGGCGCA

[1257] TGCAACTTCTTTTCTTTTTTTTTCTTTTCTCTCTCCCCCGTTGTTGTCTCACCATATC

[1258] CGCAATGACAAAAAAATGATGGATGGATGACACTAAAGGAAAAAATTAACGAC

[1259] AAAGACAGCACCAACAGATGTCGTTGTTCCAGAGCTGATGAGGGGTATCTCGAA

[1260] GCACACGAAACTTTTTCCTTCCTTCATTCACGCACACTACTCTCTAATGAGCAAC

[1261] GGTATACGGCCTTCCTTCCAGTTACTTGAATTTGAAATAAAAAAAAGTTTGCTGT

[1262] CTTGCTATCAAGTATAAATAGACCTGCAATTATTAATCTTTTGTTTCCTCGTCATT GTTCTCGTTCCCTTTCTTCCTTGTTTCTTTTTCTGCACAATATTTCAAGCTATACCA

[1263] AGCATACAATCAACTCCAAGCTG

[1264] SEQ ID NO: 55 - Amino acids

[1265] RKI1

[1266] MAAGVPKIDALESLGNPLEDAKRAAAYRAVDENLKFDDHKIIGIGSGSTVVYVAERI

[1267] GQYLHDPKFYEVASKFICIPTGFQSRNLILDNKLQLGSIEQYPRIDIAFDGADEVDENL

[1268] QLIKGGGACLFQEKLVSTSAKTFIVVADSRKKSPKHLGKNWRQGVPIEIVPSSYVRV

[1269] KNDLLEQLHAEKVDIRQGGSAKAGPVVTDNNNFIIDADFGEISDPRKLHREIKLLVGV

[1270] VETGLFIDNASKAYFGNSDGSVEVTEK

[1271] SEQ ID NO:56 - Native DNA

[1272] RKI1

[1273] ATGGCTGCCGGTGTCCCAAAAATTGATGCGTTAGAATCTTTGGGCAATCCTTTGG

[1274] AGGATGCCAAGAGAGCTGCAGCATACAGAGCAGTTGATGAAAATTTAAAATTTG

[1275] ATGATCACAAAATTATTGGAATTGGTAGTGGTAGCACAGTGGTTTATGTTGCCGA

[1276] AAGAATTGGACAATATTTGCATGACCCTAAATTTTATGAAGTAGCGTCTAAATTC

[1277] ATTTGCATTCCAACAGGATTCCAATCAAGAAACTTGATTTTGGATAACAAGTTGC

[1278] AATTAGGCTCCATTGAACAGTATCCTCGCATTGATATAGCGTTTGACGGTGCTGA

[1279] TGAAGTGGATGAGAATTTACAATTAATTAAAGGTGGTGGTGCTTGTCTATTTCAA

[1280] GAAAAATTGGTTAGTACTAGTGCTAAAACCTTCATTGTCGTTGCTGATTCAAGAA

[1281] AAAAGTCACCAAAACATTTAGGTAAGAACTGGAGGCAAGGTGTTCCCATTGAAA

[1282] TTGTACCTTCCTCATACGTGAGGGTCAAGAATGATCTATTAGAACAATTGCATGC

[1283] TGAAAAAGTTGACATCAGACAAGGAGGTTCTGCTAAAGCAGGTCCTGTTGTAAC

[1284] TGACAATAATAACTTCATTATCGATGCGGATTTCGGTGAAATTTCCGATCCAAGA

[1285] AAATTGCATAGAGAAATCAAACTGTTAGTGGGCGTGGTGGAAACAGGTTTATTC

[1286] ATCGACAACGCTTCAAAAGCCTACTTCGGTAATTCTGACGGTAGTGTTGAAGTTA

[1287] CCGAAAAGTGA

[1288] SEQ ID NO: 57 - Amino acids

[1289] TKL1

[1290] MTQFTDIDKLAVSTIRILAVDTVSKANSGHPGAPLGMAPAAHVLWSQMRMNPTNPD

[1291] WINRDRFVLSNGHAVALLYSMLHLTGYDLSIEDLKQFRQLGSRTPGHPEFELPGVEV

[1292] TTGPLGQGISNAVGMAMAQANLAATYNKPGFTLSDNYTYVFLGDGCLQEGISSEAS

[1293] SLAGHLKLGNLIAIYDDNKITIDGATSISFDEDVAKRYEAYGWEVLYVENGNEDLAGI

[1294] AKAIAQAKLSKDKPTLIKMTTTIGYGSLHAGSHSVHGAPLKADDVKQLKSKFGFNPD

[1295] KSFVVPQEVYDHYQKTILKPGVEANNKWNKLFSEYQKKFPELGAELARRLSGQLPA

[1296] NWESKLPTYTAKDSAVATRKLSETVLEDVYNQLPELIGGSADLTPSNLTRWKEALDF

[1297] QPPSSGSGNYSGRYIRYGIREHAMGAIMNGISAFGANYKPYGGTFLNFVSYAAGAVR

[1298] LSALSGHPVIWVATHDSIGVGEDGPTHQPIETLAHFRSLPNIQVWRPADGNEVSAAY KNSLESKHTPSIIALSRQNLPQLEGSSIESASKGGYVLQDVANPDIILVATGSEVSLSVE

[1299] AAKTLAAKNIKARVVSLPDFFTFDKQPLEYRLSVLPDNVPIMSVEVLATTCWGKYA

[1300] HQSFGIDRFGASGKAPEVFKFFGFTPEGVAERAQKTIAFYKGDKLISPLKKAF

[1301] SEQ ID NO: 58 - Native DNA

[1302] TKL1

[1303] ATGACTCAATTCACTGACATTGATAAGCTAGCCGTCTCCACCATAAGAATTTTGG

[1304] CTGTGGACACCGTATCCAAGGCCAACTCAGGTCACCCAGGTGCTCCATTGGGTAT

[1305] GGCACCAGCTGCACACGTTCTATGGAGTCAAATGCGCATGAACCCAACCAACCC

[1306] AGACTGGATCAACAGAGATAGATTTGTCTTGTCTAACGGTCACGCGGTCGCTTTG

[1307] TTGTATTCTATGCTACATTTGACTGGTTACGATCTGTCTATTGAAGACTTGAAACA

[1308] GTTCAGACAGTTGGGTTCCAGAACACCAGGTCATCCTGAATTTGAGTTGCCAGGT

[1309] GTTGAAGTTACTACCGGTCCATTAGGTCAAGGTATCTCCAACGCTGTTGGTATGG

[1310] CCATGGCTCAAGCTAACCTGGCTGCCACTTACAACAAGCCGGGCTTTACCTTGTC

[1311] TGACAACTACACCTATGTTTTCTTGGGTGACGGTTGTTTGCAAGAAGGTATTTCTT

[1312] CAGAAGCTTCCTCCTTGGCTGGTCATTTGAAATTGGGTAACTTGATTGCCATCTA

[1313] CGATGACAACAAGATCACTATCGATGGTGCTACCAGTATCTCATTCGATGAAGAT

[1314] GTTGCTAAGAGATACGAAGCCTACGGTTGGGAAGTTTTGTACGTAGAAAATGGT

[1315] AACGAAGATCTAGCCGGTATTGCCAAGGCTATTGCTCAAGCTAAGTTATCCAAG

[1316] GACAAACCAACTTTGATCAAAATGACCACAACCATTGGTTACGGTTCCTTGCATG

[1317] CCGGCTCTCACTCTGTGCACGGTGCCCCATTGAAAGCAGATGATGTTAAACAACT

[1318] AAAGAGCAAATTCGGTTTCAACCCAGACAAGTCCTTTGTTGTTCCACAAGAAGTT

[1319] TACGACCACTACCAAAAGACAATTTTAAAGCCAGGTGTCGAAGCCAACAACAAG

[1320] TGGAACAAGTTGTTCAGCGAATACCAAAAGAAATTCCCAGAATTAGGTGCTGAA

[1321] TTGGCTAGAAGATTGAGCGGCCAACTACCCGCAAATTGGGAATCTAAGTTGCCA

[1322] ACTTACACCGCCAAGGACTCTGCCGTGGCCACTAGAAAATTATCAGAAACTGTTC

[1323] TTGAGGATGTTTACAATCAATTGCCAGAGTTGATTGGTGGTTCTGCCGATTTAAC

[1324] ACCTTCTAACTTGACCAGATGGAAGGAAGCCCTTGACTTCCAACCTCCTTCTTCC

[1325] GGTTCAGGTAACTACTCTGGTAGATACATTAGGTACGGTATTAGAGAACACGCTA

[1326] TGGGTGCCATAATGAACGGTATTTCAGCTTTCGGTGCCAACTACAAACCATACGG

[1327] TGGTACTTTCTTGAACTTCGTTTCTTATGCTGCTGGTGCCGTTAGATTGTCCGCTTT

[1328] GTCTGGCCACCCAGTTATTTGGGTTGCTACACATGACTCTATCGGTGTCGGTGAA

[1329] GATGGTCCAACACATCAACCTATTGAAACTTTAGCACACTTCAGATCCCTACCAA

[1330] ACATTCAAGTTTGGAGACCAGCTGATGGTAACGAAGTTTCTGCCGCCTACAAGA

[1331] ACTCTTTAGAATCCAAGCATACTCCAAGTATCATTGCTTTGTCCAGACAAAACTT

[1332] GCCACAATTGGAAGGTAGCTCTATTGAAAGCGCTTCTAAGGGTGGTTACGTACTA

[1333] CAAGATGTTGCTAACCCAGATATTATTTTAGTGGCTACTGGTTCCGAAGTGTCTTT

[1334] GAGTGTTGAAGCTGCTAAGACTTTGGCCGCAAAGAACATCAAGGCTCGTGTTGTT

[1335] TCTCTACCAGATTTCTTCACTTTTGACAAACAACCCCTAGAATACAGACTATCAG

[1336] TCTTACCAGACAACGTTCCAATCATGTCTGTTGAAGTTTTGGCTACCACATGTTG

[1337] GGGCAAATACGCTCATCAATCCTTCGGTATTGACAGATTTGGTGCCTCCGGTAAG

[1338] GCACCAGAAGTCTTCAAGTTCTTCGGTTTCACCCCAGAAGGTGTTGCTGAAAGAG

[1339] CTCAAAAGACCATTGCATTCTATAAGGGTGACAAGCTAATTTCTCCTTTGAAAAA

[1340] AGCTTTCTAA

Claims

CLAIMSWhat is Claimed:

1. A method of increasing resveratrol production using a recombinant Saccharomyces cell, the method comprising:(i) cultivating a recombinant Saccharomyces cell in a medium;(ii) adding 4-coumaric acid to the medium to initiate the bioconversion of 4-coumaric acid to resveratrol; and(iii) extracting resveratrol from at least one of the recombinant cell and medium, wherein the recombinant Saccharomyces cell has been transformed to overexpress a gene encoding an acetyl-coA synthase enzyme.

2. A method of increasing resveratrol production using a recombinant Saccharomyces cell, the method comprising:(i) cultivating a recombinant Saccharomyces cell in a medium;(ii) adding 4-coumaric acid to the medium to initiate the bioconversion of 4-coumaric acid to resveratrol; and(iii) extracting resveratrol from at least one of the recombinant cell and medium, wherein the recombinant Saccharomyces cell has been transformed to overexpress one or more of the group consisting of a gene encoding a transketolase enzyme, a gene encoding a ribose- 5-phosphate ketol isomerase enzyme, a gene encoding a transaldolase enzyme, a gene encoding an enolase 2 enzyme, a gene encoding an aromatic aminotransferase I enzyme, and a gene encoding a prephenate dehydratase enzyme.

3. A method of increasing resveratrol production using a recombinant Saccharomyces cell, the method comprising:(i) cultivating a recombinant Saccharomyces cell in a medium;(ii) adding 4-coumaric acid to the medium to initiate the bioconversion of 4-coumaric acid to resveratrol; and(iii) extracting resveratrol from at least one of the recombinant cell and medium, whereinthe recombinant Saccharomyces cell has been transformed to overexpress one or more of the group consisting of a gene encoding a monocarboxylate permease enzyme.

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