Production of terpenes

Abstract

This invention provides a method for producing compound (I), comprising using a phosphorylase to catalyze the production of compound (I) from compound (II). This invention also provides recombinant engineered bacteria for producing compound (I) and their applications.

Description

[0001] This application is a divisional application of Chinese invention patent application No. 202512060437.5, filed on December 31, 2025, entitled "Production of Terpene Compounds".

[0002] RELEVANT APPLIANCES This application claims priority to Chinese patent application CN202412000065.2, filed on December 31, 2024, which is incorporated herein by reference in its entirety. Technical Field

[0003] This invention belongs to the field of biocatalytic synthesis, and particularly relates to a method for producing terpenoid compounds of formula (I) by biocatalysis and its application. Background Technology

[0004] Terpenes are a large class of isoprenoids that are widely found in nature, mainly isolated from plants, microorganisms, and marine organisms. The general formula for terpenes is (C5H8)n, where n is the number of isoprenoid units. Based on the number of n, terpenes can be classified into hemiterpenes (C5), monoterpenes (C10), sesquiterpenes (C15), diterpenes (C20), disesquiterpenes (C25), triterpenes (C30), tetraterpenes (C40), and polyterpenes (n>40). More than 50,000 terpenes have been discovered to date, with common examples including monoterpenes such as menthol, sesquiterpenes such as artemisinin, diterpenes such as paclitaxel, triterpenes such as ginsenosides, and tetraterpenoids such as carotenoids.

[0005] Currently, an increasing number of terpene compounds, including monoterpenes, sesquiterpenes, and diterpenes, are being identified. Terpene synthases (TPS) play a crucial role in this process, acting as enzymes that convert linear cis- or trans-pentadienyl diphosphate intermediates containing 5-20 carbon atoms into various terpene compounds, such as hemiterpenes, monoterpenes, sesquiterpenes, diterpenes, and triterpenes. Terpene synthases can convert terpene precursors into a variety of terpene compounds, providing a natural and sustainable production method for the fragrance industry.

[0006] Terpenes have important biological functions and applications. Firstly, many terpenes possess broad-spectrum anticancer effects and are key intermediates in the synthesis of various important drugs. Many plant-derived terpenes are aromatic volatile substances, important components of plant essential oils, and sources of aroma in fruits and flowers, thus commonly used as fragrances in aromatic foods and essential oil cosmetics. For example, farnesol (FOH), a sesquiterpene found in plants such as Brazilian sandalwood, acacia, and palmarosa; geraniol (GGOH), found in the seeds of the tropical American annatto and the oleoresin of mahogany; and lysine diol (LOH), found in plants of the rock rose genus, are widely used in the manufacture of perfumes, cosmetics, and other aromatic products due to their pleasant aromas. They can be used alone or blended with other fragrances to create different scent combinations. For instance, in some high-end perfumes, farnesol can add a soft, elegant floral scent. In addition, geraniol possesses a unique aroma and can be used as a food flavoring in the production of baked goods, candies, and beverages, adding floral and fruity aromas to meet consumers' demands for delicious food. Natural ambergris is a high-grade flavoring agent derived from the grayish-white soft stones found in the stomach and intestines of sperm whales; its extremely limited production makes it exceptionally precious. Ambroxol is one of the most crucial active ingredients in natural ambergris and can be synthesized artificially, making it an excellent substitute for natural ambergris. To keep pace with the current trend of green chemistry, research on the synthesis methods of ambroxol has been continuously moving towards greener approaches. Simultaneously, the development of novel production methods for styracil lactone and styracil diol has also attracted researchers' attention. Labdenediol, due to its structure similar to ambroxol, also provides a new direction and exploration path for the biosynthesis of ambroxol, a product with higher added value.

[0007] Currently, the main supply of these high-value-added terpenoids from plants still heavily relies on traditional plant extraction methods. These methods are labor-intensive, expensive, and yield low quantities, failing to guarantee production and application. With the rapid development of synthetic biology, there is an urgent need to construct biosynthetic pathways that meet the requirements of "more efficient, lower cost, stable production, and increased yield," enabling microorganisms to sustainably produce lysenoside diol, farnesol, etc., which will also be of great significance for the subsequent production and application of higher-value-added derivatives. Summary of the Invention

[0008] This invention provides, in one aspect, a method for producing compound (I),

[0009] R is H or a hydrocarbon group, which is cyclic or acyclic, straight or branched, saturated or unsaturated, and / or substituted or unsubstituted; The method includes the following steps: The precursor of compound (I) is catalyzed by a phosphorylase to generate compound (I); The precursor of compound (I) is compound (II) as shown below: , The R in compound (II) is the same as the R in compound (I); and The phosphatase is derived from Mg(2+)-dependent phosphatidate phosphatase, phosphatidicacid phosphatase type 2, serine / threonine-protein phosphatase, HAD-like hydrolase superfamily, phosphate (PA) phosphatase, polyphosphoinositide phosphatase, serine / threonine-protein kinases, alkaline phosphatase, phosphoprotein phosphatase family, and SIT4 phosphatase-associated protein family. The following families are listed: TAP42 / TAP46-like superfamily, dual-specificity lipid and protein phosphatase, polynucleotide kinase 3 phosphatase, 5'-deoxynucleotidase, myosin family, histidine phosphatase superfamily, S-2-haloalkanoic acid dehalogenase, phosphoglycerate mutase, HAD-hydrolase superfamily, PA-phosphatase related phosphoesterase family, squalene / phytoene synthase family, and terpene cyclase family. cyclases), phosphate phosphatase App1(phosphatidate phosphatase App1), protein phosphatase 2A (PP2A), protein phosphatase 2C (PP2C), halogen dehalogenase (HAD)-like sugar phosphate phosphatase, Fig4-like polyphosphoinositide phosphatase, casein kinase 1 Ser / Thr protein kinase, lipoprotein family, PPZ / Ppq1 family, clade-1 family, HAD-IA hydrolase family, HAD-IF subfamily, dolichoyldiphosphatase family, or haloperoxidase superfamily.

[0010] In some embodiments, the phosphatase is phosphatidylphosphatase (APP1), polyacyl-2-phosphatase (CAX4), PP2A protein phosphatase regulatory subunit B (CDC55), 2-deoxyglucose-6-phosphatase 1 (DOG1), diacylglycerol pyrophosphate phosphatase 1 (DPP1), inositol polyphosphate phosphatase (FIG4), 1-glycerol phosphate phosphatase 1 (GPP1), casein kinase I (HRR25), phosphatidylphosphatase (PAH1), alkaline phosphatase (PHO8), truncated alkaline phosphatase (PHO8^62aa), serine / threonine protein phosphatase (PPQ), serine / threonine protein phosphatase (PPZ1), serine / threonine protein phosphatase (PTC3), serine / threonine protein phosphatase (RTS1), SIT4-associated protein SAP155, SIT4-associated protein SAP185, 2A Phosphatase-associated protein (TAP42), phosphatidylinositol 3,4,5-triphosphate 3-phosphatase (TEP1), polynucleotide 3'-phosphatase (TPP1), phosphatase (YAR068W), 5'-deoxynucleotidase (YBR242W), phosphatidylinositol 3-phosphatase, phosphatase (YNL108C), hydrolase (YOR131C), histidine phosphatase family phosphatases (YOR283W), phosphatidylglycerol phosphatase (PgpA), phosphatidylglycerol phosphatase (PgpB), phosphatidylglycerol phosphatase (PgpC), carbapenyl diphosphatase (YbjG), dihydroxy diphosphatase (DOLPP1), phosphatase (PLPP6), farnesyl diphosphatase (YisP), farnesol synthase (TPS2), acyclic sesquiterpene synthase (TPS1), or farnesol synthase (TPS13).

[0011] In some embodiments, the phosphatase is a phosphatase derived from a microorganism or a functional variant thereof, said microorganism including bacteria, yeast, or fungi, said bacteria being selected from Escherichia or Bacillus, said yeast being selected from Saccharomyces, or said phosphatase is derived from plants or humans (…). Homo sapiens Phosphohydrolases or their functional variants thereof; preferably, the phosphohydrolase is a phosphohydrolase or its functional variant derived from bacteria, yeast or fungi, wherein the bacteria are selected from *Escherichia coli* (…). Escherichia coli ), Bacillus subtilis ( Bacillus subtilis The yeast is brewer's yeast (Saccharomyces cerevisiae). Saccharomyces cerevisiae ), or the phosphorylase is derived from plants or humans ( Homo sapiens Phosphorylase or a functional variant thereof, wherein the plant is selected from moso bamboo ( Phyllostachys edulis ),corn( Zea corn ) or japonica rice ( Oryza sativa subsp. japonica More preferably, the phosphorylase is derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae ), Escherichia coli ( Escherichia coli ), human beings ( Homo sapiens ), Bacillus subtilis ( Bacillus subtilis ),bamboo( Phyllostachys edulis ),corn( Corn ) or japonica rice ( Oryza sativa subsp. japonica Phosphohydrolases or their functional variants.

[0012] In some embodiments, the phosphatase comprises an amino acid sequence selected from SEQ ID NO. 11-226, or an amino acid sequence having at least 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with an amino acid sequence selected from SEQ ID NO. 12, SEQ ID NO. 17, SEQ ID NO. 20, SEQ ID NO. 36, SEQ ID NO. 38, SEQ ID NO. 45, SEQ ID NO. 58, SEQ ID NO. 63, SEQ ID NO. 95, ... ID NO.106, SEQ ID NO.107, SEQ ID NO.122, SEQ ID NO.125, SEQ ID NO.133, SEQ ID NO.157, SEQ ID NO.159, SEQ ID NO.160, SEQ ID NO.180, SEQ ID NO.181, SEQ ID NO.186, SEQ ID NO.197, SEQ ID NO.198, SEQ ID NO.206, SEQ ID NO.208, SEQ ID NO.209, SEQ ID NO.210, SEQ ID NO.217, SEQ ID NO.218, SEQ ID NO.219, SEQ ID NO.220, SEQ ID NO.221, SEQ ID NO.222, SEQ ID NO.223, SEQ ID NO.224, SEQ ID NO.225, SEQ ID The amino acid sequence of NO.226, or selected from SEQ ID NO.12, SEQ ID NO.17, SEQ ID NO.20, SEQ ID NO.36, SEQ ID NO.38, SEQ ID NO.45, SEQ ID NO.58, SEQ ID NO.63, SEQ ID NO.95, SEQ ID NO.106, SEQ ID NO.107, SEQ ID NO.122, SEQ ID NO.125, SEQ ID NO.133, SEQ ID NO.157, SEQ ID NO.159, SEQ IDNO.160, SEQ ID NO.180. SEQ ID NO.181, SEQ ID NO.186, SEQ ID NO.197, SEQ ID NO.198, SEQ ID NO.206, SEQ ID NO.208, SEQ ID NO.209, SEQ ID NO.210, SEQ ID NO.217, SEQ ID NO.218, SEQ ID NO.219, SEQ ID NO.220, SEQ ID NO.221, SEQ ID NO.222, SEQ ID NO.223, SEQ ID NO.224, SEQ ID NO.225, SEQ ID The amino acid sequence of NO. 226 has at least 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity.

[0013] In some embodiments, the phosphorylase is encoded by a nucleotide sequence selected from SEQ ID NO. 237-452, or by a nucleotide sequence having at least 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with a nucleotide sequence selected from SEQ ID NO. 238, SEQ ID NO. 243, SEQ ID NO. 246, SEQ ID NO. 262, SEQ ID NO. 264, SEQ ID NO. 271, SEQ ID NO. 284, ...43, SEQ ID NO. 246, SEQ ID NO. 262, SEQ ID NO. 264, SEQ ID NO. 261, SEQ ID NO. 271, SEQ ID NO. 284, SEQ ID NO. 238, SEQ ID NO. 243, SEQ ID NO. 246, SEQ ID NO. 243, SEQ ID NO. 246, SEQ ID NO. 243, NO.289, SEQ ID NO.321, SEQ ID NO.332, SEQ ID NO.333, SEQ ID NO.348, SEQ ID NO.351, SEQ ID NO.359, SEQ ID NO.383, SEQ ID NO.385, SEQ ID NO.386, SEQ ID NO.406, SEQ ID NO.407, SEQ ID NO.412, SEQ ID NO.423, SEQ ID NO.424, SEQ ID NO.432, SEQ ID NO.434, SEQ ID NO.435, SEQ ID NO.436, SEQ ID NO.443, SEQ ID NO.444, SEQ ID NO.445, SEQ ID NO.446, SEQ ID NO.447, SEQ ID NO.448, SEQ ID NO.449, SEQ ID The nucleotide sequence of NO.450, SEQ ID NO.451, SEQ ID NO.452, or the nucleotide sequence selected from SEQ ID NO.238, SEQ ID NO.243, SEQ ID NO.246, SEQ ID NO.262, SEQ ID NO.264, SEQ ID NO.271, SEQ ID NO.284, SEQ ID NO.289, SEQ ID NO.321, SEQ ID NO.332, SEQ ID NO.333, SEQ ID NO.348, SEQ ID NO.351, SEQ ID NO.359, SEQ IDNO.383, SEQ ID NO.385. SEQ ID NO.386, SEQ ID NO.406, SEQ ID NO.407, SEQ ID NO.412, SEQ ID NO.423, SEQ ID NO.424, SEQ ID NO.432, SEQ ID NO.434, SEQ ID NO.435, SEQ ID NO.436, SEQ ID NO.443, SEQ ID NO.444, SEQ ID NO.445, SEQ ID NO.446, SEQ ID NO.447, SEQ ID NO.448, SEQ ID NO.449, SEQ ID NO.450, SEQ ID NO.451, SEQ ID The nucleotide sequence of NO. 452 encodes a nucleotide sequence with at least 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity.

[0014] In some embodiments, the compound of formula (I) is selected from farnesol, geraniol, lysinediol, or copalol; and / or the compound of formula (II) is selected from farnesyl pyrophosphate, geraniol pyrophosphate, or lysinediol pyrophosphate, or copalol pyrophosphate.

[0015] In some embodiments, the catalysis occurs either extracellularly or intracellularly.

[0016] In some embodiments, the catalysis is described as using an isolated phosphorylase, a mixture containing the phosphorylase, a microorganism containing the phosphorylase or its cell lysate or enzyme extract to catalyze the formation of compound (II) from compound (I).

[0017] In some implementations, the microorganism containing the phosphorylase is a recombinant engineered bacterium.

[0018] Another aspect of the present invention provides a recombinant engineered bacterium containing a phosphatase capable of catalyzing the precursor of a compound of formula (I) to generate the compound of formula (I).

[0019] R is H or a hydrocarbon group, which is cyclic or acyclic, straight or branched, saturated or unsaturated, and / or substituted or unsubstituted; The precursor of compound (I) is compound (II) as shown below: , The R in compound (II) is the same as the R in compound (I); and The phosphatases mentioned are derived from Mg(2+)-dependent phosphatidate phosphatase, phosphatidic acid phosphatase type 2, serine / threonine-protein phosphatase family, HAD-like hydrolase superfamily, phosphate (PA) phosphatase, polyphosphoinositide phosphatase, serine / threonine-protein kinases, alkaline phosphatase, phosphoprotein phosphatase family, SIT4 phosphatase-associated protein family, and TAP42 / TAP46 superfamily. TAP42 / TAP46-like superfamily, dual-specificity lipid and protein phosphatase, polynucleotide kinase 3 phosphatase, 5'-deoxynucleotidase, myosin family, histidine phosphatase superfamily, S-2-haloalkanoic acid dehalogenase, phosphoglycerate mutase, HAD-hydrolase superfamily, PA-phosphatase related phosphoesterase family, squalene / phytoene synthase family, terpene cyclase family, phosphate phosphatase App1 (phosphatidate)Phosphatase App1), Protein phosphatase 2A (PP2A), Protein phosphatase 2C (PP2C), Halide dehalogenase (HAD)-like sugar phosphate phosphatase, Fig4-like polyphosphoinositide phosphatase, Casein kinase 1 Ser / Thr protein kinase, Lipin family, PPZ / Ppq1 family, Clad-1 family, HAD-IA hydrolase family, HAD-IF subfamily, Dolichoyldiphosphatase family, or Haloperoxidase superfamily.

[0020] In some embodiments, the phosphatase is phosphatidylphosphatase (APP1), polyacyl-2-phosphatase (CAX4), PP2A protein phosphatase regulatory subunit B (CDC55), 2-deoxyglucose-6-phosphatase 1 (DOG1), diacylglycerol pyrophosphate phosphatase 1 (DPP1), inositol polyphosphate phosphatase (FIG4), 1-glycerol phosphate phosphatase 1 (GPP1), casein kinase I (HRR25), phosphatidylphosphatase (PAH1), alkaline phosphatase (PHO8), truncated alkaline phosphatase (PHO8^62aa), serine / threonine protein phosphatase (PPQ), serine / threonine protein phosphatase (PPZ1), serine / threonine protein phosphatase (PTC3), serine / threonine protein phosphatase (RTS1), SIT4-associated protein SAP155, SIT4-associated protein SAP185, 2A Phosphatase-associated protein (TAP42), phosphatidylinositol 3,4,5-triphosphate 3-phosphatase (TEP1), polynucleotide 3'-phosphatase (TPP1), phosphatase (YAR068W), 5'-deoxynucleotidase (YBR242W), phosphatidylinositol 3-phosphatase, phosphatase (YNL108C), hydrolase (YOR131C), histidine phosphatase family phosphatases (YOR283W), phosphatidylglycerol phosphatase (PgpA), phosphatidylglycerol phosphatase (PgpB), phosphatidylglycerol phosphatase (PgpC), carbapenyl diphosphatase (YbjG), dihydroxy diphosphatase (DOLPP1), phosphatase (PLPP6), farnesyl diphosphatase (YisP), farnesol synthase (TPS2), acyclic sesquiterpene synthase (TPS1), or farnesol synthase (TPS13).

[0021] In some embodiments, the phosphatase is a phosphatase derived from a microorganism or a functional variant thereof, said microorganism including bacteria, yeast, or fungi, said bacteria being selected from Escherichia or Bacillus, said yeast being selected from Saccharomyces, or said phosphatase is derived from plants or humans (…). Homo sapiens Phosphohydrolases or their functional variants thereof; preferably, the phosphohydrolase is a phosphohydrolase or its functional variant derived from bacteria, yeast or fungi, wherein the bacteria are selected from *Escherichia coli* (…). Escherichia coli Bacillus subtilis ( Bacillus subtilis The yeast is brewer's yeast (Saccharomyces cerevisiae). Saccharomyces cerevisiae ), or the phosphorylase is derived from plants or humans ( Homo sapiens Phosphorylase or a functional variant thereof, wherein the plant is selected from moso bamboo ( Phyllostachys edulis ),corn( Zea corn ) or japonica rice ( Oryza sativa subsp. japonica More preferably, the phosphorylase is derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae ), Escherichia coli ( Escherichia coli ), human beings ( Homo sapiens ), Bacillus subtilis ( Bacillus subtilis ),bamboo( Phyllostachys edulis ),corn( Corn ) or japonica rice ( Oryza sativa subsp. japonica Phosphohydrolases or their functional variants.

[0022] In some embodiments, the phosphorylase comprises an amino acid sequence selected from SEQ ID NO. 11-226, or an amino acid sequence having at least 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with an amino acid sequence selected from SEQ ID NO. 11-226.

[0023] In some embodiments, the phosphorylase is encoded by a nucleotide sequence selected from SEQ ID NO.237-452, or by a nucleotide sequence having at least 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with a nucleotide sequence selected from SEQ ID NO.237-452.

[0024] In some embodiments, the compound of formula (I) is selected from farnesol, geraniol, lysinediol, or copalol; and / or the compound of formula (II) is selected from farnesyl pyrophosphate, geraniol pyrophosphate, lysinediol pyrophosphate, or copalol pyrophosphate.

[0025] In some embodiments, the recombinant engineered bacteria further includes a gene for the synthesis pathway of compound (II).

[0026] In some embodiments, the gene for the synthetic pathway of the compound of formula (II) includes: (1) Genes involved in the farnesyl pyrophosphate (FPP) synthesis pathway. (2) Farnesyl pyrophosphate (FPP) synthesis pathway genes and gerany-gerany-gerany pyrophosphate synthase (GGPPS) genes, or, (3) Farnesyl pyrophosphate (FPP) synthesis pathway gene, geraniol geraniol pyrophosphate synthase (GGPPS) gene and lysine pyrophosphate diol ester synthase (LPPS) gene.

[0027] In some embodiments, one or more of the following genes are used: transferase gene, 3-methyl-3-hydroxyglutaryl-CoA synthase gene, 3-hydroxy-3-methylglutaryl-CoA reductase gene, mevalonate kinase gene, mevalonate-5-phosphate kinase gene, mevalonate-5-pyrophosphate decarboxylase gene, pentene pyrophosphate isomerase gene, or farnesyl pyrophosphate synthase gene.

[0028] In some embodiments, the recombinant engineered bacteria further comprises one or more of the following genetic modifications: (1) At least one gene modification that enhances the activity of geraniol geraniol pyrophosphate synthase (GGPPS); and (2) At least one gene modification that enhances the activity of lysine pyrophosphate diol ester synthase (LPPS).

[0029] In some implementation schemes, wherein, At least one gene modification that enhances the activity of gerany-gerany-gerany pyrophosphate synthase (GGPPS) includes: introducing an exogenous gerany-gerany-gerany pyrophosphate synthase (GGPPS) gene, increasing the gene copy number of the gerany-gerany-gerany pyrophosphate synthase (GGPPS) gene, and / or replacing the natural promoter of the endogenous gerany-gerany pyrophosphate synthase (GGPPS) with a promoter that has a higher expression level; and / or At least one gene modification that enhances the activity of lysandrindiol pyrophosphate synthase (LPPS) includes: introducing an exogenous lysandrindiol pyrophosphate synthase (LPPS) gene, increasing the gene copy number of the lysandrindiol pyrophosphate synthase (LPPS) gene, and / or replacing the natural promoter of the endogenous lysandrindiol pyrophosphate synthase (LPPS) with a promoter that has a higher expression level.

[0030] In some implementation schemes, wherein, The exogenous gerany-gerany pyrophosphate synthase (GGPPS) comprises the amino acid sequence shown in SEQ ID NO. 9, preferably encoded by the nucleotide sequence of SEQ ID NO. 235; and / or The exogenous lysine pyrophosphate diol ester synthase (LPPS) gene encodes a truncated lysine pyrophosphate diol ester synthase (LPPS); preferably, the truncated lysine pyrophosphate diol ester synthase (LPPS) is a signal peptide with the first 63 amino acids removed; preferably, the exogenous lysine pyrophosphate diol ester synthase (LPPS) comprises the amino acid sequence shown in SEQ ID NO. 10; more preferably, the exogenous lysine pyrophosphate diol ester synthase (LPPS) is encoded by the nucleotide sequence of SEQ ID NO. 236.

[0031] In some embodiments, the recombinant engineered bacteria further comprises one or more of the following genetic modifications: (1) At least one gene modification that enhances the function of acetyl-CoA transferase; (2) At least one gene modification that enhances the activity of 3-methyl-3-hydroxyglutaryl-CoA synthase; (3) At least one gene modification that enhances the activity of 3-hydroxy-3-methylglutaryl-CoA reductase; (4) At least one gene modification that enhances the activity of mevalonate kinase; (5) At least one gene modification that enhances the activity of mevalonate-5-phosphate kinase; (6) At least one gene modification that enhances the activity of mevalonate-5-pyrophosphate decarboxylase; (7) At least one gene modification that enhances the activity of pentylene pyrophosphate isomerase; and (8) At least one gene modification that enhances the activity of farnesyl pyrophosphate synthase.

[0032] In some implementation schemes, wherein, At least one gene modification that enhances the function of acetyl-CoA transferase includes: introducing an exogenous acetyl-CoA transferase gene, increasing the gene copy number of the acetyl-CoA transferase gene, and / or replacing the natural promoter of endogenous acetyl-CoA transferase with a promoter that has a higher expression level. At least one gene modification that enhances the function of 3-methyl-3-hydroxyglutaryl-CoA synthase includes: introducing an exogenous 3-methyl-3-hydroxyglutaryl-CoA synthase gene, increasing the gene copy number of the 3-methyl-3-hydroxyglutaryl-CoA synthase gene, and / or replacing the natural promoter of endogenous 3-methyl-3-hydroxyglutaryl-CoA synthase with a promoter that has a higher expression level; At least one gene modification that enhances the activity of 3-hydroxy-3-methylglutaryl-CoA reductase includes: introducing an exogenous 3-hydroxy-3-methylglutaryl-CoA reductase gene, increasing the gene copy number of the 3-hydroxy-3-methylglutaryl-CoA reductase gene, and / or replacing the natural promoter of endogenous 3-hydroxy-3-methylglutaryl-CoA reductase with a promoter that has a higher expression level; At least one gene modification that enhances the activity of mevalonate kinase includes: introducing an exogenous mevalonate kinase gene, increasing the gene copy number of the mevalonate kinase gene, and / or replacing the natural promoter of endogenous mevalonate kinase with a promoter that has a higher expression level. At least one gene modification that enhances the activity of mevalonate-5-phosphokinase includes: introducing an exogenous mevalonate-5-phosphokinase gene, increasing the gene copy number of the mevalonate-5-phosphokinase gene, and / or replacing the natural promoter of endogenous mevalonate-5-phosphokinase with a promoter that has a higher expression level. At least one gene modification that enhances the activity of mevalonate-5-pyrophosphate decarboxylase includes: introducing an exogenous mevalonate-5-pyrophosphate decarboxylase gene, increasing the gene copy number of the mevalonate-5-pyrophosphate decarboxylase gene, and / or replacing the natural promoter of endogenous mevalonate-5-pyrophosphate decarboxylase with a promoter that has a higher expression level. At least one gene modification that enhances the activity of pentyrene pyrophosphate isomerase includes: introducing an exogenous pentyrene pyrophosphate isomerase gene, increasing the copy number of the pentyrene pyrophosphate isomerase gene, and / or replacing the natural promoter of the endogenous pentyrene pyrophosphate isomerase with a promoter that has a higher expression level; and / or At least one gene modification that enhances the activity of farnesyl pyrophosphate synthase includes: introducing an exogenous farnesyl pyrophosphate synthase gene, increasing the gene copy number of the farnesyl pyrophosphate synthase gene, and / or replacing the natural promoter of endogenous farnesyl pyrophosphate synthase with a promoter that has a higher expression level.

[0033] In some implementation schemes, wherein: The exogenous acetyl-CoA transferase comprises the amino acid sequence shown in SEQ ID NO.3, preferably, the exogenous acetyl-CoA transferase is encoded by the nucleotide sequence of SEQ ID NO.229; The exogenous 3-methyl-3-hydroxyglutaryl-CoA synthase comprises the amino acid sequence shown in SEQ ID NO.4, preferably, the exogenous 3-methyl-3-hydroxyglutaryl-CoA synthase is encoded by the nucleotide sequence of SEQ ID NO.230; The exogenous 3-hydroxy-3-methylglutaryl-CoA reductase gene encodes a truncated 3-hydroxy-3-methylglutaryl-CoA reductase, wherein the truncated 3-hydroxy-3-methylglutaryl-CoA reductase is a truncated 3-hydroxy-3-methylglutaryl-CoA reductase with 528 amino acids removed from its N-terminus; preferably, the truncated 3-hydroxy-3-methylglutaryl-CoA reductase comprises the amino acid sequence shown in SEQ ID NO. 2, and preferably, the truncated 3-hydroxy-3-methylglutaryl-CoA reductase is encoded by the nucleotide sequence of SEQ ID NO. 228; The exogenous mevalonate kinase comprises the amino acid sequence shown in SEQ ID NO.5, preferably, the exogenous mevalonate kinase is encoded by the nucleotide sequence of SEQ ID NO.231; The exogenous mevalonate-5-phosphokinase comprises the amino acid sequence shown in SEQ ID NO. 6, preferably, the exogenous mevalonate-5-phosphokinase is encoded by the nucleotide sequence of SEQ ID NO. 232; The exogenous mevalonate-5-pyrophosphate decarboxylase comprises the amino acid sequence shown in SEQ ID NO.7, preferably, the exogenous mevalonate-5-pyrophosphate decarboxylase is encoded by the nucleotide sequence of SEQ ID NO.233; The exogenous pentene pyrophosphate isomerase comprises the amino acid sequence shown in SEQ ID NO. 8, preferably, the exogenous pentene pyrophosphate isomerase is encoded by the nucleotide sequence of SEQ ID NO. 234; and / or The exogenous farnesyl pyrophosphate synthase comprises the amino acid sequence shown in SEQ ID NO.1, preferably encoded by the nucleotide sequence of SEQ ID NO.227.

[0034] In some embodiments, the engineered bacteria are bacteria or yeast; preferably, the bacteria are selected from Escherichia, Corynebacterium, or Bacillus, and the yeast is selected from Saccharomyces, Pichia, Hansenula, Kluyveromyces, Phaffia, Schizosaccharomyces, Candida, Yarrowia, Hyphozyma, or Cryptococcus; more preferably, the bacteria are selected from Escherichia coli (…). Escherichia coli ), Corynebacterium glutamicum ( Corynebacterium glutamicum ), or Bacillus subtilis ( Bacillus subtilis The yeast is selected from brewer's yeast (Saccharomyces cerevisiae). Saccharomyces cerevisiae Pichia pastoris () Shepherd's pie ), Phaffia colomata ( Komagataellaphaffii) , Saccharomyces cerevisiae ( Schizosaccharomyces pombe ), Candida albicans ( Candida albicans ), Candida utilis ( White useful ), Yarrowia lipolytica ( Yarrowia lipolytica ), Hansenula polymorpha ( Hansenula polymorpha Pichia pastoris (Canada) Pichia canadensis ), Max Kluyveromycin ( Kluyveromyces marxianus Kluyveromycin (lactic acid yeast) Kluyveromyces lactis Hyphozyma roseoniger, Cryptococcus palea ( Cryptococcus albidus ) or Red Pavlova yeast ( Phaffia rhodozyma ).

[0035] Another aspect of the invention provides a method for producing compound of formula (I), comprising culturing any of the aforementioned recombinant engineered bacteria under suitable conditions.

[0036] In some embodiments, the culture medium used to cultivate the recombinant engineered bacteria contains at least one carbon source selected from glucose, fructose, sucrose, maltose, glycerol, acetic acid, lactic acid, and succinic acid.

[0037] In some embodiments, the method further includes: separating the compound of formula (I).

[0038] In some embodiments, the method further includes: converting the compound of formula (I) into a derivative of the compound of formula (I) by chemical synthesis, biocatalysis, or a combination of both, said derivative being a hydrocarbon, diol, triol, acetal, ketal, aldehyde, acid, ether, amide, ketone, epoxide, acetate, glycoside, and / or ester of the compound of formula (I); preferably, said derivative is perillyl glycol, perillyl lactone, ambroxol, or a derivative thereof.

[0039] Another aspect of the present invention provides the use of any of the aforementioned recombinant engineered bacteria in the production of compound (I).

[0040] In some embodiments, the compound of formula (I) is selected from farnesol, geraniol, lysine diol, or copalol. Attached Figure Description

[0041] Figure 1 Metabolic diagram of the biosynthetic pathway of Chinese (I) compounds in Saccharomyces cerevisiae, as an example.

[0042] Figure 2 The example reaction formula is shown for the production of lysine diol from lysine pyrophosphate via phosphorylase catalysis.

[0043] Figure 3 Design diagram for DNA donor of phosphorylase.

[0044] Figure 4 This is the gas chromatogram of lysine diol standard.

[0045] Figure 5 This is a gas chromatogram of the product after processing the sample of strain YC6.

[0046] Figure 6 This is the mass spectrum of the YC6 strain sample after treatment. Detailed Implementation

[0047] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains.

[0048] All publications, patent applications, patents, and other references mentioned herein are incorporated herein by reference in their entirety. In case of conflict, this specification (including definitions) shall prevail. Furthermore, the materials, methods, and examples described herein are illustrative only and not intended to be restrictive.

[0049] When the terms “about” and “approximately” are used with numerical variables, they generally mean that the value of the variable and all values ​​of the variable are within the measurement or experimental error (e.g., the 95% confidence interval of the mean) or within a wider range of specified values ​​(e.g., ±10%).

[0050] The term "comprising," or its variations such as "containing," "having," or "including," means to include the stated steps or elements, but does not exclude any other steps or elements. "Constitutes of," means excluding steps or elements not listed. "Substantially constitutes of," means not excluding steps or elements that do not substantially affect the fundamental and novel features of the protected invention. The term "comprising" and its variations also include the cases of "consisting of specific steps or elements" and "substantially constitutes specific steps or elements."

[0051] When referring to a numerical range, it should be understood that the specific values ​​of its upper and lower limits are disclosed, as well as all intermediate ranges included therein, such as the intermediate range between its upper or lower limit and any intermediate value, or the intermediate range between any two intermediate values. Furthermore, any intermediate ranges, subranges, and all individual numerical values ​​described in the numerical range can be excluded from the numerical range.

[0052] The term “and / or” should be understood as any one of the multiple elements connected by the term, or a combination of any number of elements.

[0053] The natural product synthesis pathways of wild-type Escherichia coli or yeast can use glucose, ethanol, etc. as carbon sources, and through multiple catalytic reactions, generate sclareol via intermediates farnesyl pyrophosphate (FPP), geranylgeranyl pyrophosphate (GGPP), and lysparganoyl pyrophosphate (LPP). These pathways involve mevalonic acid (MVA) and / or isoprene (PDP) pathways. The inventors have discovered that lysparganoyl pyrophosphate (LPP) can also serve as a precursor for the generation of the target product lysparganoyl, farnesyl pyrophosphate (FPP) can also serve as a precursor for the generation of the target product farnesol (FOH), geranylgeranyl pyrophosphate (GGPP) can also serve as a precursor for the generation of the target product geranylgeranyol (GGOH), and copal pyrophosphate can also serve as a precursor for the generation of the target product copal alcohol, etc. These target products all belong to the terpene compounds shown in formula (I).

[0054] R is H or a hydrocarbon group, which may be cyclic or acyclic, straight or branched, saturated or unsaturated, and / or substituted or unsubstituted; The hydrocarbon group may contain more than one, such as 2, 3, 4 or 5, particularly 5 or more carbon atoms, such as 5 to 30, 5 to 25, 5 to 20, 5 to 15 or 5 to 10 carbon atoms.

[0055] The hydrocarbon group may be substituted or unsubstituted, for example, it may contain at least one, for example, 1 to 5, preferably 1 or 2 substituents. The substituent may be a hydrocarbon group or contain a heteroatom, such as O or N. Preferably, one or more substituents are independently selected from -OH, C=O or -COOH. Most preferably, the substituent is -OH.

[0056] The hydrocarbon group can be acyclic, such as straight-chain or branched, or it can be cyclic.

[0057] The hydrocarbon group can be a straight-chain or branched alkane or alkene, such as a polyene, which can have 2, 3, 4, or 5, particularly 5 or more carbon atoms, for example 5 to 30, 5 to 25, 5 to 20, 5 to 15, or 5 to 10 carbon atoms. The polyene can have 1, 2, 3, 4, 5, or more unsaturated bonds. The straight-chain or branched alkane or alkene may optionally be substituted or unsubstituted, and the substituent may be, for example, an alkyl group, such as a C1-C4 alkyl group.

[0058] Typical examples of compounds containing acyclic groups are farnesol, geraniol, and their stereoisomers.

[0059] The hydrocarbon group may comprise a monocyclic or polycyclic ring, for example, comprising one, two, or three fused (anellated) or non-fused rings, the monocyclic or polycyclic rings being, for example, substituents and / or saturated or unsaturated hydrocarbon cyclic groups (or "carbocyclic" groups). Each ring may independently comprise three to eight, for example five to seven, more particularly six cyclic carbon atoms.

[0060] Examples of monocyclic hydrocarbon groups can be “cycloalkyl” groups having 3 to 7 carbon atoms, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl; and corresponding “cycloalkenyl” groups. “Cycloalkenyl” (or “mono- or polyunsaturated cycloalkyl”) particularly represents monocyclic, monounsaturated or polyunsaturated carbocyclic groups having 5 to 8, preferably up to 6, carbon ring members, such as monounsaturated cyclopentenyl, cyclohexenyl, cycloheptenyl, and cyclooctenyl.

[0061] Examples of polycyclic hydrocarbon groups include groups in which one, two, or three cycloalkyl and / or cycloalkenyl groups are linked together, for example, through fused cyclization to form a polycyclic cycloalkyl or cycloalkenyl ring. As a non-limiting example, a bicyclic decalinyl residue consisting of two fused cyclized six-membered carbon rings may be included.

[0062] The number of substituents in a monocyclic or polycyclic hydrocarbon group can be from 1 to 10, particularly from 1 to 5. Suitable substituents for this cyclic group can be selected from lower alkyl groups, lower alkenyl groups, alkylidenes, alkenylidenes, or residues containing a heteroatom such as O or N, for example -OH or -COOH. In particular, the substituents are independently selected from -OH, -COOH, methyl, and methylidene.

[0063] "Lower alkyl" or "short-chain alkyl" refers to a saturated straight-chain or branched hydrocarbon group having 1 to 4, 1 to 5, 1 to 6, or 1 to 7, particularly 1 to 4, carbon atoms. Examples of lower alkyl or short-chain alkyl groups include methyl, ethyl, n-propyl, 1-methylethyl, n-butyl, 1-methylpropyl, 2-methylpropyl, 1,1-dimethylethyl, n-pentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 2,2-dimethylpropyl, 1-ethylpropyl, n-hexyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4 -Methylpentyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl, 1-ethylbutyl, 2-ethylbutyl, 1,1,2-trimethylpropyl, 1,2,2-trimethylpropyl, 1-ethyl-1-methylpropyl and 1-ethyl-2-methylpropyl; and n-heptyl, and their mono- or multi-branched analogs.

[0064] "Short-chain alkenyl" or "lower alkenyl" refers to a monounsaturated or polyunsaturated, particularly monounsaturated, straight-chain or branched hydrocarbon group having 2 to 4, 2 to 6, or 2 to 7 carbon atoms and a double bond at any position, such as C2-C6 alkenyl groups, including vinyl, 1-propenyl, 2-propenyl, 1-methylvinyl, 1-butenyl, 2-butenyl, 3-butenyl, 1-methyl-1-propenyl, 2-methyl-1-propenyl, 1-methyl-2-propenyl, 2-methyl-2-propenyl, 1-pentenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 1-methyl-1-butenyl, 2-methyl-1-butenyl, 3-methyl-1-butenyl, etc. alkenyl, 1-methyl-2-butenyl, 2-methyl-2-butenyl, 3-methyl-2-butenyl, 1-methyl-3-butenyl, 2-methyl-3-butenyl, 3-methyl-3-butenyl, 1,1-dimethyl-2-propenyl, 1,2-dimethyl-1-propenyl, 1,2-dimethyl-2-propenyl, 1-ethyl-1-propenyl, 1-ethyl-2-propenyl, 1-hexenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl, 1-methyl-1-pentenyl, 2-methyl-1-pentenyl, 3-methyl-1-pentenyl, 4-methyl-1-pentenyl, 1-methyl-2-pentenyl, 2-methyl -2-pentenyl, 3-methyl-2-pentenyl, 4-methyl-2-pentenyl, 1-methyl-3-pentenyl, 2-methyl-3-pentenyl, 3-methyl-3-pentenyl, 4-methyl-3-pentenyl, 1-methyl-4-pentenyl, 2-methyl-4-pentenyl, 3-methyl-4-pentenyl, 4-methyl-4-pentenyl, 1,1-dimethyl-2-butenyl, 1,1-dimethyl-3-butenyl, 1,2-dimethyl-1-butenyl, 1,2-dimethyl-2-butenyl, 1,2-dimethyl-3-butenyl, 1,3-dimethyl-1-butenyl, 1,3-dimethyl-2-butenyl, 1,3-dimethyl-2-butenyl 1-Ethyl-3-butenyl, 2,2-dimethyl-3-butenyl, 2,3-dimethyl-1-butenyl, 2,3-dimethyl-2-butenyl, 2,3-dimethyl-3-butenyl, 3,3-dimethyl-1-butenyl, 3,3-dimethyl-2-butenyl, 1-ethyl-1-butenyl, 1-ethyl-2-butenyl, 1-ethyl-3-butenyl, 2-ethyl-1-butenyl, 2-ethyl-2-butenyl, 2-ethyl-3-butenyl, 1,1,2-trimethyl-2-propenyl, 1-ethyl-1-methyl-2-propenyl, 1-ethyl-2-methyl-1-propenyl and 1-ethyl-2-methyl-2-propenyl.

[0065] The "alkylidene" group represents a straight-chain or branched hydrocarbon substituent attached to the main body of the molecule via a double bond. It can contain 1 to 6 carbon atoms. Examples of "C1-C6 alkylidenes" include methyl (=CH2), ethyl (=CH-CH2), n-propyl, n-butyl, n-pentyl, n-hexyl, and their structural isomers, such as isopropylidene.

[0066] "Alkenylidene" refers to a monounsaturated analog of the above-mentioned alkane group having more than two carbon atoms, and can be called "C3-C6 alkenylidene". Examples include n-propenyl, n-butenyl, n-pentenyl, and n-hexenyl.

[0067] The unsaturated cyclic group may contain one or more, such as one, two or three C=C bonds, and may be aromatic or, in particular, non-aromatic.

[0068] Specific examples of cyclic groups are groups of the formula Cyc-A-, where A represents a straight-chain or branched C1-C4-alkylene bridge, particularly methylene, and Cyc represents a monocyclic or polycyclic, particularly bicyclic, saturated or unsaturated hydrocarbon group, especially a bicyclic annulated hydrocarbon group, each ring containing 5 to 7, particularly 6, ring atoms, optionally substituted with 1 to 10, 1 to 5 substituents, independently selected from C1-C4 alkyl, C1-C4 alkylene, C2-C4 alkenyl, oxo, hydroxyl, or amino groups, particularly C1-C4 alkyl such as methyl, and C1-C4 alkylene such as methylene. In some embodiments, Cyc-A is a group of formula IIIa, IIIb, or IIIc:

[0069] Typical examples of compounds containing such groups are lysine diol and their stereoisomers.

[0070] Non-limiting examples of C1-C4 alkyl groups include methyl, ethyl, n-propyl, 1-methylethyl, n-butyl, 1-methylpropyl, 2-methylpropyl, and 1,1-dimethylethyl.

[0071] Non-limiting examples of C1-C4 alkyl subunits include the methyl subunit (=CH2), the ethyl subunit (=CH-CH2), the n-propyl subunit, the n-butyl subunit, and their structural isomers.

[0072] Non-limiting examples of C2-C4 alkenyl groups include vinyl, 1-propenyl, 2-propenyl, 1-methylvinyl, 1-butenyl, 2-butenyl, 3-butenyl, 1-methyl-1-propenyl, 2-methyl-1-propenyl, 1-methyl-2-propenyl, and 2-methyl-2-propenyl.

[0073] Non-limiting examples of C1-C4 alkylene groups include -CH2-, -(CH2)2-, -(CH2)3-, -(CH2)4-, -(CH2)2-CH(CH3)-, and -CH2-CH(CH3)-CH2-.

[0074] The inventors have also discovered that a specific phosphorylase can catalyze the formation of the diphosphate precursor of compound (I) (compound (II)) into the terpene compound shown in formula (I). For example... Figure 1 , 2 The specific phosphohydrolase shown can catalyze the formation of lysenoside pyrophosphate (LPP) to lysenoside diol (LOH), the formation of farnesyl pyrophosphate (FPP) to farnesol, the formation of geraniol from geraniol from geraniol- ...

[0075] The compound of formula (II) is shown below: , The R in compound (II) is the same as the R in compound (I).

[0076] This paper studies and screens phosphorylases that can efficiently catalyze the dephosphatemization of compounds of formula (II) to generate compounds of formula (I), and constructs recombinant engineered bacteria containing said enzymes. These recombinant engineered bacteria can be used to produce compounds of formula (I), particularly farnesol, geraniol, and / or lysine diol. This invention also provides a method for producing compounds of formula (I) using said phosphorylase or recombinant engineered bacteria. The recombinant engineered bacteria and production method provided by this invention have high production efficiency and yield for compounds of formula (I).

[0077] The phosphatase provided by this invention, capable of catalyzing the dephosphatemization of compound (II) to generate compound (I), can be derived from Mg(2+)-dependent phosphatidate phosphatase, phosphatidic acid phosphatase type 2, serine / threonine-protein phosphatase family, HAD-like hydrolase superfamily, phosphate (PA) phosphatase, polyphosphoinositide phosphatase, serine / threonine-protein kinases, alkaline phosphatase, phosphoprotein phosphatase family, or SIT4 phospholipase-associated protein family. The following are listed as superfamilies: phosphatase-associated protein family, TAP42 / TAP46-like superfamily, dual-specificity lipid and protein phosphatase, polynucleotide kinase 3 phosphatase, 5'-deoxynucleotidase, myosin family, histidine phosphatase superfamily, S-2-haloalkanoic acid dehalogenase, phosphoglycerate mutase, HAD-hydrolase superfamily, PA-phosphatase related phosphoesterase family, and squalene / phytoene synthase family.Syntheses, terpene cyclases, phosphatase App1, protein phosphatase 2A (PP2A), protein phosphatase 2C (PP2C), halogen dehalogenases (HAD), sugar phosphophosphate phosphatase (HAD-like), polyphosphoinositide phosphatase (Fig4-like), casein kinase 1 (Serine / Thr protein kinase), lipoprotein family, PPZ / Ppq1 family, clade-1 family, HAD-IA hydrolase family, and HAD-IF subfamily (IF). The family of halogen peroxidases, or the family of doxyl diphosphatases, or the family of halogen peroxidases.

[0078] Preferably, the phosphorylase is phosphatidylphosphatase (APP1), polyacyl diphosphatase (CAX4), PP2A protein phosphatase regulatory subunit B (CDC55), 2-deoxyglucose-6-phosphatase 1 (DOG1), diacylglycerol pyrophosphate phosphatase 1 (DPP1), inositol polyphosphate phosphatase (FIG4), 1-glycerol phosphate phosphatase 1 (GPP1), casein kinase I (HRR25), phosphatidylphosphatase (PAH1), alkaline phosphatase (PHO8), truncated alkaline phosphatase (PHO8^62aa), serine / threonine protein phosphatase (PPQ), serine / threonine protein phosphatase (PPZ1), serine / threonine protein phosphatase (PTC3), serine / threonine protein phosphatase (RTS1), SIT4-associated protein SAP155, SIT4-associated protein SAP185, 2A Phosphatase-associated protein (TAP42), phosphatidylinositol 3,4,5-triphosphate 3-phosphatase (TEP1), polynucleotide 3'-phosphatase (TPP1), phosphatase (YAR068W), 5'-deoxynucleotidase (YBR242W), phosphatidylinositol 3-phosphatase, phosphatase (YNL108C), hydrolase (YOR131C), histidine phosphatase family phosphatases (YOR283W), phosphatidylglycerol phosphatase (PgpA), phosphatidylglycerol phosphatase (PgpB), phosphatidylglycerol phosphatase (PgpC), carbapenyl diphosphatase (YbjG), dihydroxy diphosphatase (DOLPP1), phosphatase (PLPP6), farnesyl diphosphatase (YisP), farnesol synthase (TPS2), acyclic sesquiterpene synthase (TPS1), or farnesol synthase (TPS13).

[0079] In some embodiments, the phosphorylase may be derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces yeast ), Escherichia coli ( Escherichia coli ), human beings ( Homo sapiens Bacillus subtilis ( Bacillus subtilis ),bamboo( Phyllostachys edulis ),corn( Corn ) or japonica rice ( Rice sativa subsp. japonica Phosphohydrolases or their functional variants.

[0080] In some embodiments, the phosphorylase may be derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces yeastPhosphatidyl phosphatase (APP1), polyacyl diphosphatase (CAX4), PP2A protein phosphatase regulatory subunit B (CDC55), 2-deoxyglucose-6-phosphatase 1 (DOG1), diacylglycerol pyrophosphate phosphatase 1 (DPP1), polyphosphatidylinositol phosphatase (FIG4), 1-glycerophosphate phosphohydrolase 1 (GPP1), casein kinase I (HRR25), phosphatidyl phosphatase (PAH1), alkaline phosphatase (PHO8), truncated alkaline phosphatase (PHO8^62aa), serine / threonine protein phosphatase (PPQ), serine / threonine protein phosphatase (PPZ1), serine / threonine protein phosphatase (PTC3), serine / threonine protein phosphatase (RTS1), SIT4-associated protein SAP155, SIT4-associated protein SAP185, 2A Phosphatase-associated protein (TAP42), phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase (TEP1), polynucleotide 3'-phosphatase (TPP1), phosphatase (YAR068W), 5'-deoxynucleotidase (YBR242W), phosphatidylinositol 3-phosphatase, phosphatase (YNL108C), hydrolase (YOR131C), histidine phosphatase family phosphatase (YOR283W), or functional variants thereof. In some embodiments, the phosphatase comprises an amino acid sequence selected from SEQ ID NO. 11-216 or a functional variant thereof.

[0081] In some embodiments, the phosphorylase may be derived from *Escherichia coli* (…). Escherichia coli Phosphatidylglycerol phosphatase (PgpA) or a functional variant thereof. In some embodiments, the phosphatase may be derived from *Escherichia coli* (PgpA). Escherichia coli Phosphatidylglycerol phosphatase (PgpA) of K12 or a functional variant thereof. In some embodiments, the phosphatase comprises an amino acid sequence as shown in SEQ ID NO. 217 or a functional variant thereof. In some embodiments, the phosphatase is encoded by a nucleotide sequence selected from SEQ ID NO. 443.

[0082] In some embodiments, the phosphorylase may be derived from *Escherichia coli* (…). Escherichia coli Phosphatidylglycerol phosphatase (PgpB) or a functional variant thereof. In some embodiments, the phosphatase may be derived from *Escherichia coli* (PgpB). Escherichia coliPhosphatidylglycerol phosphatase (PgpB) of K12 or a functional variant thereof. In some embodiments, the phosphatase comprises an amino acid sequence as shown in SEQ ID NO. 218 or a functional variant thereof. In some embodiments, the phosphatase is encoded by a nucleotide sequence selected from SEQ ID NO. 444.

[0083] In some embodiments, the phosphorylase may be derived from *Escherichia coli* (…). Escherichia coli Phosphatidylglycerol phosphatase (PgpC) or a functional variant thereof. In some embodiments, the phosphatase may be derived from *Escherichia coli* (PgpC). Escherichia coli Phosphatidylglycerol phosphatase (PgpC) of K12 or a functional variant thereof. In some embodiments, the phosphatase comprises an amino acid sequence as shown in SEQ ID NO. 219 or a functional variant thereof. In some embodiments, the phosphatase is encoded by a nucleotide sequence selected from SEQ ID NO. 445.

[0084] In some embodiments, the phosphorylase may be derived from *Escherichia coli* (…). Escherichia coli The enzyme is a carbapenyl diphosphatase (YbjG) or a functional variant thereof. In some embodiments, the phosphatase may be derived from *Escherichia coli* (YbjG). Escherichia coli The phosphatase is a carbapenyl diphosphatase (YbjG) of K12 or a functional variant thereof. In some embodiments, the phosphatase comprises an amino acid sequence as shown in SEQ ID NO. 220 or a functional variant thereof. In some embodiments, the phosphatase is encoded by a nucleotide sequence selected from SEQ ID NO. 446.

[0085] In some embodiments, the phosphorylase may be derived from human ( Homo sapiens The phosphatase is a dihydroxy diphosphatase (DOLPP1) or a functional variant thereof. In some embodiments, the phosphatase comprises an amino acid sequence as shown in SEQ ID NO. 221 or a functional variant thereof. In some embodiments, the phosphatase is encoded by a nucleotide sequence selected from SEQ ID NO. 447.

[0086] In some embodiments, the phosphorylase may be derived from human ( Homo sapiens The phosphorylase (PLPP6) or a functional variant thereof. In some embodiments, the phosphorylase comprises an amino acid sequence as shown in SEQ ID NO. 222 or a functional variant thereof. In some embodiments, the phosphorylase is encoded by a nucleotide sequence selected from SEQ ID NO. 448.

[0087] In some embodiments, the phosphorylase may be derived from Bacillus subtilis (Bacillus subtilis) Bacillus subtilis The enzyme is a farnesyl diphosphatase (YisP) or a functional variant thereof. In some embodiments, the phosphatase comprises an amino acid sequence as shown in SEQ ID NO. 223 or a functional variant thereof. In some embodiments, the phosphatase is encoded by a nucleotide sequence selected from SEQ ID NO. 449.

[0088] In some embodiments, the phosphorylase may be derived from moso bamboo (… Phyllostachys edulis The phosphorylase is farnesol synthase (TPS2) or a functional variant thereof. In some embodiments, the phosphorylase comprises an amino acid sequence as shown in SEQ ID NO. 224 or a functional variant thereof. In some embodiments, the phosphorylase is encoded by a nucleotide sequence selected from SEQ ID NO. 450.

[0089] In some embodiments, the phosphorylase may be derived from corn ( Zea mays The noncyclic sesquiterpene synthase (TPS1) or a functional variant thereof. In some embodiments, the phosphorylase comprises an amino acid sequence as shown in SEQ ID NO. 225 or a functional variant thereof. In some embodiments, the phosphorylase is encoded by a nucleotide sequence selected from SEQ ID NO. 451.

[0090] In some embodiments, the phosphorylase may be derived from japonica rice ( Oryza sativa subsp. japonica) The enzyme is farnesol synthase (TPS13) or a functional variant thereof. In some embodiments, the phosphorylase comprises an amino acid sequence as shown in SEQ ID NO. 226 or a functional variant thereof. In some embodiments, the phosphorylase is encoded by a nucleotide sequence selected from SEQ ID NO. 452.

[0091] In this invention, through exemplary catalytic experiments of lysandrindiol pyrophosphate (LPP) to lysandrindiol (LOH) and comparative analysis of sequence results of phosphorylases from different sources, it was found that there is approximately 80% homology difference among phosphorylases from different sources.

[0092] In some embodiments, the phosphatase comprises an amino acid sequence selected from SEQ ID NO. 11-226, or an amino acid sequence having at least 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with an amino acid sequence selected from SEQ ID NO. 11-226. Preferably, the phosphatase comprises an amino acid sequence selected from SEQ ID NO. 11-226.

[0093] In some embodiments, the phosphohydrolase comprises an amino acid sequence selected from SEQ ID NO.12, SEQ ID NO.17, SEQ ID NO.20, SEQ ID NO.36, SEQ ID NO.38, SEQ ID NO.45, SEQ ID NO.58, SEQ ID NO.63, SEQ ID NO.95, SEQ ID NO.106, SEQ ID NO.107, SEQ ID NO.122, SEQ ID NO.125, SEQ ID NO.133, SEQ ID NO.157, SEQ ID NO.159, SEQ ID NO.160, SEQ ID NO.180, SEQ ID NO.181, SEQ ID NO.186, SEQ ID NO.197, SEQ ID NO.198, SEQ ID NO.206, SEQ ID NO.208, SEQ ID NO.209, SEQ ID NO.210, SEQ ID NO.217, SEQ ID NO.218, SEQ ID NO.219, SEQ ID NO.220, SEQ ID NO.221, SEQ ID NO.222, SEQ ID NO.223, SEQ ID NO.224, SEQ ID NO.225, SEQ ID NO.226, or is identical to an amino acid sequence selected from SEQ ID NO.12, SEQ ID NO.17, SEQ ID NO.20, SEQ ID NO.36, SEQ ID NO.38, SEQ ID NO.45, SEQ ID NO.58, SEQ ID NO.63, SEQ ID NO.95, SEQ ID NO.106, SEQ ID NO.107, SEQ ID NO.122, SEQ ID NO.125, SEQ ID NO.133, SEQ ID NO.157, SEQ ID NO.159, SEQ ID NO.160, SEQ ID NO.180, SEQ ID NO.181, SEQ ID NO.186, SEQ ID NO.197, SEQ ID NO.198, SEQ ID NO.206, SEQ ID NO.208, SEQ ID NO.209, SEQ ID NO.210, SEQ ID NO.217, SEQ ID NO.218, SEQ ID NO.219, SEQ ID NO.220, SEQ ID NO.221, SEQ ID NO.222, SEQ ID NO.223, SEQ ID NO.224, SEQ ID NO.225. The amino acid sequence of SEQ ID NO. 226 has at least 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity. The phosphatase containing the above amino acid sequence can effectively catalyze the conversion of lysandrindiol pyrophosphate (LPP) to lysandrindiol (LOH).

[0094] In some embodiments, the phosphorylase is encoded by a nucleotide sequence selected from SEQ ID NO. 237-452, or by a nucleotide sequence having at least 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with a nucleotide sequence selected from SEQ ID NO. 237-452. Preferably, the phosphorylase is encoded by a nucleotide sequence selected from SEQ ID NO. 237-452. In some embodiments, the gene encoding the phosphorylase is codon-optimized for expression in a host bacterium (e.g., Saccharomyces cerevisiae). In some embodiments, the phosphohydrolase is encoded by a nucleotide sequence selected from SEQ ID NO.238, SEQ ID NO.243, SEQ ID NO.246, SEQ ID NO.262, SEQ ID NO.264, SEQ ID NO.271, SEQ ID NO.284, SEQ ID NO.289, SEQ ID NO.321, SEQ ID NO.332, SEQ ID NO.333, SEQ ID NO.348, SEQ ID NO.351, SEQ ID NO.359, SEQ ID NO.383, SEQ ID NO.385, SEQ ID NO.386, SEQ ID NO.406, SEQ ID NO.407, SEQ ID NO.412, SEQ ID NO.423, SEQ ID NO.424, SEQ ID NO.432, SEQ ID NO.434, SEQ ID NO.435, SEQ ID NO.436, SEQ ID NO.443, SEQ ID NO.444, SEQ ID NO.445, SEQ ID NO.446, SEQ ID NO.447, SEQ ID NO.448, SEQ ID NO.449, SEQ ID NO.450, SEQ ID NO.451, SEQ ID NO.452, or by a sequence that is homologous to a sequence selected from SEQ ID NO.238, SEQ ID NO.243, SEQ ID NO.246, SEQ ID NO.262, SEQ ID NO.264, SEQ ID NO.271, SEQ ID NO.284, SEQ ID NO.289, SEQ ID NO.321, SEQ ID NO.332, SEQ ID NO.333, SEQ ID NO.348, SEQ ID NO.351, SEQ ID NO.359, SEQ ID NO.383, SEQ ID NO.385, SEQ ID NO.386, SEQ ID NO.406, SEQ ID NO.407, SEQ ID NO.412, SEQ ID NO.423, SEQ ID NO.424, SEQ ID NO.432, SEQ ID NO.434, SEQ ID NO.435, SEQ ID NO.436, SEQ ID NO.443, SEQ ID NO.444, SEQ ID NO.445, SEQ ID NO.446, SEQ ID NO.447, SEQ ID NO.448, SEQ ID NO.449, SEQ ID NO.Nucleotide sequences 450, SEQ ID NO. 451, and SEQ ID NO. 452 have at least 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity. The phosphorylase encoded by the above nucleotide sequences can efficiently catalyze the conversion of lysandrindiol pyrophosphate (LPP) to lysandrindiol (LOH).

[0095] In some embodiments, the compound of formula (I) is selected from farnesol, geraniol, lysenoside diol, or copal; and / or the compound of formula (II) is selected from farnesyl pyrophosphate, geraniol-geraniol pyrophosphate, lysenoside diol pyrophosphate, or copal pyrophosphate. The phosphorylhydrolase can catalyze the production of lysenoside diol pyrophosphate (LPP) to lysenoside diol (LOH), catalyze the production of farnesol from farnesyl pyrophosphate, and / or catalyze the production of geraniol from geraniol-geraniol from geraniol-geraniol.

[0096] In some embodiments, the catalysis can occur extracellularly (e.g., in a cell-free environment) or intracellularly. Extracellular catalysis refers to a catalytic reaction that occurs outside of cells and is independent of their presence. Extracellular catalysis can occur in the presence or absence of cells, but the substrate (or precursor), enzymes, and other substances involved in the catalytic reaction are present outside the cells. Intracellular catalysis refers to a catalytic reaction that occurs within an organism, such as the cells, microorganisms, or recombinant engineered bacteria described herein. In the case of intracellular catalysis, the cells, microorganisms, or recombinant engineered bacteria can express the enzymes required for the catalytic reaction intracellularly and provide the substrates (or precursors) for the reaction to proceed intracellularly. The substrates (or precursors) for the reaction can be transported from outside the cell to inside the cell or synthesized via endogenous synthetic pathways.

[0097] In some embodiments, in intracellular catalysis, a microbial catalytic compound of formula (II) containing the phosphatase described herein can be used to generate a compound of formula (I). A microorganism containing the phosphatase is one that expresses the phosphatase or contains the gene for the phosphatase. The microorganism containing the phosphatase can be a naturally occurring or isolated microorganism that naturally contains the phosphatase gene, or a genetically modified recombinant microorganism (also referred to herein as a recombinant engineered microorganism) with altered (typically increased) expression of the phosphatase. This recombinant microorganism can be, for example, constructed by introducing the phosphatase gene exogenously, increasing the copy number of its naturally occurring (i.e., endogenous) phosphatase gene, and / or replacing the natural promoter of its naturally occurring (i.e., endogenous) endogenous phosphatase gene with a promoter that has a higher expression level.

[0098] In some embodiments, intracellular catalysis can be performed using an isolated phosphatase, a mixture containing the phosphatase, an enzyme extract of a microorganism containing the phosphatase, or a cell lysate thereof, to catalyze the formation of compound (I) from compound (II). In some embodiments, an enzyme preparation of the phosphatase can be used to catalyze the formation of compound (I) from compound (II), such as a crude or purified enzyme, enzyme solution, or lyophilized enzyme powder. A mixture containing the phosphatase refers to a mixture of the phosphatase with other substances (which may be enzymes or non-enzymes). An enzyme extract refers to an enzyme extracted from a microorganism containing the phosphatase, which may be a crude or purified enzyme. The enzyme extract contains the phosphatase. In some embodiments, the enzyme extract may be a total protein extract from a microorganism containing the phosphatase. In some embodiments, the enzyme extract may be a supernatant obtained by lysing a microorganism containing the phosphatase, which can be obtained by standing or centrifuging cell lysates and may contain very little or virtually no cell membrane components. Cell lysates are substances obtained by disrupting the cell membrane and releasing the cell contents. Disruption of the cell membrane (or cell lysis) can be achieved by any suitable means known to those skilled in the art, such as physical and / or chemical methods.

[0099] In this document, "recombinant engineered bacteria containing the phosphatase" means that the recombinant engineered bacteria express the phosphatase, or contain the coding gene for the phosphatase. The phosphatase can be endogenous or heterologous to the host bacteria. In some embodiments, the recombinant engineered bacteria are genetically modified to alter (typically increase) the expression and / or activity of the phosphatase in the recombinant engineered bacteria. For example, the gene for the phosphatase can be introduced exogenously into the recombinant engineered bacteria, or the copy number of the phosphatase gene naturally present (i.e., endogenous) in the recombinant engineered bacteria can be increased, and / or the natural promoter of the endogenous phosphatase gene naturally present (i.e., endogenous) in the recombinant engineered bacteria can be replaced with a promoter that has a higher expression level. In some embodiments, the recombinant engineered bacteria contain an exogenously introduced phosphatase gene. The exogenously introduced phosphatase gene can be contained in a free expression vector introduced into the host bacteria or integrated into the chromosome of the host bacteria.

[0100] In some embodiments, the recombinant engineered bacteria may further include a gene for the synthetic pathway of compound (II) to synthesize compound (II) intracellularly via an endogenous synthetic pathway and catalyze its formation into compound (I), for example, to perform whole-cell synthesis of compound (I). In some embodiments, compound (I) includes, but is not limited to, farnesol, geranylgeranyl, lysine-enrichediol, or copal. In some embodiments, compound (II) includes, but is not limited to, farnesyl pyrophosphate, geranylgeranyl pyrophosphate, lysine-enrichediol pyrophosphate, or copal pyrophosphate. In some embodiments, the gene for the synthetic pathway of compound (II) includes, but is not limited to: (1) Genes involved in the farnesyl pyrophosphate (FPP) synthesis pathway. (2) Farnesyl pyrophosphate (FPP) synthesis pathway genes and gerany-gerany-gerany pyrophosphate synthase (GGPPS) genes, or (3) Farnesyl pyrophosphate (FPP) synthesis pathway gene, geraniol geraniol pyrophosphate synthase (GGPPS) gene and lysine pyrophosphate diol ester synthase (LPPS) gene.

[0101] One or more, or all, of the genes in any of the synthetic pathways mentioned herein may be endogenous or exogenous. When the host bacterium naturally possesses the synthetic pathway, all genes in the synthetic pathway may be endogenous. In some embodiments, when the host bacterium does not naturally possess a certain synthetic pathway, for example, lacking one or more enzymes in any of the synthetic pathways mentioned herein, the missing one or more enzymes may be provided by introducing exogenous enzyme genes into the host bacterium to express the missing one or more enzymes in the host bacterium. In some embodiments, one or more, or all, of the genes in any of the synthetic pathways mentioned herein may be introduced exogenously into the host bacterium. In some embodiments, the exogenous gene may be contained in a free expression vector introduced into the host bacterium or integrated into the chromosome of the host bacterium.

[0102] In some embodiments, the recombinant engineered bacteria of the present invention may further include gene modifications that enhance the function of one or more enzymes in any of the synthetic pathways mentioned herein, in order to further improve the production efficiency and / or yield of product compound (I), such as farnesol, geraniol, or lysine diol.

[0103] For one or more of the enzymes described above, gene modifications to enhance their function may include increasing the enzyme's activity and / or overexpressing the enzyme. Increasing the enzyme's activity may, for example, include introducing a foreign enzyme gene, which may be a foreign gene with a sequence different from the endogenous gene, particularly a foreign enzyme gene with higher enzyme activity. The foreign enzyme may be an enzyme derived from a species different from the engineered bacteria, or a mutant of the wild-type enzyme. Introducing a foreign gene may retain the presence of the endogenous gene with higher enzyme activity, or it may replace the endogenous gene with a foreign gene. Overexpressing the enzyme may, for example, include increasing the copy number of the endogenous enzyme gene, and / or replacing the enzyme's natural promoter with a promoter that has a higher expression level. In some embodiments, increasing the gene copy number of the enzyme includes introducing an additional exogenous enzyme gene into the engineered bacteria without altering the expression of the endogenous enzyme gene. The exogenous enzyme gene can be one, two, three, or more copies, and can have the same or different sequences as the endogenous enzyme. For example, the exogenous enzyme can originate from the same species as the engineered bacteria, or it can have higher enzyme activity compared to the endogenous enzyme, for example, it can be an enzyme from a different species than the engineered bacteria, or a mutant of the wild-type enzyme. The overexpression can also be achieved by modifying the regulatory sequence (e.g., the promoter) operatively linked to the gene encoding the enzyme in the engineered bacteria, for example, by replacing the original promoter (e.g., the promoter of the gene naturally present in the host cell) with a stronger promoter, or by introducing mutations or inserting new regulatory elements into the promoter region to enhance its activity. Those skilled in the art will understand that the term "stronger promoter" refers to a promoter that has stronger promoter activity relative to a pre-existing promoter in the host cell (e.g., a promoter of the gene naturally present in the host cell), such as a stronger ability to bind to the transcription initiation complex and / or a stronger RNA polymerase binding ability. As is known to those skilled in the art, using a stronger promoter can increase the expression level of a gene operatively linked to the promoter (e.g., increase the expression level of the protein encoded by that gene).

[0104] In some embodiments, the recombinant engineered bacteria may be further genetically modified to eliminate or attenuate the role of one or more endogenous enzymes involved in the competitive metabolic pathway of compounds of formula (I), such as farnesol, geraniol, or lysparganide. For example, when the target product is farnesol or geraniol, the role of enzymes catalyzing the conversion of farnesol or geraniol to other substances may be eliminated or attenuated, for example, by eliminating or attenuating the role of endogenous geraniol-geraniol pyrophosphate synthase (GGPPS) to prevent or reduce the reaction proceeding along the direction from farnesol pyrophosphate (FPP) to the formation of geraniol-geraniol pyrophosphate (GGPP), and / or by eliminating or attenuating the role of endogenous lysparganide pyrophosphate synthase (LPPS) to prevent or reduce the reaction proceeding along the direction from farnesol pyrophosphate (FPP) to the formation of lysparganide pyrophosphate (LPP).

[0105] Eliminating or attenuating endogenous gene modifications includes gene modifications that partially or completely inactivate the endogenous gene encoding the enzyme, including but not limited to: knocking out or knocking down the endogenous gene, such as deleting all or part of the endogenous gene sequence, mutating the endogenous gene, or inserting an exogenous sequence into the endogenous gene, so as to cause the enzyme activity encoded by the endogenous gene to be lost or attenuated. Gene modifications that partially or completely inactivate the endogenous gene encoding the enzyme may also include: knocking out or knocking down the natural regulatory sequence (e.g., the natural promoter) of the endogenous gene, such as deleting all or part of the regulatory sequence, mutating the regulatory sequence, or inserting an exogenous sequence into the regulatory sequence, so as to partially or completely inactivate the regulatory sequence, thereby eliminating or reducing the expression of the endogenous gene.

[0106] By knocking out or downregulating endogenous genes, the proteins encoded by these endogenous genes in the engineered bacteria can be rendered nonfunctional or their activity reduced. This can be achieved, for example, by deleting all or part of the endogenous gene sequence, mutating the endogenous gene, or inserting an exogenous sequence into the endogenous gene. These gene modification techniques can also be used to alter the regulatory sequences (e.g., promoters) of endogenous genes to reduce their expression. Those skilled in the art can select appropriate methods to genetically modify engineered bacteria based on the engineered bacteria and the exogenous or endogenous nucleic acid sequences used (A Laboratory Manual (2nd Ed.), Vols. 1-3, Cold Spring Harbor Laboratory (1989) and Ausubel et al, eds., Current Protocols in Molecular Biology, John Wiley & Sons, Inc., New York (1997)).

[0107] Biosynthesis of labda-7-epi-13-hydroxy-labda-8(17),14-dien-19-oic acid (LOH) In some embodiments, the recombinant engineered bacteria further includes a lysine pyrophosphate (LPP) synthesis pathway gene to produce lysine pyrophosphate in the recombinant engineered bacteria.

[0108] In this article, “Labdenediol (LOH)” includes (E)-Labdenediol-13-en-8,15-diol. For example, the term “Labdenediol (LOH)” can include compounds with the chemical name (1R,2R,4aS,8aS)-1-[(E)-5-hydroxy-3-methylpentan-3-enyl]-2,5,5,8a-tetramethyl-3,4,4a,6,7,8-hexahydro-1H-naphth-2-ol] with the molecular formula C 20 H 36 O2, CAS No. 10267-31-9.

[0109] In some embodiments, the lysine pyrophosphate (LPP) synthesis pathway genes include farnesyl pyrophosphate (FPP) synthesis pathway genes, geraniol geraniol pyrophosphate synthase (GGPPS) genes, and lysine pyrophosphate synthase (LPPS) genes.

[0110] In some implementations, the "Farnesy pyrophosphate (FPP) synthesis pathway" includes the following enzymatically catalyzed reactions: (1) acetyl-coenzyme A (acetyl-CoA) is converted to acetoacetyl-CoA via acetyl-CoA transferase; (2) acetoacetyl-CoA is converted to 3-hydroxy-3-methylglutaryl-CoA via 3-methyl-3-hydroxyglutaryl-CoA synthase; (3) mevalonic acid (MVA) is converted to 3-hydroxy-3-methylglutaryl-CoA via 3-hydroxy-3-methylglutaryl-CoA reductase; (4) (5) Mevalonate (MVA) catalyzed by mevalonate kinase to generate mevalonate phosphate (MVAP); (6) Mevalonate phosphate (MVAP) catalyzed by mevalonate-5-phosphate kinase to generate mevalonate pyrophosphate (MVAP); (7) Isopentyl pyrophosphate (IPP) catalyzed by mevalonate-5-pyrophosphate decarboxylase to generate dimethylallyl diphosphate (DMAPP), or Isopentyl pyrophosphate (DMAPP) catalyzed by mevalonate pyrophosphate isomerase to generate isopentenyl pyrophosphate (IPP); and (8) Isopentyl pyrophosphate (IPP) and / or dimethylallyl pyrophosphate (DMAPP) catalyzed by farnesyl pyrophosphate synthase to generate farnesyl diphosphate (FPP).

[0111] In some embodiments, the farnesyl pyrophosphate (FPP) synthesis pathway genes include one or more of the following: acetyl-CoA transferase gene, 3-methyl-3-hydroxyglutaryl-CoA synthase gene, 3-hydroxy-3-methylglutaryl-CoA reductase gene, mevalonate kinase gene, mevalonate-5-phosphate kinase gene, mevalonate-5-pyrophosphate decarboxylase gene, pentene pyrophosphate isomerase gene, or farnesyl pyrophosphate synthase gene.

[0112] In some implementations, the “lysine pyrophosphate diol ester (LPP) synthesis pathway gene” includes the mevalonate (MVA) pathway gene.

[0113] The mevalonate pathway (MVA) is a metabolic pathway that synthesizes isopentenyl pyrophosphate (IPP) and dimethylpropene pyrophosphate (DMAPP) from acetyl-CoA. It is present in all eukaryotes, bacteria, and many viruses. The products of this pathway can be considered as activated isoprene units, which are precursors for the synthesis of biomolecules such as steroids and terpenoids. Its synthetic pathway can include the following enzymatic reactions: (1) acetyl-CoA is converted to acetoacetyl-CoA via acetyl-CoA transferase; (2) acetoacetyl-CoA is converted to acetoacetyl-CoA via 3-methyl-3-hydroxyglutaryl-CoA synthase. (3) 3-hydroxy-3-methylglutaryl-CoA is generated by acetoacetyl-CoA; (4) 3-hydroxy-3-methylglutaryl-CoA is converted to mevalonic acid (MVA) by 3-hydroxy-3-methylglutaryl-CoA reductase; (5) mevalonic acid phosphate (MVAP) is generated by mevalonic acid phosphate (MVAP) by mevalonic acid kinase; (6) isopentenyl pyrophosphate (IPP) is generated by mevalonic acid pyrophosphate (MVAP) by mevalonic acid 5-phosphate kinase; and (7) dimethylallyl diphosphate is generated by isopentenyl pyrophosphate (IPP) by isopentenyl pyrophosphate isomerase. The synthesis route can be catalyzed by DMAPP to produce isopentenyl pyrophosphate (IPP) from dimethylallyl diphosphate (DMAPP). This exemplary synthetic route is described herein as follows: Figure 1 As shown.

[0114] In some embodiments, the “lysandrin diol pyrophosphate (LPP) synthesis pathway gene” includes an enzyme gene for synthesizing an enzyme that can be catalyzed to produce lysandrin diol pyrophosphate (LPP) or its precursors. In some embodiments, the precursors may, for example, include farnesyl diphosphate (FPP) and / or geranylgeranyl diphosphate (GGPP). In some embodiments, the lysandrin diol pyrophosphate (LPP) synthesis pathway gene includes a farnesyl pyrophosphate synthase gene for the production of farnesyl diphosphate (FPP) from isopentenyl pyrophosphate (IPP) and / or dimethylpropene pyrophosphate (DMAPP), a geranylgeranyl pyrophosphate synthase (GGPPS) gene for the production of geranylgeranyl diphosphate (GGPP) from farnesyl diphosphate (FPP), and / or a lysandrin diol pyrophosphate synthase (LPPS) gene for the production of lysandrin diol pyrophosphate (LPP) from geranylgeranyl diphosphate (GGPP).

[0115] In some embodiments, the “lysine pyrophosphate diol ester (LPP) synthesis pathway” may include the following enzymatically catalyzed reactions: (1) acetyl-coenzyme A (acetyl-CoA) to acetoacetyl-CoA catalyzed by acetyl-CoA transferase; (2) acetoacetyl-CoA catalyzed by 3-methyl-3-hydroxyglutaryl-CoA synthase. (3) 3-hydroxy-3-methylglutaryl-CoA is generated by acetoacetyl-CoA; (4) 3-hydroxy-3-methylglutaryl-CoA is converted to mevalonic acid (MVA) by 3-hydroxy-3-methylglutaryl-CoA reductase; (5) mevalonic acid phosphate (MVAP) is generated by mevalonic acid phosphate (MVAP) by mevalonic acid kinase; (6) isopentenyl pyrophosphate (IPP) is generated by isopentenyl pyrophosphate (IPP) by isopentenyl pyrophosphate isomerase; (7) dimethylallyl pyrophosphate (IPP) is generated by isopentenyl pyrophosphate (IPP) by isopentenyl pyrophosphate isomerase. (7) dimethylallyl diphosphate (DMAPP) catalyzed by pentyle pyrophosphate isomerase to generate isopentenyl pyrophosphate (IPP); (8) isopentenyl diphosphate (IPP) and / or dimethylallyl pyrophosphate (DMAPP) catalyzed by farnesyl pyrophosphate synthase to generate farnesyl diphosphate (FPP); (9) farnesyl diphosphate (FPP) catalyzed by geranylgeranyl pyrophosphate synthase (GGPPS) to generate geranylgeranyl diphosphate (GGPP); and (10) geranylgeranyl diphosphate (GGPP) catalyzed by lysine pyrophosphate synthase (LPPS) to generate lysine pyrophosphate (LPP); this exemplary synthetic route is described herein as follows. Figure 1 As shown.

[0116] In some embodiments, the recombinant engineered bacteria used to produce lysine diol may further comprise one or more of the following genetic modifications: (1) At least one gene modification that enhances the activity of geraniol geraniol pyrophosphate synthase (GGPPS); and (2) At least one gene modification that enhances the activity of lysine pyrophosphate diol ester synthase (LPPS). In some embodiments, at least one gene modification enhancing the activity of geraniol-geraniol pyrophosphate synthase (GGPPS) includes: introducing an exogenous geraniol-geraniol pyrophosphate synthase (GGPPS) gene, increasing the copy number of the geraniol-geraniol pyrophosphate synthase (GGPPS) gene, and / or replacing the natural promoter of the endogenous geraniol-geraniol pyrophosphate synthase (GGPPS) with a promoter having a higher expression level. In some embodiments, the exogenously introduced geraniol-geraniol pyrophosphate synthase (GGPPS) gene encodes a geraniol-geraniol pyrophosphate synthase (GGPPS) derived from *Saccharomyces cerevisiae* or a functional variant thereof. In some embodiments, the exogenous geraniol-geraniol pyrophosphate synthase (GGPPS) comprises the amino acid sequence shown in SEQ ID NO. 9. In some embodiments, the exogenous geraniol-geraniol pyrophosphate synthase (GGPPS) is encoded by the nucleotide sequence of SEQ ID NO. 235.

[0117] In some embodiments, at least one gene modification enhancing the activity of lysine pyrophosphate diol ester synthase (LPPS) includes: introducing an exogenous lysine pyrophosphate diol ester synthase (LPPS) gene, increasing the copy number of the LPPS gene, and / or replacing the natural promoter of the endogenous lysine pyrophosphate diol ester synthase (LPPS) with a promoter that has a higher expression level. In some embodiments, the introduced exogenous lysine pyrophosphate diol ester synthase (LPPS) gene encodes a gene derived from *Perilla frutescens* (a type of perilla frutescens). Salvia sclarea The introduced exogenous lysine pyrophosphate diol ester synthase (LPPS) or a functional variant thereof. In some embodiments, the introduced exogenous lysine pyrophosphate diol ester synthase (LPPS) gene encodes a truncated lysine pyrophosphate diol ester synthase (LPPS). In some embodiments, the truncated lysine pyrophosphate diol ester synthase (LPPS) has a signal peptide with the first 63 amino acids removed. In some embodiments, the introduced exogenous lysine pyrophosphate diol ester synthase (LPPS) gene is codon-optimized for a host bacterium (e.g., Saccharomyces cerevisiae). In some embodiments, the introduced exogenous lysine pyrophosphate diol ester synthase (LPPS) comprises the amino acid sequence shown in SEQ ID NO. 10. In some embodiments, the exogenous lysine pyrophosphate diol ester synthase (LPPS) is encoded by the nucleotide sequence of SEQ ID NO. 236. In some embodiments, the recombinant engineered bacteria for producing lysine diol may further comprise one or more of the following genetic modifications: (1) At least one gene modification that enhances the function of acetyl-CoA transferase; (2) At least one gene modification that enhances the activity of 3-methyl-3-hydroxyglutaryl-CoA synthase; (3) At least one gene modification that enhances the activity of 3-hydroxy-3-methylglutaryl-CoA reductase; (4) At least one gene modification that enhances the activity of mevalonate kinase; (5) At least one gene modification that enhances the activity of mevalonate-5-phosphate kinase; (6) At least one gene modification that enhances the activity of mevalonate-5-pyrophosphate decarboxylase; (7) At least one gene modification that enhances the activity of pentylene pyrophosphate isomerase; and (8) At least one gene modification that enhances the activity of farnesyl pyrophosphate synthase.

[0118] In some embodiments, at least one gene modification enhancing the function of acetyl-CoA transferase includes: introducing an exogenous acetyl-CoA transferase gene, increasing the copy number of the acetyl-CoA transferase gene, and / or replacing the natural promoter of the endogenous acetyl-CoA transferase with a promoter having a higher expression level. In some embodiments, the introduced exogenous acetyl-CoA transferase gene encodes an acetyl-CoA transferase derived from Saccharomyces cerevisiae or a functional variant thereof. In some embodiments, the introduced exogenous acetyl-CoA transferase comprises the amino acid sequence shown in SEQ ID NO. 3, preferably, the exogenous acetyl-CoA transferase is encoded by the nucleotide sequence of SEQ ID NO. 229.

[0119] In some embodiments, at least one gene modification enhancing the activity of 3-methyl-3-hydroxyglutaryl-CoA synthase includes: introducing an exogenous 3-methyl-3-hydroxyglutaryl-CoA synthase gene, increasing the copy number of the 3-methyl-3-hydroxyglutaryl-CoA synthase gene, and / or replacing the natural promoter of the endogenous 3-methyl-3-hydroxyglutaryl-CoA synthase with a promoter having a higher expression level. In some embodiments, the introduced exogenous 3-methyl-3-hydroxyglutaryl-CoA synthase gene encodes a 3-methyl-3-hydroxyglutaryl-CoA synthase derived from *Saccharomyces cerevisiae* or a functional variant thereof. In some embodiments, the introduced exogenous 3-methyl-3-hydroxyglutaryl-CoA synthase comprises the amino acid sequence shown in SEQ ID NO. 4, preferably, the exogenous 3-methyl-3-hydroxyglutaryl-CoA synthase is encoded by the nucleotide sequence of SEQ ID NO. 230.

[0120] In some embodiments, at least one gene modification enhancing the activity of 3-hydroxy-3-methylglutaryl-CoA reductase includes: introducing an exogenous 3-hydroxy-3-methylglutaryl-CoA reductase gene, increasing the copy number of the 3-hydroxy-3-methylglutaryl-CoA reductase gene, and / or replacing the natural promoter of the endogenous 3-hydroxy-3-methylglutaryl-CoA reductase with a promoter having a higher expression level. In some embodiments, the introduced exogenous 3-hydroxy-3-methylglutaryl-CoA reductase gene encodes a 3-hydroxy-3-methylglutaryl-CoA reductase derived from *Saccharomyces cerevisiae* or a functional variant thereof. In some embodiments, the introduced exogenous 3-hydroxy-3-methylglutaryl-CoA reductase gene encodes a truncated 3-hydroxy-3-methylglutaryl-CoA reductase. The truncated 3-hydroxy-3-methylglutaryl-CoA reductase may be referred to as tHMG1 and is a functional variant. In this study, truncated 3-hydroxy-3-methylglutaryl-CoA reductase can possess stronger catalytic activity than untruncated 3-hydroxy-3-methylglutaryl-CoA reductase. In some embodiments, the truncated 3-hydroxy-3-methylglutaryl-CoA reductase can be a 3-hydroxy-3-methylglutaryl-CoA reductase with 528 amino acids removed from its N-terminus. In some embodiments, the introduced exogenous 3-hydroxy-3-methylglutaryl-CoA reductase comprises the amino acid sequence shown in SEQ ID NO. 2, preferably, the truncated 3-hydroxy-3-methylglutaryl-CoA reductase is encoded by the nucleotide sequence of SEQ ID NO. 228.

[0121] In some embodiments, at least one gene modification enhancing the activity of mevalonate kinase includes: introducing an exogenous mevalonate kinase gene, increasing the copy number of the mevalonate kinase gene, and / or replacing the natural promoter of endogenous mevalonate kinase with a promoter that has a higher expression level. In some embodiments, the introduced exogenous mevalonate kinase gene encodes mevalonate kinase derived from Saccharomyces cerevisiae or a functional variant thereof. In some embodiments, the introduced exogenous mevalonate kinase comprises the amino acid sequence shown in SEQ ID NO. 5, preferably, the exogenous mevalonate kinase is encoded by the nucleotide sequence of SEQ ID NO. 231.

[0122] In some embodiments, at least one gene modification enhancing the activity of mevalonate-5-phosphokinase includes: introducing an exogenous mevalonate-5-phosphokinase gene, increasing the copy number of the mevalonate-5-phosphokinase gene, and / or replacing the natural promoter of endogenous mevalonate-5-phosphokinase with a promoter having a higher expression level. In some embodiments, the introduced exogenous mevalonate-5-phosphokinase gene encodes mevalonate-5-phosphokinase derived from Saccharomyces cerevisiae or a functional variant thereof. In some embodiments, the introduced exogenous mevalonate-5-phosphokinase gene comprises the amino acid sequence shown in SEQ ID NO. 6, preferably, the exogenous mevalonate-5-phosphokinase is encoded by the nucleotide sequence of SEQ ID NO. 232.

[0123] In some embodiments, at least one gene modification enhancing the activity of mevalonate-5-pyrophosphate decarboxylase includes: introducing an exogenous mevalonate-5-pyrophosphate decarboxylase gene, increasing the copy number of the mevalonate-5-pyrophosphate decarboxylase gene, and / or replacing the natural promoter of the endogenous mevalonate-5-pyrophosphate decarboxylase with a promoter having a higher expression level. In some embodiments, the introduced exogenous mevalonate-5-pyrophosphate decarboxylase gene encodes mevalonate-5-pyrophosphate decarboxylase derived from Saccharomyces cerevisiae or a functional variant thereof. In some embodiments, the introduced exogenous mevalonate-5-pyrophosphate decarboxylase gene comprises the amino acid sequence shown in SEQ ID NO. 7, preferably, the exogenous mevalonate-5-pyrophosphate decarboxylase is encoded by the nucleotide sequence of SEQ ID NO. 233.

[0124] In some embodiments, at least one gene modification enhancing the activity of pentyrene pyrophosphate isomerase includes: introducing an exogenous pentyrene pyrophosphate isomerase gene, increasing the copy number of the pentyrene pyrophosphate isomerase gene, and / or replacing the natural promoter of the endogenous pentyrene pyrophosphate isomerase with a promoter having a higher expression level. In some embodiments, the introduced exogenous pentyrene pyrophosphate isomerase gene encodes a pentyrene pyrophosphate isomerase derived from Saccharomyces cerevisiae or a functional variant thereof. In some embodiments, the introduced exogenous pentyrene pyrophosphate isomerase gene comprises the amino acid sequence shown in SEQ ID NO. 8, preferably, the exogenous pentyrene pyrophosphate isomerase is encoded by the nucleotide sequence of SEQ ID NO. 234.

[0125] In some embodiments, at least one gene modification enhancing the activity of farnesyl pyrophosphate synthase includes: introducing an exogenous farnesyl pyrophosphate synthase gene, increasing the copy number of the farnesyl pyrophosphate synthase gene, and / or replacing the natural promoter of endogenous farnesyl pyrophosphate synthase with a promoter having a higher expression level. In some embodiments, the introduced exogenous farnesyl pyrophosphate synthase gene encodes farnesyl pyrophosphate synthase derived from Saccharomyces cerevisiae or a functional variant thereof. In some embodiments, the introduced exogenous farnesyl pyrophosphate synthase gene comprises the amino acid sequence shown in SEQ ID NO. 1, preferably, the exogenous farnesyl pyrophosphate synthase is encoded by the nucleotide sequence of SEQ ID NO. 227.

[0126] Biosynthesis of geranylgeraniol (GGOH) In this document, "Geranylgeraniol (GGOH)" includes ALL TRANS-3,7,11-15-tetramethyl-2,6,10,14-hexadecanetetraen-1-ol. For example, the term "Geranylgeraniol" can include compounds with the chemical name ALL TRANS-3,7,11-15-tetramethyl-2,6,10,14-hexadecanetetraen-1-ol and the molecular formula C6H2O. 20 H 34 O, CAS No. 24034-73-9.

[0127] In some embodiments, the recombinant engineered bacteria contains a gene for the geranyl-geranyl pyrophosphate (GGPP) synthesis pathway to produce geranyl-geranyl (GGOH) in the recombinant engineered bacteria.

[0128] In some embodiments, the geraniol-geraniol pyrophosphate (GGPP) synthesis pathway genes include farnesyl pyrophosphate (FPP) synthesis pathway genes and geraniol-geraniol pyrophosphate synthase (GGPPS) genes. The farnesyl pyrophosphate (FPP) synthesis pathway genes and geraniol-geraniol pyrophosphate synthase (GGPPS) genes are as described in the foregoing sections of this invention (e.g., the same description as in the foregoing "Biosynthesis of Lisperidone Diol (LOH)" section).

[0129] In some embodiments, the “geranylgeranyl pyrophosphate (GGPP) synthesis pathway gene” includes the mevalonate (MVA) pathway gene. Regarding the mevalonate (MVA) pathway gene, it is as described in the foregoing sections of this invention (e.g., the same description as in the foregoing “Biosynthesis of Lisperidone Diol (LOH)” section).

[0130] In some embodiments, the “geranylgeranyl pyrophosphate (GGPP) synthesis pathway gene” includes an enzyme gene for synthesizing an enzyme that can be catalyzed to produce geranylgeranyl pyrophosphate (GGPP) or its precursors. In some embodiments, the precursor may, for example, include farnesyl diphosphate (FPP). In some embodiments, the geranylgeranyl pyrophosphate (GGPP) synthesis pathway gene includes a farnesyl pyrophosphate synthase gene for the production of farnesyl diphosphate (FPP) from isopentenyl pyrophosphate (IPP) and / or dimethylpropene pyrophosphate (DMAPP) and / or a geranylgeranyl pyrophosphate synthase (GGPPS) gene for the production of geranylgeranyl diphosphate (GGPP) from farnesyl diphosphate (FPP).

[0131] In some implementations, the “geranyl-geranyl pyrophosphate (GGPP) synthesis pathway gene” may include the following enzymatically catalyzed reactions: (1) acetyl-coenzyme A (acetyl-CoA) to acetoacetyl-CoA catalyzed by acetyl-CoA transferase; (2) acetoacetyl-CoA catalyzed by 3-methyl-3-hydroxyglutaryl-CoA synthase. (3) 3-hydroxy-3-methylglutaryl-CoA is generated by acetoacetyl-CoA; (4) 3-hydroxy-3-methylglutaryl-CoA is converted to mevalonic acid (MVA) by 3-hydroxy-3-methylglutaryl-CoA reductase; (5) mevalonic acid phosphate (MVAP) is generated by mevalonic acid phosphate (MVAP) by mevalonic acid kinase; (6) isopentenyl pyrophosphate (IPP) is generated by isopentenyl pyrophosphate (IPP) by isopentenyl pyrophosphate isomerase; (7) dimethylallyl pyrophosphate (IPP) is generated by isopentenyl pyrophosphate (IPP) by isopentenyl pyrophosphate isomerase. (7) diphosphate (DMAPP) or dimethylallyl diphosphate (DMAPP) catalyzed by pentyle pyrophosphate isomerase to generate isopentenyl pyrophosphate (IPP); (8) isopentenyl pyrophosphate (IPP) and / or dimethylallyl pyrophosphate (DMAPP) catalyzed by farnesyl pyrophosphate synthase to generate farnesyl diphosphate (FPP); and (9) farnesyl diphosphate (FPP) catalyzed by geranylgeranyl pyrophosphate synthase (GGPPS) to generate geranylgeranyl diphosphate (GGPP).

[0132] In some embodiments, the recombinant engineered bacteria used to produce geraniol (GGOH) may further include the following gene modifications: (1) at least one gene modification that enhances the activity of geraniol pyrophosphate synthase (GGPPS). In some embodiments, at least one gene modification enhancing the activity of geraniol-geraniol pyrophosphate synthase (GGPPS) includes: introducing an exogenous geraniol-geraniol pyrophosphate synthase (GGPPS) gene, increasing the copy number of the geraniol-geraniol pyrophosphate synthase (GGPPS) gene, and / or replacing the natural promoter of the endogenous geraniol-geraniol pyrophosphate synthase (GGPPS) with a promoter having a higher expression level. In some embodiments, the introduced exogenous geraniol-geraniol pyrophosphate synthase (GGPPS) gene encodes a geraniol-geraniol pyrophosphate synthase (GGPPS) derived from Saccharomyces cerevisiae or a functional variant thereof. In some embodiments, the exogenous geraniol-geraniol pyrophosphate synthase (GGPPS) gene comprises the amino acid sequence shown in SEQ ID NO. 9.

[0133] In some embodiments, the recombinant engineered bacteria used to produce geraniol (GGOH) may further comprise one or more of the following genetic modifications: (1) At least one gene modification that enhances the function of acetyl-CoA transferase; (2) At least one gene modification that enhances the activity of 3-methyl-3-hydroxyglutaryl-CoA synthase; (3) At least one gene modification that enhances the activity of 3-hydroxy-3-methylglutaryl-CoA reductase; (4) At least one gene modification that enhances the activity of mevalonate kinase; (5) At least one gene modification that enhances the activity of mevalonate-5-phosphate kinase; (6) At least one gene modification that enhances the activity of mevalonate-5-pyrophosphate decarboxylase; (7) At least one gene modification that enhances the activity of pentylene pyrophosphate isomerase; and (8) At least one gene modification that enhances the activity of farnesyl pyrophosphate synthase.

[0134] Regarding any of the above-mentioned gene modifications, for example, as described in the foregoing section of this invention (for example, the same as the description in the foregoing section on "Biosynthesis of Lisperidone Diol (LOH)").

[0135] In some embodiments, the recombinant engineered bacteria used to produce geraniol (GGOH) may contain at least one gene modification that eliminates or weakens the activity of endogenous lysine pyrophosphate diol ester synthase (LPPS).

[0136] In some embodiments, at least one gene modification that eliminates or weakens the function of endogenous lysine pyrophosphate diol ester synthase (LPPS) includes: knocking out or knocking down the endogenous lysine pyrophosphate diol ester synthase (LPPS) gene, and / or knocking out or knocking down the natural promoter of the endogenous lysine pyrophosphate diol ester synthase (LPPS) gene.

[0137] Gene modifications that eliminate or attenuate lysine dopant synthase (LPPS) include gene modifications that partially or completely inactivate the endogenous gene encoding the LPPS, including but not limited to: knocking out or downactivating the endogenous gene, for example, deleting all or part of the endogenous gene sequence, mutating the endogenous gene, or inserting an exogenous sequence into the endogenous gene to cause loss or attenuation of the enzyme activity encoded by the endogenous gene. Gene modifications that partially or completely inactivate the endogenous gene encoding the enzyme may also include: knocking out or downactivating the natural regulatory sequence (e.g., the natural promoter) of the endogenous gene, for example, deleting all or part of the regulatory sequence sequence, mutating the regulatory sequence, or inserting an exogenous sequence into the regulatory sequence to cause partial or complete inactivation of the regulatory sequence, thereby eliminating or reducing the expression of the endogenous gene.

[0138] Biosynthesis of farnesol (FOH) In this document, "Farnesol (FOH)" includes 3,7,11-trimethyl-2,6,10-dodecanetrien-1-ol. For example, the term "Farnesol (FOH)" can include compounds with the chemical name 3,7,11-trimethyl-2,6,10-dodecanetrien-1-ol and the molecular formula C64. 15 H 26 O, CAS No. 4602-84-0. In some embodiments, the recombinant engineered bacteria contains a farnesyl pyrophosphate (FPP) synthesis pathway gene to produce farnesol (FOH) in the recombinant engineered bacteria. Regarding the farnesyl pyrophosphate (FPP) synthesis pathway gene and the geranylgeranyl pyrophosphate synthase (GGPPS) gene, for example, as described in the foregoing sections of this invention (e.g., the same description as in the foregoing "Biosynthesis of Lisperidone Diol (LOH)" section).

[0139] In some embodiments, the "Farnesy Pyrophosphate (FPP) Synthesis Pathway Gene" includes the mevalonate (MVA) pathway gene. Regarding the mevalonate (MVA) pathway gene, it is as described in the foregoing sections of this invention (e.g., the same description as in the foregoing "Biosynthesis of Lisperidone Diol (LOH)" section).

[0140] In some implementations, the "farnesyl pyrophosphate (FPP) synthesis pathway gene" includes a farnesyl pyrophosphate synthase gene that generates farnesyl diphosphate (FPP) from isopentenyl pyrophosphate (IPP) and / or dimethylpropene pyrophosphate (DMAPP).

[0141] In some implementations, the "farnesyl pyrophosphate (FPP) synthesis pathway gene" may include the following enzymatically catalyzed reactions: (1) acetyl-coenzyme A (acetyl-CoA) to acetoacetyl-CoA catalyzed by acetyl-CoA transferase; (2) acetoacetyl-CoA catalyzed by 3-methyl-3-hydroxyglutaryl-CoA synthase. (3) 3-hydroxy-3-methylglutaryl-CoA is generated by acetoacetyl-CoA; (4) 3-hydroxy-3-methylglutaryl-CoA is converted to mevalonic acid (MVA) by 3-hydroxy-3-methylglutaryl-CoA reductase; (5) mevalonic acid phosphate (MVAP) is generated by mevalonic acid phosphate (MVAP) by mevalonic acid kinase; (6) isopentenyl pyrophosphate (IPP) is generated by isopentenyl pyrophosphate (IPP) by isopentenyl pyrophosphate isomerase; (7) dimethylallyl diphosphate is generated by isopentenyl pyrophosphate (IPP) by isopentenyl pyrophosphate isomerase. (8) isopentenyl diphosphate (FPP) produced by catalysis of dimethylallyl diphosphate (DMAPP) by pyrophosphate isomerase; and (9) farnesyl diphosphate (FPP) produced by catalysis of isopentenyl diphosphate (IPP) and / or dimethylallyl diphosphate (DMAPP) by farnesyl pyrophosphate synthase.

[0142] In some embodiments, the recombinant engineered bacteria used to produce farnesol (FOH) may further comprise one or more of the following genetic modifications: (1) At least one gene modification that enhances the function of acetyl-CoA transferase; (2) At least one gene modification that enhances the activity of 3-methyl-3-hydroxyglutaryl-CoA synthase; (3) At least one gene modification that enhances the activity of 3-hydroxy-3-methylglutaryl-CoA reductase; (4) At least one gene modification that enhances the activity of mevalonate kinase; (5) At least one gene modification that enhances the activity of mevalonate-5-phosphate kinase; (6) At least one gene modification that enhances the activity of mevalonate-5-pyrophosphate decarboxylase; (7) At least one gene modification that enhances the activity of pentylene pyrophosphate isomerase; and (8) At least one gene modification that enhances the activity of farnesyl pyrophosphate synthase.

[0143] Regarding any of the above-mentioned gene modifications, for example, as described in the foregoing section of this invention (for example, the same as the description in the foregoing section on "Biosynthesis of Lisperidone Diol (LOH)").

[0144] In some embodiments, the recombinant engineered bacteria used to produce farnesol (FOH) may contain one or more of the following genetic modifications: (1) At least one gene modification that eliminates or weakens the activity of endogenous geranyl geranyl pyrophosphate synthase (GGPPS); and (2) At least one gene modification that eliminates or weakens the activity of endogenous lysine pyrophosphate diol ester synthase (LPPS).

[0145] In some embodiments, at least one gene modification that eliminates or weakens the function of endogenous gerany-gerany pyrophosphate synthase (GGPPS) includes: knocking out or knocking down the endogenous gerany-gerany pyrophosphate synthase (GGPPS) gene, and / or knocking out or knocking down the natural promoter of the endogenous gerany-gerany pyrophosphate synthase (GGPPS) gene.

[0146] Gene modifications to eliminate or attenuate gerany-gerany-pyrophosphate synthase (GGPPS) include gene modifications that partially or completely inactivate the endogenous gene encoding the gerany-gerany-gerany-pyrophosphate synthase (GGPPS), including but not limited to: knocking out or knocking down the endogenous gene, for example, deleting all or part of the sequence of the endogenous gene, mutating the endogenous gene, or inserting a foreign sequence into the endogenous gene to cause loss or attenuation of the enzyme activity encoded by the endogenous gene. Gene modifications that partially or completely inactivate the endogenous gene encoding the enzyme may also include: knocking out or knocking down the natural regulatory sequence (e.g., the natural promoter) of the endogenous gene, for example, deleting all or part of the sequence of the regulatory sequence, mutating the regulatory sequence, or inserting a foreign sequence into the regulatory sequence to cause partial or complete inactivation of the regulatory sequence, thereby eliminating or reducing the expression of the endogenous gene.

[0147] In some embodiments, at least one gene modification that eliminates or weakens the function of endogenous lysine pyrophosphate diol ester synthase (LPPS) includes: knocking out or knocking down the endogenous lysine pyrophosphate diol ester synthase (LPPS) gene, and / or knocking out or knocking down the natural promoter of the endogenous lysine pyrophosphate diol ester synthase (LPPS) gene.

[0148] Gene modifications that eliminate or attenuate lysine dopant synthase (LPPS) include gene modifications that partially or completely inactivate the endogenous gene encoding the LPPS, including but not limited to: knocking out or downactivating the endogenous gene, for example, deleting all or part of the endogenous gene sequence, mutating the endogenous gene, or inserting an exogenous sequence into the endogenous gene to cause loss or attenuation of the enzyme activity encoded by the endogenous gene. Gene modifications that partially or completely inactivate the endogenous gene encoding the enzyme may also include: knocking out or downactivating the natural regulatory sequence (e.g., the natural promoter) of the endogenous gene, for example, deleting all or part of the regulatory sequence sequence, mutating the regulatory sequence, or inserting an exogenous sequence into the regulatory sequence to cause partial or complete inactivation of the regulatory sequence, thereby eliminating or reducing the expression of the endogenous gene.

[0149] Methods for genetically modifying engineered bacteria are well known to those skilled in the art. Genetic modification techniques can be used to introduce free exogenous nucleic acid sequences (e.g., in the form of plasmids) into engineered bacteria, or to insert exogenous nucleic acid sequences or delete endogenous nucleic acid sequences into the genome of engineered bacteria, or to replace a segment of endogenous nucleic acid sequence in the genome of engineered bacteria with a segment of exogenous nucleic acid sequence, so as to change the genes of engineered bacteria and thus change their phenotype.

[0150] Expressing exogenous proteins (such as one or more enzymes mentioned above) in engineered bacteria can include introducing exogenous genes into the engineered bacteria to express the protein encoded by those genes. This can be achieved, for example, by introducing a nucleic acid sequence (e.g., a vector) containing the exogenous gene into the engineered bacteria. The nucleic acid sequence containing the exogenous gene can be linear or circular, and can be single-stranded or double-stranded. The vector can be a self-replicating vector. The vector can be a free vector or an integrative vector. The vector can be, for example, a plasmid vector, a phage vector, a bacterial artificial chromosome, a transposon-based vector, or a CRISPR / Cas-based vector. The vector can also be a suicide vector, such as a suicide plasmid vector.

[0151] The expression vector may contain a foreign gene expression cassette, which may include a foreign gene and a regulatory sequence operatively linked thereto, the regulatory sequence guiding the expression of the foreign gene in suitable engineered bacteria. The regulatory sequence may include, but is not limited to, promoters, enhancers, terminators, and other expression control elements. The promoter may be a constitutive promoter to enable sustained expression of the foreign gene; or an inducible promoter to induce expression of the foreign gene upon the addition of an inducer. The vector may also contain one or more selectable marker genes that allow convenient selection of transformed, transfected, or transduced cells, such marker genes as genes providing resistance to antibiotics, heavy metals, and / or negative selection marker genes (e.g., ...). sac (B gene, etc.)

[0152] Suitable vectors can be selected based on different purposes (e.g., autonomous replication within engineered bacteria or integration into the genome of engineered bacteria) and / or different engineered bacteria. Vectors and regulatory sequences suitable for introducing exogenous proteins into different engineered bacteria are well known to those skilled in the art. For example, for *E. coli*, vectors that can be used include, but are not limited to, pJC1, pET22b(+), pBR322, pBR325, pUC57, pUC118, pUC119, pUC18, pUC19, pBluescript, or plasmids based on them; for *Corynebacterium glutamicum*, vectors that can be used include, but are not limited to, pBL1, pEKEx1, p... For Bacillus subtilis, plasmid vectors such as EKEx2, pXMJ19, pJC1, pHM1519, pVWEx1, pZ8-1, pECTAC-K99, pECTAC-XK99E, pECTAC-XC99E, pECTAC-XT99A, pNG2, and pAPE12, or plasmid vectors based thereon, may be used; for Bacillus subtilis, vectors that can be used include, but are not limited to, pHT43, pUB110, pE194, pUCX05-bgaB, and pWB980. pHP13, pBE2, pHP13, pHP13-43, pHT01, pHT304, pMK3, pHCMC05, pMA5, pHY300PLK, or pMUTIN4; for yeast, the vectors that can be used include, but are not limited to, pGal1, pGal7, pGal10, pGal2, pPIC9, pPIC9k, pHIL-S1, pPICza, pYAM75P6, pHIL-D2, pA0815, and pPIC3. K, pPICZ, pHWO10, pGAPZ, pGAPZa, pYES2, pYES2 / NT, pYES2 / CT, pYES3, pYES6, pYCplac22-GFP, pAUR123, pRS303TEF, pRS304, pRS305, pRS306, pY13TEF, pY14TEF, pY15TEF, pY16TEF, pSH47, pLacZi, pHIS2, or pGAD42. Suitable promoters for use in bacteria include, but are not limited to, inducible promoters such as Ptac, Plac, and Ptrc, or constitutive promoters such as Psod, PcspB, Ptuf, and PgapA. In some embodiments, promoters pGal1, pGal7, pGal10, and / or pGal2 are used to express exogenous genes in engineered bacteria.

[0153] The vector may also contain one or more selectable marker genes that allow for convenient selection of transformed, transfected, or transduced cells, such as genes that provide resistance to antibiotics or heavy metals.

[0154] The foreign gene, after being introduced into the engineered bacteria, can exist in and be expressed from a free vector (e.g., a free plasmid), for example, by introducing an expression vector (e.g., a plasmid vector) containing a foreign gene expression cassette into the engineered bacteria. The foreign gene can also be integrated into the genome of the engineered bacteria for expression, for example, by introducing an integrative plasmid vector containing the foreign gene (the plasmid may, for example, contain homologous arms for integration into the engineered bacteria genome via homologous recombination), a phage vector, a CRISPR / Cas system, or a transposon system (e.g., the Piggybac or Sleeping Beauty system). The foreign gene can be randomly integrated into the engineered bacteria, or it can be targeted to a suitable site in the engineered bacteria (e.g., via homologous recombination or a CRISPR / Cas system). The expression cassette containing the foreign gene can be randomly or targeted into the genome of the engineered bacteria, or the foreign gene can be targeted to a suitable site in the engineered bacteria to express the foreign gene using endogenous regulatory sequences within the engineered bacteria. In some implementations, the exogenous gene can be targeted and integrated into any one or more of the lpp1, dpp1, ho, gal80, gal2, dit1, and gal2 sites of the recombinant yeast engineer (e.g., recombinant Saccharomyces cerevisiae).

[0155] In some implementations, an expression cassette containing a foreign gene can be targeted and integrated into the genome of an engineered bacterium using a CRISPR / Cas system, or the foreign gene can be targeted and integrated into a suitable site within the engineered bacterium to express the foreign gene using endogenous regulatory sequences within the engineered bacterium. A CRISPR / Cas system typically comprises at least two components: a Cas9 protein, an enzyme capable of cleaving double-stranded DNA at a specific DNA sequence; and guide RNA (gRNA), which guides the Cas9 protein to a specific gene site for cleavage. Those skilled in the art are familiar with how to introduce foreign genes or knock out endogenous genes using a CRISPR / Cas9 system, for example, by constructing plasmids containing both the Cas9 protein and gRNA coding sequences. Donor plasmids are commonly used in CRISPR / Cas system-mediated gene editing technologies; donor plasmids may, for example, contain the complete expression cassette of a foreign gene (e.g., one or two or more foreign genes) and upstream and downstream homologous arms at the integration site. Donor plasmids may also contain regulatory sequences such as promoters and terminators that are operatively linked to foreign genes, as well as resistance genes and / or signal sequences.

[0156] Methods for expressing multiple foreign genes in engineered bacteria are well known to those skilled in the art. For example, a separate transcription unit can be constructed for each foreign gene, each with its own promoter and capable of being transcribed into its own mRNA. Appropriate promoters can be selected for different genes as needed. Alternatively, two or more (e.g., two, three, or four) foreign genes can be included in the same transcription unit, sharing the same promoter. Each of the multiple foreign genes in the same transcription unit may have a ribosome binding site (RBS) to facilitate individual translation of each gene, with multiple genes transcribed and translated in a polycistronic manner. Multiple transcription units can be contained in different vectors or in the same vector. These transcription units can be introduced into engineered bacteria using the methods described above.

[0157] Suitable methods for introducing exogenous nucleic acid sequences (e.g., vectors) into engineered bacteria are known to those skilled in the art, including but not limited to calcium phosphate transfection, protoplast fusion, electroporation, liposomes, lipid nanoparticles, microinjection, naked DNA or RNA (e.g., mRNA) transfection, plasmid vector transformation, phage vector transduction, etc.

[0158] The engineered bacteria of this invention can be microbial cells, including bacteria, yeast cells, archaea, fungal cells, etc. The microorganisms can be GRAS (Generally Recognized As Safe) microorganisms. The bacteria can be, for example, Gram-negative or Gram-positive bacteria. The bacteria can be, for example, Escherichia bacteria, such as *Escherichia coli*. Escherichia coli Corynebacterium bacteria, such as Corynebacterium glutamicum (…); Corynebacterium glutamicum Corynebacterium pingeri () Corynebacterium pekinense ), Corynebacterium obliterans ( Corynebacterium crenatum ), Corynebacterium thermophilum ( Corynebacterium thermoaminogenes ), Corynebacterium ammoniagenic ( Corynebacterium aminogenes ) etc.; Bacillus bacteria, such as Bacillus subtilis ( Bacillus subtilis ), Bacillus licheniformis ( Bacillus licheniformis ), Bacillus coagulans ( Bacillus coagulans ), Bacillus cereus ( Bacillus cereus ), thermophilic steatobacterium ( Bacillus stearothermophilus ), Bacillus megaterium ( Bacillus megaterium ) etc.; Lactobacillus bacteria, such as Lactobacillus acidophilus ( Lactobacillus acidophilus ), Lactobacillus casei ( Lactobacillus casei Lactobacillus delbrueckii (), Lactobacillus delbrueckii Lactobacillus plantarum ( Lactococcus lactisBifidobacterium bacteria; Streptococcus bacteria; Lactococcus bacteria; Streptmyces bacteria; Pseudomonas bacteria, such as Pseudomonas aeruginosa. Pseudomonas aeruginosa Clostridium bacteria; Brevibacillus bacteria; Enterococcus bacteria; Pediococcus bacteria; Leuconostoc bacteria, etc. Yeast cells can be, for example, yeast cells of the genera *Saccharomyces*, *Saccharomycopsis*, *Pichia*, *Hansenula*, *Kluyveromyces*, *Yarrowia*, *Hyphozyma*, *Cryptococcus*, *Rhodotorula*, *Phaffia*, *Schizosaccharomyces*, or *Candida*, such as *Saccharomyces cerevisiae*. Saccharomyces cerevisiae ), Yarrowia lipolytica ( Yarrowia lipolytica ), Candida utilis ( Candida utilis ), or Pichia pastoris ( Pichia pastoris ), Phaffia colomata ( Komagataella phaffii) , Saccharomyces cerevisiae ( Schizosaccharomyces pombe ), Candida albicans ( Candida albicans ), Candida utilis ( Candida utilis ), Yarrowia lipolytica ( Yarrowia lipolytica ), Hansenula polymorpha ( Hansenula polymorpha Pichia pastoris (Canada) Pichia canadensis ), Max Kluyveromycin ( Kluyveromyces marxianus Kluyveromycin (lactic acid yeast) Kluyveromyces lactis Hyphozyma roseoniger, Cryptococcus palea ( Cryptococcus albidus ) or Red Pavlova yeast ( Phaffia rhodozyma ).

[0159] In some embodiments, the engineered bacteria are bacteria or yeast; preferably, the bacteria are selected from Escherichia, Corynebacterium, or Bacillus, and the yeast is selected from Saccharomyces, Pichia, Hansenula, Kluyveromyces, Phaffia, Schizosaccharomyces, Candida, Yarrowia, Hyphozyma, or Cryptococcus; more preferably, the bacteria are selected from Escherichia coli (…). Escherichia coli ), Corynebacterium glutamicum ( Corynebacterium glutamicum ), or Bacillus subtilis ( Bacillus subtilis The yeast is selected from brewer's yeast (Saccharomyces cerevisiae). Saccharomyces cerevisiae Pichia pastoris () Pichia pastoris ), Phaffia colomata ( Komagataellaphaffii) , Saccharomyces cerevisiae ( Schizosaccharomycespombe ), Candida albicans ( Candidaalbicans ), Candida utilis ( Candida utilis ), Yarrowia lipolytica ( Yarrowia lipolytica ), Hansenula polymorpha ( Hansenulapolymorpha Pichia pastoris (Canada) Pichia canadensis ), Max Kluyveromycin ( Kluyveromycesmarxianus Kluyveromycin (lactic acid yeast) Kluyveromyces lactis Hyphozyma roseoniger, Cryptococcus palea ( Cryptococcus albidus ) or Red Pavlova yeast ( Phaffia rhodozyma More preferably, the brewing yeast is yeast strain CEN.PK2-1C.

[0160] The present invention also provides the use of the recombinant engineered bacteria in the production of compounds of formula (I), such as farnesol, geraniol, and lysine diol.

[0161] The present invention also provides a method for culturing the recombinant engineered bacteria under suitable conditions to produce compounds of formula (I), such as farnesol, geraniol, and lysine diol.

[0162] The recombinant engineered bacteria can be cultured using any suitable culture medium, such as those well known to those skilled in the art. In some embodiments, the culture medium contains at least one carbon source, which may be selected from, but is not limited to, glucose, fructose, sucrose, maltose, glycerol, acetic acid, lactic acid, and / or succinic acid. The carbon source may be replenished at appropriate times during the cultivation of the recombinant engineered bacteria. In some embodiments, the carbon source concentration in the culture medium is from 10 g / L to 50 g / L, for example, 20 g / L to 50 g / L, 30 g / L to 50 g / L, 10 g / L to 40 g / L, 20 g / L to 40 g / L, 30 g / L to 40 g / L, 10 g / L to 30 g / L, or 20 g / L to 30 g / L.

[0163] When the genes encoding one or more enzymes contained in engineered bacteria are expressed in an inducible manner, an inducer is added during cell culture to induce the expression of the enzyme.

[0164] The cultivation of engineered microorganisms can be carried out in several ways. First, batch fermentation involves using a closed culture system with a specific culture medium at the start of fermentation, and optimizing growth using specific temperature, pressure, aeration, and other environmental conditions. No nutrients are added during cell culture, and no fermentation broth is released. Second, fed-batch fermentation involves adding nutrients intermittently or continuously during fermentation, but without releasing the fermentation broth. Third, continuous fermentation involves continuously adding nutrients and releasing the fermentation broth, thus maintaining a constant volume of culture medium in the fermentation system. Finally, fermentation can be a combination of two or three of these methods.

[0165] Suitable conditions for culturing the recombinant engineered bacteria include suitable temperature, pH, dissolved oxygen levels, osmotic pressure, and other conditions. The suitable conditions may vary depending on the specific engineered bacteria, which can be readily determined by those skilled in the art. In some embodiments, the culture step is carried out at about 25°C to about 35°C, preferably at about 28°C to about 32°C, and more preferably at about 30°C. In some embodiments, the culture step is carried out at about pH 6.0 to about pH 8.0, preferably at about pH 6.0 to about pH 7.0.

[0166] In some implementations, the culture step is carried out for about 12 hours or longer, such as about 36 hours or longer, about 48 hours or longer, about 53 hours or longer, about 60 hours or longer, or about 72 hours or longer; or for about 12 hours or less, such as about 36 hours or less, about 48 hours or less, about 53 hours or less, about 60 hours or less, or about 72 hours or less.

[0167] The production method of the present invention can produce compounds of formula (I) at a concentration of about 10 mg / L or more after fermentation for 48 hours, such as farnesol, geraniol, and lysine diol, for example, at a concentration of about 20 mg / L or more, about 30 mg / L or more, about 40 mg / L or more, about 50 mg / L or more, about 60 mg / L or more, about 70 mg / L or more, about 80 mg / L or more, about 90 mg / L or more, about 100 mg / L or more, or about 120 mg / L or more.

[0168] In some embodiments, the produced formula (I) compounds, such as farnesol, geraniol, and lysandrindiol, are present in the cytoplasm or are transported extracellularly. In some embodiments, the method for producing formula (I) compounds, such as farnesol, geraniol, and lysandrindiol, includes isolating, purifying, or recovering the generated formula (I) compounds, such as farnesol, geraniol, and lysandrindiol.

[0169] For example, the product can be separated, purified, or recovered from the culture medium and / or the supernatant of the cell lysate. Cell lysis can be performed by chemical or physical methods known in the art. The terms “separation,” “purification,” and “recovery” refer to the separation of the product from other components in the engineered bacterial culture, which may include, for example, the removal of impurities and unwanted byproducts, such as cells, ions, salts, and / or substances other than the desired compound of formula (I), such as farnesol, geraniol, and lysine diol.

[0170] Separation, purification, or recovery can be performed using techniques known to those skilled in the art. For example, the product can be purified from the culture medium using methods known to those skilled in the art, such as column chromatography with activated carbon, elution with a concentration gradient of ethanol, or size exclusion chromatography or ion exchange chromatography. Purity can be assessed by any known method, such as thin-layer chromatography or other electrophoretic or chromatographic techniques commonly known in the art.

[0171] Compounds of formula (I) produced using the method of this invention, such as farnesol, geraniol, and lysandrindiol, can be used to further produce derivatives thereof, for example, by chemical synthesis, biocatalysis (e.g., by enzyme-catalyzed reactions), or a combination of both. The chemical synthesis includes, but is not limited to, oxidation, reduction, alkylation, acylation, and / or rearrangement. The biocatalysis involves contacting the compound of formula (I) with an enzyme, such as, but not limited to, oxidoreductases, monooxygenases, dioxygenases, and transferases. The derivatives may be, for example, hydrocarbons, glycols, triols, acetals, ketals, aldehydes, acids, ethers, amides, ketones, epoxides, acetates, glycosides, and / or esters.

[0172] When producing derivatives of the compound of formula (I) using the method of the present invention, the compound of formula (I) may be isolated from the reaction mixture of the method or from a culture of recombinant engineered bacteria, or may not be isolated. The reaction mixture or the recombinant engineered bacteria may be used directly as a raw material to provide the compound of formula (I) for the production of derivatives of the compound of (I). Alternatively, genes for an enzyme that can convert the compound of formula (I) into its derivatives may be further introduced into the recombinant engineered bacteria of the present invention to produce the derivatives intracellularly.

[0173] Term The term "derivative" refers to a compound obtained by substituting one or more atoms or groups of atoms into other atoms or groups of atoms; such a derivative is called a derivative of the parent compound. The term "derivative" is structurally similar to the parent compound and can refer to compounds that can theoretically and / or practically be generated from the parent compound through a chemical reaction.

[0174] The term "gene" refers to the nucleotide sequence that encodes a gene product. The gene product can be a protein or ribonucleic acid.

[0175] The terms “nucleic acid,” “nucleic acid sequence,” or “polynucleotide” refer to a single- or double-stranded polymer of deoxynucleotide or ribonucleotide bases, including DNA or RNA, including linear or circular DNA or RNA.

[0176] The terms "peptide" and "protein" are used interchangeably, referring to polymers of amino acid residues. The enzyme in this invention is a protein capable of catalyzing a chemical reaction of its substrate.

[0177] The term "recombinant" when used to refer to cells, nucleic acids, proteins, or vectors indicates that the cells, nucleic acids, proteins, or vectors have been modified by introducing heterologous nucleic acids or proteins or by altering native nucleic acids or proteins, or that the cells are derived from cells that have been modified in this way. Therefore, recombinant cells express genes that are not present in the natural (non-recombinant) form of the cell; or express natural genes that are otherwise abnormally, insufficiently, or not expressed at all.

[0178] The terms "genetic modification," "genetic alteration," "engineering," and "engineering" refer to the artificial manipulation of altering the sequence of a polypeptide or polynucleotide, or altering the gene sequence contained in an engineered bacterium, to include a sequence not naturally present in the polypeptide, polynucleotide, or engineered bacterium. When an engineered bacterium is "engineered" to exhibit a certain characteristic (e.g., containing a gene encoding a specific protein, expressing a specific protein, or overexpressing a specific gene), it means that the engineered bacterium did not possess that characteristic before modification but acquires it after modification. The term "synthetic pathway" refers to a series of enzyme-controlled and catalyzed reactions that result in the synthesis of a chemical substance, such as lysandrindiol (LOH), lysandrindiol pyrophosphate (LPP), or farnesyl pyrophosphate (FPP) as described herein. In some embodiments, the term "synthetic pathway" may include a series of reactions starting from a carbon source and catalyzed by an enzyme to synthesize a specific substance. The term "synthetic pathway gene" refers to the gene encoding an enzyme that catalyzes a series of reactions included in a synthetic pathway, and these genes may be expressed in engineered bacteria to catalyze the synthesis of a specific chemical substance.

[0179] The term "exogenous" is used in contrast to engineered bacteria, referring to substances or molecules originating from or produced outside of engineered bacteria. "Exogenous gene" or "exogenous enzyme" refers to nucleic acids that are not naturally occurring in the cell but are introduced into the cell artificially. The sequence of an exogenous gene or exogenous enzyme may be the same as or different from the naturally occurring endogenous sequence in the cell. Genes or enzymes that differ from the naturally occurring endogenous sequence in the cell are called heterologous genes or heterologous enzymes, and they may originate from strains or species that are the same as or different from engineered bacteria. In this document, unless otherwise stated, the use of "exogenous gene" or "exogenous enzyme" includes the case of "heterologous gene" or "heterologous enzyme."

[0180] The term "endogenous" refers to genes or proteins (e.g., wild-type genes or wild-type enzymes) or synthetic pathways that are naturally present in engineered bacteria.

[0181] The term "wild-type" refers to a naturally occurring organism or cell, or a nucleic acid sequence present in a naturally occurring organism or cell, or a protein expressed by a naturally occurring organism or cell.

[0182] The term "naturally occurring" refers to nucleic acid sequences, amino acid sequences, complexes, pathways, or cells that exist in nature without human intervention.

[0183] The term "separated" means that a component, material, or substance has been separated from the environment in which it was produced. "Separated" can refer to a component, material, or substance being separated from other components, materials, or substances normally associated with it in the environment in which it was produced, and resulting in an increase in purity due to this separation. The purity of a "separated" component, material, or substance can be at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% by weight.

[0184] The term "derived from" when applied to a protein or gene sequence refers to a protein or gene sequence that is derived from a specific organism, meaning that the protein or gene sequence has the same structure or sequence as proteins or gene sequences naturally present in that organism, and is not limited to being directly isolated from that organism.

[0185] The term "mutant" refers to a polypeptide that has one or more amino acid insertions, deletions, and / or substitutions relative to the parent polypeptide. Substitution means replacing an amino acid occupying a position with a different amino acid; deletion means removing an amino acid occupying a position; insertion means adding one or more amino acids (e.g., 1-5) adjacent to an amino acid occupying a position. Mutants retain at least one activity of the parent polypeptide, but may have variations at the activity level; for example, a mutant may remain unchanged or improve upon at least one activity or property relative to the parent polypeptide.

[0186] The term "functional variant," when applied to polypeptides or proteins, refers to a polypeptide that shares at least 60%, 65%, 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with its parent polypeptide and has the same or substantially the same function as the parent polypeptide. A functional variant may also refer to a polypeptide that has the insertion, deletion, and / or substitution of one or more amino acids (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, or more) compared to its parent polypeptide and has the same or substantially the same function as the parent polypeptide. Modifications or methods for creating functional variants of polypeptides or proteins are well known to those skilled in the art. Polypeptides known in the art that have the same or substantially the same function as their parent polypeptide are also included within the scope of the enzymes or their functional variants of the present invention.

[0187] The term "parent" refers to a polypeptide that has been modified to produce a mutant, and the parent can be a naturally occurring (wild-type) polypeptide or a mutant thereof.

[0188] The term “sequence identity” refers to the percentage of identical nucleotide or amino acid residues at corresponding positions in two or more sequences, when sequences are aligned to maximize sequence matching, i.e., gaps and insertions are taken into account. Sequence alignment and the calculation of sequence identity percentages can be performed using appropriate computer programs known in the art. These programs include, but are not limited to, BLAST, ALIGN, ClustalW, EMBOSS Needle, etc. For example, global sequence alignment can be performed based on the Needleman-Wunsch algorithm (Needleman, Saul B.; and Wunsch, Christian D. (1970), “A general method applicable to the search for similarities in the amino acidsequence of two proteins”, Journal of Molecular Biology 48(3): 443-53), which is available at http: / / www.ebi.ac.uk / Tools / psa / and can be performed using default parameters. Local alignment can be performed using BLAST (Basic Local Alignment Search Tool), first described in Altschul et al. (1990) J. Mol. Biol. 215; 403. Biol. 215; 403-410. The BLAST alignment tool is available from the website of the National Center for Biotechnology Information (http: / / www.ncbi.nlm.nih.gov / / ), and default parameters can be used for alignment, for example.

[0189] The term "vector" refers to a tool that allows or facilitates the transfer of nucleic acid fragments from one environment to another (such as engineered bacteria). Vectors allow the insertion of another nucleic acid fragment to achieve replication of the inserted fragment.

[0190] The term "expression vector" refers to a vector used to express a gene product, which typically includes one or more expression control sequences for controlling and regulating the transcription and / or translation of a gene sequence that can express the product.

[0191] The term "expression cassette" refers to a nucleotide sequence containing relevant nucleic acids that are controlled by and operatively linked to appropriate promoters or other regulatory elements to enable transcription of the relevant nucleic acids in engineered bacteria.

[0192] The term "transcription unit" refers to a nucleic acid sequence containing one or more genes to be transcribed. Genes within a transcription unit are operatively linked to each other in a manner such that all genes within the unit are under the transcriptional control of the same promoter and / or enhancer, thereby enabling the transcription of more than one protein or product.

[0193] The term "operable linking" refers to placing a regulatory sequence necessary for the expression of a coding sequence in the appropriate position within the DNA molecule relative to the coding sequence, thereby affecting the expression of the coding sequence.

[0194] The term "knockout" refers to the manipulation of genes to prevent cells or organisms from producing the functional products encoded by those genes.

[0195] The term "knockdown" refers to the process of manipulating genes to reduce the functional activity of functional products encoded by said genes produced by cells or organisms.

[0196] The term "eliminating or weakening the effect of an enzyme" means that the reaction catalyzed by the enzyme is eliminated or weakened, which can be specifically manifested as the absence of reaction products catalyzed by the enzyme or a reduction in the amount of products generated by the reaction catalyzed by the enzyme.

[0197] The term "enhancing enzyme action" refers to the enhancement of the reaction catalyzed by the enzyme, which can be specifically manifested as an increase in the amount of product generated by the reaction catalyzed by the enzyme.

[0198] The term "enzyme activity" refers to the ability of an enzyme to catalyze the conversion of a substrate into a product, which can be evaluated by the amount of product produced.

[0199] The term "overexpression" refers to the expression level of a gene product or peptide in engineered bacteria that is higher after genetic modification than before the modification. "Overexpression" can also refer to any detectable expression caused by introducing a specific gene product into the engineered bacteria if the bacteria did not contain the specific gene product before modification.

[0200] The term "natural promoter" refers to the promoter of a gene that is naturally present in engineered bacteria.

[0201] The term "homological protein" refers to a protein that has similar activity and / or similar structure to a protein of interest (e.g., a reference protein). In some embodiments, the sequence identity of the homologous protein to the reference protein is at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%.

[0202] The term "acetyl-CoA transferase," also known as "acetoacetyl-CoA thiolysis enzyme," refers to the enzyme that catalyzes the conversion of acetyl-coenzyme A (acetyl-CoA) to acetoacetyl-CoA. In yeast, the acetyl-CoA transferase can be referred to as ERG10.

[0203] The term "3-methyl-3-hydroxyglutaryl-CoA synthase," also known as "hydroxymethylglutaryl-CoA synthase" or "3-hydroxy-3-methylglutary-CoA synthase (HMGS)," refers to the enzyme that catalyzes the synthesis of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) from acetoacetyl-CoA. In yeast, the 3-methyl-3-hydroxyglutaryl-CoA synthase can be referred to as ERG13.

[0204] The term "3-hydroxy-3-methylglutaryl-CoA reductase," also known as "hydroxymethylglutaryl-CoA reductase (HMGR)," and referred to herein as "untruncated 3-hydroxy-3-methylglutaryl-CoA reductase," refers to the enzyme that catalyzes the production of mevalonic acid (MVA) from 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA). In yeast, the 3-hydroxy-3-methylglutaryl-CoA reductase may be referred to as HMG1.

[0205] The term "mevalonate kinase," also known as "MK," refers to the enzyme that catalyzes the conversion of mevalonate (MVA) to mevalonate phosphate (MVAP). In yeast, mevalonate kinase is referred to as ERG12.

[0206] The term "mevalonate-5-phosphokinase," also known as "phosphomevalonate kinase (PMK)," refers to the enzyme that catalyzes the conversion of mevalonate phosphate (MVAP) to mevalonate pyrophosphate (MVAP). In yeast, mevalonate-5-phosphokinase can also be referred to as ERG8.

[0207] The term "5-pyrophosphate decarboxylase," also known as "pyrophosphate decarboxylase (MDC)," refers to the enzyme that catalyzes the conversion of mevalonic acid pyrophosphate (MVAP) to isopentenyl pyrophosphate (IPP). In yeast, 5-pyrophosphate decarboxylase can also be referred to as ERG19 or MVD1.

[0208] The term "pentene pyrophosphate isomerase," also known as "isopentenyldiphosphate isomerase (IDI)," refers to the enzyme that catalyzes the formation of dimethylallyl diphosphate (DMAPP) from isopentenyl pyrophosphate (IPP), or vice versa. In yeast, the pentenene pyrophosphate isomerase can also be referred to as IDI1.

[0209] The term "farnesyl pyrophosphate synthase," also known as "farnesyl pyrophosphate synthase (FPS / ERG20)," refers to the enzyme that catalyzes the production of farnesyl diphosphate (FPP) from IPP and DMAPP. In yeast, farnesyl pyrophosphate synthase can also be referred to as ERG20.

[0210] The term "geranylgeranyl pyrophosphate synthase," also known as "geranylgeranyl diphosphate synthase (GGPPS)," refers to the enzyme that catalyzes the conversion of farnesyl diphosphate (FPP) to geranylgeranyl diphosphate (GGPP). In yeast, geranylgeranyl pyrophosphate synthase can also be referred to as BTS1 or GGPPS.

[0211] The term "lysandrin diol pyrophosphate synthase" refers to the enzyme that catalyzes the conversion of geranylgeranyl diphosphate (GGPP) to lysandrin diol pyrophosphate (LPP). Lysandrin diol pyrophosphate synthase in yeast can also be referred to as LPPS.

[0212] It should be understood that for enzymes with specific activities, the sequences of homologous proteins in different organisms (including different species or different strains of the same species) are readily available to those skilled in the art, for example, by searching public databases (e.g., GenBank).

[0213] Enzymes and their encoding genes with the same biological activity are known in the art to have different names, sometimes related to the microorganism from which the enzyme originates. The enzymes described herein are intended to cover enzymes with the defined functions, and unless otherwise stated, should cover enzymes with the defined functions from any organism (including microorganisms, animals, etc.).

[0214] In this invention, it should be understood that when an abbreviation is shown in parentheses after the name of an enzyme, the abbreviation should not be regarded as a limitation on a specific sequence or specific source of the enzyme, but is merely an example for reference and understanding.

[0215] Unless otherwise stated, nucleic acids are written from left to right in the 5' to 3' direction in this document, and amino acid sequences are written from left to right in the direction from the amino terminus to the carboxyl terminus.

[0216] To further illustrate the technical means and effects of this invention, the following description, in conjunction with embodiments and accompanying drawings, provides a further explanation of the invention. It is understood that the specific embodiments described herein are merely illustrative of the invention and not intended to limit it.

[0217] Where specific techniques or conditions are not specified in the examples, they shall be performed in accordance with the techniques or conditions described in the literature in this field, or in accordance with the product instructions. Reagents or instruments whose manufacturers are not specified are all conventional products that can be purchased through legitimate channels.

[0218] Example 1 This embodiment provides a method for culturing brewer's yeast and a method for detecting the product.

[0219] (1) Cultivation method The strain was cultured using two different culture media: seed medium LGM1 and fermentation medium LGM2.

[0220] The seed culture medium LGM1 is based on LGM medium with 20 g / L glucose added. The LGM medium consisted of the following components: ammonium sulfate 15 g / L, potassium dihydrogen phosphate 8 g / L; magnesium sulfate heptahydrate 6.15 g / L; biotin 0.05 g / L; calcium pantothenate 1 g / L; nicotinic acid 1 g / L; inositol 25 g / L; thiamine hydrochloride 1 g / L; pyridoxal hydrochloride 1 g / L; para-aminobenzoic acid 0.2 g / L; zinc sulfate heptahydrate 0.0575 g / L; manganese chloride tetrahydrate 0.0032 g / L; copper sulfate pentahydrate 0.0032 g / L; cobalt chloride hexahydrate 0.0047 g / L; sodium molybdate dihydrate 0.0048 g / L; ferrous sulfate heptahydrate 0.028 g / L; calcium chloride dihydrate 0.029 g / L; 0.5 M EDTA (80 mL / L); succinic acid 5.9 g / L, adjusted to pH 6.0.

[0221] The fermentation medium LGM2 is based on LGM medium with 40 g / L glucose added.

[0222] The seed culture medium and fermentation medium were sterilized by autoclaving (121℃, 20 min). An additional 2% agar was added to the medium when preparing solid plates.

[0223] When performing plate fermentation, colonies from the bacterial strain were picked from the plate and transferred to a 96-well plate containing seed medium. After incubation at 30°C, 900 rpm, and 80% humidity for 48 h, a 5% inoculum was added to a 96-well plate containing fermentation medium. The plates were then incubated at 30°C, 900 rpm, and 80% humidity for another 48 h. An appropriate amount of ethyl acetate was added to the sample in the plate, and the mixture was vigorously shaken for 30 min before centrifugation. A suitable amount of supernatant was collected to determine the titer of the cultured product.

[0224] (2) Detection of product titer Analysis was performed on an Agilent GC8890 gas chromatograph equipped with an Agilent HP-5 capillary column (30.0 m × 0.32 mm × 0.25 μm). The sample injection volume was 1 μL, the split ratio was 50:1, the air flow rate was 300 mL / min, the hydrogen flow rate was 30 mL / min, and the carrier gas flow rate was 25 mL / min. The injector and FID detector temperatures were set to 280 °C and 300 °C, respectively. The gas flow rate through the column was set to 2 mL / min for the first 3 min and 3 mL / min for the next 1.675 min. The initial column temperature was maintained at 150 °C for 1.5 min, increased to 230 °C at a rate of 20 °C / min, held for 1 min, and then increased to 300 °C at a rate of 60 °C / min, held for 2 min. Quantification was performed using the internal standard method. A standard curve was established based on the gas chromatography to determine the concentration of lysine diol in the intact culture medium.

[0225] Example 2 This embodiment constructs a background yeast strain for producing lysine diol.

[0226] This invention uses the wild-type yeast strain CEN.PK2-1C (purchased from Euroscarf) as the starting strain for the production of lysenoside diol. CRISPR-Cas9-mediated genome editing is a commonly used synthetic biology tool in Saccharomyces cerevisiae. The CRISPR-Cas9 method was used to integrate key enzymes in the lysenoside diol biosynthesis pathway into the genome. One copy of the farnesyl pyrophosphate synthase gene ERG20 (amino acid sequence SEQ ID NO.1, nucleotide sequence SEQ ID NO.227) and one copy of a truncated 3-hydroxy-3-methylglutaryl-CoA reductase tHMG1 (amino acid sequence SEQ ID NO.2, nucleotide sequence SEQ ID NO.228) were inserted at the lpp1 site in the genome. The gRNA-N20 sequence used was ATGTAAAACTGACGTTCGAA (SEQ ID NO.454), and the corresponding gRNA-1 plasmid was constructed. One copy of acetyl-CoA transferase ERG10 (amino acid sequence SEQ ID NO.3, nucleotide sequence SEQ ID NO.229) and one copy of 3-methyl-3-hydroxyglutaryl-CoA synthase ERG13 (amino acid sequence SEQ ID NO.4, nucleotide sequence SEQ ID NO.230) were inserted at the dpp1 site, using the gRNA-N20 sequence CCAGGGATATCTCCGAATAG (SEQ ID NO.455) to construct the corresponding gRNA-2 plasmid. One copy of mevalonate kinase ERG12 (amino acid sequence SEQ ID NO.5, nucleotide sequence SEQ ID NO.231) and one copy of mevalonate-5-phosphate kinase ERG8 (amino acid sequence SEQ ID NO.6, nucleotide sequence SEQ ID NO.232) were inserted at the ho site on the genome, using the gRNA-N20 sequence GCCGGCTTGATCGACTCAGA (SEQ ID NO.456) to construct the corresponding gRNA-3 plasmid. One copy of mevalonate-5-pyrophosphate decarboxylase ERG19 (amino acid sequence SEQ ID NO.7, nucleotide sequence SEQ ID NO.233) and one copy of isopentenyl pyrophosphate isomerase IDI1 (amino acid sequence SEQ ID NO.8, nucleotide sequence SEQ ID NO.234) were inserted at the gal80 site on the genome. The gRNA-N20 sequence used was ATAAGGCTGCTGCTGAACGT (SEQ ID NO.457), and the corresponding gRNA-4 plasmid was constructed.

[0227] Donor plasmids were constructed as follows: pYC1 containing the complete expression cassettes of ERG20 and tHMG1 and homologous arms upstream and downstream of the integration site lpp1; pYC2 containing the complete expression cassettes of ERG10 and ERG13 and homologous arms upstream and downstream of the integration site dpp1; pYC3 containing the complete expression cassettes of ERG12 and ERG8 and homologous arms upstream and downstream of the integration site ho; and pYC4 containing the complete expression cassettes of ERG19 and IDI1 and homologous arms upstream and downstream of the integration site gal80. Using the CEN.PK2-1C genome as a template, the required fragments were amplified using primers (see Table 1). After gel recovery using the Tiangen Gel Recovery Kit, these fragments were ligated into the linearized backbone fragment of the expression vector pUC19 digested with HindIII using the Novizan ClonExpress Multis One Step Cloning Kit (Vazyme, catalog number: C113-02) via homologous recombination. The reaction system and conditions were performed according to the kit instructions. After seamless assembly, Trans1 T1 competent cells were transformed. After sequencing confirmation, donor plasmids pYC1, pYC2, pYC3, and pYC4 were obtained.

[0228] Table 1. Fragments, primers, and primer sequences required for vector construction in Example 2.

[0229] Using primers PF1 / PR7 and plasmid pYC1 as a template, the Donor 1 fragment was amplified. This fragment, along with plasmids containing Cas9 and gRNA-1, was then transformed into competent cells of yeast strain CEN.PK2-1C using the PEG / LiAC method, yielding strain YC1. Next, using primers PF8 / PR14 and plasmid pYC2 as a template, the Donor 2 fragment was amplified. This fragment, along with plasmids containing Cas9 and gRNA-2, was then transformed into competent cells of yeast strain YC1 using the PEG / LiAC method, yielding strain YC2. Finally, using primers PF15 / PR21 and plasmid pYC3 as a template, the Donor 3 fragment was amplified. This fragment, along with plasmids containing Cas9 and gRNA-3, was then transformed into competent cells of yeast strain YC2 using the PEG / LiAC method, yielding strain YC3. Using primers PF22 / PR28 and plasmid pYC4 as a template, the Donor4 fragment was amplified and transformed into competent cells of yeast strain YC3 via PEG / LiAC method, along with plasmids containing Cas9 and gRNA-4, to obtain strain YC4.

[0230] Example 3 This embodiment constructs a lysine diol synthesis carrier. (1) Preparation of target gene The geraniol geraniol pyrophosphate synthase gene BTS1, derived from Saccharomyces cerevisiae and provided by NCBI, was selected. Its amino acid sequence is shown in SEQ ID NO.9 and its nucleotide sequence is SEQ ID NO.235. It can be directly amplified from the Saccharomyces cerevisiae genome.

[0231] Selected from sage (sweet citrus) provided by NCBI Salvia sclarea The amino acid sequence of the SsLPPS gene (GenBank accession number: JQ478434.1), encoding lysine pyrophosphate diol ester synthase, was obtained by removing the signal peptide sequence of the first 63 amino acids, as shown in SEQ ID NO. 10. After codon optimization, the gene was synthesized using Genewiz, and its nucleotide sequence is shown in SEQ ID NO. 236. This nucleotide sequence was then inserted into the plasmid pUC-GW-kan (purchased from Genewiz) to obtain the plasmid pUC-GW-kan-tSsLPPS. As provided in the exemplary lysine-2-diol biosynthesis pathway ( Figure 1 Labdenediol pyrophosphate (LPP) is a direct precursor for the production of the target product, Labdenediol. Therefore, this invention aims to discover effective phosphorylases to dephosphate LPP and generate Labdenediol. Twenty-six phosphorylases derived from *Saccharomyces cerevisiae* (Saccharomyces cerevisiae) provided by NCBI were selected, with amino acid sequences as shown in SEQ ID NO. 11-216 and nucleotide sequences as shown in SEQ ID NO. 237-442. In addition to endogenous phosphorylases from *Saccharomyces cerevisiae*, enzyme genes from other species were also selected, including those derived from... Escherichia coli Phosphatidylglycerol phosphatase PgpA (amino acid sequence SEQ ID NO. 217), phosphatidylglycerol phosphatase PgpB (amino acid sequence SEQ ID NO. 218), phosphatidylglycerol phosphatase PgpC (amino acid sequence SEQ ID NO. 219), carbapenyl bisphosphatase YbjG (amino acid sequence SEQ ID NO. 220), and phosphatidylglycerol phosphatase derived from K12 Homo sapiens The dihydroxy diphosphatase DOLPP1 (amino acid sequence SEQ ID NO. 221) and phosphatase PLPP6 (amino acid sequence SEQ ID NO. 222) are derived from... Bacillus subtilis The farnesyl diphosphatase YisP (amino acid sequence SEQ ID NO. 223), or derived from... Phyllostachys edulis Farnesol synthase TPS2 (amino acid sequence SEQ ID NO. 224), or derived from...Zea mays The noncyclic sesquiterpene synthase TPS1 (amino acid sequence SEQ ID NO. 225), or derived from... Oryza sativa subsp. japonica The farnesol synthase TPS13 (amino acid sequence SEQ ID NO. 226) was synthesized using Genewiz after codon optimization. Its nucleotide sequence is shown in SEQ ID NO. 443~SEQ ID NO. 452. This synthesized enzyme was then inserted into plasmid pUC-GW-kan (purchased from Genewiz) to obtain plasmids pUC-GW-kan-PgpA, pUC-GW-kan-PgpB, pUC-GW-kan-PgpC, pUC-GW-kan-YbjG, pUC-GW-kan-DOLPP1, pUC-GW-kan-PLPP6, pUC-GW-kan-YisP, pUC-GW-kan-TPS2, pUC-GW-kan-TPS1, and pUC-GW-kan-TPS13.

[0232] (2) Construction of recombinant plasmid for the synthesis of lysine-3-enediol This invention integrates the geraniol pyrophosphate synthase gene BTS1 into the dit1 site of the genome, using the gRNA-N20 sequence AAAGATACTCGTTTCGATAT (SEQ ID NO. 514). The truncated lysine pyrophosphate diol ester synthase encoding gene tSsLPPS is integrated into the gal2 site of the genome, using the gRNA-N20 sequence ATCCCCACGTTATTTATGTG (SEQ ID NO. 515). Candidate phosphatases are integrated into the adh5 site of the genome, using the gRNA-N20 sequence TCCAACACAAGATCCAACGA (SEQ ID NO. 516). The gRNA expression cassettes required for these three integration sites are sequentially tandemly constructed into the same vector, ultimately obtaining a tandem gRNA plasmid capable of editing three sites (dit1, gal2, and adh5) at once, named pYC-3gRNA. The nucleotide sequence of this recombinant plasmid is shown in SEQ ID NO. 453.

[0233] First, using the genome of Saccharomyces cerevisiae CEN.PK2-1C as a template, PCR amplification was performed using specific gene primers for PF29 / PR29, PF30 / PR30, PF31 / PR31, PF32 / PR32, and PF33 / PR33 (PCR system using 2×Phanta MaxMaster Mix, (Dye Plus), Vazyme). The upstream homologous arm dit1-US, promoter pGAL1 fragment, geranylgeranyl pyrophosphate synthase gene BTS1 fragment, terminator T-BTS1 fragment, and downstream homologous arm dit1-DS of the dit1 integration site were obtained. After gel recovery using the Tiangen Gel Recovery Kit, these fragments were ligated into the linearized backbone fragment of the expression vector pUC19 digested with HindIII. The ligation was performed using the Novizan ClonExpressMultis One Step Cloning Kit (Vazyme, catalog number: C113-02), following the kit's instructions. After seamless assembly, the cells were transformed into Trans1 T1 competent cells. Following sequencing confirmation, a donor plasmid containing the complete BTS1 expression cassette and the upstream and downstream homologous arms of the integration site dit1 was obtained and named pYC5.

[0234] Using plasmid pUC-GW-kan-tSsLPPS as a template, PCR amplification was performed using primer pair PF36 / PR36 (PCR system: 2×Phanta Max Master Mix, (Dye Plus), Vazyme) to obtain a truncated SsLPPS fragment encoding the lysine pyrophosphate synthase gene. Using *Saccharomyces cerevisiae* CEN.PK2-1C as a template, PCR amplification was performed using specific gene primer pairs PF34 / PR34, PF35 / PR35, PF37 / PR37, and PF38 / PR38, respectively, to obtain the upstream homologous arm fragment gal2-US, the promoter pGAL1 fragment, the terminator tADH1 fragment, and the downstream homologous arm fragment gal2-DS of the gal2 integration site. These fragments were recovered using a Tiangen gel extraction kit and ligated into the HindIII-digested linearized vector pUC19, followed by seamless assembly and transformation into Trans1 T1 competent cells. After sequencing confirmed that there were no errors, a donor plasmid containing the complete tSsLPPS expression cassette and the upstream and downstream homologous arms of the integration site gal2 was obtained and named pYC6.

[0235] Construction of candidate phosphatase gene donor plasmids (as shown in the schematic diagram) Figure 3As shown, candidate phosphatolases were integrated into the adh5 site on the genome. Using the *Saccharomyces cerevisiae* CEN.PK2-1C genome as a template, PCR amplification was performed using specific gene primers PF39 / PR39, PF40 / PR40, PF41 / PR41, and PF42 / PR42, respectively, to obtain the upstream homologous arm fragment adh5-US, the promoter pGAL1 fragment, the terminator tPGK1 fragment, and the downstream homologous arm fragment adh5-DS of the integration site adh5. For the construction of recombinant plasmids of endogenous candidate phosphatolases (i.e., SEQ ID NO. 237~442) in *Saccharomyces cerevisiae*, gene fragments were obtained by amplification using the *Saccharomyces cerevisiae* CEN.PK2-1C genome as a template. For the construction of recombinant plasmids for exogenous phosphorylase candidate enzymes, plasmids pUC-GW-kan-PgpA, pUC-GW-kan-PgpB, pUC-GW-kan-PgpC, pUC-GW-kan-YbjG, pUC-GW-kan-DOLPP1, pUC-GW-kan-PLPP6, pUC-GW-kan-YisP, pUC-GW-kan-TPS2, pUC-GW-kan-TPS1, and pUC-GW-kan-TPS13 were used as templates for amplification to obtain exogenous candidate phosphorylase gene fragments (i.e., SEQ ID NO.443~452). After gel recovery of the above fragments using the Tiangen Gel Recovery Kit, the upstream and downstream homologous arm fragments adh5-US and adh5-DS, the promoter fragment pGAL1, and the terminator fragment tPGK1 were ligated, respectively, with 216 different phosphorylase gene fragments into the HindIII-digested linearized vector pUC19. Homologous recombination was then performed using the Novizan Seamless Assembly Kit (ClonExpress Multis One Step Cloning Kit, Vazyme, catalog number: C113-02). The reaction system and conditions were performed according to the kit instructions. After seamless assembly, Trans1 T1 competent cells were transformed. After sequencing confirmation, donor plasmids containing complete expression cassettes of different phosphorylases and the integration site adh5 upstream and downstream homologous arms were obtained and named pYC7~pYC222, respectively.

[0236] Table 2 Primers and their sequences required for Example 3

[0237] Example 4 This embodiment constructs a strain of lysine diol synthesizing bacteria and a well plate fermentation.

[0238] Using primers PF29 / PR33 and plasmid pYC5 as a template, the Donor5 fragment, namely dit1-US-pGAL1-BTS1-T-BTS1-dit1-DS, was amplified; using plasmid pYC6 as a template, the Donor6 fragment, namely gal2-US-pGAL1-tSsLPP1-tADH1-gal2-DS, was amplified; and using plasmids pYC7 to pYC222 as templates, 216 Donor DNA fragments containing different candidate phosphorylase expression cassettes, namely adh5-US-pGAL1-Phosphohydrolase-tPGK1-adh5-DS, were amplified and named Donor7 to Donor222, respectively. Donor7~Donor222, along with Donor5 fragment, Donor6 fragment, plasmid containing Cas9, and pYC-3gRNA plasmid, were transformed into competent cells of yeast strain YC4 using the PEG / LiAC method to obtain strains YC5~YC220.

[0239] After the above-mentioned strains YC5~YC220 were cultured in well plates and fermented according to Example 1, the samples were analyzed by gas chromatography. The gas chromatogram of the lysine diol standard is shown below. Figure 4 As shown, the peak time of lysine diol was 6.080 min. After analysis of the fermentation samples, 36 strains were found to have a peak at 6.080 min. Taking the gas chromatogram of sample strain YC6 as an example (…), Figure 5 It was inferred that the product lysantandrindiol had been formed, with a maximum concentration of 120 mg / L. Further mass spectrometry identification confirmed it as the target product lysantandrindiol. Figure 6 This indicates the successful discovery of an effective phosphorylase capable of converting the precursor lysandrindiol pyrophosphate (LPP) into the target product, lysandrindiol. Information on phosphorylases capable of successfully converting LPP to lysandrindiol is listed in Table 3. The specific family classifications of these phosphorylases are listed in Table 4.

[0240] Table 3. Fermentation levels of lysine-containing plate-grown phosphorylase strains

[0241] Table 4. Classification of Phosphohydrolases

[0242] The sequence used in the example: SEQ ID NO.1, ERG20 derived from Saccharomyces cerevisiae( Saccharomycescerevisiae ) with amino acid sequence MASEKEIRRERFLNVFPKLVEELNASLLAYGMPKEACDWYAHSLNYNTPGGKLNRGLSVVDTYAILSNKTVEQLGQEEYEKVALIGWCIELLQAYFLVADDMMDKSITRRGQPCWYKVPEVGEIINDAFMLEAAIYKLLKSHFRNEKYYIDITELFHEVTFQTELGQLMDLITAPEDKVDLSKFSLKKHSFIVTFKTAYYSFYLPVALAMYVAGITDEKDLKQARDVLIPLGEYFQIQDDYLDCFGTPEQIGKIGTDIQDNKCSWVINKALELASAEQRKTLDENYGKKDSVAEAKCKIFNDLKIDQLYHEYEESVAKDLKAKISQVDESRGFKADVLTAFLNKVYKRSK SEQ ID NO.2, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae) Saccharomyces cerevisiae tHMG1, amino acid sequence Column MAADQLVKTEVTKKSFTAPVQKASTPVLTNKTVISGSKVKSLSSAQSSSSGPSSSSEEDDSRDIESLDKKIRPLEELEALLSSGNTKQLKNKEVAALVIHGKLPLYALEKKLGDTTRAVAVRRKALSILAEAPVLASDRLPYKNYDYDRVFGACCENVIGYMPLPVGVIGPLVIDGTSYHIPMATTEGCLVASAMRGCCKAINAGGGATTVLTKDGMTRGPVVRFPTLKRSGACKIWLDSEEGQNAIKKAFNSTSRFARLQHIQTCLAGDLLFMRFRTTTGDAMGMNMISKGVEYSLKQMVEEYGWEDMEVVSVSGNYCTDKKPAAINWIEGRGKSVVAETATIPGDVVRKVLKSDVSALVELNIAKNLVGSAMAGSVGGFNAHAANLVTAVFLALGQDPAQNVESSNCITLMKEVDGDLRISVSMPSIEVTGGGTVLEPQGAMLDLLGVRGPHATAPGTNARQLARIVACAVLAGELSLCAALAAGHLVQSHMTHNRKPAEPTKPNNLDATDINRLKDGSVTCIKS SEQ ID NO.3, derived from brewer's yeast ( Saccharomyces cerevisiae ERG10, amino acid sequence Column MSQNVYIVSTARTPIGSFQGSLSSKTAVELGAVALKGALAKVPELDASKDFDEIIFGNVLSANLGQAPARQVALAAGLSNHIVASTVNKVCASAMKAIILGAQSIKCGNADVVVAGGCESMTNAPYYMPAARAGAKFGQTVLVDGVERDGLNDAYDGLAMGVHAEKCARDWDITREQQDNFAIESYQKSQKSQKEGKFDNEIVPVTIKGFRGKPDTQVTKDEEPARLHVEKLRSARTVFQKENGTVTAANASPINDGAAAVILVSEKVLKEKNLKPLAIKGWGEAAHQPADFTWAPSLAVPKALKHAGIEDINSVDYFEFNEAFSVVGLVNTKILKLDPSKVNVYGGAVALGHPLGCSGARVVVTLLSILQQEGGKIGVAAICNGGGGASSIVIEKI SEQ ID NO.4, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae ERG13, amino acid sequenceColumn MKLSTKLCGIKGRLRPQKQQQLHNTNLQMTELKKQKTAEQKTRPQNVGIKGIQIYIPTQCVNQSELEKFDGVSQGKYTIGLGQTNMSFVNDREDIYSMSLTVLSKLIKSYNIDTNKIGRLEVGTETLIDKSKSVKSVLMQLFGENTDVEGIDTLNACYYGGTNALFNSLNWIESNAWDGRDAIVVCGDIAIYDKGAARPTGGAGTVAMWIGPDAPIVFDSVRASYMEHAYDFYKPDFTSEYPYVDGHFSLTCYVKALDQVYKSYSKKAISKLVSDPAGSDALNVLKYFDYNVFHVPTCKLVTKSYGRLLYNDFRANPQLFPEVDAELATRDYDESLTDKNIEKTFVNVAKPFHKERVAQSLIVPTNTGNMYTASVYAAFASLLNYVGSDDLQGKRVGLFSYGSGLAASLYSCKIVGDVQHIIKELDITNKLAKRITETPKDYEAAIELRENAHLKKNFKPQGSIEHLQSGVYYLTNIDDKFRRSYDVKK SEQ ID NO.5, derived from Saccharomyces cerevisiae (Saccharomyces cerevisia Saccharomyces cerevisiae ERG12, amino acid sequence Column MSLPFLTSAPGKVIIFGEHSAVYNKPAVAAASVSALRTYLLISESSAPDTIELDFPDISFNHKWSINDFNAITEDQVNSQKLAKAQQATDGLSQELVSLLDPLLAQLSESFHYHAAFCFLYMFVCLCPHAKNIKFSLKSTLPIGAGLGSSASISVSLALAMAYLGGLIGSNDLEKLSENDKHIVNQWAFIGEKCIHGTPSGIDNAVATYGNALLFEKDSHNGTINTNNFKFLDDFPAIPMILTYTRIPRSTKDLVARVRVLVTEKFPEVMKPILDAMGECALQGLEIMTKLSKCKGTDDEAVETNNELYEQLLELIRINHGLLVSIGVSHPGLELIKNLSDDLRIGSTKLTGAGGGGCSLTLLRRDITQEQIDSFKKKLQDDFSYETFETDLGGTGCCLLSAKNLNKDLKIKSLVFQLFENKTTTKQQIDDLLLPGNTNLPWTS SEQ ID NO.6, derived from brewer's yeast ( Saccharomyces cerevisiae ERG8, amino acid sequence MSELRAFSAPGKALLAGGYLVLDPKYEAFVVGLSARMHAVAHPYGSLQESDKFEVRVKSKQFKDGEWLYHISPKTGFIPVSIGGSKNPFIEKVIANVFSYFKPNMDDYCNRNLFVIDIFSDDAYHSQEDSVTEHRGNRRLSFHSHRIEEVPKTGLGSSAGLVTTALASFFVSDLENNVDKYREVIHNLSQVAHCQAQGKIGSGFDVAAAAYGSIRYRRFPPALISNLPDIGSATYGSKLAHLVNEEDWNITIKSNHLPSGLTLWMGDIKNGSETVKLVQKVKNWYDSHMPESLKIYTELDHANSRFMDGLSKLDRLHETHDDYSDQIFESLERNDCTCQKYPEITEVRDAVATIRRSFRKITKESGADIEPPVQTSLLDDCQTLKGVLTCLIPGAGGYDAIAVIAKQDVDLRAQTADDKRFSKVQWLDVTQADWGVRKEKDPETYLDK SEQ ID NO.7, derived from Saccharomyces cerevisiae (Saccharomyces cerevisia Saccharomyces cerevisiae ERG19, amino acid sequence Column MTVYTASVTAPVNIATLKYWGKRDTKLNLPTNSSISVTLSQDDLRTLTSAATAPEFERDTLWLNGEPHSIDNERTQNCLRDLRQLRKEMESKDASLPTLSQWKLHIVSENNFPTAAGLASSAAGFAALVSAIAKLYQLPQSTSEISRIARKGSGSACRSLFGGYVAWEMGKAEDGHDSMAVQIADSSDWPQMKACVLVVSDIKKDVSSTQGMQLTVATSELFKERIEHVVPKRFEVMRKAIVEKDFATFAKETMMDSNSFHATCLDSFPPIFYMNDTSKRIISWCHTINQFYGETIVAYTFDAGPNAVLYYLAENESKLFAFIYKLFGSVPGWDKKFTTEQLEAFNHQFESSNFTARELDLELQKDVARVILTQVGSGPQETNESLIDAKTGLPKE SEQ ID NO.8, derived from brewer's yeast ( Saccharomyces cerevisiae IDI1, amino acid sequence MTADNNSMPHGAVSSYAKLVQNQTPEDILEEFPEIIPLQQRPNTRSSETSNDESGETCFSGHDEEQIKLMNENCIVLDWDDNAIGAGTKKVCHLMENIEKGLLHRAFSVFIFNEQGELLLQQRATEKITFPDLWTNTCCSHPLCIDDELGLKGKLDDKIKGAITAAVRKLDHELGIPEDETKTRGKFHFLNRIHYMAPSNEPWGEHEIDYILFYKINAKENLTVNPNVNEVRDFKWVSPNDLKTMFADPSYKFTPWFKIICENYLFNWWEQLDDLSEVENDRQIHRML SEQ ID NO.9, derived from Saccharomyces cerevisiae (Saccharomyces cerevisia Saccharomyces cerevisiae BTS1, amino acid sequence MEAKIDELINNDPVWSSQNESLISKPYNHILLKPGKNFRLNLIVQINRVMNLPKDQLAIVSQIVELLHNSSLLIDDIEDNAPLRRGQTTSHLIFGVPSTINTANYMYFRAMQLVSQLTTKEPLYHNLITIFNEELINLHRGQGLDIYWRDFLPEIIPTQEMYLNMVMNKTGGLFRLTLRLMEALSPSSHHGHSLVPFINLLGIIYQIRDDYLNLKDFQMSSEKGFAEDITEGKLSFPIVHALNFTKTKGQTEQHNEILRILLLRTSDKDIKLKLIQILEFDTNSLAYTKNFINQLVNMIKNDNENKYLPDLASHSDTATNLHDELLYIIDHLSEL SEQ ID NO.10, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae tSsLPPS, amino acids Sequence MASQASEKDISLVQTPHKVEVNEKIEESIEYVQNLLMTSGDGRISVSPYDTAVIALIKDLKGRDAPQFPSCLEWIAHHQLADGSWGDEFFCIYDRILNTLACVVALKSWNLHSDIIEKGVTYIKENVHKLKGANVEHRTAGFELVVPTFMQMATDLGIQDLPYDHPLIKEIADTKQQRLKEIPKDLVYQMPTNLLYSLEGLGDLEWERLLKLQSGNGSFLTSPSSTAAVLMHTKDEKCLKYIENALKNCDGGAPHTYPVDIFSRLWAIDRLQRLGISRFFQHEIKYFLDHIESVWEETGVFSGRYTKFSDIDDTSMGVRLLKMHGYDVDPNVLKHFKQQDGKFSCYIGQSVESASPMYNLYRAAQLRFPGEEVLEEATKFAFNFLQEMLVKDRLQERWVISDHLFDEIKLGLKMPWYATLPRVEAAYYLDHYAGSGDVWIGKSFYRMPEISNDTYKELAILDFNRCQTQHQLEWIHMQEWYDRCSLSEFGISKRELLRSYFLAAATIFEPERTQERLLWAKTRILSKMITSFVNISGTTLSLDYNFNGLDEIISSANEDQGLAGTLLATFHQLLDGFDIYTLHQLKHVWSQWFMKVQQGEGSGGEDAVLLANTLNICAGLNEDVLSNNEYTALSTLTNKICNRLAQIQDNKILQVVDGSIKDKELEQDMQALVKLVLQENGGAVDRNIRHTFLSVSKTFYYDAYHDDETTELHIFKVLFRPVV SEQ ID NO.11, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae ADR1, amino acid sequence Column SEQ ID NO.12, derived from Saccharomyces cerevisiae (Saccharomyces cerevi Saccharomyces cerevisiae APP1, amino acid sequence Column MNSQGYDESSSSTAATSGPTSGDPRMGKKQRFMNLIRTTKDVYIPNLTSSISQKTMDGIRSTTNSFEGYNDLPMELPHNTTITYFPTYTTTNLVDPDGLSAPRKDFETTVRCAVSYPGNPTSRRNRWLLSLCKQYLRTGTAEADVAPVVPPHLEEDSGDLNDSQSSIESSLSSKSENRYSHMGIQEEDVLNERIQGFLSKKVPNTPVVVDLLPKDKLRGDTASFFGTTDSYGNLLIKAETDFLPSKINITLDTPIEGHADPISETFPANYVSPYGIGLISDIDDTIKHTGVTGDRRSMFRNVFIHDVQSWVIDGVPLWYKTLHDVADVDFFYVSNSPIQTFTLLKQYICANFPPGPIFLKQYSGNFFSTIMTSSANRKIQPIANILKDFPKKKFILVGDSGEHDLEAYTTTALQFPNQILAIYIRCCSNSMSDVPSHDEEVMNEVNNIIELQQRPMQMTKSTVRTRRRPPPPPIPSTQKPSLTEEQTESIRMSRRNKDENNTKRVAPPPLPNRQLPNLDANTYYVPSSQNDYGMYGAFMDKKADEWKRRVMDSIQKLSNQDTTLMFFSDPALSLEDSIRRIREKYSN SEQ ID NO.13, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae ARR2, amino acid sequence Column MVSFITSRQLKGLIENQRKDFQVVDLRREDFARDHITNAWHVPVTAQITEKQLNQLIKGLSDTFSSSQFVKVIFHCTGSKNRGPKVAAKFETYLQEEDITSKFESCILVGGFYAWETHCRESNLKLIVSG SEQ ID NO.14, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae BNI4, amino acid sequence ColumnMSDSVSDSKSSELLNSTFYSTSINTLDHARTFRNSLILKEISGQSLNSSIKPCESVLDRDVESSVLQRSFGDSNARDSEVQTVNMTTSPSLSALADILNERSKYADQKTRKAQNIESSIIEEEEEEAEEQNNSINYEDITGSRLSVREDANENLAMTSPNLIDIDGSNSIQVAPLSLPSFEEPDFLSTPRVKPDSQGPRSKVSTQRTILERDNNFPVKREENTIISSETESTTHSVPFLKEDPKPSPPSSKLYNPKVRLNKAEARKYTDSSAQRTSAGSVLEDTSMHKKKKSIFSFLKKKEPKPVIGNNSVTNEKNKMSSSSTFSMNIQTSLKTPEKLKKKSHSSSIFNSFLKGIETSDSPRKEPIRQKKRTPKSKDKKQDTEQIIDAASVLSTESPLLRKNHDDTPVKIDHVTRLIDQRKPTPLNMDLILGGDKQINTPLQ EHVKEDDDAKNDLQLPTKDNFLSLDYEAPSPAFSKHDTGEVLFPKFLDNHEVDSIVSLERTRSTKSNKRSSMNSQRRSLTDTLSIKAQSEGMFITEASSVVLSTPDLTKSPASSILKNGRFEYSDNFSREHSYEGTTNEDFLDIRDDSGPLKKDDIFLESIEQKFDQLVMASDEEKTEVERDVPKPREEPLKKDSERQSVYADDDNELISDIMEFASFINFGDDDLNLDLDGDTTASYATETPEVGNDEVNSDTFDARNNKEDSYKEKETQSYSAAGEATTYGDERQGQLHTFEQDGSEINDNEFENEDFNKHIEQPIEVTPRNNAYLPEFEPNRPVSMSFKGLKAPRMNTSFIDSMTPDSPVKSDLTSLGEVYVNSNNDQGVRFSSQIILYDTYGEFEYDRHPEISTCNQLTPQLAQMIKLELNELKSAMEVHDDSRCYTHFY SEQ ID NO.15, derived from Saccharomyces cerevisiae (Saccharomyces cerevi Saccharomyces cerevisiae BSP1, amino acid sequence ColumnMTKYERDPELVNFLSKVEDLNSKRYSNIPSSKPAGEALSPVRSHNSGEYRRADMMTGKNVEGCDNLAYRSAYNYEMTFSPKKTHYSLSELNLERITPRPDLEGSASQKEKKFLISEEDYLLLQKLKASQTYNDSNADKNLPSFEKGPRMPSRGRPRPREKEIITIQYDFELPGRADIPSSSSSSSPPPLPTRRDHIKITDGNEEKPLLPTRPNKAEVTESPSSRSIKPDAVVPERVKPAPPVSRSTKPASFLSSLEDNKLTKAKSYNSEMETPKTTVKSSHIDYLDSI QLKPTTLSPTMKNKPKPTPPPSPPAKRIPRSESFIKSMLNSNLTTTSKPSLPEKPQKLRNANLAAHKTKPSIPPKKVELNIVLPELRPVETSPTKQNFENSIDLPKLRSSNRNIKKEEEDSIPEAIKGIQNLKKTKQQKPAIPQKKSFLTNNSKNTTLKNGDDINKLNDEIEALSLRNNLKRPPTAPQRKISLPEALRRKVELMKKSKTEPVLESSNELSINAKLDAIIASRNLRASNTLPELSGVNTNIATSDKYTTSRDETVKETKPLVHPNKNRTRGPRRKLPTRV SEQ ID NO.16, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae BUD14, amino acid sequence ColumnMSNKEEHVDETSASGVKEVSSIAARHDNGYAPSLITSTSGMDSFQSHALLNDPTLIEDYSDIINNRPTSGSKLTLGNEDSESMGGSVVVTPTSNKSSPFNSKLNILSNAAEKGHDVLRNRDDDKELEENVEKHMHSNSKRDQRHYKENSSELPDSYDYSDSEFEDNLERRLQEIET DSVDSADKDEVHFSVNNTMNPDVDDFSDGLKYAISEDEEENYSDDDDFDRKFQDSGFQGEKDDLEEENDDYQPLSPPRELDPDKLYALYAFNGHDSSHCQLGQDEPCILLNDQDAYWWLVKRITDGKIGFAPAEILETFPERLARLNCWKNENMSSQSVASSDSKDDSISSGNKN QSDAESIIPTPALNGYKGGNKSVSFNDVVGYADRFIDDAIEDTSLDSNDDGGEGNQSYDDDVDNDKETKVTHRDEYTEAKNLFGFQDDTSDVVSDVSFSTSLNTPLNVKKVRRQDNKNESEPKTSSSKDREDDYNANRYVGQEKSEPVDSDYDTDLKKVFEAPRMPFANGMAKS DSQNSLSTIGEFSPSSSEWTNESPSTPIVEESSSIPSSRAIKDISQYIHAKSKIEETTNVENTEGQIQASLGSSGGMANQTDAEQPKEELEKHHSTPEEEKQSTLSLHSSSEEDFYMDEQRAVSSASINSSLSGSRALSNTNMSDPASKPNSLVQHLYAPVFDRMDVLMKQLDEIRK SEQ ID NO.17, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae CAX4, amino acid sequence Column MNSTAAAINPNPNVIPFDDTYILYDSHDFLSFLSFLSAYFSLMPILVLAFYLSWFIITRELEACIVAFGQLMNEIFNNVIKNIIKQPRPVSFGASFQNDTIRSGYGMPSAHSQFMGFCFTYNSLKIYTSWKNLNFLEKCIFSGALALLSFCVCFSRVYLHYHNLDQVIVGFSVGALTGSLYFFIVGIIRELGLINWFLKLRIVRLFYMTDSYNLAPLTLKENYEAYWKRINQRSFNDKSKRD SEQ ID NO.18, derived from Saccharomyces cerevisiae (Saccharomyces cerevi Saccharomyces cerevisiae CDC14, amino acid sequence Column MRRSVYLDNTIEFLRGRVYLGAYDYTPEDTDELVFFTVEDAIFYNSFHLDFGPMNIGHLYRFAVIFHEILNDPENANKAVVFYSSASTRQRANAACMLCCYMILVQAWTPHQVLQPLAQVDPPFMPFRDAGYSNADFEITIQDVVYGVWRAKEKGLIDLHSFNLESYEKYEHVEFGDFNVLTPDFIAFASPQEDHPKGYLATKSSHLNQPFKSVLNFFANNNVQLVVRLNSHLYNKKHFEDIGIQHLDLIFEDGTCPDLSIVKNFVGAAETIIKRGGKIAVHCKAGLGRTGCLIGAHLIYTYGFTANECIGFLRFIRPGMVVGPQQHWLYLHQNDFREWKYTTRISLKPSEAIGGLYPLISLEEYRLQKKKLKDDKRVAQNNIEGELRDLTMTPPSNGHGALSARNSSQPSTANNGSNSFKSSAVPQTSPGQPRKGQNGSNTIEDINNNRNPTSHANRKVVIESNNSDDESMQDTNGTSNHYPKVSRKKNDISSASSSRMEDNEPSATNINNAADDTILRQLLPKNRRVTSGRRTTSAAGGIRKISGSIKK SEQ ID NO.19, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae CDC48, amino acid sequence ColumnMGEEHKPLLDASGVDPREEDKTATAILRRKKKDNMLLVDDAINDDNSVIAINSNTMDKLEFRGDTVLVKGKKRKDTVLIVLIDDELEDGACRINRVVRNNLRILRGDLVTIHPCPDIKYATRISVLPIADTIEGITGNLFDVFLKPYFVEAYRPVRKGDHFVVRGGMRQVEFKVVDVEPEEYAVVAQDTIIHWEGEPINREDEENNM NEVGYDDIGGCRKQMAQIREMVELPLRHPQLFKAIGIKPPRGVLMYGPPGTGKTLMARAVANETGAFFFLINGPEVMSKMAGESESNLRKAFEEAEKNAPAIIFIDEISIAPKRDKTNGEVERRVVSQLLTLMDGMKARSNVVVIAATNRPNSIDPALRRFGRFDREVDIGIPDATGRLEVLRIHTKNMKLADDVDLEALAAETHGYV GADIASLCEAAMQQIREKMDLIDLDEDEIDAEVLDSLGVTMDNFRFALGNSNPSALRETVVESVNVTWDDVGGLDEIKEELKETVEYPVLHPDQYTKFGLSPSKGVLFYGPPGTGKTLLAKAVATEVSANFISVKGPELLSMWYGESESNIRDIFDKARAAAPTVVFLDELDSIAKARGGSLGDAGGASDRVVNQLLTEMDGNMNAKKNVFVIGATNRPDQIDPAILRPGRLDQLIYVPLPDENARSILNAQLRKTPLEPGLELTAIAKATQGFSGADLLYIVQRAAKYAIKDSIEAHRQHEAEKEVKVEGEDVEMTDEGAKAEQEPEVDPVPYITKEHFAEAMKTAKRSVSDAELRRYEAYSQQMKASRGQFSNFNFNDAPLGTTATDNANSNNSAPSGAGAAFGSNAEEDDDLYS SEQ ID NO.20, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae CDC55, amino acid sequence ColumnMAQNNFDFKFSQCFGDKADIVVTEADLITAVEFDYTGNYLATGDKGGRVVLFERSNSRHCEYKFLTEFQSHDAEFDYLKSLEIEEKINEIKWLRPTQRSHFLLSTNDKTIKLWKVYEKNIKLVSQNNLTEGVTFAKKGKPDNNHNSRGGSVRAVLSLQSLKLPQLSQHDKIIAATKPRIYSNAHTYHINSISLNSDQETFLSADDLRINLWNLDIPDQSFNIVDIKPTNMEELTEVITASAEFHPQECNLFMYSSSKGTIKLCDMRQNSLCDNKTFEEYLDPINHNFFETEITSSISDIKFSPNGRYIASRDYLTVKIWDVNMDNKPLKTINIHEQLKERLSDTYENDAIFDKFEVNFSGDSSSVMTGSYNNNFMIYPNVVTSGDNDNGIVKTFDEHNAPNSNSNKNIHNSIQNKDSSSNGHKRRSNGRNTGMVGSSNSSRSSIAGGEGANPEDSGTEMNEIVLQADKTAFRNKRYGSLAQRSARNKDWGDDIDFKKNILHFSWHPRENSIAVAATNNLFIFSAL SEQ ID NO.21, derived from Saccharomyces cerevisiae (Saccharomyces cerevi Saccharomyces cerevisiae CET1, amino acid sequence ColumnMSYTDNPPQTKRALSLDDLVNHDENEKVKLQKLSEAANGSRPFAENLESDINQTETGQAAPIDNYKESTGHGSHSQKPKSRKSSNDDEETDTDDEMGASGEINFDSEMDFDYDKQHRNLLSNGSPPMNDGSDANAKLEKPSDDSIHQNSKSDEEQRIPKQGNEGNIASNYITQVPLQKQKQKQTEKKIAGNAVGSVVKKEEANAAVDNIFEEKATLQSKKNNIKRDLEVLNEISASSKPSKYRNVPIWAQKWKPTIKALQSINVKDLKIDPSFLN IIPDDDLTKSVQDWVYATIYSIAPELRSFIELEMKFGVIIDAKGPDRVNPPVSSQCVFTELDAHLTPNIDASLFKELSKYIRGISEVTENTGKFSIIESQTRDSVYRVGLSTQRPRFLRMSTDIKTGRVGQFIEKRH VAQLLLYSPKDSYDVKISLNLELPVPDNDPPEKYKSQSPISERTKDRVSYIHNDSCTRIDITKVENHNQNSKSRQSETTHEVELEINTPALLNAFDNITNDSKEYASLIRTFLNNGTIIRRKLSSLSYEIFEGSKKVM SEQ ID NO.22, derived from Saccharomyces cerevisiae (Saccharomyces cerevi Saccharomyces cerevisiae CMD1, amino acid sequence Column MSSNLTEEQIAEFKEAFALFDKDNNGSISSSELATVMRSLGLPSEAEVNDLMNEIDVDGNHQIEFSEFLALMSRQLKSNDSEQELLEAFKVFDKNGDGLISAAELKHVLTSIGEKLTDAEVDDMLREVSDGSGEINIQQFAALLSK SEQ ID NO.23, derived from Saccharomyces cerevisiae (Saccharomyces cerevi Saccharomyces cerevisiae CMP2, amino acid sequence ColumnMSSDAIRNTEQINAAIKIIENKTERPQSSTTPIDSKASTVAAANSTATETSRDLTQYTLDDGRVVSTNRRIMNKVPAITSHVPTDEELFQPNGIPRHEFLRDHFKREGKLSAAQAARIVTLATELFSKEPNLISVPAPITVCGDIHGQYFD LLKLFEVGGDPATTSYLFLGDYVDRGSFSFECLIYLYSLKLNFNDHFWLLRGNHECKHLTSYFTFKNEMLHKYNLDIYEKCCESFNNLPLAALMNGQYLCVHGGISPENLSQDINNLNRFREIPSHGLMCDLLWADPIEEYDEVLDKDLT EEDIVNSKTMVPHHGKMAPSRDMFVPNSVRGCSYAFTYRAACHFLQETGLLSIIRAHEAQDAGYRMYKNTKTLGFPSLLTLFSAPNYLDTYNNKAAILKYENNVMNIRQFNMTPHYWLPDFMDVFTWSLPFVGEKVTEMLVAILNICTEDELENDTPVIEELVGTDKKLPQAGKSEAPQPATSASPKHASILDDEHRRKALRNKILAVAKVSRMYSVLREETNKVQFLKDHNSGVLPRGALSNGVKGLDEALSTFERARKHDLINEKLPPSLDELKNENKKYYEKVWQKVHEHDAKNDSK SEQ ID NO.24, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae CNA1, amino acid sequence ColumnMSKDLNSSRIKIIKPNDSYIKVDRKKDLTKYELENGKVISTKDRPIASVPAITGKIPSDEEVFDSKTGLPNHSFLREHFFHEGRLSKEQAIKILNMSTVALSKEPNLLKLKAPITICGDIHGQYYDLLKLFEVGGDPAEIDYLFLGDYVDRGAFSFECLIYLYSLKLNNLGRFWMLRGNHECKHLTSYFTFKNEMLHKYDMEVYDACCRSFNVLPLAALMNGQYFCVHGGISPELKSVEDVNKINRFREIPSRGLMCDLLWADPVENYDDARDGSE FDQSEDEFVPNSLRGCSFAFTFKASCKFLKANGLLSIIRAHEAQDAGYRMYKNNKVTGFPSLITMFSAPNYLDTYHNKAAVLKYEENVMNIRQFHMSPHPYWLPDFMDVFTWSLPFVGEKVTSMLVSILNICSEQELDPESEPKAAEETVKARANATKETGTPSDEKASSAILEDETRRKALRNKILAIAKVSRMFSVLREESEKVEYLKTMNAGVLPRGALARGTEGLNETLSTFEKARKEDLINEKLPPSLSEVEQEKIKYYEKILKGAEKKPQL SEQ ID NO.25, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae CNB1, amino acid sequence Column MKLDRDSSGSIDKNEFMSIPGVSSNPLAGRIMEVFDADNSGDVDFQEFITGLSIFSGRGSKDEKLRFAFKIYDIDKDGFISNGELFIVLKIMVGSNLDDEQLQQIVDRTIVENDSDDGGRLSFEEFKNAIETTEVAKSLTLQYDV SEQ ID NO.26, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae CSS1, amino acid sequence ColumnMFNRLNKFQAALALALYSQSALGQYYSNSTSISSNSSSTSVVSSSSGSVSISSSIAETSSSATDILSSITQSASSTSGVSSSVGPSSSSVVSSSVSQSSSSVSDVSSSVSQSSSSASDVSSSVSQSASSTSDVSSSVSQSSSSASDVSSSVSQSSSSASDVSSSVSQSASSASDVSSSVSQSASSTSDVSSSVSQSSSSASDVSSSVSQSSSSASDVSSSVSQSASSTSDVSSSVSQSASSTSGVSSSGSQSVSSASGSSSSFPQSTSSASTASGSATSNSLSSITSSASSASATASNSLSSSDGTIYLPTTTISGDLTLTGKVIATEGVVVAAGAKLTLLDGDKYSFSADLKVYGDLLVKKSKETYPGTEFDISGENFDVTGNFNAEESAATSASIYSFTPSSFDNSGDISLSLSKSKKGEVTFSPYSNSGAFSFSNAILNGGSVSGLQRRDDTEGSVNNGEINLDNGSTYVIVEPVSGKGTVNIISGNLYLHYPDTFTGQTVVFKGEGVLAVDPTETNATPIPVVGYTGKNQIAITADITALSYDGTTGVLTATQGNRQFSFAIGTGFSSSDFSVSEGIFAGAYAYYLNYNGVVATSAASSSTASGASASVTGSTSFGASVTGSTASTSFGASVTGSTASTSFGASVTGSTSVYTTTLDYVNATSTVVVSCSETTDSNGNVYTITTTVPCSSTTATITSCDETGCHVSTSTGAVVTETVSSKSYTTATVTHCDDNGCNTKTVTSECSKETSATTASPKSYTTVTVTHCDDNGCNTKTVTSEAPEATTTTTVSSQSYTTATVTHCDDNGCKTKTVTSEAPEATTTTVSPKTYTTATVTQCDDNGCSTKTVTSECPEETSATTTSPKSYTTVTVTHCDDNGCNTKTVTSEAPEATTTTVSPKTYTTATVTQCDDNGCSTKTVTSEAPKETSETSETSAAPKDIHYCHWLLNGDDNGCNVKIITSKIPEATSTVTQLVLLQSHTLLSLLRVLKQPH SEQ ID NO.27, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae CTK1, amino acid sequence Column MSYNNGNTYSKSYSRNNKRPLFGKRSPNPQSLARPPPPKRIRTDSGYQSNMDNISSHRVNSNDQPGHTKSRGNNNLSRYNDTSFQTSSRYQGSRYNNNNTSYENRPKSIKRDETKAEFLSHLPKGPKSVEKSRYNNSSNTSNDIKNGYHASKYYNHKGQEGRSVIAKKVPVSVLTQQRSTSVYLRIMQVGEGTYGKVYKAKNTNTEKLVALKKLRLQGEREGFPITSIREIKLLQSFDHPNVSTIKEIMVESQKTVYMIFEYADNDLSGLLLNKEVQISHSQCKHLFKQLLLGMEYLHDNKILHRDVKGSNILIDNQGNLKITDFGLARKMNSRADYTNRVITLWYRPPELLLGTTNYGTEVDMWGCGCLLVELFNKTAIFQGSNELEQIESIFKIMGTPTINSWPTLYDMPWFFMIMPQQTTKYVNNFSEKFKSVLPSSKCLQLAINLLCYDQTKRFSATEALQSDYFKEEPKPEPLVLDGLVSCHEYEVKLARKQKRPNILSTNTNNKGNGNSNNNNNNNNDDDDK SEQ ID NO.28, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae CTK2, amino acid sequence Column MPSTFESQLFFSRPFLSKRQIQRAQKNTISDYRNYNQKKLAVFKFLSDLCVQLKFPRKTLETAVYFYQRYHLFNRFETEVCYTVATSCLTLGCKEVETIKKTNDICTLSLRLRNVVKINTDILENFKKRVFQIELRILESCSFDYRVNNYVHIDEYVIKIGRELSFDYKLCNLAWVIAYDALKLETILVIPQHSIALAILKIAYELLDNKNWSSKRYSLFETDEKSVNEAYFDIVNFYINSFDMCDLQRHLPADLLPIGVERFMELKKNAGPESGLPQIPDHLLNADPYITITRDNNVQERRYVLSLELINGESSINSSTRHA SEQ ID NO.29, derived from Saccharomyces cerevisiae (Saccharomyces cerevi Saccharomyces cerevisiae CTK3, amino acid sequence ColumnMDSLEARLQFIQVLKNLQKTLHKTRDSITSSSTTTPPSSQQKLNNDPIQFYLRNYRHHYEDFHQCLFDTTMKMDPLDRLDVVIYYVRIIRNLYPHSHSNVTKVNLEVLLMDIDLVFELCLPCQDWKSLTNQATCKELFLDLSKLIH YDATSVTHTPSDTTLIDATTWYSVKTERTTKDYKESLQRTESLLKDRDLKKLAFFQQFNSDTTAINPDLQTQPTNANILLHRMEADRELHKRSKETSWYIERPSNDILDESEFKSLWTHFETTDSGFDKDDYKNIKALNDIAKASYMY SEQ ID NO.30, derived from brewer's yeast ( Saccharomyces cerevisiae CTL1, amino acid sequence Column MSDQPETPSNSRNSHENVGAKKADANVASKFRSLHISETTKPLTSTRALYKTTRNNSRGATEFHKHVCKLAWKYLACIDKSSISHIEIEMKFGVITDKRTHRRMTPHNKPFIVQNRNGRLVSNVPEQMFSSFQELLRSKSENPSKCAPRVVKQVQKYTKDSIYNCNNASKVGKLTSWRCEDLRNKELKLTYIKKVRVKDFLIRYPQSSLDAKISILEVPEYETSAAFRNGFILQRTKSRSTYTFNDKMPLHLDLTKVTTTTRNSHQYTSHEVEVEMDPIFKETISANDREKFNEYMCSFLNASDLIRKAAERDNMLTT SEQ ID NO.31, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae CTO1, amino acid sequence ColumnMKTIIISDFDETITRVDTICTIAKLPYLLNPRLKPEWGHFTKTYMDGYHKYKYNGTRSLPLLSSGVPTIISQSNFNKLFADELKYQNHNRVVELNSVNEITKQQIFKSISLDQMKTFARDQNHEDCLLRDGFKTFCSSVVKNFESDFYVLSINWSKEFIHEVIGDRRLKNSHIFCNDLKKVSDKCSQSYNGEFDCRLLTGSDKVKILGEILDKIDSGCNKEGNSCSYWYIGDSETDLLSILHPSTNGVLLINPQENPSKFIKITEKIIGIPKDKISSFEADNGPAWLQFCEKEGGKGAYLVKSWDSLKDLIMQVTKM SEQ ID NO.32, derived from Saccharomyces cerevisiae (Saccharomyces cerevi Saccharomyces cerevisiae DCR2, amino acid sequence Column MIRLPRLYQRYLLYLLVVFVVIALFYFLQAPRVEEHIGFDLALPISHVDNLWFQNKGLEGFSNDDKLVVNIGYDECFHIGRFYEGCFNRHELKSTLTDGHQYLQRKRIHKDLRGSFGRRWFGKSEYLYYDVLYPALVDYFGSNLEKLNVEAVTGISKYPKDKSLPFMDVSITFEPISIELLQKRSYISDINILFGVDCIQPIANWTLQKEFPLVKYRYSEPAYLTYKFVGTRPVDTGAQRLQETDEGKFKIVQLADLHLGVGESECIDEYPKHEACKADPKTETFVQQVL DIEKPQLVVFTGDQIMGDRSIQDSETVLLKAVAPVIARKIPWAMVWGNHDDEGSLTRWQLSEIASVLPYSLFKFSPHDTHDNTFGVGNYIYQIFSNNDTEPVVGTLYFLDSHKYSTVGKIYPGYDWIKESQWKYIEDYHDVNLK FKTGLSMAFFHIPLPEYLNIESKTHPGEKNPLIGMYKEGVTAPKYNSEGITTLDRLSVDVVSCGHDHCNDYCLRDDSTPNKIWLCYGGGGGEGGYAGYGGTERRIRIYEINVNENNIHTWKRLNGSPKEIFDFQSMLDGNSPESV SEQ ID NO.33, derived from brewer's yeast ( Saccharomyces cerevisiae DDP1, amino acid sequence ColumnMGKTADNHGPVRSETAREGRENQVYSPVTGARLVAGCICLTPDKKQVLMITSSAHKKRWIVPKGGVEKDEPNYETTAQRETWEEAGCIGKIVANLGTVEDMRPPKDWNKDIKQFENSRKDSEVAKHPPRTEFHFYELEIENLLDKFPECHKRHRKLYSYTEAKQNLIDAKRPELLEALNRSAIIKDDK SEQ ID NO.34, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae DET1, amino acid sequence Column MCEENVHVSEDVAGSHGSFTNARPRLIVLIRHGESESNKNKEVNGYIPNHLISLTKTGQIQARQAGIDLRVLNVDDHNLVEDLAKKYIKDESSRRTLPLKDYTRLSREKDTNIVFYTSPYRRARETLKGILDVIDEYNELNSGVRICEDMRYDPHGKQKHAFWPRGLNNTGGVYENNEDNICEGKPGKCYLQYRVKDEPRIREQDFGNFQKINSMQDVMKKRSTYGHFFFRFPHGESAADVYDRVASFQETLFRHFHDRQERRPRDVVVLVTHGIYSRVFLMKWFRWTYEEFEFSFTNVPNGSVMVMELDESINRYVLRTVLPKWTDCEGDLTT SEQ ID NO.35, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae DIA3, amino acid sequence ColumnMVKPVIFAICLGVLLSKALSIPLRSFADIELIGSQKSLFPFLGGSAPYFSFPANYGIPTDIPEGCRLTQVQMIGRHGERYPTRSEAKDIFEVWYKISNYTGKYEGSLSFLNNGYEFFIPDESLLEMETTLQNSIDVLNPYTGEMNAKRHAREFLAKYGKLMENCTNFPIFTTNSKRIYDTAQYFAEALGDGFNISLQTLSENSSSGANTLAAKSSCPNWNSNANNDILMSYSRDYLENISDRLNDENKGLNLSRKDAAALFSWCAFELNAKGYSNICDIFSAAAELIHYSYETDLTSFYQNGPGYKLIKSIGANLFNATVKLIRQSAHLDQKVWLSFTHDTDILNYLTTAGLIDDTRNLTTNHVPFRDHSYHRSWYIPQGARVYTEKFQCSNDSYVRYVVNDAVVPIESCSSGPGFSCEEGTFFYEYAKDRLRGVSFYEDCDVSKVSKEKELTFYWDWNTTRYNASLVNQ SEQ ID NO.36, derived from brewer's yeast ( Saccharomyces cerevisiae DOG1, amino acid sequence Column MAEFSDLCLFDLDGTIVSTTVAAEKAWTKLCYEYGVDPSELFKHSHGARTQEVLRRFFPKLDDTDNKGVLALEKDIAHSYLDTVSLIPGAENLLLSLDVDTETQKKLPERKWAIVTSGSPYLAFSWFETILKNVGKPKVFITGFDVKNGKPDPEGYSRARDLLRQDLQLTGKQDLKYVVFEDAPVGIKAGKAMGAITVGITSSYDKSVLFDAGADYVVCDLTQVSVVKNNENGIVIQVNNPLTRA SEQ ID NO.37, derived from Saccharomyces cerevisiae (Saccharomyces cerevi Saccharomyces cerevisiae DOG2, amino acid sequence ColumnMPQFSVDLCLFDLDGTIVSTTTAAESAWKKLCRQHGVDPVELFKHSHGARSQEMMKKFFPKLDNTDNKGVLALEKDMADNYLDTVSLIPGAENLLLSLDVDTETQKKLPERKWAIVTSGSPYLAFSWFETILKNVGKPKVFITGFDVKNGKPPDPEGYSRARDLRQDLQLTGKQDLKYVVFEDAPVGIKAGKAMGAITVGITSSYDKSVLFDAGADYVVCDLTQVSVVKNNENGIVIQVNNPLTRD SEQ ID NO.38, derived from brewer's yeast ( Saccharomyces cerevisiae DPP1, amino acid sequence Column MNRVSFIKTPFNIGAKWRLEDVFLLIIMILLLNYPVYYQQPFERQFYINDLTISHPYATTERVNNMLFVYSFVVPSLTILIISILADRRHLIFILYTSLLGLSLAWFSTSFFTNFIKNWIGRLRPDFLDRCQPVEGLPLDTLF TAKDVCTTKNHERLLDGFRTTPSGHSSESFAGLGYLYFWLCGQLLTESPLMPLWRKMVAFLPLLGAALIALSRTQDYRHHFVDVILGSMLGYIMAHFPYRRIPPPIDDPLPFKPLMDDSDVTLEEAVTHQRIPDEELHPLSDEGM SEQ ID NO.39, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae DSK2, amino acid sequence Column MSLNIHIKSGQDKWEVNVAPESTVLQFKEAINKANGIPVANQRLIYSGKILKDDQTVESYHIQDGHSVHLVKSQPKPQTGSAAEANNATATGAAAGTGATPNMSSGQSAGFNPLADLTSARYAGYLNMPSADMFGPDGGALNNDSNNQDELLRMMENPIFQSQMNEMLSNPQMLDFMIQSNPQLQA MGPQARQMLQSPMFRQMLTNPDMIRQSMQFARMMDPNAGMGSAGGAASAFPAPGGDAPEEGSNTNTTSSSNTGNAGTNAGTNAGANTAANPFASLLNPALNPFANAGNAASTGMPAFDPALLASMFQPPAQASQAEDTRPPEERYEHQLRQLNDMGFFDFDRNVAALRRSGGSVQGALDSLLNGDV SEQ ID NO.40, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae DUT1, amino acid sequence Column MTATSDKVLKIQLRSASATVPTKGSATAAGYDIYASQDITIPAMGQGMVSTDISTVPVGTYGRIAPRSGLAVKNGIQTGAGVVDRDYTGEVKVVLFNHSQRDFAIKKGDRVAQLILEKIVDDAQIVVVDSLEESARGAGGFGSTGN SEQ ID NO.41, derived from Saccharomyces cerevisiae (Saccharomyces cerevi Saccharomyces cerevisiae FAB1, amino acid sequence Column SEQ ID NO.42, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae FBP1, amino acid sequence Column MPTLVNGPRRDSTEGFDTDIITLPRFIIEHQKQFKNATGDFTLVLNALQFAFKFVSHTIRRAELVNLVGLAGASNFTGDQQKKLDVLGDEIFINAMRASGIIKVLVSEEQEDLIVFPTNTGSYAVCCDPIDGSSNLDAGVSVGTIASIFRLLPDSSGTINDVLRCGKEMVAACYAMYGSSTHLVLTLGDGVDGFTLDTNLGEFILTHPNLRIPPQKAIYSINEGNTLYWNETIRTFIEKVKQPQADNNNKPFSARYVGSMVADVHRTFLYGGLFAYPCDKKSPNGKLRLLYEAFPMAFLMEQAGGKAVNDRGERILDLVPSHIHDKSSIWLGSSGEIDKFLDHIGKSQ SEQ ID NO.43, derived from Saccharomyces cerevisiae (Saccharomyces cerevi Saccharomyces cerevisiae FBP26, amino acid sequence Column MGYSTISNDNDIKVCVIMVGLPARGKSFISQKIIRYLSWLSIKAKCFNVGNYRRDVSGNVPMDAEFFNFENTDNFKLRELAAQNAIKDIVNFFTKEDGSVAVFDATNSTRKRKWLKDICEKNNIQPMFLESWSNDHELIINNAKDIGSTPDYENFEPHVAEADFLERIRQYERFYEPLDPQKDKDMTFIKLVNIIEEVVINKIRTYLESRIVFYVMNIRPKPKYIWLSRHGESIYNVEKKIGGDSLSERGFQYAKKLEQLVKESAGEINLTVWTSTLKRTQQTANYLPYKKLQWKALDELDAGVCDGMTYEEIEKEYPEDFKARDNDKYEYRYRGGESYRDVVIRLEPVIMELERQENVLIITHQAVLRCIYAYFMNVPQEESPWMSIPLHTLIKLEPRAYGTKVTKIKANIPAVSTYKEKGTSQVGELSQSSTKLHQLLNDSPLEDKF SEQ ID NO.44, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae FCP1, amino acid sequence ColumnMTTQIRSPQGLPYPIQIDKLIPSVGSYLHEGDRLLVYKFWYLVERASDTGDDDNEHDVSPGGSAGSNGVSPPTKQLRESIEFFESPYEGDLISWNVDVGDEVATANQVICEIKRPCNHDIVYGGLCTQCGKEVSADAFDGVPLDVVGDVDLQISETEAIRTGKALKEHLRRDKKLILVVDLDQTIIHCGVDPTIAEWKNDPNNPNFETLRDVKSFTLDEELVLPLMYMNDDGSMLRPPPVRKCWYYVKVRPGLKEFFAKVAPLFEMHIYTMATRAYALQIAKIVDPTGELFGDRILSRDENGSLTTKSLAKLFPTDQSMVVVIDDRGDVWNWCPNLIKVVPYNFFVGVGDINSNFLPKQSTGMLQL GRKTRQKSQESQELLTDIMDNEKKLQEKIDKEVKRQEEKLNHQLATAEEPPANESKEELTKKLEYSASLEVQQQNRPLAKLQKHLHDQKLLVDDDELYYLMGTLSNIHKTYYDMLSQQNEPEPNLMEIIPSLKQKVFQNCYFVFSGLIPLGTDIQRSDIVIWTSTFGATSTPDIDYLTTHLI TKNPSTYKARLAKFNPQIKIVHPDWIFECLVNWKKVDEKPYTLIVDSPISDEELQNFQTQLQKRQEYLEETQEQQHMLTSQENLNLFAAGTSWLNNDDDEPIDTASDDDDDDHDDESDDENNSEGIDRKRSIEDNHDDTSQKKTKAEPSQDGPVQHKGEGDDNEDSDSQLEEELMDMLDD SEQ ID NO.45, derived from Saccharomyces cerevisiae (Saccharomyces cerevi Saccharomyces cerevisiae FIG4, amino acid sequence ColumnMNNDAMEHTLGGGILTTSGSKQRKTSKFVMGKYTLYETKDRMYIVGSNKRETMFRILEIDLTVPRGELTVLEDNVFFTRNEIMNVLASLEEATEDGLHKKITGYGLLGFIKFTCWYYLIMVTKYSQVAVIGGHGIYHIDGIDIIPITPITNNYKKPEKSSDEARLLNIFKDLDTKTFYFSYTITNTLQTNILREKLKAVDRCDITIPCGITDYNEMFVWNNNNLLSPIFACIDTVFDWFQCIIHGFIDQVNVSVLGKSIYITLIARRSHHFAGARFLKRGVNNKGHVANEVETEQIVTDMILTPFHQPGNGFFDSDRYTSFVQHRGSIPLYWTQDASNLTTKPPIRINVVDPFFSPAALHFDNLFQRYGGGTIQILNLIKTKEKTPRETKLLWEFEQCIDYLNEFLPTLKKLDYTSWDMSRASKQDGQGVIEFLEKYAVN TVTTTGIFHNGPDFASTKIQEGICRSNCIDCLDRTNAAQFVIGKRALGCQLKSLGIIDNSYLEYDSDIVNILTELFHDLGDTIALQYGGSHLVNTMETYRKINQWSSHSRDMIESIKRFYSNSFVDAQRQDAINLFLGHYSWREGFPSLWEMNTDFYLHNAYSLNMPKRSYIHWWNDYNIKSVKELINEELIATGNDVTREKIIKNVRGYPGAFDNYWNEYYLPRSVTWIRDLFAYNMNSTRRYHNALSKQDKAMSPFTSRKQSWLNNKLKMITSSKSLEKAEGRVVETTDLDRDTSPKQELELYEHYLHIISDRSQKLEEKMNSFSYSKYPIFISHESSEIPPMRKVIGEPLVDIAEDFTDVYDDDDDDGDDENDEMTTEALLIAPDHVSVDEKFYEKVLNVDDYKPALDDYSAVIHIKPDNLQLYRDLCFSKDIQLDFQ SEQ ID NO.46, derived from Saccharomyces cerevisiae (Saccharomyces cerevi Saccharomyces cerevisiae FIN1, amino acid sequence ColumnMSNKSNRRSLRDIGNTIGRNNIPSDKDNVFVRLSMSPSRTTSQKEFLKPPMRMSPNKTDGMKHSIQVTPRRIMSPECLKGYVSKETQSLDRPQFKNSNKNVKIQNSDHITNIIFPTSPTKLTFSNENKIGDGSLTRIRARFKNGLMSPERIQQQQQQHILPSDAKSNADLCSNTELKDAPFENDLPRAKLKGKNLLVELKKEEEEDVGNGIESLTKSNTKLNSMLANEGKIHKASFQKSVKFKLPDNIVTEETVELKEIKDLLLQMLRRQREIESRLSNIELQLTEISKHK SEQ ID NO.47, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae FPY1, amino acid sequence Column MVKVTAACIIIGDEVLNGKVVDTNSTFFAKYCFDHGIQLKEIATIGDDETQIVDTVRRLVKNYDFIISTGGIGPTHDDITYECMAKSFNLPCELDEECKERMRHKSDPEARLDADALKAHYQMATMPKGTNVKNYYV CDDLWVPICSISHKMYILPGIPQLFARMLKAFTPTLKKIYNLDKDPREYVRYFVRTHLTESQISKELKLIQDESTKVSEAIKIGSYPHFGMGFNTVSILGEKKDDSYLKSIVNRVVNNLEGEVISSELENKFSNQES SEQ ID NO.48, derived from Saccharomyces cerevisiae (Saccharomyces cerevi Saccharomyces cerevisiae GAC1, amino acid sequence ColumnMVIQTATTLSPAKARSFPHNDLIKSMSDSLISRPTHPPIRKLKSSLKISHPEPISRSKSEIFCTSPEKNVRFAIELTTVKRFDKNAEPSSISNENSPTLSPVDSNTAADDVQLFNNEDCWFNDSSLVTNLLKNEKKFRYMNSLNNMFKLDLYDSEDEDDIDEHINSQAEYGYTYNSLSTRGKTSENKSATSSLATQATNICDWKLHCTDLVPFKIAPPLFTKTLSASDLQGQLTKYLNGQNVKLHSLTQLGDDSSSKITGLVYVKNLSFEKYLEIKFTFNSWRDIHYVTANFNRTINSNVDEFKFTIDLNSLKYILLIKRIITMEKNTSSCPLNIELCCRYDVNNETYYDNNNGKNYHLFMTTFKKGGETKEKIPVVVEPASQTDAAMSPKEMKAR FVSSNPTLSRFLPQSRKFSEDTDYYNTSPLKHLYHNDTTSWVKPKRLNVVLDKLENATPPPSSALANDTARTGKITKDKNNVLAPPTASNSIDLPILGSQHQSLYGSSSSYSSSSSSISSSLSFASSNNSSTNSSSASCSFPLTELDNFDYANLYEPNDTFTTANLFNHSLNSLMPEISTPSFFGGFRNENTINNND SKNLVTSLEDSYEDKQSVITDTTMDENNKTSTINNSTDTLIKPSKENGTVKENKSSANSTSAPSSSQNRASTILNDHSNGKSDLKYVNYQSLLDSHCFYNHPSPSPNLQSTSFSSAAPFSGISQASDIFDYENEDSDSSNQIAGEIDNNSFPPHFYLDEDDKSACLSDDALIDHHRNTNPFINTFSSSPPILSQEVDRWRL SEQ ID NO.49, derived from Saccharomyces cerevisiae (Saccharomyces cerevi Saccharomyces cerevisiae GDA1, amino acid sequence ColumnMAPIFRNYRFAIGAFAVIMLILLIKTSSIGPPSIARTVTPNASIPKTPEDISILPVNDEPGYLQDSKTEQNYPELADAVKSQTSQTCSEEHKYVIMIDAGSTGSRVHIYKFDVCTSPPTLLDEKFDMLEPGLSSFDTDSVGAANSLDPLKVAMNYVPIKARSCTPVAVKATAGLRLGDAKSSKILSAVRDHLEKDYPFPVVEGDGVSIMGDEEGVFAWITTNYLLGNIGANGPKLPTAAVFDLGGGSTQIVFEPTFPINEKMVDGEHKFDLKFGDENYTLYQFSHLGYGLKEGRNKVNSVLVENALKDGKILKGDNTKTHQLSSPCLPPKVNATNEKVTLESKETYTIDFIGPDEPSGAQCRFLTDEILNKDAQCQSPPCSFNGVHQPSLVRTFKESNDIYIFSYFYDRTRPLGMPLSFTLNELNDLARIVCKGEETWNSVFSGIAGSLDELESDSHFCLDSFQVSLLHTGYDIPLQRELRTGKKIANKEIGWCLGASLPLLKADNWKCKIQSA SEQ ID NO.50, derived from Saccharomyces cerevisiae (Saccharomyces cerevi Saccharomyces cerevisiae GEP4, amino acid sequence Column MNISGTLNTLRLLYNPSLCKPSLVVPTFNDLPIPIHDSIKAVVLDKDNCIAFPHDDKIWPDYLQHWETLRSKYSNKALLIVSNTAGSNSDKDYSQAKLLEDKTGIPVLRHSTKKPGCHNEILDYFYRNKTITNPKEVAVVGDRLFTDILMANLMGSYGVWIRDGVKVSANPLSKFEKKLYNFLGF SEQ ID NO.51, derived from Saccharomyces cerevisiae (Saccharomyces cerevi Saccharomyces cerevisiae GIP1, amino acid sequence ColumnMETILQPKARPFESLKRKRFREWLRPSTAHGSLLHSDTLDLRDFAKPNPADTFSNLDSGHCPLVTTPIKYECPDGKSSFFRGDTKFETLFSNRKFYEFKDNLKRGLKKIRHGRNGHQSEKRCPVVEETKKSVSDNLDKPDNNTPCFDRFHTNSKEFETQFDHSNRSQNSEKAYLDNESCWNLSEKFIPFNNLKYEDLKHFEENLQSLAPATFTPIESNESLDRSDSTRGTKRSIRNDSSDTTSEKRLCLKQYSDEPESDHSMESTPSIYITKEVQERIEALSSTDSFLIEKVDFPSNKIGSSASDYESDNEYRNMDEDSINDVTTEKEGNVVIPDSNTSTVDAMEKPIEVSSALKDDTLDKDIDDASSSYSDDVETTFEPVESEELSDLSDTSSSGSSKIYTIPTFRGLTNRTNISQILSKVGKADLSQDNLTHLIKSHQKKKRCVNFRNKRFYDAFNPYVDNEEDAELSDSENISEMDTDLCIKDRSTSSVRFDENSRLLIYKKSKKLNKDETQSGYSTTEMRSILKTKMNSQHDEESQRASKCDTVGVAQFLHYFQYTEYKRQRNEAENYRLRGEQLSKYYSEEYPLDFAAVECEDSVNDKSDIILSMRATERNIGRQLKGISSQGAQIISLDEDVF SEQ ID NO.52, derived from Saccharomyces cerevisiae (Saccharomyces cerevi Saccharomyces cerevisiae GIP2, amino acid sequence ColumnMYIKAEQKPQQFERKNEKLDRKKNQQLPDLETDFKGYRVNSDLYNKERDGSTEETLNSLKFLHKPQRVTQMRANRFPEEVQRNTDLNKRIFSAGNDENVDNESCWSKIAAAKNHTSVESLNGSTRPPFKIELPPLSPKSTVPKSFQAEYPEAKSPGNDMNFEYDEEILIPFAPPVYKKSGELLKSSLKRRSKSLPTTPGIRSGNGVQARDGSPMLIRSKSVHFDQAAPVKYFAEDESPINVNKTEQHDNCLSFKHKPVNLMVDPEEETKMLSS GLETTSIDDDLTTVAPKGFAHPAKISSPNNGKGTNNTKLRKSKRFQNLLKNRTDMPPSKSNKKFVNGGGAHEISDRNSKNYHVVGLYSKNFPILSNKNPKSLKLNIFINLSQNKKVFLQELSLYIHRDNNYFSNSSSFNNIPNSHNGNDCNGVAKGYNAGCTRLIAGRILVKNIFYDKRVVVRYTWDSWRTTHEVECVYISDGDGILPGTNMDIFHFIIDDASKVDPRGKLEFCIHYSTRNDYEREEYWDNNNGNNYKVDVVMDGFNDPFAAAA SEQ ID NO.53, derived from Saccharomyces cerevisiae (Saccharomyces cerevi Saccharomyces cerevisiae GIP3, amino acid sequence Column SEQ ID NO. 54, derived from Saccharomyces cerevisiae (Saccharomyces cer Saccharomyces cerevisiae GIP4, amino acid sequence Column MVDVQKRKKLLAKAAASASIPAIKGSVPLDSYDIKIIQYKNALYKLNELNRLLNVLVPHLKKKRDNDESYKIIPLVNFILSLCEGPIFNVSPVLAKRYHLLCRFQLIKLSEVQQRLSTNFIDVEGWMFPEEVPLDHYKSCIYNNSLQWKILNSLSCIAQNAIKIYNAKLRQILLERDAYKARSLPFDTSI IEDLLNPVEMTLILDLAVLINDPVRDKSTHSFYKLQWQVMEKNLSCVHSKIFPILRTYYNQLQKFSETRPTSLSNLQKDLPHWEWTHLRIYTFHLRVFSVLCVIISFSRQIFLPNKQHFLDIKTRLSSENVYHYDLIICELMALLSPECDDVTALFELQENLKFWTQTARTDNNSSRTPIFHLQPGLVVE LFNNHICKIIPKLRSIMGLLSNWMDCWKYIEKNYKTFDETNDLRENLKEKLERDKALYLEVKNAKSKLKKKPSITKLPASSSPSPTSSASPSRQASLESIRTRARAHLASNSSRSPSVSPVRTTFNNKNAETKKSVVSPEKRKLINGRRPRSSSLQSYTNKQQTSYLNSTRHPSIAPPSKLNNQRSNSLQSSTMTLNQKIVQDTVRHLMNKSASTPNPSASSSLAPSPKVSSINNTSSGKSSSTLIANSDTLAIETLLDPESNSSELSIKRVRFAGVPPMTEAENPKPTKVGWYKKPAVLHYPPIPASAMIKPLQHKSKYNTLRQEEGFTFRKSLRDGLEWENGESGSETTMMPFGIEIKESTGHRIASKIRSKLR SEQ ID NO. 55, derived from Saccharomyces cerevisiae (Saccharomyces cer Saccharomyces cerevisiae GLC7, amino acid sequence ColumnMDSQPVDVDNIIDRLLEVRGSKPGQQVDLEENEIRYLCSKARSIFIKQPILLELEAPIKVCCTSQSRDRMPRASGVLCVLLLLRQDSYSSYFRLTERIYQASDVSLLICRDSRDNVCVLFIFLSYAFFYQDFLMFCIIIRPAPPIFRKIPLAHTKKRRHFFVMKKTNLFFFAREKGRTKTKKCGFAEGIGRNEAFLTAVIVLLKSTEARFSDKFIYLIFFYFFFFICGDIHGQYYDLLRLFEYGGFPPESNYLFLGDYVDRGKQSLETICLLLAYKIKYPENFFILRGNHECASINRIYGFYDECKRRYNIKLWKTFTDCFNCLPIAAIIDEKIFCMHGGLSPDLNSMEQIRRVMRPTDIPDVGLLCDLLWSDPDKDIVGWSENDRGVSFTFGPDVVNRFLQKQDMELICRAHQVVEDGYEFFSKRQLVTLFSAPNYCGEFDNAGAMMSVDESLLCSFQILKPAQKSLPRQAGGRKKK SEQ ID NO. 56, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae GLC8, amino acid sequence Column MGGILKNPLALSPEQLAQQDPETLEEFRRQVYENTQKNAKLTSHKRNIPGLDNTKEEGEIIGTSSTFLPKDTLSLKHEQDMLAKMTPEERVQWNQRNLAENEITKKQFQDIHIDEPKTPYQGAVDPHGEYYRVDDDEDEDNSDKKPCQVANDDIDDLSLGEPEFEIKENKQPDFETNDENDEDSPEARHKKFEEMRKKHYDVRAIFNKKSREALKDEDEDEDDSTTKEP SEQ ID NO. 57, derived from Saccharomyces cerevisiae (Saccharomyces cer Saccharomyces cerevisiae GLN3, amino acid sequence ColumnMQDDPENSKLYDLLNSHLDVHGRSNEEPRQTGDSRSQSSGNTGENEEDIAFASGLNGGTFDSMLEALPDLYFTDFVSPFTAAATTSVTTKTVKDTTPATNHMDDDIAMFDSLATTQPIDIAASNQQNGEIAQLWDFNVDQFNMTPSNSSGSATISAPNSFTSDIPQYNHGSLGNSVSKSSL FSYNSSTSNSNINQPSINNNSNTNAQSHHSFNIYKLQNNNSSSAMNITNNNNSNNSNIQHPFLKKSDSIGLSSSNTTNSVRKNSLIKPMSSTSLANFKRAASVSSSISNMEPSGQNKKPLIQCFNCKTFKTPLWRRSPEGNTLCNACGLFQKLHGTMRPLSLKSDVIKRISKKRAKQDTSN IAQNTPNASATSSTSVTTTNAKPIRSRKKSLQQNSLSRVIPEEIISDNIGNTNNILNVNRGGYNFNSVPSPVLMNSQSYNSNANFNGASNANLNSNNLMRHNSNTVTPNFRRSSRRSSTSSNTSSSKSSSRSVVPILPKPSPNSANSQQFNMNLMNTTNNISAGNSVASSPRIISSANFNSNSPLQQNLLSNSFQRQGMNIPRRKMSRNASYSSSFMAASLQQLHEQQVDVNSNTNTNSNRQNWNSSNSVSTNSRSSNFVSQKPNFDIFNTPIDSPSVSRPSSRKSHTSLLSQQLQNSESNSFISNHKFNNRLSSDSTSPIKYEADVSTGGKISEDNSTKGSSSKESSAIADELDWLKFGI SEQ ID NO. 58, derived from Saccharomyces cerevisiae (Saccharomyces cer Saccharomyces cerevisiae GPP1, amino acid sequence ColumnMPLTTKPLSLKINAALFDVDGTIIISQPAIAAFWRDFGKDKPYFDAEHVIHISHGWRTYDAIAKFAPDFADEEYVNKLEGEIPEKYGEHSIEVPGAVKLCNALPKEKWAVATSGTRDMAKKWFDILKIKRPEYFITANDVKQGKPPHEPYLKGRNGLGFPINEQDPSKSKVVVFEDAPAGIAAGKAAGCKIVGIATTFDLDKEKGCDIIVKNHESRVGEYNAETDEVELIFDDYLYAKDDLLKW SEQ ID NO. 59, derived from Saccharomyces cerevisiae (Saccharomyces cer Saccharomyces cerevisiae GPP2, amino acid sequence Column MGLTTKPLSLKVNAALFDVDGTIIISQPAIAAFWRDFGKDKPYFDAEHVIQVSHGWRTFDAIAKFAPDFANEEYVNKLEAEIPVKYGEKSIEVPGAVKLCNALNALPKEKWAVATSGTRDMAQKWFEHLGIRRPKYFITANDVKQGKPHPEPYLKGRNGLGYPINEQDPSKSKVVVFEDAPAGIAAGKAAGCKIIGIATTFDDLFLKEKGCDIIVKNHESIRVGGYNAETEDEVEFIFDDYLYAKDDLLKW SEQ ID NO. 60, derived from Saccharomyces cerevisiae (Saccharomyces cer Saccharomyces cerevisiae GSY2, amino acid sequence ColumnMSRDLQNHLLFETATEVANRVGGIYSVLKSKAPITVAQYKDHYHLIGPLNKATYQNEVDILDWKKPEAFSDEMRPVQHALQTMESRGVHFVYGRWLIEGAPKVILFDLDSVRGYSNEWKGDLWSLVGIPSPENDFETNDAILLGYTVAWFLGEVAHLDSQHAIVAHFHEWLAGVALPLCRKRRIDVVTIFTTHATLLGRYLCASGSFDFYNCLESVDVDHEAGRFGIYHRYCIERAAAHSADVFTTVSQITAFEAEHLLKRKPDGILPNGLNVIKFQAFHEFQNLHALKKEKINDFVRGHFHGCFDFDLDNTLYFFIAGRYEYKNKGADMFIEALARLNYRLKVSGSKKTVVAFIVMPAKNNSFTVEALKGQAEVRALENTVHEVTTSIGKRIFDHAIRYPHNGLTTELPTDLGELLKSSDKVMLKRRILALRRPEGQLPPIVTHNMVDDANDLILNKIRQVQLFNSPSDRVKMIFHPEFLNANNPILGLDYDEFVRGCHLGVFPSYYEPWGYTPAECTVMGVPSITTNVSGFGSYMEDLIETNQAKDYGIYIVDRRFKAPDESVEQLVDYMEEFVKKTRRQRINQRNRTERLSDLLDWKRMGLEYVKARQLALRRGYPDQFRELVGEELNDSNMDALAGGKKLKVARPLSVPGSPRDLRSNSTVYMTPGDLGTLQEVNNADDYFSLGVNPAADDDDDGPYADDS SEQ ID NO. 61, derived from Saccharomyces cerevisiae (Saccharomyces cer Saccharomyces cerevisiae HIS2, amino acid sequence ColumnMHSHHSHSGDYSAHGTDPLDSVVDQVVNLNFHTYCLTEHIPRIEAKFIYPEEQSLGKNPEEVISKLETSFKNFMSHAQEIKTRYADRPDVRTKFIIGMEIESCDMAHIEYAKRLMKENNDTLKFCVGSVHHVNGIPIDFDQQQWYNSLHSFNDNLKDFLLSYFQSQYEMLINIKPLVVGHFDLYKLFLPNDMLVNQKSGNCNEETGVPVASLDVISEWPEIYDAVVRNLQFIDSYGGAIEINTSALRKGLEEPYPSKTLCNLVKKHCGSRFVLSDDAHGVAQVGVCYDKVKKYIVDVLQLEYICYLEESQSPENVLTVKRLPISQFVNDPFWANI SEQ ID NO. 62, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae HNT2, amino acid sequence Column MPESQDYFKTLQLIHRFIKWQYKADSINVAIQDGPEAGQSVPHLHTHIIPRYKINNVGDLIYDKLDHWDGNGTLTDWQGRRDEYLGVGGRQARKNNSTSATVDGDELSQGPNVLKPDSQRKVRALTEMKKEAEDLQARLEEFVSSDPGLTQWL SEQ ID NO. 63, derived from Saccharomyces cerevisiae (Saccharomyces cer Saccharomyces cerevisiae HRR25, amino acid sequence ColumnMDLRVGRKFRIGRKIGSGSFGDIYHGTNLISGEEVAIKLESIRSRHPQLDYESRVYRYLSGGVGIPFIRWFGREGEYNAMVIDLLGPSLEDLFNYCHRRFSFKTVIMLALQMFCRIQYIHGRSFIHRDIKPDNFLMGVGRRGSTVHVIDFGLSKKYRDFNTHRHIPYRENKSLTGTARYASVNTHLGIEQSRRDDLESLGYVLIYFCKGSLPWQGLKATTKKQKYDRIMEKKLNVSVETLCSGLPLEFQEYMAYCKNLKFDEKPDYLFLARLFKDLSIKLEYHNDHLFDWTMLRYTKAMVEKQRDLLIEKGDLNANSNAASASNSTDNKSETFNKIKLLAMKKFPTHFHYYKNEDKHNPSPEEIKQQTILNNNAASSLPEELLNALDKGMENLRQQQPQQQVQSSQPQPQPQQLQQQPNGQRPNYYPEPLLQQQQRDSQEQQQQVPMATTRATQYPPQINSNNFNTNQASVPPQMRSNPQQPPQDKPAGQSIWL SEQ ID NO. 64, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae ICE2, amino acid sequence ColumnMTSLSKSFMQSGRICAACFYLLFTLLSIPISFKVGGLECGLSFTVTLFTLYFITTTLNVLARRHGGRLYIFFTNCLYYSQHFIIASLLYLFLSGFSNDELGNVLKNKYNESESFLEALKNSLNSNQINYVLYYYYYRFVVQPWQFVLTKSTPFFTLSEGFFTILAIQAVGETNRWLSNDLNSNTWIISSLLTSGGVITASLYYLYRIYVTPIWPLSIQTASLLGLVLSMVCGLGLYGIVSQKGSVIESSLFFAYIVRCIYEISPKLATTATDEILNLFKDVWQKHQRNLPTADNLLCYFHNVILKNAEVLWGSFIPRGRKKTGDFHDKLISILSFEKVSLISKPFWKFFKNFTFSVPLSINEFCQVTIKMASESVSPAIVINLCFRVLMFYSATRIIPALQRKNDKQLRKSRRIMKGLYWYSPCILIAMYTHLILQYSGELKKDLCIWGCSEKWFGVDQPEIIVDSWGFWNWCNIFCTILVYATELIGSGS SEQ ID NO. 65, derived from Saccharomyces cerevisiae (Saccharomyces cer Saccharomyces cerevisiae IGO1, amino acid sequence Column MSNENLSPNSSNPDLTKLNNGESGTIDTSKFSPNEMKLYKMYGKLPSKKDIFKHTMQKRKYFDSGDYALQKAGIQNNDPINYGKNNLPLTNPSKLREDIIKRRISTCPSTASTAGVVDNATLIQKEGSISSGPPSSNNGTIGGGSTSSTPVGNHSSSSSSLYTESPIR SEQ ID NO. 66, derived from Saccharomyces cerevisiae (Saccharomyces cer Saccharomyces cerevisiae IGO2, amino acid sequence Column MSEDLSPTSSRVDLSNPHGFTKEGVDLSKLSPQELKLYKMYGKLPSKKDLLRHKMQDRQYFDSGDYALKKAGVIKSDDVIVNNSSNNLPVTNPSGLRESIIRRRMSSSSGGDSISRQGSISSGPPPRSPNK SEQ ID NO. 67, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae INM1, amino acid sequence ColumnMTIDLASIEKFLCELATEKVGPIIKSKSGTQKDYDLKTGSRSVDIVTAIDKQVEKLIWESVKTQYPTFKFIGEESYVKGETVITDDPTFIIDPIDGTTNFVHDFPSFSCTSGLTVNKEPVVGVIYNPHINLLVSASKGNGMRVNNKDYDYKSKLESMGSLILNKSVVALQPGSAREGKNFQTKMATYEKLLSCDYGFVHGFRNLGSSAMTMAYIAMGYLDSYWDGGCYSWDVCAGWCILKEVGGRVVGANPGEWSIDVDNRTYLAVRGTINNESDEQTKYITDFWNCVDGHLKYD SEQ ID NO. 68, derived from brewer's yeast ( Saccharomyces cerevisiae INM2, amino acid sequence Column MVLTRQVLEEVENTFIELLRSKIGPLVKSHAGTNFCSYDDKANGVDLVTALDKQIESIIKENLTAKYPSFKFIGEETYVKGVTKITNGPTFIVDPIDGTTNFIHGYPYSCTLGLAEMKGKPVVGVVFNPHNLNQLFHASKGNGAFLN DQEIKVSKRPLILQKSLIALEGGSERTEGSQGNFDKKMNTYKNLLSESGAFVHGFRSAGSAAMNICYVASGMLDAYWEGGCWAWDVCAGWCILEEAGGIMVGGNCGEWNIPLDRRCYLAIRGGCESMEQKRFAESFWPHVAGELEY SEQ ID NO. 69, derived from Saccharomyces cerevisiae (Saccharomyces cer Saccharomyces cerevisiae INP51, amino acid sequence ColumnMRLFIGRRRSRSIVISSNNYCLSFQRLRSIPGASSQQRQLSKTPSVTIKSYPDTDLSSDSNYLEVKSCIFNGLLGLVCLNGDIYVAVISGVQNVGFPRWKLIDHQVRPSESIYKVLDVDFYSLENDVFDYLLCERSEQNYDKLIHEHPCGPLKKLFSDGTFYYSRDFDISNIVKNHGLSHNLEYTVDNQDLSFIWNANLASEVINWRSKISNEEKQLFANAGFLTFVIRGYCKTALI EDGPNTASITIISRISTESKQDTLELEGISEDGRVSLFVETEIVVTTEKFIFSYTQVNGSIPLFWESVESQLLYGKKIKVTKDSIEAQGAFDRHFDNLTSKYGVVSIVNIIKPKSESQEKLALTYKDCAESKGIKITNIEYSSSVLTKSPHKLLYLLKQDIYEFGAFAYDISRGIYFAKQTGVLRISAFDSIEKPNTVERLVSKEVLELTTNEIDVFELTSPFLDAHDKLWSENYW LDRTYTKHTKNSGKYTKVYSKLFGSRVRLYDPLHIYISQYLKQLRSKYTFEKDISIFAGTFNISGKIPKDDIKDWIFPKSMSKEDEMADLYVIGLEEVVELTPGHMLATDPYVRQFWEKKILTLNGPGRKKKYIRLWSTQLGGILLLLFMNETEYSKVKHIEGDVKKTGFGGMASNKGAVAVSFKYSATRFCVLVSHLAAGLENVEQRHNDYKTIAKSIRFSKGLRIKDHDAIIWMGDFNYRILMSNEDVRRKIVSKEYASLFEKDQLNQQMIAGESFPYFHEMAIDFPPTYKFDPGTKNYDTSEKMRIPAWTDRILSRGEVLEQLEYKCCEDILFSDHRPVYAIFRARVTVVDEQKKTTLGTQIYEKIMERLEGLDDDEKIAVLSDDAFVIESFEGSDSIAGPTHSPTIPEPKRGRKPPPPSSDLKKWWIGSGKQVKVVLDVDPAVYMINPKRDPNPFVENEDEPLFIER SEQ ID NO.70, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae INP52, amino acid sequence Column SEQ ID NO.71, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae INP53, amino acid sequence Column SEQ ID NO.72, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae INP54, amino acid sequence Column MNKTNWKVSVTTFNCGKEFPVENSKAIVKQLLFPYDDGISQLELQDLYVLGFQEVVPIWQGSFPAVNRDLIDRITTTAVNCLNEKVSATQGDEQYSCLGVNSLGAITIIVLYNNNALKVKDDILKRNGKCGWFGTHLKGGTLISFQMTRNGEENWERFSYICAHLNANEGVNNRNQRIDDYKRIMSEVCDSEVAKSDHFFLGDLNFRVTSTYDPTTNYSSTTTLRRLLENHEELNLLRKGEDEPLCKGFQELKITFPPTYKFKLFEKETYNTKRIPSWCDRILYKSYAVPTFAQEGTYHSVPRSNALLFSDHQPVNLTVRLPRSTGTPVPLSLHIEKYPLSWSSGLIGQIGDAVIGYCGWLVTKNVHYWILGSLLLYLLLKIL SEQ ID NO.73, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae IPP1, amino acid sequence Column MTYTTRQIGAKNTLEYKVYIEKDGKPVSAFHDIPLYADKENNIFNMVVEIPRWTNAKLEITKEETLNPIIQDTKKKGKLRFVRNCFPHHGYIHNYGAFPQTWEDPNVSHPETKAVGDNDPIDVLEIGETIAYTGQVKQVKALGI MALLDEGETDWKVIAIDINDPLAPKLNDIEDVEKYFPGLRATNEWFRIYKIPDGKPENQFAFSGEAKNKKYALDIIKETHDSWKQLIAGKSSDSKGIDLTNVTLPDTPTYSKAASDAIPPASPKADAPIDKSIDKWFFISGSV SEQ ID NO.74, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae ISN1, amino acid sequence ColumnMSSRYRVEYHLKSHRKDEFIDWVKGLLASPFVLHAVSHEGDYNDDLATTQRVRSQYADIFKDIEGLIKDKIEFDSRNMSQDEIEDGASSQSLNILGQSRLNLLVPSIGTFFTELPLEQAFLWEDSQRAISARRMVAPSFNDIRHILNTAQIFHFKKQENLHNGKVLRLVTFDGDVTLYEDGGSLVYTNPVIPYILKLLRCGINVGIVTAAGYDEAGTYENRLKGLIVALHDSTDIPVSQKQNLTIMGGESSYLFRYYEDPEEDNFGFRQIDKEEWLLPRMKAWSLEDVEKTLDFAERTLNRLRKRLNLPSEISIIRKVRAVGIVPGERYDEASKRQVPVKLDREQLEEIVLTLQNTLESFAPSRRIQFSCFDGGSDVWCDIGGKDLGVRSLQQFYNPESPIQPSETLHVGDQFAPVGSANDFKARLAGCTLWIASPQETVNYLHRLLETD SEQ ID NO.75, derived from Saccharomyces cerevisiae (Saccharomyces cerevi Saccharomyces cerevisiae KAE1, amino acid sequence Column MVNLNTIPPKNGRDYYIALGLEGSANKLGVGIVKHPLLPKHANSDLSYDCEAEMLSNIRDTYVTPPGEGFLPRDTARHHRNWCIRLIKQALAEADIKSPTLDIDVICFTKGPGMGAPLHSVVIAARTCSLLWDVPLVGVNHCIGHIEMGREITKAQNPVVLYVSGGNTQVIAYSEKRYRIFGETLDIAIGNCLDRFARTLKIPNEPSPGYNIEQLAKKAPHKENLVELPYTVKGMDLSMSGILASIDLLAKDLFKGNKKNKILFDKTTGEQKVTVEDLCYSLQENLFAMLVEITERAMAHVNSNQVLIVGGVGCNVRLQEMMAQMCKDRANGQVHATDNRFCIDNGVMIAQAGLLEYRMGGIVKDFSETVVTQKFRTDEVYAAWRD SEQ ID NO.76, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae LCB3, amino acid sequence ColumnMVDGLNTSNIRKRARTLSNPNDFQEPNYLLDPGNHPSDHFRTRMSKFRFNIREKLLVFTNNQSFTLSRWQKKYRSAFNDLYFTYTSLMGSHTFYVLCLPMPVWFGYFETTKDMVYILGYSIYLSGFFKDYWCLPRPRAPPLHRITLSEYTTKEYGAPSSHTANATGVSLLFLYNIWRMQESSVMVQLLLSCVVLFYYMTLVFGRIYCGMHGILDLVSGGLIGIVCFVVRMYFKYRFPGLRIEEHWWFPLFSVGWGLLLLFKHVKPVDECPCFQDSVAFMGVVSGIECCDWLGKVFGITLVYNLKPNCGWRLTLARLLVGLPCVVIWKYVISKPMIYTLLIKVFHLKDDRNVAARKRLEATHKEGASKYECPLYIGEPKIDILGRFIIYAGVPFTVVMCSPVLFSLLNIA SEQ ID NO.77, derived from Saccharomyces cerevisiae (Saccharomyces cerevi Saccharomyces cerevisiae LPP1, amino acid sequence Column MISVMADEKHKEYFKLYYFQYMIIGLCTILFLYSEISLVPRGQNIEFSLDDPSISKRYVPNELVGPLECLILSVGLSNMVVFWTCMFDKDLLKKNRVKRLRERPDGISNDFHFMHTSILCLMLIISINAALTGALKLIIGNLRPDFVDRCIPDLQKMSDSDSLVFGLDICKQTNKWILYEGLKSTPSGHSSFIVSTMGFTYLWQRVFTTRNTRSCIWCPLLALVVMVSRVIDHRHHWYDVVSGAVLAFLVIYCCWKWTFTNLAKRDILPSPVSV SEQ ID NO.78, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae LSB6, amino acid sequence ColumnMSNEAYQHDHTVNPHQKIVVNSYDWLQFRDEQDHCKSKNPITHASPGVGSNAQNSDIAEAPQVFHPSYQSLVNVPSESPRPDQTSGSNPAVGLLHNAEDKASGQEEEGSQYEIQYSVFRPLHAYPTKGLAYEQLRRKEEQEQRENFNHLVSDCIEAVETFGRELERIQTGSSGSYFVYGTRADESVPVGVFKPKDEEPYGPFSPKWTKWAHRTFFPCLFGRSCLIPNLGYICESAASLLDRRLETHLVPYTDTASIESFNFYDNRKKWVLGYNLQKKKQKKLGSFQLFLKEYINADEFFHKYPLPGMYSDVKHSFHRKSSGEDINHKPETTRNLTDETEPSKQINSSPISTESEENSKFEWTESSLSQFRLELEKLIILDYIMRNTDRGLDNWMVKLIKLSNNKWRLKLAAIDNGLSFPWKHPDEWRLYPYGWLYLPLQLLAKPFSEQMRSHFLPILTSTNWWEESYQEFLALFSRDQDFNVRMWKKQWAVLKGQAFNVVETLKDPRQGPLELVRRTRCQVIDEKMQVPCCPPPVSIFKNAIDEPIGSYSTSPMVLPSTPSTIPFHAHNQSNSNPVYYDSTLHPFANKTVIAERLQIVNSTPVFTWC SEQ ID NO.79, derived from Saccharomyces cerevisiae (Saccharomyces cerevi Saccharomyces cerevisiae LTE1, amino acid sequence Column SEQ ID NO.80, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae LTP1, amino acid sequence Column MTIEKPKISVAFICLGNFCRSPMAEIFKHEVEKANLENRFNKIDSFGTSNYHVGESPDHRTVSICKQHGVKINHKGKQIKTKHFDEYDYIIGMDESNINNNLKKIQPEGSKAKVCLFGDWNTNDGTVQTIIEDPWYGDIQDFEYNFKQITYFSKQFLKKEL SEQ ID NO.81, derived from Saccharomyces cerevisiae (Saccharomyces cerevi Saccharomyces cerevisiae MET22, amino acid sequence Column MALERELLVATQAVRKASLLTKRIQSEVISHKDSTTITKSDNSPVTTGDYAAQTIIINAIKSNFPDDKVVGEESSSGLSDAFVSGILNEIKANDEVYNKNYKKDDFLFTNDQFPLKSLEDVRQIIDFGNYEGGRKGRFWCLDPIDGTKGFLRGEQFAVCLALIVDGVVQLGCIGCPNLVLSSYGAQDLKGHESFGYIFRAVRGLGAFYSPSSDAESWTKIHVRHLKDTKDMITLEGVEKGHSSHDEQTAIKNKLNISKSLHLDSQAKYCLLALGLADVYLRLPIKLSYQEKIWDHAAGNVIVHEAGGIHTDAMEDVPLDFGNGRTLATKGVIASSGPRELHDLVVSTSCDVIQSRNA SEQ ID NO.82, derived from Saccharomyces cerevisiae (Saccharomyces cerevi Saccharomyces cerevisiae MIG1, amino acid sequence ColumnMQSPYPMTQVSNVDDGSLLKESKSKSKVAAKSEAPRPHACPICHRAFHRLEHQTRHMRIHTGEKPHACDFPGCVKRFSRSDELTRHRRIHTNSHPRGKRGRKKKVVGSPINSASSSATSIPDLNTANFSPPLPQQHLSPLIPIAIAPKENSSRSSTRKGRKTKFEIGESGGNDPYMVSSPKTMAKIPVSVKPPPSLALNNMNYQTSSASTALSSLSNSHSGSRLKLNALSSLQMMTPIASSAPRTVFIDGPEQKQLQQQQNSLSPRYSNTVILPRPRSLTDFQGLNNANPNNNGSLRAQTQSSVQLKRPSSVLSLNDLLVGQRNTNESDSDFTTGGEDEEDGLKDPSNSSIDNLEQDYLQEQSRKKSKTSTPTTMLSRSTSGTNLHTLGYVMNQNHLHFSSSSPDFQKELNNRLLNVQQQQQEQHTLLQSQNTSNQSQNQNQNQMMASSSSLSTTPLLLSPRVNMINTAISTQQTPISQSDSQVQELETLPPIRSLPLPFPHMD SEQ ID NO.83, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae MIH1, amino acid sequence ColumnMNNIFHGTEDECANEDVLSFQKISLKSPFGKKNIFRNVQTFFFKSKHSNVDDDLINKENLAFDKSPLLTNHRSKEIDGPSPNIKQLGHRDELDENENENDDIVLSMHFASQTLQSPTRNSSRRSLTNNRDNDLLSR IKYPGSPQRSSSFSRSRSLSRKPSMNSSSNSSRRVQRQDGKIPRSSRKSSQKFSNITQNTLNFTSASSSPLAPNSVGVKCFESCLAKTQIPYYYYDRNSNDFFPRISPETLKNILQNNMCESFYNSCRIIDCRFEYEYT GGHIINSVNIHSRDELEYEFIHKVLHSDTSNNNTLPTLLIIHCEFSSHRGPSLASHLRNCDRIINQDHYPKLFYPDILILDGGYKAVDFNFPELCYPRQYVGMNSQENLLNCEQEMDKFRRESKRFATKNNSFRKLASPNFYRDSHQSSTTMASSALSFRFEPPKLSLNHRVSSGSSLNSSESTGDENFFPILSKSSMSSNSNLSTSHMLLMDGLDTPSYFSFEDERGNHQQVSGDEEQDGDFTFVGSDREDLPRPARRSLFPSLETEDKK SEQ ID NO.84, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae MSG5, amino acid sequence ColumnMQFHSDKQHLDSKTDIDFKPNSPRSLQNRNTKNLSLDIAALHPLMEFSSPSQDVPGSVKFPSPTPLNLFMKPKPIVLEKCPPKVSPRPTPPSLMRRSEASIYTLPTSLKNRTVSPSVYTKSSTVSSISKLSSSSPLSSFSEKPHLNRVHSLSVKTKDLKLKGIRGRSQTISGLETSTPISSTREGTLDSTDVNRFSNQKNMQTTLIFPEEDSDLNIDMVHAEIYQRTVYLDGPLLVLPPNLYLYSEPKLEDILSFDLVINVAKEIPNLEFLIPPEMAHKIKYYHIEWTHTSKIVKDLSRLTRIIHTAHSQGKKILVHCQCGVSRSASLIVAYIMRYYGLSLNDAYNKLKGVAKDISPNGLIFQLMEWGTMLSKNSPGEEGETVHMPEEDDIGNNEVSSTTKSYSSASFRSFPMVTNLSSSPNDSSVNSSEVTPRTPATLTGARTALATERGEDDEHCKSLSQPADSLEASVDNESISTAPEQMMFLP SEQ ID NO.85, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae MSS4, amino acid sequence ColumnMSVLRSQPPSVVPLHLTTSTRKTEKEPSSLHLHSAIIERHQDRSVPNSNSNPDSNHRIKKDRNNHTSYHSSSNSNMESPRLSDGESSTPTSIEELNPTINNSRLVKRNYSISIDPLHDNSNNNTDDDHPNTITSPRPNSTSKEMQKYSFPEGKESKKITTPSLNSNNCLDLDNSSLVHTDSYIQDLNDDHILLNKRVSRRSSRISAVTATSTTIKQRRNTQDSNLPNIPFHASKHSQILPMDDSDVIKLANGDTSMKPSATKISHSMTSLPLHPLPQPSQKSKQYHMISKSTTSLPPENDHYYQHSRGTNHNHAANAAAAVNNNTTTTTAATGLKRSESAATAEIKKMRQSLLHKREMKRKRKTFLVDDDRVLIGNKVSEGHVNFIIA YNMLTGIRVAVSRCSGIMKPLTPADFRFTKKLAFDYHGNELTPSSQYAFKFKDYCPEVFRELRALFGLDPADYLVSLTSKYILSELNSPGKSFFYYSRDYKYIIKTIHHSEHIHLRKHIQEYYNHVRDNPNTLICQFYGLHRVKMPISFQNKIHRKIYFLVMNNLFPPHLDIHITYDLKGSTWGRFTNLDKERLAKDRSYRPVMKDLNWLEEGQKIKFGPLKKKTFLTQLKKDVELLAKLNTMDYSLLIGIHDINKAKEDDLQLADTASIEEQPQTQGPIRTGTGTVVRHFFREFEGGIRASDQFNNDVDLIYYVGIIDFLTNYSVMKKLETFWRSLRHDTKLVSAIPPRDYANRFYEFIEDSVDPLPQKKTQSSYRDDPNQKNYKD SEQ ID NO.86, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae NEM1, amino acid sequence ColumnMNALKYFSNHLITTKKQKKINVEVTKNQDLLGPSKEVSNKYTSHSENDCVGEVDQQYDHSSSHLKESDQNQERKNSVPKKPKALRSILKEKIASILWALLLFLPYYLIIKPLMSLWFVFTFPLSVIERRVKHTDKRNRGSNASENELPVSSSNINDSSEKTNKPKNCNLNTIPEAVDDLNASDEIILQRDNVKGSLLRAQSVKSRPRSYSKSELSLSNHSSSSNTVFGTKRMGRFLFPKKLIPKSVLNTQKKKKLVIDLDETLIHSASRSTTHSNSSQGHLVEVKFGLSGIRTLYFIHKRPYCDLFLTKVSKWYDLIIFTASMKEYADPVIDWLESSFPSFSSKRYYRSDCVLRDGVGYIKDLSIVKDSEENGKGNSSSLDDVIIIDNSPVSYAMNVDNAIQVEGWISDPTDTDLLNLLPFLEAMRYSTDVRNILALKHGEKAFNIN SEQ ID NO.87, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae NET1, amino acid sequence Column SEQ ID NO.88, derived from brewer's yeast ( Saccharomyces cerevisiae NPP1, amino acid sequence Column MELQNDLESLDNELNDFSEDPFRDDFITDEDAVRSGWRSAWTRMKYWFYKNRLKWTNNPIVIGDAKDSRDGSNFRRGIPLYELDANGQPIDTELVDENELSFGTGFHSKVPFKIIFRTLFGSLVFAIFLILMINIAKPHHSTRVLSHFGSPEFDPYVKYFNGTHEFFPLTIVISLDGFHPSLISKRNTPFLHDLYELKYDGGMNITSTPFMVPSFPTETFPNHWTLVTGQYPIHHGIVSNVFWDPDLNEEFHPGVLDPRIWNNNDTEPIWQTVQSAFDGDIPFKAATHMWPGSDVNYTKYNEEKLQPEHKNPIARERTPFYFDEFNAKEPLSQKLSKIIEYVDMSTLNERPQLILGYVPNVDAFGHKHGYPSESEYYYEDFTETLGEVDTFLKQLVESLQERNLTSFTNLVIVSDHGMSDIVVPSNVIIWEDLLDEKLRKDYVSHAYLEGPMMAISLKDSGNINEVYHNLKTSIDEDKYTVYVNGNFPKEWNFNDGKNHHMASIWIVPEPGYAVMKKEQLKKVAKGDHKDKNEDNVFTIGSHGYDNNAIDMRSVFIGMGPYFPQGYIEPFQNTEIYNLLCDICGVAEKDRNSNDGTGMLMNQLREPQSSEEVEIEDDFDYLVSKFGEFSTYNIIWGGYPEETEQDNVDNDNDDNDDGNTDEIAAMPSSSLTIKLEMTTSIPSATETLLGETSPSSRSSSSSSIQASATASTVGDWLQDIINDAKDLIDDIIDSIDDLVDSDT SEQ ID NO.89, derived from Saccharomyces cerevisiae (Saccharomyces cerevi Saccharomyces cerevisiae NPP2, amino acid sequence ColumnMLLFEQPVDLEKNNEDDTNIKPFAISRHFLLKLLLCGIILIELLLYSKCPKPIDNGPRTIANRSNTYFNGTHDFKTLTILISIDGFHPRLIDAKYTPFLYNLHNLRSPYDMNITTAPYMIPSFPTQTFPNHWSMVTGKYPIEHGIVSNIFWDNFTSSEFRPNNLDARIWSNTADPIWQLLQTESQGEYKVATHMWPGSEVVYEDHGDVPRERMPFYFGKFNQWEKLQDKLAQIFRYIDMPQLKDRP ELVISYIPNVDSYGHSFGYDLRDKRLQKLIGEVDGFFLDLIEGLQKRNLLKISNVMIVSDHGMSNVNANDGEHVVVWERVFPADAMSAFISHLYNEGPMMMVCLKNPRDKQWICDLIEAQLEKAYGDEISRKFHILVKEDDFDPSWKYFQYDNRKHRYDDRVGDIWILADEYYAIVKEMGDVPIGIMGTHGYNFNNCSDMASIFIGMGPMFNNEVVPPFENIEVYNMLIKASALLGEEKTKKEKSLLQ SEQ ID NO.90, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae NPY1, amino acid sequence Column MSTAVTFFGQHVLNRVSFLRCSKEFIKKSLNHDSTVFIPFIEALISPENGDLVQLSNSVKSYKNILSAIVPLYTTLLNTTRSRSDESGINVTFLGLLEGTDSAFNFEWSNISYKGTPPYFGLDIRVTESTLFKKVDFEPIFSYKPVTRDHIFKQTNEDASLYSQGKMYLDWLAKYKFCPGCGSPLFVEAG TKLQCSNENRNVYCNVRDARINNVCFPRTDPTVIIALTNSDYSKCCLARSKKRYGDFVLYSTIAGFMEPSETIEEEACIREIWEETGISCKNIDIVRSQPWPYPCSLMIGCLGIVQFNSKNEVINLNHDDELLDAQWFDTTEIIQALDKYAGGYRVPFKNDINLPGSTTIAFQLINHVCENYKNLRKTSSSHL SEQ ID NO.91, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae OCA1, amino acid sequence ColumnMTSKVGEYEDVPEDESRLTEENVSVPEEEVEDEDEEEDDDDDHIYINEETESGREKVLVSHAPQERIVPPLNFCPVERYLYRSGQPSPVNFPFLLNLKLKTIIWLSNEEPQDTLLEFCDTHRINLQFAAINPDAGEDDNPWDGLTEHSIINVLQTIVTQENYPLLVCCGMGRHRTGTVIGCLRRIMGWNLASVSEEYRRFTGSRGGRILVELLIEAFDTNLVKIDKNKAPSWLLTALE SEQ ID NO.92, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). OCA2, amino acid sequence Saccharomyces cerevisiae MKYIPPLNFSPVVSTDVSLYRSGYPMPLNYSFIKHQLHLKTIIYIGDKDRPLEEYQSFLESEKIKYYHIFMDSSRDEGIQERMNQVLHLVLDVRNYPILVHSNKGKHRVGVVVGIIRKLLQGWSTAGICQEYGLFSGGMKDGVDLEFITMFETNLKIPRNVIPGFAKHCLYLNELEAAEGSDDESGSESILTAKQPI SEQ ID NO.93, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Column OCA4, amino acid sequence Saccharomyces cerevisiae MLVPPANFGIAEEGIYRCSKVETLNLSFLETLNLKTAIFIGGQEPSKFFKDFFTRSSIKWIVLRMSDFSAAAVPVKSSSVSNANLYSNNNSTLSLQEEKKKSTANGSQNSTTGDPVIQEELAYHLTDNDDLMLIKSTCLKRTFKTLLNVDNYNVLLVDKTALVIGILRKIQKWNIASIINEYRLFSGKNRNYFAETFLEIINIEIEQEKDNKTIVDNKAKKLPLENNRTHSIEYKANSGKLIRVNEDDLCREPEVPQRLLTLINQIETKVKNNKVLQVSGVLGDDLKKTSSDLGIFGHRYRLAFNKKENGDYGYYKARGKDNVKIRIPCDSELPDWFKFQRDLWEKENVPEEHHFYREHIFT SEQ ID NO.94, derived from Saccharomyces cerevisiae (Saccharomyces cerevi Column OCA6, amino acid sequence Saccharomyces cerevisiaeMTLVTPLQFSTVQPNLYRGSYPREINLPFLRTLRLKYILSLTPEPLSTDPLMVKFCEENNIKTIHIKCQSERKADKTKPKIKRKKKTVPIEYDVVVRCVKFLIDKGHYPCYMHCTNGELIISLVVACMRKFSYWSTVSILNEFLVYNSSINIHERNFIENFNSEIEVDDLDIKDKVPWITVRYIARTATESKDELRVDDANASEKVARVSSVSNSLPKLKFHSM SEQ ID NO.95, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Column PAH1, amino acid sequence Saccharomyces cerevisiaeMQYVGRALGSVSKTWSSINPATLSGAIDVIVVEHPDGRLSCSPFHVRFGKFQILKPSQKKVQVFINEKLSNMPMKLSDSGEAYFVFEMGDQVTDVPDELLVSPVMSATSSPQSPETSILEGGTEGEGEGENENKKKEKKVLEEPDFLDINDTGDSGSKNSETTGSLSPTESSTTTPLDSVEERKLEQRTKNFQQKLNKKLKTEIHIPSKLDNNGDLLDTEGYKPNKNMMHDDDIQLKQLLKDEFGNDSDISSFIKEDKNGNIKIVNPYEHLTDLSPPGTTPMATSGSVLGLDAMESGSTLNSLSSSPSGSDTEDETSFSKEQSSKSEKTSKKGTAGSGETEKRYIRTIRLTNDQLKCLNLTYGENDLKFSVDHGKAIVTSKLFVWRWDVPIVISDIDGTITKSDALGHVLAMIGKDWTHLGVAKLFSE ISRNGYNYLYLTARSAGQADSTRSYLRSIEQNGSKLPNGPVILSPDRTMAALRREVILKKPEVFKIACLNDIRSLYFEDSDNEMDTEEKSTPFFAGFGNRITDALSYRTVGIPSSRIFTINTEGEVHMELLELAGYRSSYIHINELVDHFFPPVSLDSVDLRTNTSMVPGSPPNRTLDNFDSEITSGRKTLFRGNQEEKFTDVNFWRDPLVDIDNLSDISNDDSDNIDEDTDVSQQSNVSRNRANSVKTAKVTKAPQRNVSGSTNNNEVLAASSDVENASDLVGSHSSSGSTPNKSTMSKGDIGKQIYLEGSPLASPKLRYLDDMDDEDSNYNRTKSRRASSAAATSIDKEFKKLSVSKAGAPTRIVSKIDVSNDVHSLGNSDTESRREQSVNETGRNQLPHNSMDDKDLDSRVSDEFDDDEFDEDEFED SEQ ID NO.96, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Column PCD1, amino acid sequence Saccharomyces cerevisiaeMILSQRRMLSSKQLIENLIRYKFHKTPYTRSSIWPFKRNSAVIILLFIGMKGELRVLLTKRSRTLRSFSGDVSFPGGKADYFQETFESVARREAEEEIGLPHDPEVLHKEFGMKLDNLVMDMPCYLSRTFLSVKPMVCFLYKDKLEKHEDKYKVPLDIRKFFGKLNPGETSSLFSVPLNDLVIHLLPEADEDVKSYQAEYFERKEYKLNWGGIKWLIMHYHFHVANNNEMPWLQTIEDLSSSDEDGVDGGIFRFRDLWGLTCKILFDVSCIANGLMDEKLKGELGHEDLIVGLHDYGNQMQPNGRSEWEIGMINGDRNLKYSDVIPEYYMKHLLECRSLW SEQ ID NO.97, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Column PDL32, amino acid sequence Saccharomyces cerevisiae MTGSLNRHSLLNGVKKMRIILCDTNEVVTNLWQKSIPHAYIQNDKYLCIHHGHLQSLMDSMRKGDAIHHGHSYAIVSPGNSYGYLGGGFDKALYNYFGGKPFETWFRNQLGGRYHTVGSATVVDLQRCLEEKTIECRDGIRYIIHVPTVVAPSAPIFNPQNPLKTGFEPVFNAMWNALMHSPKDIDGLIIPGLCTGYAGVPPIISCKSMAFALRLYMAGDHISKELKNVLIMYYLQYPFEPFFPESCKTECQKLGIDIEMLKSFNVEKDAIELLIPRRILTLNL SEQ ID NO.98, derived from brewer's yeast ( Column PEP4, amino acid sequence Saccharomyces cerevisiaeMFSLKALLPLALLLVSANQVAAKVHKAKIYKHELSDEMKEVTFEQHLAHLGQKYLTQFEKANPEVVFSREHPFFTEGGHDVPLTNYLNAQYYTDITLGTPPQNFKVILDTGSSNLWVPSNECGSLACFLHSKYDHEASSSYKANGTEFAIQYGTGSLEGYISQDTLSIGDLTIPKQDFAEATSEPGLTFAFGKFDGILGLGYDTISVDKVVPPFYNAIQQDLLDEKRFAFYLGDTSKDTENGGEATFGGIDESKFKGDITWLPVRRKAYWEVKFEGIGLGDEYAELESHGAAIDTGTSLITLPSGLAEMINAEIGAKKGWTGQYTLDCNTRDNLPDLIFNFNGYNFTIGPYDYTLEVSGSCISAITPMDFPEPVGPLAIVGDAFLRKYYSIYDLGNNAVGLAKAI SEQ ID NO.99, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Column PHM8, amino acid sequence Saccharomyces cerevisiae MTIAKDYRTIYRNQIKKQIRLNQEHLQSLTHLGSQINFEVDPPKLPDPDPARKVFFFDIDNTLYRKSTKVQLLMQQSLSNFFKYELGFDDDEAERLIESYYQEYGLSVKGLIKNKQIDDVLQYNTFIDDSLPLQDYLKPDWKLRELLINLKKKKLGKFDKLWLFTNSYKNHAIRCVKILGIADLFDGITYCHYDRPIEEEFICKPDPKFFETAKLQSGLSSFANAWFIDDNESNVRSALSMGMGHVIHLIEDYQYESENIVTKDHKNKQQFSILKDILEIPLIMDVEVYRPSSIAIKEMEELEEEGEAVNWSNQQINVQSS SEQ ID NO.100, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Column PHO11, amino acids Saccharomyces cerevisiaeMLKSAVYSILAASLVNAGTIPLGKLSDIDKIGTQTEIFFPLGGSGPYYSFPGDYGISDRLPESCEMKQVQMVGRHGERYPTVSKASIMTTWYKLSNYTGQFSGALSFLNDDYEFFIRDTKNLEMETTLANSVNVLNPYTGEMNAKRHARDFLAQYGYMVENQTSFAVFTSNSRCHDTAQYFIDGLDKFNISLQTISEAESAGANTLSAHHSCPAWDDDVNDDILKKYDTKYLSGIAKRLNKENKGLNLTSSDANTFFAWCAYEINARGYSDICNIFTKDELVRFSYGQDLETYYQTGPGYDVVRSVGANLFNASVKLLKESEVQDQKVWLSFTHDTDILNYLTTIGIIDDKNNLTAEHVPFMENTFHRSWYVPQGARVYTEKFQCSNDTYVRYVINDAVVPIETCSTGPGFSCEINDFYDYAEKRVAGTDFLKVCNVSSVSNSTELTFFWDWNTKHYNDTLLKQ SEQ ID NO.101, derived from Saccharomyces cerevisiae (Saccharomyces cer Sequence PHO12, amino acids Saccharomyces cerevisiae MLKSAVYSILAASLVNAGTIPLGKLSDIDKIGTQTEIFFPLGGSGPYYSFPGDYGISDRLPESCEMKQVQMVGRHGERYPTVSKASIMTTWYKLSNYTGQFSGALSFLNDDYEFFIRDTKNLEMETTLANSVNVLNPYTGEMNAKRHARDFLAQYGYMVENQTSFAVFTSNSRCHDTAQYFIDGLDKFNISLQTISEAESAGANTLSAHHSCPAWDDDVNDDILKKYDTKYLSGIAKRLNKENKGLNLTSSDANTFFAWCAYEINARGYSDICNIFTKDELVRFSYGQDLETYYQTGPGYDVVRSVGANLFNASVKLLKESEVQDQKVWLSFTHDTDILNYLTTIGIIDDQNNLTAEHVPFMENTFHRSWYVPQGARVYTEKFQCSNDTYVRYVINDAVVPIETCSTGPGFSEINDFYGYAEKRVAGTDFLKVCNVSSVSNSTELTFFWDWNTKHYNDTLLKQ SEQ ID NO.102, derived from Saccharomyces cerevisiae (Saccharomyces cer Sequence PHO13, amino acidSaccharomyces cerevisiae Sequence MTAQQGVPIKITNKEIAQEFLDKYDTFLFDCDGVLWLGSQALPYTLEILNLLKQLGKQLIFVTNNSTKSRLAYTKKFASFGIDVKEEQIFTSGYASAVYIRDFLKLQPGKDKVWVFGESGIGEELKLMGYESLGGADSRLDTPFDAAKSPFLVNGLDKDVSCVIAGLDTKVNYHRLAVTLQYLQKDSVHFVGTNVDSTFPQKGYTFPGAGSMIESLAFSSNRRPSYCGKPNQNMLNSIISAFNLDRSKCCMVGDRLNTDMKFGVEGGLGGTLLVLSGIETEERALKISHDYPRPKFYIDKLGDIYTLTNNEL SEQ ID NO.103, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae PHO2, amino acid sequence Column MMEEFSYDHDFNTHFATDLDYLQHDQQQQQQQHDQQHNQQQQPQPQPIQTQNLEHDHDQHTNDMSASSNASDSGPQRPKRTRAKGEALDVLKRKFEINPTPSLVERKKISDLIGMPEKNVRIWFQNRRAKLRKKQHGSNKDTIPSSQSRDIANDYERGSTDNNLVTTTSTSSIFHDEDLTFFDRIPLNSNNNYYFFDICSITVGSWNRMKSGALQRRNFQSIKELRNLSPIKINNIMSNATDLMVLISKKNSEINYFFSAMANNTKILFRIFFPLSSVTNCSLTLETDDDIINSNNTSDKNNSNTNNDDDNDDNSNEDNDNSSEDKRNAKDNFGELKLTVTRSPTFAVYFLNNAPDEDPNLNNQWSICDDFSEGRQVNDAFVGGSNIPHTLKGLQKSLRFMNSLILDYKSSNEILPTINTAIPTAAVPQQNIAPPFLNTNSSATDSNPNTNLEDSLFFDHDLLSSSITNTNNGQGSNNGRQASKDDTLNLLDTTVNSNNNHNANNEENHLAQEHLSSDADIVANPNDHLLSLPTDSELPNTPDFLKNTNELTDEHRWI SEQ ID NO.104, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae PHO3, amino acid sequence ColumnMFKSVVYSVLAAALVNAGTIPLGELADVAKIGTQEDIFPFLGGAGPYFSFPGDYGISRDLPEGCEMKQLQMLARHGERYPTYSKGATIMKTWYKLSNYTRQFNGSLSFLNDDYEFFIRDDDLEMETTFANSDNVLNPYTGEMDAKRHAREFLAQYGYMFENQTSFPIFAASSERVHDTAQYFIDGLDQFNISLQTVSEAMSAGANTLSAGNACPGWDEDANDDILDKYDTTYLDDIAKRLNKENKGLNLTSKDANTLFAWCAYELNARGYSDVCDIFTEDELVRYSYGQDLVSFYQDGPGYDMIRSVGANLFNATLKLLKQSETQDLKVWLSFTHDTDILNYLTTAGIIDDKNNLTAEYVPFMGNTFHKSWYVPQGARVYTEKFQCSNDTYVRYVINDAVVPIETCSTGPGFSEINDFYDYAEKRVAGTDFLKVCNVSSVSNVTELTFYWDWNTTHYNDTLLKQ SEQ ID NO.105, derived from Saccharomyces cerevisiae (Saccharomyces cer Saccharomyces cerevisiae PHO5, amino acid sequence Column MFKSVVYSILAASLANAGTIPLGKLADVDKIGTQKDIFPFLGGAGPYYSFPGDYGISRDLPEGCEMKQLQMVGRHGERYPTVSLAKTIKSTWYKLSNYTRQFNGSLSFLNDDYEFFIRDDDLEMETTFANSDDVLNPYTGEMNAKRHARDFLAQYGYMVENQTSFAVFTSNSKRCHDTAQYFIDGLDQFNITLQTVSEAESAGANTLSACNSCPAWDYDANDDIVNEYDTTYLDDIAKRLNKENKGLNLTSTDASTLFSWCAFEVNAKGYSDVCDIFTKDELVHYSYYQDLHTYYHEGPGYDIIKSVGSNLFNASVKLLKQSEIQDQKVWLSFTHDTDILNFLTTAGIIDDKNNLTAEYVPFMGNTFHRSWYVPQGARVYTEKFQCSNDTYVRYVINDAVVPIETCSTGPGFSEINDFYDYAEKRVAGTDFLKVCNVSSVSNSTELTFYWDWNTTHYNASLLRQ SEQ ID NO.106, derived from Saccharomyces cerevisiae (Saccharomyces cer Saccharomyces cerevisiae PHO8, amino acid sequenceColumn MMTHTLPSEQTRLVPGSDSSSRKPKRRISKRSKIIVSTVVCIGLLLVLVQLAFPSSFALRSASHKKKNVIFFVTDGMGPASLSMARSFNQHVNDLPIDDILTLDEHFIGSSRTRSSDSLVTDSAAGATAFACALKSYNGAI GVDPHHRPCGTVLEAAKLAGYLTGLVVTTRITDATPASFSSHVDYRWQEDLIATHQLGEYPLGRVVDLLMGGGRSHYPQGEKASPYGHHGARKDGRDLIDEAQSNGWQYVGDRKNFDSLLKSHGENVTLPFLGLFADNDIP FEIDRDEKEYPSLKEQVKVALGALEKASNEDKDSNGFFLMVEGSRIDHAGHQNDPASQVREVLAFDEAFQYVLEFAENSDTETVLVSTSDHETGGLVTSRQVTASYPQYVWYPQVLANATHSGEFLKRKLVDFVHEHKGASSKIENFIKHEILEKDLGIYDYTDSDLETLIHLDDNANAIQDKLNDMVSFRAQIGWTTHGHSAVDVNIYAYANKKATWSYVLNNLQGNHENTEVGQFLENFLELNLNEVTDLIRDTKHTSDFDATEIASEVQHYDEYYHELTN SEQ ID NO.107, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae PHO8 ^62aa, ammonia Amino acid sequenceMSHKKKNVIFFVTDGMGPASLSMARSFNQHVNDLPIDDILTLDEHFIGSSRTRSSDSLVTDSAAGATAFACALKSYNGAIGVDPHRPCGTVLEAAKLAGYLTGLVVTTRITDATPASFSSHVDYRWQEDLIATHQLGEYPLGRVVDLLMGGGRSHFYPQGEKASPYGHHGARKDGRDLIDEAQSNGWQYVGDRKNFDSLLKSHGENVTLPFLGLFADNDIPFEIDRDEKEYPSLKEQVKVALGALEKASNEDKDSNGFFLMVEGSRIDHAGHQNDPASQVREVLAFDEAFQYVLEFAENSDTETVLVSTSDHETGGLVTSRQVTASYPQYVWYPQVLANATHSGEFLKRKLVDFVHEHKGASSKIENFIKHEILEKDLGIYDYTDSDLETLIHLDNANAIQDKLNDMVSFRAQIGWTTHGHSAVDVNIYAYANKKATWSYVLNNLQGNHENTEVGQFLENFLELNLNEVTDLIRDTKHTSDFDATEIASEVQHYDEYYHELTN SEQ ID NO.108, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae PIG1, amino acid sequence ColumnMPYSHGKKLKPSLKLAKTISTSSFVSSTTSNSFSPLEDSTSASLSTSSSSSGKSVRFAAHLYTVKKFNTKLAPISISEKAASNLTRNLHNNAIPLTFPFIGGEDHRYSLDILDYSDLEYDNKDVEYDNESDVEDNAMLMHDRSMFIEKEILCFGEEETFDMADWKLVSNNLNPFKSDCKVDVTELEDKIFKYLNGQNIKVHSLELSDPVSYEDICSNNFGNCQIWGLIFVNNLNFEKKIEIKFTLNNWADIHYINAHYNKSVTPHVDEFKFIIDISALKLNLISKNLIYANFFERKTTCLLNLQFCCRYDVNGFDYRSFYDNNDYKNYEITISLSAINLNRAVSNSSIFNSNLGPSKMRASNAEVTMSKNNKNSKKPLRKFIKDTDYYNDSPLKHKFYQSFETKAACKTEPVPQTFKAETIDCEIEPFNYFFEPPDSQTNEDMSDSSYDLSLQDFNYWEFSNHGLGKALADSDILQFKNYPKPEPFSRPPIIDDTFTLNTDDRTLGLKTEKLEDNLAKEWKSAKTRTTLNETPLHDDEHRTSFTYTTWNNSTDTLMKKQEERPVESASCSQLSIATIKAEEDLLYQDYINSGRESSSPEISPLNNTTSLPFFPGDNMSDSSGEYKERISLSPNKIHIFRDYFYKSPSP SEQ ID NO.109, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae PIG2, amino acid sequence ColumnMATTTQPQNILMDEPLNLPNNSAHNNNYGNINANIRTSAGMSMHMHPARLNSLEFLHKPRRLSNVKLHRLPQDELQRNTDMNKGMYFNGKQVHAHHPFINSGANFNAHHQDVSKLGEEEDEISPLSHDNFQYESEENGNPSPPIYKKSGELVKSSLKRRSKSLPITPKSIFNKTGSKSKHVNLDHVDTRLLQRSKSVHFDRVLPIKLFNENEKPIDVGKQMVQQDVLNFKHKPLTRLSALNGGSDSVPIEDLLSENNQNEYGDTWLQNPKGVFLFGTNSNNRRNKKKKFKLSDDDSDIENDNDSDDAINRLVRQQDKDQAHLAHGLKNLLINDDDDYLETRTNSAKSGANLFIGNSKRIVGLYNKNFPILSDRDRKSLKLNIFLNLSRGRPVFLQEITLLTGFHNMVIIGKVFVKNIYFDKKIIVRYTWDAWRTFHESECVYFSNANGILPGSNMDIFKFSIDDIHNPNDKDSNISQLEFCIQYLTWGVDRSRKEYWDNNDSANYKIDVVTNETRTGPTTDVNDNYEMKHSLFRNPFH SEQ ID NO. 110, derived from Saccharomyces cerevisiae (Saccharomyces Saccharomyces cerevisiae PIK1, amino acid sequence Column SEQ ID NO.111, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae PMU1, amino acid sequence Column MSLRAVPGYFAAYPSEGFQGLDSTKYDHLELINHKNWKELYHAIPRNTKNRHYKLLILARHGQGYHNAAILRYGMEKWDAYWSLLSGDEHGEWLDSKLTPLGKDQVRRTGSNVLLPMAKQLGMLPHVFFSSPMRRCLETFIESWTPVLAETQELPAGTKISTRIIEGLRETLGSHTCDKRVAHSMAVDEYQDFSTESGHTVHWQYVPDYPEDDELWLPDHRETCAEMDKRTLNGLFELFNQLSSEEKFISLTCHSGVIQSVLRNLQHPPIYNLDTGKVVAVVVEVPVNTADRGRL SEQ ID NO.112, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae POA1, amino acid sequence Column MSNITYVKGNILKPKSYARILIHSCNCNGSWGGGIAYQLALRYPKAEKDYVEVCEKYGSNLLGKCMLLPSYENSDLLICCLFTSSFGGSSHGEKQSILNYTKLALDKLKTFREAKDKTRTSEDIIGDYLNGHIKYPIGEYKLEMPQINSGIFGVPWKETERVLEEFSGDMSFTVYQL SEQ ID NO.113, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae PPA2, amino acid sequence Column MNLLRMNALTSKTRSIERLKQTLNILSIRNHRQFSTIQQGSKYTLGFKKYLTLLNGEVGSFFHDVPLDLNEHEKTVNMIVEVPRWTTGKFEISKELRFNPIVQDTKNGKLRFVNNIFPYHGYIHNYGAIPQTWEDPTIEHKLGKCDVALKGDNDPLDCCEIGSDVLEMGSIKKVKVLGSLALIDNGELDWKVIVIDVNDPLSSKIDDLEKIEEYFPGILDATREWFRKYKVPAGKPLNSFAFHEQYQNSNKTIQTIKECHNSWKKLISGSLQEKYDNLPNTERAGNGVTLEDSVKPPSQIPPEVQKWYYV SEQ ID NO.114, derived from Saccharomyces cerevisiae (Saccharomyces cer Saccharomyces cerevisiae PPE1, amino acid sequence ColumnMSDDLRRKIALSQFERAKNVLDATFQEAYEDDENDGDALGSLPSFNGQSNRNRKYTGKTGSTTDRISSKEKSSLPTWSDFFDNKELVSLPDRDLDVNTYYTLPTSLLSNTTSIPIFIFHHGAGSSGLSANLAKELNTKLEGRCGCFAFDARGHAETKFKKADAPICFDRDSFIKDFVSLLNYWFKSKISQEPLQKVSVILIGHSLGGSICTFAYPKLSTELQKKILGITMLDIVEEAAIMALNKVEHFLQNTPNVFESINDAVDWHVQHALSRLRSSAEIAIPALFAPLKSGKVVRITNLKTFSPFWDTWFTDLSHSFVGLPVSKLLILAGNENLDKELIVGQMQGKYQLVVFQDSGHFIQEDSPIKTAITLIDFWKRNDSRNVVIKTNGQHKTVQNT SEQ ID NO.115, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae PPG1, amino acid sequence Column MELDECLERLYKAQLLPEVTVRALCFKLKEMLVKESNVIHIQTPVTVVGDMHGQFHDMLEIFQIGGPVPDTNYLFLGDYVDRGLYSVETIMLLIVLKLYPSRIHLRGNHESRQITQSYGFYTECLNKYGGNSRVWQYLTDIFDYLLVLCCIIDDEIFCVHGGLSPNVQTIDQIKIIDRFREIP HDGAMADLVWSDPEENNNPTLDHPDNGSQHFQVSPRGAGYTFGRSVVEKFLRMNDMNRIIRAHQLCNEGYQIYFDGLVTTVWSAPNYCYRCGNKASILELYSKDQFYFNVFEEAPENKLLKENSMNDNALEDSISNPVANRKLIADYFEDDSASADGSTDPEMYIFSDVYQARSASNRHVDYFL SEQ ID NO.116, derived from Saccharomyces cerevisiae (Saccharomyces cer Saccharomyces cerevisiae PPH21, amino acids SequenceMDTDLDVPMQDAVTEQLTPTVSEDMDLNNNSSDNNAEEFSVDDLKPGSSGIADHKSSKPLELNNTNINQLDQWIEHLSKCEPLSEDDVARLCKMAVDVLQFEENVKPINVPVTICGDVHGQFHDLLELFKIGGPCPDTNYLFMGDYVDRGYYSVETVSYLVAMKVRYPHRITILRGNHESRQITQVYGFYDECLRKYGSANVWKMFTDLFDYFPITALVDNKIFCLHGGLSPMIETIDQVRELNRIQEVPHEGPMCDLLWSDPDDRGGWGISPRGAGFTFGQDVSEQFNHTNDLSLIARAHQLVMEGYAWSHQQNVVTIFSAPNYCYRCGNQAAIMEVDENHNRQFLQYDPSVRPGEPSVSRKTPDYFL SEQ ID NO.117, derived from Saccharomyces cerevisiae (Saccharomyces cer Saccharomyces cerevisiae PPH22, amino acids Sequence MAVDVLQFEENVKPINVPVTICGDVHGQFHDLLELFKIGGPCPDTNYLFMGDYVDRGYYSVETVSYLVAMKVRYPHRITILRGNHESRQITQVYGFYDECLRKYGSANVWKMFTDLFDYFPITALVDNKIFCLHGGLSPMIETIDQVRELNRIQEVPHEGPMCDLLWSDPDDRGGWGISPRGAGFTFGQDVSEQFNHTNDLSLIARAHQLVMEGYSWSHQQNVVTIFSAPNYCYRCGNQAAIMEVDENHNRQFLQYDPSVRPGEPTVTRKTPDYFL SEQ ID NO.118, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae PPH3, amino acid sequence ColumnMMDLDKIIASLRDGKHIPEETVFRCLNSQELLMNEGNVTQVDTPVTICGDIHGQLHDLLTLFEKSGGVEKTRYIFLGDFVDRGFYSLESFLLLLCYKLRYPDRITLIRGNHETRQITKVYGFYDEVVRKYGNSNVWRYCCEVFDYLSLGAIINNSIFCVHGGLSPDMTTVDEIRTIDRKQEVPHEGAMCDLLWSDPEDDVDTWSLSPRGAGFLFGKREVDQFLEKNNVELIARAHQLVMEGYKEMFDGGLVTWSAPNYCYRCGNVAAVLKIDDDLNREYTIFEAVQAQNEVGNAIIPTKKSQMDYFL SEQ ID NO.119, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae PPM1, amino acid sequence Column MERIIQQTDYDALSCKLAAISVGYLPSSGLQRLSVDLSKKYTEWHRSYLITLKKFSRRAFGKVDKAMRSSFPVMNYGTYLRTVGIDAAILEFLVANEKVQVVNLGCGSDLRMLPLQMFPHLAYVDIDYNESVELKNSILRESEILRISLGLSKEDTAKSPFLIDQGRYKLAACDLNDITETTRLLDVCTKREIPTIVISECLLCYMHNNESQLLINTIMSKFSHGLWISYDPIGGSQPNDRFGAIMQSNLKESRNLEMPTLMTYNSKEKYASRWSAAPNVIVNDMWEIFNAQIPESERKRLRSLQFLDELEELKVMQTHYILMKAQW SEQ ID NO.120, derived from Saccharomyces cerevisiae (Saccharomyces cer Saccharomyces cerevisiae PPM2, amino acid sequence ColumnMKNLTTIKQTNKNVKQERRKKYADLAIQGTNNSSIASKRSVELLYLPKLSSANNFQMDKNNKLLEYFKFFVPKKIKRSPCINRGYWLRLFAIRSRLNSIIEQTPQDKKIVVVNLGCGYDPLPFQLLDTNNIQSQQYHDRVSFIDIDYSDLLKIKIELIKTIPELSKIIGLSEDKDYVDDSNVDFLTTPKYLARPCDLNDSKMFSTLLNECQLYDPNVVKVFVAEVSLAYMKPERSDSIIEATSKMENSHFIILEQLIPKGPFEPFSKQMLAHFKRNDSPLQSVLKYNTIESQVQRFNKLGFAYVNVGDMFQLWESADEATKKELLKVEPFDELEEFHLFCHHYVLCHATNYKEFAFTQGFLFDRSISEINLTVDEDYQLLECECPINRKFGDVDVAGNDVFYMGGSNPYRVNEILQLSIHYDKIDMKNIEVSSSEVPVARMCHTFTTISRNNQLLLIGGRKAPHQGLSDNWIFDMKTREWSMIKSLSHTRFRHSACSLPDGNVLILGGVTEGPAMLLYNVTEEIFKDVTPKDEFFQNSLVSAGLEFDPVSKQGIILGGGFMDQTTVSDKAIIFKYDAENATEPITVIKKLQHPLFQRYGSQIKYITPRKLLIVGGTSPSGLFDRTNSIISLDPLSETLTSIPISRRIWEDHSLMLAGFSLVSTSMGTIHIIGGGATCYGFGSVTNVGLKLIAIAK SEQ ID NO.121, derived from Saccharomyces cerevisiae (Saccharomyces cer Saccharomyces cerevisiae PPN2, amino acid sequence ColumnMEDKRKRRAATLSTALILFVACVYTLYIFKFDNPRLSPPVSLLPTISTLKIEHVTDLNKEYVFVGDVHGNYDEFIELIDDKIGGGLGENITMILLGDFIHKGPDSDKVVSYILNHKDQVKCVLGNHEILVMMAYLNPDFSKWVRRPKLMTPLTFSTETNFIPQDISKISNAHGRLARELGFSKLSQLAEHCSMAIELDLDITGDILFGAHAGMVPDGDFMKPNQIPGVSSLSNMKYVDKKNWSKTSREKENKNYVRWYTLWDKYGDHFSNAKVFYGHDASMGLNLRRQTKGLDTACIKNNLLSSMKVKYDIKKGQYDYELIQVQCS SEQ ID NO.122, derived from Saccharomyces cerevisiae (Saccharomyces cer Saccharomyces cerevisiae PPQ1, amino acid sequence Column MRRSPSRSNNNFAVPNCSTNSNSSQQQLTTPSDDLNSNEPNDPDDSRSLPTIKKFNNKHSINNYNTLASAGKNNNNKRASNDNLLIPGENAHKQKIYTKDENLKSLYLDIDVSVAKALSSSATAPKLINTARTSSTTTATTSNNILTSPSSYRESNYSSPSSYSFSSYYSSATSASSSTSSFLKSSGLSSRVKSPSSSVKAGSFGAPSSPTSGIPNPKSSKKPIFLRRYSHDTSSNEGLDIDVAIEKLLQVGESREITKTSKKKNFPFHSWEIQL ICYHAREIFLNQPTLLRLQAPIKVVGDVHGQFNDLRILKLSGVPSDTNYLLFLGDYVDRGKNSLETILLLLCYKIKYKDNFFMLRGNHESANVTKMYGFYDECKRRLSSKVWKMFVDVFNTLPLAAIIQDKIFCVHGGISPDLHDMKQIEKVARPTDIPESGLVTDLLWSDPDPQVTDWSENDRGVSYTFSKRNVLDFCAKFKFDLILRGHMVVEDGYEFFARKKFVTIFSAPNYCGEFHNWGAVMSVTTGMMCSFELLKPRALKNKKKLYKTKV SEQ ID NO.123, derived from Saccharomyces cerevisiae (Saccharomyces cer Saccharomyces cerevisiae PPS1, amino acid sequence ColumnMVLEVPSITPGELHDLMRLHQDAEWPECKKMFPWAHDISFGQPPDFPHSLAIVKSQSDANNSALLRNSLEVNDIFQSWKVRTSFHREGDTCETGNDSNGFQYPNNTKELLNLLKFQIRQLELQVDDVALENAATYCHNHSILPFLKVDPRGLSLELKRYSRNKVGSNTTLKRSGQDVWGRRGLFRRFDLQCAKMIEMVDNIVIYCSRTGGSTDMQTESAPACSHEGNCPNCTTLALLLQICLMFVQKGYVGSGGSLYKTNLFICTYQNFNTDIPQTLIGTPLLDNEFFKNNTPLNLCSSPSEIVCFNNVDKNMVLCEKLELNKLTSATRLEETGLICGNTTDWHNYQIIKKNNISLTHRFEENTSIVNLKSLNYDTDNPTTSISQLYNIPNTKEVWKLIIKCTSNSQMPSLTKIRTYLDLLLDDDASKSQEHLHLTFPASGSIGLGNLNIQSVEILLNVCYLIFQVSQVQELLTFMYCEDGYTETSLLLTAYIIFHFNIPLQDALLRIHPRPFFLFPSDLQILGHLQPVLREFSPQNGSNLKLYANALKFRDKSFQLHISSELFSSIFFMKIPLESNFVNLKGPLPSRILRHLYLGSLDHAQNPALLKSLGITHIVSVGEVVSWTLNKDKIAHPVRPHRAITMTNTNEVAGNTTCNKSRNRADTVVSDKQENGSNVVISENSGFQICQIENLDDNGKDPLFHQIDKVLDFISNSEATGGKVLVHCMVGVSRSATVCIAECMRYLQCDLASAYLFVRVRRLNVIIQPNLFFVYELFKWWKKHYNREKDKTMDWHIICRGIAEVNMKYT SEQ ID NO.124, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae PPT1, amino acid sequence ColumnMSTPTAADRAKALERKNEGNVFVKEKHFLKAIEKYTEAIDLDSTQSIYFSNRAFAHFKVDNFQSALNDCDEAIKLDPKNIKAYHRRALSCMALLEFKKARKDLNVLLKAKPNDPAATKALLTCDRFIREERFRKAIGGAENEAKISLCQTLNLSSFDANADLANYEGPKLEFEQLYDDKNAFKGAKIKNMSQEFISKMVNDLFLKGKYLPKKYVAAIISHADTLFRQEPSMVELENNSTPDVKISVCGDTHGQFYDVLNLFRKFGKVGPKHTYLFNGDFVDRGSWSCEVALLFYCLKILHPNNFFLNRGNHESDNMNKIYGFEDECKYKYSQRIFNMAQSFESLPLATLINNDYLVMHGGLPSDSPASTLSDFKNIDRFAQPPRDGAFMELLWADPQEANGMGPSQRGLGHAFGPDITDRFLRNNKLRKIRSKIRFSHELRMGGVQFEQKGKLMTVFSAPNYCDSQGNLGGVIHVVPGHGILQAGRNDDQNLIIETFEAVEHPDIKPMAYSNGGFGL SEQ ID NO.125, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae PPZ1, amino acid sequence ColumnMGNSSSKSSKKDSHSNSSSRNPRPQVSRTETSHSVKSAKSNKSSRSRRSLPSSSTTNTNSNVPDPSTPSKPNLEVNHQRHSSHTNRYHFPSSSHSHSNSQNELLTTPSSSSTKRPSTSRRSSYNTKAAADLPPSMIQMEPKSPILKTNNSSTHVSKHKSSYSSTYYENALTDDDNDDKDNDISHTKRFSRSSNSRPSSIRSGSVSRRKSDVTHEEPNNGSYSSNNQENYLVQALTRSNSHASSLHSRKSSFGSDGNTAYSTPLNSPGLSKLTDHSGEYFTSNSTSSLNHHSSRDIYPSKHISNDDDIENSSQLSNIHASMENVNDKNNNITDSKKDPNEEFNDIMQSSGNKNAPKKFKKPIDIDETIQKLLDAGYAAKRTKNVCLKNNEILQICIKAREIFLSQPSLLELSPPVKIVGDVHGQYGDLLRLFTKCGFPPSSNYLFLGDYVDRGKQSLETILLLFCYKIKYPENFFLLRGNHECANVTRVYGFYDECKRRCNIKIWKTFIDTFNTLPLAAIVAGKIFCVHGGLSPVLNSMDEIRHVVRPTDVPDFGLINDLLWSDPTDSPNEWEDNERGVSYCYNKVAINKFLNKFGFDLVCRAHMVVEDGYEFFNDRSLVTVFSAPNYCGEFDNWGAVMSVSEGLLCSFELLDPLDSAALKQVMKKGRQERKLANQQQQMMETSITNDNESQQ SEQ ID NO.126, derived from Saccharomyces cerevisiae (Saccharomyces cer Saccharomyces cerevisiae PPZ2, amino acid sequence ColumnMGNSGSKQHTKHNSKKDDHDGDRKKTLDLPPLTKSDTTHSLKSSRSLRSLRSKRSEASLASNVQAQTQPLSRRSSTLGNGNRNHRRSNNAPITPPNNHYLTSHPSSSRRLSSSSRRSSMGNNNNSELPPSMIQMEPKSPILKNSTSMHSTSSFNSYENALTDDDDDRGDDGGESPSMAKVTRINTSSSADRGSKRTPLRRHNSLQPEKGVTGFSSTSSKLRRRSDNTLPASYPLNAEAGGNGSDYFSNRSNSHASSRKSSFGSTGNTAYSTPLHSPALRKMSSRDNDDSGDNVNGRGTSPIPNLNIDKPSPSASSASKREYLSAYPTLAHRDSSSSLSPRGKGQRSSSSSSSSQRIYVSPPSPTGDFVHGSCADGDNGSRTNTMVEMKRKKPVRPVDIDEIIQRLLDAGYAAKRTKNVCLKNSEIIQICHKARELFLAQPALLELSPSVKIVGDVHGQYADLLRLFTKCGFPPMANYLFLGDYVDRGKQSLETILLLLCYKIKYPENFFLLRGNHECANVTRVYGFYDECKRRCNIKIWKTFVDTFNTLPLAAIVTGKIFCVHGGLSPVLNSMDEIRHVSRPTDVPDFGLINDLLWSDPTDSSNEWEDNERGVSFCYNKVAINKFLNKFGFDLVCRAHMVVEDGYEFFNDRSLVTVFSAPNYCGEFDNWGAVMTVSEGLLCSFELLDPLDSTALKQVMKKGRQERKLANR SEQ ID NO.127, derived from Saccharomyces cerevisiae (Saccharomyces cer Saccharomyces cerevisiae PSR1, amino acid sequence ColumnMGFISSILCCSSETTQSNSNSAYRQQQSSSLNKNRSVKHSNTKSRTRGVHQTNSPPSKTNSAATFSSTERSTGKSGISTNDNEKKKQSSPTAAVTATTTNNMTKVEKRISKDDLYEEKYEVDEDEEIDDEDNRRSRGIVQEKGDAVKDTSRQKKQQQQQQQQSQSQPQPQPQSQSQSQSQSQSQSQSQQRGPTVQVSSDHLIQDMNLSRVSSSSQASETSNDVDDEDDEDEEYIDLTLLQQGQYHAPGYNTLLPPQDESTKGKKCLILDLDETLVHSSFKYLRSADFVLPVEIDDQVHNVYVIKRPGVEEFLERVGKLFEVVVFTASVSRYGDPLLDILDTDKVIHHRLFREACYNYEGNYIKNLSQIGRPLSDIIILDNSPASYIFHPQHAIPISSWFSDTHDNELLDIIPLLEDLSVKTSLDVGKILDVTI SEQ ID NO.128, derived from Saccharomyces cerevisiae (Saccharomyces cer Saccharomyces cerevisiae PSR2, amino acid sequence Column MGFIANILCCSSDTSKTHRQRQPPETNHNRNRNRKHSSNKAQTQGRKQKATPNGDKMQYSTPKILLSSSDSGSNAGSKTMQENGNSGNGKLAPLSRDHSNNSYDEEKEYEDYNEGDVEMTEVNNAGEEEEEDDEAKEKQDHVVHEYNVDADRNSSINDEAPPQQGLYQVDQEDMNPQYVASSPDNDLNLIPTTEEDFSDLTHLQPDQYHAPGYDTLLPPKLQEFKQKKCLILDLDETLVHSSFKYMHSADFVLPVEIDDQVHNVYVIKRPGVDEFLNRVSQLYEVVVFTASVSRYANPLLDTLDPNGTIHHRLFREACYNYEGNYIKNLSQIGRPLSETIILDNSPASYIFHPQHAVPISSWFSDTHDNELLDIIPLLEDLSSGNVLDVGSVLDVTI SEQ ID NO.129, derived from Saccharomyces cerevisiae (Saccharomyces cer Saccharomyces cerevisiae PSY2, amino acid sequence ColumnMSLPGTPTTSPTPMDEDTEQAVSVNTEPKRVKVYILENNEWKDTGTGFCIGEVDEGKFAYLVVSDEDSPTETLLKSKLEGNIEYQRQEETLIVWKDLGGKDIALSFEESMGCDTLCEFIVHVQRNIESNISLVTVKSSDNGLGSVHDIITGPVTLPSNDQQQNSQTLLEALKILNENTSFDFLKNETIEFILQSNYIDTLISHFHKAEEEKIPKDLFLLSNIIKTLILYNKRDILESMVEDDRIMGIVGILEYDTEYPTSKANHRKYLGSKGPNFKEVIPLENEDLKIIMKKCFRLQFLKDVVLVRFLDDHNFNLISEIVMDLETCIIDFLQVGTFLDRLIELYDTKTLPESSSEKFVQKRKDGIRLLQQCVQMSINLDAVDRSKFYKTLVRKGLFKVLDYAFHMETDSNVRILATDTIIIHEHDI LLIHNVQNEDSFKRQHKSAPDDKSSHRKYPQDYSSSTDSKLLILSTILLSDRSPGLREQVVQALNTLLHPEGCVGNGEGSYDLMGRSNYEAKNTSEDFPSFSYGLNSDSINLNNYHYSSDEMNNLEPESESEFQVMEYFANFYNKIAPILFGPLIKKDITTEMAEIDGQIEKVTKDDLLLIHLVKLVSFVCTEHDRVLSRRFILENGILDSVSKLIGGNHMMQLRLTAVRCIKNLMCLDDKYYHRYMISKNLYAPVFKLFQENIDKNNLANSCIQDFFRIIITECRAYQSDGHNRKEKTNGSYDGNGNDVKTNVNNNRTNFTILNKYLVQTYGDVLRKATDIPFIQDMLETGEENQPDHSSFENSIEGGNDISVNMSTDGFASNHLEDIDIKNVKRLHSEIEHFENDPHYSGDQLAFKKSVDQMNAST SEQ ID NO.130, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae PSY4, amino acid sequence ColumnMGIKSISLYELLSDVVKQGDKTRLVTAGPEQVLPDLIRHITETIPFDLFINLKNEMNDARNLVTRLNWLGKFLNDFLQNHTFPFTILRICELCYDPFKYYKINELEKFVNALEKCCMVTSSWQVFDKTHGEKQEDDKEKDINFIKNQEDVSLMKIPWMTENNTRELAPFIREIDSIMSVNLGYDDEEDEDNGDGEEEGFFDGDEDREMGNSKRN VLLKDENFMVEEYYEDDCGINDDNTDNKGQNCQSDVTKNNSDDEDDDDNDDDYREDGADEDDDHMGSTDDDEDDEDRQAGESTKVQNFDKKNETPRKRKPTDLDNFEYDESPSFTNMDLTTPKKYKHTATGRFSIIESPSSSLLNAMDGSNEISSSQEEKEDARENHEGGSEGLLPGDELVSPTMSSSQEDKMVAIAGITYRENISSPLGKKSR SEQ ID NO.131, derived from Saccharomyces cerevisiae (Saccharomyces cer Saccharomyces cerevisiae PTC1, amino acid sequence Column MSNHSEILERPETPYDITYRVGVAENKNSKFRRTMEDVHTYVKNFASRLDWGYFAVFDGHAGIQASKWCGKHLHTIIEQNILADETRDVRDVLNDSFLAIDEEINTKLVGNSGCTAAVCVLRWELPDSVSDDSMDLAQHQRKLYTANVGDSRIVLFRNGSIRLTYDHKASDTLEMQRVEQAGGLIMKSRVNGMLAVTRSLGDKFFDSLVVGSPFTTSVEITSEDKFLILACDGLWDVIDDQDACELIKDITEPNEAKVLVRYALENGTTDNVTVMVVFL SEQ ID NO.132, derived from Saccharomyces cerevisiae (Saccharomyces cer Saccharomyces cerevisiae PTC2, amino acid sequence ColumnMGQILSNPVIDKESHGADSLTAFGLCAMQGWRMSMEDSHILEPNVLTKSDKDHIAFYGIFDGHGGAKVAEYCGNKIVEILQEQKSFHEGNLPRALIDTFINTDVKLLQDPVMKEDHSGCTATSILVSKSQNLLVCGNAGDSRTVLATDGNAKALSYDHKPTLASEKSRIVAADGFVEMDRVNGNNLALSRAIGDFEFKSNPKLGPEEQIVTCVPDILEHSLDYDRDEFVILACDGIWDCLTSQDCVDLVHLGLREGKTLNEISSRIIDVCCAPTTEGTGIGCDNMSIVVALLKEGEDVAQWSDRMKSKAHRTSVRSFADKRRRVFSYYDFSKCNDEQVFAITTKKPQDKFTRDHEAAVASVTAADNDDPMDIDDTDADTDAENLDPSSQSKSKTSGPIDLASLEALLGATGGVKTDSNGNKVTYTLPQSALAQLLQTMGHDPASSHPENDSNTDHKAGRSHLQ SEQ ID NO.133, derived from Saccharomyces cerevisiae (Saccharomyces cer Saccharomyces cerevisiae PTC3, amino acid sequence Column MGQILSNPIIDKEHHSGTDCLTAFGLCAMQGWRMSMEDAHIVEPNLLAESDEEHLAFYGIFDGHGGSSVAEFCGSKMISILKKQESFKSGMLEQCLIDTFLATDVELLKDEKLKDDHSGCTATVILVSQLKKLLICANSGDSRTVLSTGGNSKAMSFDHKPTLLSEKSRIVAADGFVEMDRVNGNLALSRAIGDFEFKSNTKLGPHEQVVTCVPDIICHNLNYDEDEFVILACD GIWDCLTSQECVDLVHYGISQGNMTLSDISSRIVDVCCSPTTEGSGIGCDNMSISIVALLKENESESQWFERMRSKNYNIQTSFVQRRKSIFDFHDFSDDDNEVFAITTKKLQDRLNRSKDNDDMEIDDLDTELGSSATPSKLSGEDRTGPIDLFSLEALLEAGIQIRQRPSSSDGNTSYFHGASLSDMLASLSNAAAGETPNDADDNDDNDGEENGKNENAKKGSKIEEIE SEQ ID NO.134, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae PTC4, amino acid sequenceColumn MGQLLSHPLTEKTIEYNEYKNNQASTGIVPRFYNCVGSMQGYRLTQEDAHLIRNENSVVYVRFFNPFIDKYETLSLNVFAVFDGHGGDDCSKFLSGGRHHRDGNGSSNGEPNAGLIKWIAYSFENHYTSTTNNDSSKFKRSFNTLEGLVSQIFKDAFILQDEELYRHFANSSCGSTAVVACIINEESLYVANCGDSRCILSKSNGIKTMSFDHKPQHIGELIRINDNGGTVSLGRVGGVLALSRAFSDFQFKRGVTYPHRRTKLTNITQNLTYGTPPQEAQVTVEPDVLMHKIDYSKDEFLVLACDGIWDIYNNKQLIHFIKYHLVSGTKLDTIITKLLDHGIAQANSNTGVGFDNMTAIIVVLNRKGETLQDWFNKMKTRLERERGLV SEQ ID NO.135, derived from Saccharomyces cerevisiae (Saccharomyces cer Saccharomyces cerevisiae PTC5, amino acid sequence ColumnMSPLTRTVAIKKTVVLSKCQSGREYTQKFLQRAYSTSHANSTYYSRTKLFISSHSKALNIALLSGSLLLTYSYYSPKKILSLDTINGIKDYSTNTSGNINMPSPNPKGTETQKSQRSQNDQSVLILNDSKIEAKLHDREESHFVNRGTGIFRYDVAQLPSNHPIEDDHVEQIITIPIESEDGKSIEKDLYFFGIFDGHGGPFTSEKLSKDLVRYVAYQLGQVYDQNKTVFHSNPNQLIDSAISKGFLKLDNDLVIESFRKLFQDPNNTNIANTLPAISGSCALLS LYNSTNSILKVAVTGDSRALICGLDNEGNWTVKSLSTDQTGDNLDEVRRIRKEHPGEPNVIRNGRILGSLQPSRAFGDYRYKIKEVDGKPLSDLPEVAKLYFRREPRDFKTPPYVTAEPITSAKIGENTKFMVMGSDGLFELLTNEEIASLVIRWMDKNMNLAPVKAEPGKLPKVIDVSEDKEAQRPAFRYKDNNSSSPSGSNPEYLIEDKNVATHLIRNALSAGGRKEYVSALVSIPSPMSRRYRDDLTVTVAFFGDSGTPSIVSNATSIVMNPEATTKPKPRL SEQ ID NO.136, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae PTC6, amino acid sequence ColumnMRLGNAYAYCKPSQNVGLKLDLRGLPGYVGHATSRINRLENQDNYSIKMMRSWPNAYGSALNCSVFDGHGEKGAQLSQLLADKLCSSLDFPEPSWDKQDLKKLVQEYARRFPEGNYWKHKLSTFEKFYNKFIKNCNSKQELLLMKEGDSAILGQNGGRMIFDKMGNIIDKIALTELDLLRLFYGFARFDLDQCCGLGTAAGSTASSIFLYPYDDPNAPI DEGKDDDSWIISHGSGLLKLIVTQVGDSKIILCDQDGIAHALTTTTHHINSSRERHRLSIDPSRLDPAFGETRFLNNFANTRSFGDVAGKPYGISSEPDIFSFLVGNTLHLPRSERSKLPFNGDECFLALVTDGITNKLADQEVVDLITSTVNSWGLKKATPQFVAEETIKFIQAIATKHSDNATCVVVRLSNWGNWPNVDRTGPQRETKLMNAQSNETKLN SEQ ID NO.137, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae PTC7, amino acid sequence Column MFANVGFRTLRVSRGPLYGMFIVLFIGVLIAKFAGQMLIDSETNFSHIIGSCSQIISFSKRTFYSSAKSGYQSNNSHGDAYSSGSQSGPFTYKTAVAFQPKDRDDLIYQKLKDSIRSPTGEDNYFVTSNNVHDIFAGVADGVGGWAEHGYDSSAISRELCKKMDEISTALAENSSKETLLTPKKIIGAAYAKIRDEKVVKVGGTTAIVAHFPSNGKLEVANLGDSWCGVFRDSKLVFQTKFQTVGFNAPYQLSIIPEEMLKEAERRGSKYILNTPRDADEYSFQLKKKKDIIILATDGVTDNIATDDIELFLKDNAARTNDELQLLSQKFVDNVVSLSKDPNYPSVFAQEISKLTGKNYSGGKEDDITVVVVRVD SEQ ID NO.138, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae PTP1, amino acid sequence ColumnMAAAPWYIRQRDTDLLGKFKFIQNQEDGRLREATNGTVNSRWSLGVSIEPRNDARNRYVNIMPYERNRVHLKTLSGNDYINASYVKVNVPGQSIEPGYYIATQGPTRKTWDQFWQMCYHNCPLDNIVIVMVTPLVEYNREKCYQYWPRGGVDDTVRIASKWESPGGANDMTQFPSDLKIEFVNVHKVKDYYTVTDIKLTPTDPLVGPVKTVHHFYFDLWKDMNKPEEVVPIMELCAHSHSLNSRGNPIIVHCSAGVGRTGTFIALDHLMHDTLDFKNITERSRHSDRATEEYTRDLIEQIVLQLRSQRMKMVQTKDQFLFIYHAAKYLNSLSVNQ SEQ ID NO.139, derived from Saccharomyces cerevisiae (Saccharomyces cer Saccharomyces cerevisiae PTP2, amino acid sequence ColumnMDRIAQQYGSGKRDNNGNRMASSAISEKGHIQVNQTRTPGQMPVYRGETINLSNLPQNQIKPCKDLDDVNIRRNNSNRHSKILLLDLCAGPNTNSFLGNTNAKDITVLSLPLPSTLVKRSNYPFENLLKNYLGSDEKYIEFTKIIKDYDIFIFSDSFSRISSCLKTTFCLIEKFKKFICHFFPSPYLKFFLLEGSLNDSKAPSLGKNKKNCILPKLDLNLNVNLTSRSTLNLRINIPPPNDSNKIFLQSLKKDLIHYSPNSLQKFFQFNMPADLAPNDTILPNWLKFCSVKENEKVILKKLFNNFETLENFEMQRLEKCLKFKKKPLHQKQLSQKQRGPQSTDDSKLYSLTSLQRQYKSSLKSNIQKNQKLKLIIPKNNTSSSPSPLSSDDTIMSPINDYELTEGIQSFTKNRYSNILPYEHSRVKLPHSPKPPAVSEASTTETKTDKSYPMCPVDAKNHSCKPNDYINANYLKLTQINPDFKYIATQAPLPSTMDDFWKVITLNKVKVIISLNSDDELNLRKWDIYWNNLSYSNHTIKLQNTWENICNINGCVLRVFQVKKTAPQNDNISQDCDLPHNGDLTSITMAVSEPFIVYQLQYKNWLDSCGVDMNDIIKLHKVKNSLLFNPQSFITSLEKDVCKPDLIDDNNSELHLDTANSSPLLVHCSAGCGRTGVFVTLDFLLSILSPTTNHSNKIDVWNMTQDLIFIIVNELRKQRISMVQNLTQYIACYEALLNYFALQKQIKNALPC SEQ ID NO.140, derived from Saccharomyces cerevisiae (Saccharomyces cer Saccharomyces cerevisiae PTP3, amino acid sequence ColumnMKDSVDCPSILPTDRTSVLSETSTLVGSSSHVYSKHAPMNSYHNSMNSNIYHSPKASSPLVSYKTSSPVLLKRATAPVLPSFKPKEQRYNKPQGCSLITAVELGKIIETLPDEKVLLLDVRPFTEHAKSIITNSIHVCLPSTLLRRKNFTFSKLLDNLTPSEQSVLKSKLAIDNLRIIIYDSTANQTESSVSLPCYGIASKLIEFDTNVKKTVSILMCGFPQFKILFPDHINTNTFNSDCISSAEPKSPKTNLMNSLHNTAPHMTATTPLSSPQMNLKLKVPDDSRSDHSNFSSSPSPRNVLSDSPMSSSSPISALFKFQLPAPQTNINQMFKFSQNEEIMDLETYLSAVNIKEEHERWYNNDSAKKSLQNFQFPKNQNSLEKDTNKDKLGFQIRYENLSKNYEKEVIDSVIPEWFQHLMSIPKIELVSQFQKLDFLEKRRLNHSVSFRKKENSFILEKPSSYPEQLTSTSSSTIMPPKFPDVNKVQKRSHSQPIFTQYSKYKSMLSLESDSDSESDNVIISSGVELGAKNRYKDIFPYEHSRVILKKGLQSSKGIKHSHSTSDGGILDNYINANYLSLPRFSVEQNSSFQTTSTTTRRVRYIATQAPMPSTVHDFYTCILNNGVPLVLSLTNDFENGIEKCYRYWQEGNYNGIHVKLLEKKILKMPSTTSMRKNTTGTQNSSLYSAGVHGNSSNYSTDNDNDNDNNNNNNNNSNIAVTAAACDDDDDDDDDDAILIRKILLTYHDQEKPYELLQIQVKNWPDLGTLLNPTSILQAINVKNHIIDTLFARNYYQNDQLPTILVHCSAGCGRTGTLCTIDSILSNFEMFEMLQKEFVKLKYPAKLFDPISWTINIFRKQRISMVQNINQFIFIYDCLLFYFRLRLDDITERTDGDGSNKDNISLSALIEQIEKLEILQTFVDDKLKELPQ SEQ ID NO.141, derived from Saccharomyces cerevisiae (Saccharomyces cer Saccharomyces cerevisiae PYP1, amino acid sequence ColumnMVKAVIFTDFDGTVTLEDSNDYLTDTLGFGKEKRLKVFEGVLDDTKSFRQGFMEMLESIHTPFPECIKILEKKIRLDPGFKDTFEWAQENDVPVIVVSSGMKPIIKVLLTRLVGQESIHKIDIVSNEVEIDAHDQWKIIYKDESPFGHDKSRSIDAYKKKFESTLKAGEQRPVYFCGDGVSDLSAAKECDLLFAKRGKDLVTYCKKQNVPHEFDTFKDILASMKQVLAGEKTVAELMEN SEQ ID NO.142, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae QRI7, amino acid sequence Column MISIKGTGRFLLDNYRIWQRRASNRPIQLRKGYKVLAIETSCDDTCVSVLDRFSKSAAPNVLANLKDTLDSIDEGGIIPTKAHIHHQARIGPLTERALISNAREGIDLICVTRGPGMPGSLSGGLDFAKGLAVAWNKPLIGVHMLGHLLIPRMGTNGKVPQFPFVSLLVSGGHTTFVLSRAIDDHEILCDTIDIAVGDSLD KCGRELGFKGTMIAREMEKFINQDINDQDFALKLEMPSPLKNSASKRNMLSFSFSAFITALRTNLTKLGKTEIQELPEREIRSIAYQVQESVFDHIINKLKHVLKSQPEKFKNVREFVCSGGVSSNQRLRTKLETELGTLNSTSFFNFYYPPMDLCSDNSIMIGWAGIIEWESLRLVSDLDICPIRQWPLNDLLSVDGWRTDQL SEQ ID NO.143, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae RAD53, amino acids SequenceMENITQPTQQSTQATQRFLIEKFSQEQIGENIVCRVICTTGQIPIRDLSADISQVLKEKRSIKKVWTFGRNPACDYHLGNISRLSNKHFQILLGEDGNLLLNDISTNGTWLNGQKVEKNSNQLLSQGDEITVGVGVESDILSLVIFINDKFKQCLEQNKVDRIRSNLKNTSKIASPGLTSSTASSMVANKTGIFKDFSIIDEVVGQGAFATVKKAIERTTGKTFAVKIISKRKVIGNMDGVTRELEVLQKLNHPRIVRLKGFYEDTESYYMVMEFVSGGDLMDFVAAHGAVGEDAGREISRQILTAIKYIHSMGISHRDLKPDNILIEQDDPVLVKITDFGLAKVQGNGSFMKTFCGTLAYVAPEVIRGKDTSVSPDEYEERNEYSSLVDMWSMGCLVYVILTGHLPFSGSTQDQLYKQIGRGSYHEGPLKDFRISEEARDFIDSLLQVDPNNRSTAAKALNHPWIKMSPLGSQSYGDFSQISLSQSLSQQKLLENMDDAQYEFVKAQRKLQMEQQLQEQDQEDQDGKIQGFKIPAHAPIRYTQPKSIEAETREQKLLHSNNTENVKSSKKKGNGRFLTLKPLPDSIIQESLEIQQGVNPFFIGRSEDCNCKIEDNRLSRVHCFIFKKRHAVGKSMYESPAQGLDDIWYCHTGTNVSYLNNNRMIQGTKFLLQDGDEIKIIWDKNNKFVIGFKVEINDTTGLFNEGLGMLQEQRVVLKQTAEEKDLVKKLTQMMAAQRANQPSASSSSMSAKKPPVSDTNNNGNNSVLNDLVESPINANTGNILKRIHSVSLSQSQIDPSKKVKRAKLDQTSKGPENLQFS SEQ ID NO.144, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae RCN1, amino acid sequence ColumnMGNIITDTIIITSDKCDIVDNDNVERIQVWLSKNILRKFQINENEPLQLIILKRFKRILLICPSHDISQHVMDASRALEMENFNFSYSLQDGQRNLTKQYLKVPESEKMFLISPPASPPPEFDFSKCEDAPQRHIQSHIQQDQQQRLEASQLLPNNPDKNNNGTFTLLKSKVGAITIDRCPTNDGNGQMQLADHVKTAFPPKSIFDTDDDD SEQ ID NO.145, derived from Saccharomyces cerevisiae (Saccharomyces cer Saccharomyces cerevisiae REG1, amino acid sequence Column SEQ ID NO.146, derived from Saccharomyces cerevisiae (Saccharomyces cer Saccharomyces cerevisiae REG2, amino acid sequence Column MTLSNCDSLDNLFQDPPEEEESSKFVEAVRTLMNRNDMGYPPAAANGTYCLKKIKSLNAKQWKINKKRMCMLPAVKKKNFDFHEQRSLILNLNLWKFIKFINCSSKNNYNKNNKHVRSSNNTVKNENVLPLQKHKKVDNDQRLENLFWRSWFKARKRRDIMGKPRERHIKFNDNVEQCIITDEHFIQRLPSTRLNSTDEQRPCSKSELDPCIGNAASKRSFYDYNSVYVASDAIITTAAATAIISSNSGDYQRGHDVRDVPRNVLLQAGETDFSSVLRVDSDLKLSNISHHSPVKPSSTSSHSTFIFESETDTDTDTDAETENDIDAYIDTSIPNLLL SEQ ID NO.147, derived from Saccharomyces cerevisiae (Saccharomyces cer Saccharomyces cerevisiae RPT1, amino acid sequence Column MPPKEDWEKYKAPLEDDDKKPDDDKIVPLTEGDIQVLKSYGAAPYAAKLKQTENDLKDIEARIKEKAGVKESDTGLAPSHLWDIMGDRQRLGEEHPLQVARCTKIIKGNGESDETTTDNNNSGNSNSNSNQQSTDADEDDEDAKYVINLKQIAKFVVGLGERVSPTDIEEGMRVGVDRSKYNIELPLPPRIDPSVTMMTVEEKPDVTYSDVGGCKDQIEKLREVVELPLLSPERFATLGIDPPKGILLYGPPGTGKTLCARAVANRTDATFIRVIGSELVQKYVGEGARMVRELFEMARTKKACIIFFDEIDAVGGARFDDGAGGDNEVQRTMLELITQLDGFDPRGNIKVMFATNRPNTLDPALLRPGRIDRKVEFSLPDLEGRANIFRIHSKSMSVERGIRWELISRLCPNSTGAELRSVCTEAGMFAIRARRKVATEKDFLKAVDKVISGYKKFSSTSRYMQYN SEQ ID NO.148, derived from Saccharomyces cerevisiae (Saccharomyces cer Saccharomyces cerevisiae RPT2, amino acid sequence ColumnMGQGVSSGQDKKKKKGSNQKPKYEPPVQSKFGRKKRKGGPATAEKLPNIYPSTRCKLKLLRMERIKDHLLLEEEFVSNSEILKPFEKQEEEKKQLEEIRGNPLSIGTLEEIIDDDHAIVTSPTMPDYYVSILSFVDKELLEPGCSVLLHHKTMSIVGVLQDDADPMVSVMKMDKSPTESYSDIGGLESQIQEIKESVELPLTHPELYEEMGIKPPKG VILYGAPGTGKTLLAKAVANQTSATFLRIVGSELIQKYLGDGPRLCRQIFKVAGENAPSIVFIDEIDAIGTKRYDSNSGGEREIQRTMLELLNQLDGFDDRGDVKVIMATNKIETLDPALIRPGRIDRKILFENPDLSTKKILGIHTSKMNLSEDVNLETLVTTKDDLSGADIQAMCTEAGLLALRERMRQVTAEDFKQAKERVMKNKVEENLEGLYL SEQ ID NO.149, derived from Saccharomyces cerevisiae (Saccharomyces cer Saccharomyces cerevisiae RPT3, amino acid sequence Column MEELGIVTPVEKAVEEKPAVKSYASLLAQLNGTVNNNSALSNVNSDIYFKLKLEKEYELLTLQEDYIKDEQRHLKRELKRAQEEVKRIQSVPLVIGQFLEPIDQNTGIVSSTTGMSYVVRILSTLDRELLKPSMSVALHRHSNALVDILPPDDSSISVMGENEKPDVTYADVGGLDMQKQEIREAVELPLVQADLYEQIGIDPPRGVLLYGPPGTGKTMLVKAVANSTKAAFIRVNGSEFVHKYLGEGPRMVRDVFRLARENAPSIIFIDEVDSIATKRFDAQTGSDREVQRILIELLTQMDGFDQSTNVKVIMATNRADTLDPALLRPGRLDRKIEFPSLRDRRERRLIFGTIASKMSLAPEADLDSLIIRNDSLSGAVIAAIMQEAGLRAVRKNRYVILQSDLEEAYATQVKTDNTVDKFDFYK SEQ ID NO.150, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae RPT4, amino acid sequence ColumnMSEEQDPLLAGLGETSGDNHTQQSHEQQPEQPQETEEHHEEPSRVDPEQEAHNKALNQFKRKLLEHRRYDDQLKQRRQNIRDLEKLYDKTENDIKALQSIGQLIGEVMKELSEEKYIVKASSGPRYIVGVRNSVDRSKLKKGVRVTLDITTLTIMRILPRETDPLVYNMTSFEQGEITFDGIGGLTEQIRELREVIELPLKNPEIFQRVGIKPPKGV LLYGPPGTGKTLLAKAVAATIGANFIFSPASGIVDKYIGESARIIREMFAYAKEHEPCIIFMDEVDAIGGRRFSEGTSADREIQRTLMELLTQMDGFDNLGQTKIIMATNRPDTLDPALLRPGRLDRKVEIPLPNEAGRLEIFKIHTAKVKKTGEFDFEAAVKMSDGFGADIRNCATEAGFFAIRDDRDHINPDDLMKAVRKVAEVKKLEGTIEYQKL SEQ ID NO.151, derived from Saccharomyces cerevisiae (Saccharomyces cer Saccharomyces cerevisiae RPT5, amino acid sequence Column MATLEELDAQTLPGDDELDQEILNLSTQELQTRAKLLDNEIRIFRSELQRLSHENNVMLEKIKDNKEKIKNNRQLPYLVANVVEVMDMNEIEDKENSESTTQGGNVNLDNTAVGKAAVVKTSSRQTVFLPMVGLVDPDKLKPNDLVGVNKDSYLILDTLPSEFDSRVKAMEVDEKPTETYSDVGGLDKQIEELVEAIVLPMKRADKFKDMGIRAPKGALMYGPPGTGKTLLARACAAQTNATFLKLAAPQLVQMYIGEGAKLVRDAFALAKEKAPTIIFIDELDAIGTKRFDSEKSGDREVQRTMLELLNQLDGFSSDDRVKLAATNRVDVLDPALLRSGRLDRKIEFPLPSEDSRAQILQIHSRKMTDDINWQELARSTDEFNGAQLKAVTVEAGMIALRNGQSSVKHEDFVEGISEVQARKSKSVSFYA SEQ ID NO.152, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae RPT6, amino acid sequence ColumnMTAAVTSSNIVLETHESGIKPYFEQKIQETELKIRSKTENVRRLEAQRNALNDKVRFIKDELRLLQEPGSYVGEVIKIVSDKKVLVKVQPEGKYIVDVAKDINVKDLKASQRVCLRSDSYMLHKVLENKADPLVSLMMVEKVPDSTYDMVGGLTKQIKEIKEVIELPVKHPELFESLGIQPKGVILYGPPGTGKTLLARAVAHHTDCKFIRVSGAELVQKYIGEGSRMVRELFVMAREHAPSIIFMDEIDSIGSTRVEGSGGGDSEVQRTMLELLNQLDGFETSKNIKIIMATNRLDILDPALLRPGRIDRKIEFPPSVAARAEILRIHSRKMNLTRGINLRKVAEKMNGCSGADVKGVCTEAGMYALRERRRIHVTQEDFELAVGKVMNKNQETAISVAKLFK SEQ ID NO.153, derived from Saccharomyces cerevisiae (Saccharomyces cer Saccharomyces cerevisiae RRD1, amino acid sequence Column MSLDRWDWPHATFSTPVKRIFDTQTTLDFQSSLAIHRIKYHLHKYTTLISHCSDPDPHATASSIAMVNGLMGVLDKLAHLIDETPLPGPRRYGNLACREWHHKLDERLPQWLQEMLPSEYHEVVPELQYYLGNSFGSSTRLDYGTGHELSFMATITALDLLGMFPHMRGADVFLLFNKYYTIMRRLILTYTLEPA GSHGVWGLDDHHFHLVYILGSSQWQLLDAQAPLQPREILDKSLVREYKDTNFYCQGINFINEVKMGPFEEHSPILYDIAVTVPRWSKVCKGLLKMYSVEVLKKFPVVQHFWFGTGFFPWVNIQNGTDLPVFEEKEEESIEQANAGSPGREQTSTRFPTSTSMPPPGVPPSGNSINYLLSHQNQSHRNQTSFSRDRLRR SEQ ID NO.154, derived from Saccharomyces cerevisiae (Saccharomyces cer Saccharomyces cerevisiae RRD2, amino acid sequence ColumnMLPEKRLLTPDDMKLWEESPTRAHFTKFIIDLAESVKGHENSQYKEPISESINSMMNLLSQIKDITQKHPVIKDADSSRFGKVEFRDFYDEVSRNSRKILRSEFPSLTDEQLEQLSIYLDESWGNKRRIDYGSGHELNFMCLLYGLYSYGIFNLSNDSTNLVLKVFIEYLKIMRILETKYWLEPAGSHGVWGLDDYHFLPFLFGAFQLTTHKHLKPISIHNNELVEMFAHRYLYFGCIAFINKVKSSASLRWHSPMLDDISGVKTWSKVAEGMIKMYKAEVLSKLPIMQHFYFSEFLPCPDGVSPPRGHIHDGTDKDDECNFEGHVHTTWGDCCGIKLPSAIAATEMNKKHHKPIPFD SEQ ID NO.155, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae RTR1, amino acid sequence Column MATIEDIKETALIPFQKHRQLSMHEAEVITLEIIGLLCDSECKDEKTLKYLGRFLTPDMYQDLVDERNLNKRCGYPLCGKSPERIRDPFSMNDTTKKFLLENNPYAYLSHYCSKFHFRCSQFYQVQLSDEALFARTGVHLFEDPEQDKHDIDFKVTLFEELLREKASEEDIKSLISGLKKLGLNPDSGTTEKDDTELEDDLSKWLAQIKIVENDNPSILGDFTRED SEQ ID NO.156, derived from Saccharomyces cerevisiae (Saccharomyces cer Saccharomyces cerevisiae RTR2, amino acid sequence Column MQIITTTFIQNVILGSHQLHEQLSIVEARMIESAIVSMLTESFCENEQTLKYLARLLSPMSYMDVINARRGKKICGYPLCYKSAAENSSDGFFIHSMYCNNYHSKCSLYLMRQLSQTPLHERRGVHLTSYINLEFDDMYSVSLLEELVGSEVPIDTVKSLITSFKDLEFDDTYKNEPLPLDVYFGQLTTDEETCIE SEQ ID NO.157, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae RTS1, amino acid sequence ColumnMMRGFKQRLIKKTTGSSSSSSSKKKDKEKEKEKSSTTSSTSKKPASASSSSHGTTHSSASSTGSKSTTEKGKQSGSVPSQGKHHSSSTSKTKTATTPSSSSSSSRSSSVSRSGSSSTKKTSSRKGQEQSKQSQQPSQSQKQGSSSSSAAIMNPTPVLTVTKDDKSTSGEDHAHPTLLGAVSAVPSSPISNASGTAVSSDVENGNSNNNNMNINTSNTQDANHASSQSIDIRRSSHSFERLPTPTKLNPDTDLELIKTPQRHSSSRFEPSRYTPLTKLPNFNEVSPEERIPLFIAKVDQCNTMFDFNDPSFDIQGKEIKRSTLDELIEFLVTNRFTYTNEMYAHVVNMFKINLFRPIPPPVNPVGDIYDPDEDEPVNELAWPHMQAVYEFFLRFVESPDFNHQIAKQYIDQDFILKLLELFDSEDIRERDCLKTTLHRIYGKFLSLRSFIRRSMNNIFLQFIYETEKFNGVAELLEILGSIINGFALPLKEEHKVFLVRILIPLHKVRCLSLYHPQLAYCIVQFLEKDPLLTEEVVMGLLRYWPKINSTKEIMFLNEIEDIFEVIEPLEFIKVEVPLFVQLAKCISSPHFQVAEKVLSYWNNEYFLNLCIENAEVILPIIFPALYELTSQLELDSANGEDSISDPYMLVEQAINSGSWNRAIHAMAFKALKIFLETNPVLYENCNALYLSSVKETQQRKVQREENWSKLEEYVKNLRINNDKDQYTIKNPELRNSFNTASENNTLNEENENDCDSEIQ SEQ ID NO.158, derived from Saccharomyces cerevisiae (Saccharomyces cer Saccharomyces cerevisiae SAC1, amino acid sequence ColumnMTGPIVYVQNADGIFFKLAEGKGTNDAVIHLANQDQGVRVLGAEEFPVQGEVVKIASLMGFIKLKLNRYAIIANTVEETGRFNGHVFYRVLQHSIVSTKFNSRIDSEEAEYIKLLELHLKNSTFYFSYTYDLTNSLQRNEKVGPAASWKTADERFFWNHYLTEDLRNFAHQDPRIDSFIQPVIYGYAKTVDAVLNATPIVLGLITRRSIFRAGTRYFRRGVDKDGNVGNFNETEQILLAENPESEKIHVFSFLQTRGSVPIYWAEINNLKYKPNLVLGENSLDATKKHFDQQKELYGDNYLVNLVNQKGHELPVKEGYESVVHALNDPKIHYVYFDFHHECRKMQWHRVKLLIDHLEKLGLSNEDFFHKVIDSNGNTVEIVNEQHSVVRTNCMDCLDRTNVVQSVLAQWVLQKEFESADVVATGSTWEDNAPLLTSYQNLWADNADAVSVAYSGTGALKTDFTRTGKRTRLGAFNDFLNSASRYYQNNWTDGPRQDSYDLFLGGFRPHTASIKSPFPDRRPVYIQLIPMIICAALTVLGATIFFPKDRFTSSKNLLYFAGASIVLALSTKFMFKNGIQFVNWPKLADVGFLVVHQTHDKEQQFKGLKYAQSPKFSKPDPLKRD SEQ ID NO.159, derived from Saccharomyces cerevisiae (Saccharomyces cer Saccharomyces cerevisiae SAP155, amino acids Sequence SEQ ID NO.160, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae SAP185, amino acids Sequence SEQ ID NO.161, derived from Saccharomyces cerevisiae (Saccharomyces cer Saccharomyces cerevisiae SAP190, amino acids Sequence SEQ ID NO.162, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae SAP4, amino acid sequence Column MSLWPFGETLSHSGIDSILEEYYLIFRSLEGNETSSTDDKKNEPSMESESEFGTESRDRSDLNQSFIDRILLETALLDELNGGANDRLVDFICLGYFYDDRSQQVRHMDYLVGMLMAYLKDIDRTGYRTPFLLENSFHQTGEYEDQDDEDPMLYVNIISSIFCSKSAPIVEALVQNTPFLSLFEVFQFENIEAENCPILAVFLKINETLLFEQTSSYLEFFKSQPNIVDKFLYHIEVSPLVEFLIKIMLTDQVESPTNIIDFLYHQDLIPKCLNLLDNSKYSPGIQNSSGELLKALISISTNFKLDTLWIGPNRLTRQLASPQYVDQLINIILFQRGHAMGVAVSIIIELIRKNNSDYDEVDLLSTTIVDNPPSQRDPVYLGHLLYELTMHMEDFYALLIKLENDDD DHDTASKALPSVKHHLLENQLHESFRPLGFERVKITELISEMLHCSNMGLMNSKRGEKIARTRDKCRDTLDQNSLEKAMKNLNINDNTITSNTLEDKCNNNDSNDSNQKQKKNIKKKFHDNELYSTFDTSDDNIDDDMSFEIPYVSETQNLKIRKNPTIGDLFKIKLHDLGFFPKFLQLFLRYPWNNFWHNIVFDIIQQIFNGRMDFSYNSFLVYSLFDFKKSTRFIPKPLYGSNQKLPVKDFHIISDFILQGHKDSFEFYEKEKTNLGYMGQLVLIAEEIAKYSKIYKTDLIAPDIYAFLQDEVWMSYSSDILNETRTMCSIILGGGQFCAESDENTNQDFLEKADMSKPAHPSTMDENEIVHEEDVKLHDKVAELIDELGQLTELDIHDKIKDVIVDHHSDLN SEQ ID NO.163, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae SCD5, amino acid sequence ColumnMSFDWLNVPGLDLSSGDQAEKRPSNGLGPPSVSFDFGINTAAPHDSSFWDQGSRSHSDTTLSYRNNHSNTAADNATNVSSPQKDNPPNGEVRTLSGGDVYAESPEDMQVPLSLSQNQLTHEEIRTYLRWYHYICLRTHGKLVRLNDVFRFLTNFNLSQKVKDRIVEIFRSCKNALNIGQFFAVLRLVSRAIIYGILPLRRMILEKAPVPKPRPILSSENHEEVYEEVEDDDSSAKTGDQKVDFDSFASLLLTGKTTRKRVRRRIKNLNFKSKKVRFSEHITFQDPPNLNQESSNNSEARKQDPDAEDEDQDSNNDSPLDFTLPMDQLLKRLYKRRKNSGLVSSLPSEQQETEEEKKVLEDMKDSLSHFKQIQTVDSASLPISSVFLQNGNTLPTSNVNNTTVPQQLPLEPLKPTATGSANHLVREEYNQGLHPSNGAIQTGLQPLKPTATGSANYLMRSHMEQPQSIKPSSTPETVTNSGGLQPLKPTATGSANYLMKQHISPSVNNPVSSMFQAQFTNQSSSPQSTGPAFLNSPNITLPQSNQQQPYQEVNPTQAKIEPSNISPQHTYSNNVRINNGNIVSMPKVEITGAFPPQNTLPQHQQSHLLSPQNTIPQHQRSQLISPQNTFTQNQPILSPQHTYSNNQATMISPQNTYTNNQQQPQHLPPPPPPRAQQQQQGAIVPPQHMYSNVQKQNNLVPTQPSYTNSPSIQSPNFLSPQNAANSYFQSLLSSSPSPNPTPSNASTVNGNNASNGISSFQNTSAAMNNTQSHQTYIQQQQQQQTQQRIYGGQLSQMQQHPGQLHLNNSDIHSQPNKPNYGMLGQQVHQQQQQQQQQFPFTADVNRSNSSDILGNLQSLQQQVDALQIQYNRRP SEQ ID NO.164, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae SDP1, amino acid sequence ColumnMNIYTSPTRTPNIPKSGQRPSLPMLATDERSTDKESPNEDREFVPCSSLDVRRIYPKGPLLVLPEKIYLYSEPTVKELLPFDVVINVAEEANDLRMQVPAVEYHHYRWHEDSQIALDPLSTLsIIHAATTKREKILIHCQCGLSRSATLIIAYIMKYHNLSLRHSYDLLKSRADKINPSIGLIFQLMEWEVALNAKTNVQANSYRKVP SEQ ID NO.165, derived from Saccharomyces cerevisiae (Saccharomyces cer Saccharomyces cerevisiae SDS22, amino acids Sequence MDKNSVNKDSEEKDERHKIEVVDDTNPDFITADSELTQDLPDDDVEVIDLVHLKIKSLEDLNLYRFKNLKQLCLRQNLIESISEVEVLPHDKIVDLDFYDNKIKHISSNVNKLTKLTSLDLSFNKIKHIKNLENLTDLENLYFVQNSISKIENLSTLKSLKNLELGGNKVHSIEPDSFEGLSNLEEIWLGKNSIPRLINLHPLKNLKILSIQSNKLKIENLEELTNLEELSHNFITKIEGLEKNLKLTTLDVTSNKITSLENLNHLSNLTDIWASFNKIDQSFESLGENLSGLSRLETIYLEGNPIQLENKTSYRRKLTMNLPPSLQKIDATYIRG SEQ ID NO.166, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae SDS23, amino acids SequenceMPQNTRHTSIVEMLSTPPQLPNSTDLNSLSEQTDKNTEANKSDTESLHKSISKSSSSSSLSTLDNTEYSNNNGNSLSTLNSQNLLSVHRQEWQHTPLSNLVEQNKLIFIRGSISVEEAFNTLVKHQLTSLPVENFPGDMNCLTFDYNDLNAYLLLVLNRIKVSNDKITSDCQNGKSVPVGEIVKLTPKNPFYKLPETENLSTVIGILGSGVHRVAITNVEMTQIKGILSQRRLIKYLWENARSFPNLKPLLDSSLEELNIGVLNAARDKPTFKQSRVISIQGDEHLIMALHKMYVERISSIAVVDPQGNLIGNISVTDVKHVTRTSQYPLLHNTCRHFVSVILNLRGLETGKDSFPIFHVYPTSSLARTFAKLVATKSHRLWIVQPNDNQPTASSEKSSSPSPSTPPVTTLPSLASSYHSNTQSSRMANSPVLKSSDTSNNKINVNINLSGPSPSQPQSPSATMPPPQSPSNCPASPTPAHFEKEYRTGKLIGVVSLTDILSVLARKQTHHKEIDPQMARKQRGHIG SEQ ID NO.167, derived from Saccharomyces cerevisiae (Saccharomyces cer Saccharomyces cerevisiae SDS24, amino acids SequenceMASTSNTFPPSQSNSSNNLPTSRHASIVEMLSTPPLLPHVQVNDTDDKEQPEESTPPTATAAAPGPGSAATPAPLRDEKPQFKLSAVPMTQTPSQCLSCVHAQKWQHIPLSQLIEQNKLIFVPGSISVEEAFNTLIKYHLNSIPVESFPGDMNCFTFDYNDLNSYLLLVLNKITVSNKQLTADCQNGKPVPVGEMVKLTPKNSFYKLPENESLSTVMGILGSGVHRVAITNEEMTKVKGILSQRRLIKYLWDNARSFTSLEPLLNSSLQDLHIGVLNIQSKPTSRQSRVISIQGEEPLIMGLYKMHVERISSIAVIDKQGNLLGNISVTDVKHVTRTSQYPLLHKTCRHFISVILNSRGLETGKDSFPIFHVYPSSSLARTLAKLVATKSHRLWIVQPPESSTSASSTNLTAANTAANAVSATAQSSANGATPMSKSSSSTSLNSHSPLMTAMEDPPSPRSSAIAIPPPSPASSTNTPNLFEKEYRTGKLIGVVSLTDIINLLARKQTGNKEVDPQSARRQRGSIAM SEQ ID NO.168, derived from Saccharomyces cerevisiae (Saccharomyces cer Saccharomyces cerevisiae SDT1, amino acid sequence Column MTVEYTASDLATYQNEVNEQIAKNKAHLESLTHPGSKVTFPIDQDISATPQNPNLKVFFFDIDNCLYKSSTRIHDLMQQSILRFFQTHLKLSPEDAHVLNNSYYKEYGLAIRGLVMFHKVNALEYNRLVDDSLPLQDILKPDIPLRNMLLRLRQSGKIDKLWLFTNAYKNHAIRCLRLLGIADLFDGLTYCDYSRTDTLVCKPHVKSFEKAMKESGLARYENAYFIDDSGKNIETGIKLGMKTCIHLVENEVNEILGQTPEGAIVISDILELPHVVPDLF SEQ ID NO.169, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae SER2, amino acid sequence ColumnMSKFVITCIAHGENLPKETIDQIAKEITESSAKDVSINGTKKLSARATDIFIEVAGSIVQKDLKNKLTNVIDSHNDVDVIVSVDNEYRQAKKLFVFDMDSTLIYQEVIELIAAYAGVEEQVHEITERAMNNELDFKESLREVKLLQGLQVDTLYDEIKQKLEVTKGVPELCKFLHKKNCKLAVLSGGFIQFAGFIKDQLGLDFCKANLEVDTDGKLTGKTLGPIVDGQCKSETLLQLCNDYNVPVEASCMVGDGGNDLPAMATAGFGIAWNAKPKVQKAAPCKLNTKSMTDILYILGYTDDEIYNRQ SEQ ID NO.170, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae SHB17, amino acids Sequence MPSLTPRCIIVRHGQTEWSKSGQYTGLTDLPLTPYGEGQMLRTGESVFRNNQFLNPDNITYIFTSPRLRARQTVDLVLKPLSDEQRAKIRVVVDDDLREWEYGDYEGMLTREIIELRKSRGLDKERPWNIWRDGC ENGETTQQIGLRLSRAIARIQNLHRKHQSEGRASDIMVFAHGHALRYFAAIWFGLGVQKKCETIEEIQNVKSYDDDTPYVKLESYRHLVDNPCFLLDAGGIGVLSYAHNIDEPALELAGPFVSPPEEESQHGDV SEQ ID NO.171, derived from Saccharomyces cerevisiae (Saccharomyces cer Saccharomyces cerevisiae SHP1, amino acid sequence ColumnMAEIPDETIQQFMALTNVSHNIAVQYLSEFGDLNEALNSYYASQTDDQKDRREEAHWNRQQEKALKQEAFSSTNSNKAINTEHVGGLCPKPGSSQGSNEYLKRKGSTSPEPTKGSSRSGSNNSRFMSFSDMVRGQADDDDEDQPRNTFAGGETSGLEVTDPSDPNSLLKDLLEKARRGGQMGAENGSRDDEDQEMGANRFTGRGFRLGSTIDAADEVVEDNTSQSQRRPEKVTREITFWKEGFQVADGPLYRYDDPANSFYLSELNQGRAPLKLLDVQFGQEVEVNVYKKLDESYKAPKRKLGGFSGQQQRLGSPIPGESSPAEVPKNETPAAQEQPMPNNEPKQGDTSIQIRYANGKREVLRCNSTDTVKFLYEHVTSNANTDPSRNFTLNYAFPIKPISNDETTLKDADLLNSVVQRWA SEQ ID NO.172, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae SIA1, amino acid sequence ColumnMRLHYRRRFNFLRRILFILCITSLYLSRDSLKLHAKNVLMDHNVAEYHGGMIDDIQILRCYHWYRQCSSLYAPKLHPSNTAKKIKDKNSILWTRVSKNITVETLYSLQSGPFYNSYLYVHLKDFQSNPKNTIKELAIARDSALIPLQVLRDINKLVKSSDSSVFHNHVYLREKPTSSWWKLLFGISVDTDNIAVFGEEWVYKGSGIWCKYILNDDDNDAPITNLEIYLGSSFIESRPSWKEVIHEFHRNNIPSLPISITRKLETKNHHHKFSNGLLGSLRTPSKDINIQVDADYKITSPHIQFSRGQRSFKILQITDFHFKCTDNSMTVINEIKTVNFIDRVLASENPDLVVITGDLLDSHNTIDYQTCIMKVVQPMISNKIPYAISLGVSDESNLATSAQIRDFIRNLPYTFNNVASEEGHMAIEVSFKKKLTKNTLLERDIDTEDETNPSEALFFVFDSFAPVNNFLQDYNDLIGKIDFGLAFQYFPLSEYRPHGLFPIIGQYNERSTLTVDTPRSRGQVSMTINGKHYKSFLDILSLWNIKGVSCGHEHNNDCCLQSKNEMWLCYGGSAGIGLPRIQGIYPTVRLFNLDDILDEITSWKRNSNLVDEVYDYQYIYKGKQ SEQ ID NO.173, derived from Saccharomyces cerevisiae (Saccharomyces cer Saccharomyces cerevisiae SIS2, amino acid sequence ColumnMTAVASTSGKQDADHNQSIECPRFSRGQKEILLDHEDAKGKDSIINSPVSGRQSISPTLSNATTTTTKSIMNATGTSGAVVSNTPEPGLKRVPAVTFSDLKQQQKQDSLTQLKNDSERTKSPNSNPAPVSNSIPGNHAVIPNHTNTSRTTQLSGSPLVNEMKDYDPKKKDSALKIVDTMKPDKIMATSTPISRENNKVTAKAPTSITLRKEDAQDQANNVSGQINVRSTPEETPVKQSVIPSIIPKRENSKNLDPRLPQDDGKLHVLFGATGSLSVFKIKPMIKKLEEIYGRDRISIQVILTQSATQFFEQRYTKKIIKSSEKLNKMSQYESTPATPVTPTPGQCNMAQVVELPPHIQLWTDQDEWDAWKQRTDPVLHIELRRWADILVVAPLTANTLSKIALGLCDNLLTSVIRAWNPSYPILLAPSMVSSTFNSMMTKKQLQTIKEEMSWVTVFKPSEKVMDINGDIGLGGMMDWNEIVNKIVMKLGGYPKNNEEEDDDEDEEEDDDEEEDTEDKNENNNDDDDDDDDDDDDDDDDDDDDEDEDEAETPGIIDKHQ SEQ ID NO.174, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae SIT4, amino acid sequence Column MVSRGPDEWLETIKKCQALTENEMKQLCEMVKELLMEESNIQPVQTPVTVCGDIHGQFHDLLELFRTAGGFPDDINYIFLGDYVDRGYYSLETFTLLMCLKVKYPAKITLVRGNHESRQITQVYGFYEECLNKYGSTTVWKYCCQVFDFLTLAAIIDGKILCVHGGLSPEIRMLDQIRVLSRAQEVPHEGGFSDLLWSDPDNVEAWQVSPRGAGWLFGSKVAREFNHVNGLNLIARAHQLVMEGFKYHFPEKDVVTVWSAPNYCYRCGNVASVMKVDEDLEPTFKIFSAVPDDYIRESTANHNNQRAGYFL SEQ ID NO.175, derived from Saccharomyces cerevisiae (Saccharomyces cer Saccharomyces cerevisiae SIW14, amino acids SequenceMGLYQAKNDEGSDPKSSSKIDDLIENEAEIIRLIKEDGKLLIDNGDGRDIHNIIQEDKLLSVEFNEVLKRFHGEEKSDIPRKEFDEDEDDGYDSNEHHQKTIEVMNTLNHVINKEVIPPENFSHVVGEIYRSSFPRQENFSFLHERLKLKSILVLIPEEYPQENLNFLKLTGIKLYQVGMSGNKEPFVNIPSHLLTKALEIVLNPANQPILIHCNRGKHRTGCLIGCIRKLQNWSLTMIFDEYRRFAFPKARALDQQFIEMYDDDEIKRIASKNNWLPLQW SEQ ID NO.176, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae SMN1, amino acid sequence Column MILKLVHCLVALTGLIFAKPYQQQQAVLAPSQDVPLRDIHIGDINFIHTTDTHGWLGSHLSQNDYDADWGDFVAFVDILREKILRQSRDVIVIDTGDKRDGNGLSDATWPPGLRSSEIFNMMDYDLLTLGNHELYTAESAILEYRGTSQSSKFKDKYVCSNVEFIEDDGTRVPFGNKYITFETPIMKQRVLALSFLFSFQRANNRAIVTPPLEEITQKSWFQNMVETNREEEIDLIIVFGHLPATDPTEREMHKIHALIRKYYPNTVIQYFGGHTHIRDFVQLDSKSTCLQSGRFAETVGFLSINMTDPVDAESPIFSRRYIDFNKEAFKYHLSKLGHDSNVPVSTKKGKTISRLVNDLRHELNLNEKLGYIPQTYYVSTRPLNSEENLYHLITHKILPNLIPPKNYEPSMSRFILINTGSVRYDLYKGPFTKDTEYIVMPFNNDWRFITVPLVVASRVETYLNKGPVIASLGIPSSSHHKQHFGGFQKCPFINNPNLSEGYTTEDDFGCHGDDTPHNSQREYDIPNVVQCKEVKKVQEEEADPSKMVHVIFYSFMELDILNAVNSIINDLGLRMENLTTNDCSHYGGDSTKKLLRDYFSQF SEQ ID NO.177, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae SpO7, amino acid sequence ColumnMEPESIGDVGNHAQDDSASIVSGPRRRSTSKTSSAKNIRNSSNISPASMIFRNLLLILEDDLRRQAHEQKILKWQFTLFLASMAGVGAFTFYELYFTSDYVKGFHRVILQFTLSFISITVVLFHISGQYRRTIVIPRRFFTSTNKIRQFNVKLVKVQSTWDEKYTDSVRFVSRTIAYCNIYCLKKFLWLKDDNAIVKFWKSVTIQSQPRIGAVDVKLVLNPRAFSAEIREGWEIYRDEFWAREGARRRKQAHELRPKSE SEQ ID NO.178, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae SSU72, amino acids Sequence MPSHRNSNLKFCTVCASNNNRSMESHKVLQEAGYNVSSYGTGSAVRLPGLSIDKPNVYSFGTPYNDIYNDLLSQSADRYKSNGLLQMLDRNRRLKKAPEKWQESTKVFDFVFTCEERCFDAVCEDLMNRGGKLNKIVHVINVDIKDDDENAKIGSKAILELADMLNDKIEQCEKDIPFEDCIMDILTEWQSSHSQLPSLYAPSYY SEQ ID NO.179, derived from Saccharomyces cerevisiae (Saccharomyces cer Saccharomyces cerevisiae STT4, amino acid sequence Column SEQ ID NO.180, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae TAP42, amino acids Sequence MASVTEQFNDIISLYSTKLEHTSLRQDSPEYQGLLSTIKKLLNLKTAIFDRLALFSTNETIDDVSTASIKFLAVDYYLGLLISRRQSNDSDVAQRQSMKLIYLKKSVESFINFLTLLQDYKLLDPLVGEKLGNFKDRYNPQLSELYAQPKNNKDLSGAQLKRKKEIELFQRNKEISTKLHCLELELKNNDEDHDHDELLRELYLMRLHHFSLDTINNIEQNLFECEMLSNFLKNSVHEVKSSGTQIRKESNDDDSTGFTDKLENINKPLIDKKQVLRNFTLVDKRQQLQQKVRGYGQYGPTMSVEEFLDKEFEEGRVLQGGEEPEQAPDEENMDWQDRETYKAREWDEFKESHAKGSGNTMNRG SEQ ID NO.181, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae TEP1, amino acid sequence List MREEGSELEMEKGFLKWKPVNLMKKILSLPMKKTKKNDIGLRLDISYILVNLIVCSYPVNTYPKLLYRNSLDDLILFLTVYHGKGNFRIFNFRGEKEDSDYKDNDLIGIAAKFESKDFEIQELRSTLINDGKIPISPIDLETRTLVEEEETNNVICERIGWLDHFPPPFELLEEIVDGIENYLSVSKNRVAVLHCRMGKGRSGMITVAYLMKYLQCPLGEARLIFMQARFKYGMTNGVTIPSQLRYLRYHEFFITHEKAAQEGISNEAVKFKFKFRLAKMTFLRPSSLITSESAIVTTKIQHYNDDRNALLTRKVVYSDIMAHECGGNMTFIFGRDYLTLENDCRIEFTLGTSKSKAASSIISWTSCASCWLNIYLETLMHIIKDDSSPDYFQVERLKRDEMLGTTISWQELDGFGELSTHGLKLFQALKLEWEII SEQ ID NO.182, derived from Saccharomyces cerevisiae (Saccharomyces cer Saccharomyces cerevisiae TFC7, amino acid sequence ListMVVNTIYIARHGYRSNWLPEGPYPDPLTGIDSDVPLAEHGVQQAKELAHYLLSLDNQPEAAFASPFYRCLETVQPIAKLLEIPVYLERGIGEWYRPDRKPVIPVPAGYEILSKFFPGVISQEWDSTLTPNEKGETEQEMYMRFKKFWPLFIERVEKEYPNVECILLVTHAASKIALGMSLLGYDNPRMSLNENGDKIRSGSCSLDKYEILKKSYDTIDETDDQTSFTYIPFSDRKWVLTMNGNTEFLSSGEEMNWNFDCVAEAGSDADIKKRQMTKKTSSPIPEADDQTEVETVYISVDIPSGNYKERTEIAKSAILQYSGLETDAPLFRIGNRLYEGSWERLVGTELAFPNAAHVHKKTAGLLSPTEENETTNAGQSKGSSTANDPNIQIQEEDVGLPDSTNTSRDHTGDKEEVQSEKIYRIKERIVLSNVRPM SEQ ID NO.183, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae TFG1, amino acid sequence ListMSRRNPPGSRNGGGPTNASPFIKRDRMRRNFLRMRMGQNGSNSSSPGVPNGDNSRGSLVKKDDPEYAEEREKMLLQIGVEADAGRSNVKVKDEDPNEYNEFPLRAIPKEDLENMRTHLLKFQSKKKINPVTDFHLPVRLHRKDTRNLQFQLTRAEIVQRQKEISEYKKKAEQERSTPNSGGMNKSGTVSLNNTVKDGSQTPTVDSVTKDNTANGVNSSIPTVTGSSVPPASPTTVSAVESNGLSNGSTSAANGLDGNASTANLANGRPLVTKLEDAGPAEDPTKVGMVKYDGKEVTNEPEFEEGTMDPLADVAPDGGGRAKRGNLRRKTRQLKVLDENAKKLRFEYPWVMEDFDGYNTWVGSYEA GNSDSYVLLSVEDDGSFTMIPADKVYKFTARNKYATLTIDEAEKRMDKKSGEVPRWLMKHLDNIGTTTTRYDRTRRKLKAVADQQAMDEDDRDDNSEVELDYDEEFADDEEAPIIDGNEQENKESEQRIKKEMLQANAMGLRDEEAPSENEEDELFGEKKIDGERIKKALQKTELAALYSSD ENEIPYLSDIENKENESPVKKEEDSDTLSKSKRSSPKKQQKKATNAHVHKEPTLRVKSIKNCVIILKGDKKILKSFPEGEWNPQTTKAVDSSNNASNSTVPSPIKQEEGLNSTVAEREETPAPTITEKDIIEAIGDGKVNIKEFGKFIRRKYPGAENKKLMFAIVKKLCRKVGNDHMELKKE SEQ ID NO.184, derived from Saccharomyces cerevisiae (Saccharomyces cer Saccharomyces cerevisiae TOF2, amino acid sequence ListMIKMWRLQIVLVPPSAQDIITFLEARLNTPQSVSPMVQYNEDIITHNNSINNCSDSPSTPSPSSQNSIQSNRSSDFINYLPNCCKKFLHFTDGDNTLLQLSNEILTKFDRLYPNFKESIEIVSLQDRHGCDLDSEFIIKDVFENDGVVLVILKDELDWSRNQHISLLQLARQRRRQDNKPSTKSIVTEKRKKISKEDLSSISNKDTMHLIAKSSLKNNFINKSRVSTPLMNEILPLASKYDALNKEKCPMPLTSTVVASNVHKDVKDHARAKEGVVTQGSDNNKENIPSSTQQQKNDGAKRAESKDLLLRNSSEDADYEPADENSPQISFDSIDTDFQLSTTSHTNSDMHIQYSNPSSGAHSPRKSSLEIKVQNKKGDDLPLNDKD IGENCRRIEAFSDEEDFNETDNDRADSFINNSKKASMGFRDINSDLDSVSFNSDIENAVQSTQSTKNVVSPPFFPEKELNNRLHQSQGKEALFRLVEKEFPDKSLGAASSTSHAKDVKIQETIRKLNRFKPTGETKVQKRNSITEPYYGKFGIMKKDKPKSITSKGVSLETKHFDDPNTIISGEKFAKFGKIKVKRKTDDVGSKVIEFKRKRNMGNRSLKDIFANAGKPPNAASTIKVVKLMRDPVDNSKDKVEATSNSTAQEQEQVSPKLPVMNSTPGKRKNGQAIPSSLERTPQLKKVKVTRSHSSPSSSSSMSLESSLDSSSSDDSDDDSRNVQVKKINFKTSHGPAGNSNGKPMLDVDDNEINTKKYQTPKYVESDEDDQ SEQ ID NO.185, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae TPD3, amino acid sequence ListMSGARSTTAGAVPSAATTSTTSTTSNSKDSDSNESLYPLALLMDELKHDDIANRVEAMKKLDTIALALGPERTRNELIPFLTEVAQDDEDEVFAVLAEQLGKFVPYIGGPQYATILLPVLEILASAEETLVREKAVDSLNNVAQELSQEQLFSDFVPLIEHLATADWFSSKVSACGLFKSVIVRIKDDSLRKNILALYLQLAQDDTPMVKRAVGKNLPILIDLLTQNLGLSTDEDWDYISNIFQKIINDNQDSVKFLAVDCLISILKFFNAKGDESHTQDLLNSAVKLIGDEAWRVRYMAADRFSDLASQFSSNQAYIDELVQPFLNLCEDNEGDVREAVAKQVSGFAKFLNDPSIILNKILPAVQNLSMDESETVRSALASKITNIVLLLNKDQVINNFLPILLNMLRDEFPDVRLNIIASLKVVNDVIGIELLSDSLLPAITELAKDVNWRVRMAIIEYIPILAEQLGMQFFDQQLSDLCLSWLWDTVYSIREAAVNNLKRLTEIFGSDWCRDEIISRLLKFDLQLLENFVSRFTILSALTTLVPVVSLDVVTEQLLPFISHLADDGVPNIRFNVAKSYAVIVKVLIKDEAKYDALIKNTILPSLQTLCQDEDVDVKYFAKKSLAECQELLKN SEQ ID NO.186, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae TPP1, amino acid sequence List MSHKLTILPFLIKFTPKFPQSIDHDEHGLNVYAFDLDHTIIKPKSPNISFSRSASDWQFINFNSKKSTLDYLCNIIDNDPTAVIVIFSNQGGVITVPRTSKSCTKYTNKILLFLKAIKNDERGETLSHRLWLYAAPKRPKTFAANHSKITFASLGESYNNDPNIFEKVRKPMTGMVEFFKRDLESAYRVSEQISPIKLNWIYYCGDAAGRKKDFSDSDIKFAENLHVEFKYPEEIFHG SEQ ID NO.187, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae TPS1, amino acid sequence ListMTTDNAKAQLTSSSGGNIIVVSNRLPVTITKNSSTGQYEYAMSSGGLVTALEGLKKTYTFKWFGWPGLEIPDDEKDQVRKDLLEKFNAVPIFLSDEIADLHYNGFSNSILWPLFHYHPGEINFDENAWLAYNEANQTFTNEIAKTMNHNDLIWVHDYHLMLVPEMLRVKIHEKQLQNVKVGWFLHTPFPSSEIYRILPVRQEILKGVLSCDLVGFHTYDYARHFLSSVQRVLNVNTLPNGVEYQGRFVNVGAFPIGIDVDKFTDGLKKESVQKRIQQLKETFKGCKIIVGVDRLDYIKGVPQKLHAMEVFLNEHPEWRGKVVLVQVAVPSRGDVEEYQYLRSVVNELVGRINGQFGTVEFVPIHFMHKSIPFEELISLYAVSDVCLVSSTRDGMNLVSYEYIACQEEKKGSLILSEFTGAAQSLNGAIIVNPWNTDDLSDAINEALTLPDVKKEVNWEKLYKYISKYTSAFWGENFVHELYSTSSSSTSSSATKN SEQ ID NO.188, derived from Saccharomyces cerevisiae (Saccharomyces cer Saccharomyces cerevisiae TPS2, amino acid sequence ListMTTTAQDNSPKKRQRIINCVTQLPYKIQLGESNDDWKISATTGNSALFSSLEYLQFDSTEYEQHVVGWTGEITRTERNLFTREAKEKPQDLDDDPLYLTKEQINGLTTTLQDHMKSDKEAKTDTTQTAPVTNNVHPVWLLRKNQSRWRNYAEKVIWPTFHYILNPSNEGEQEKNWWYDYVKFNEAYAQKIGEVYRKGDIIWIHDYYLLLLPQLLRMKFNDESII IGYFHHAPWPSNEYFRCLPRRKQILDGLVGANRICFQNESFSRHFVSSCKRLLDATAKKSKNSSNSDQYQVSVYGGDVLVDSLPIGVNTTQILKDAFTKDIDSKVLSIKQAYQNKKIIIGRDRLDSVRGVVQKLRAFETFLAMYPEWRDQVVLIQVSSPTANRNSPQTIRLEQQVNELVNSINSEYGNLFSPVQHYYMRIPKDVYLSLLRVADLCLITSVRDG MNTTALEYVTVKSHMSNFLCYGNPLILSEFSGSSNVLKDAIVVNPWDSVAVAKSINMALKLDKEEKSNLESKLWKEVPTIQDWTNKFLSSLKEQASSNDDMERKMTPALNRPVLLENYKQAKRRLFLDYDGTLTPIVKDPAAAIPSARLYTILQKLCADPHNQIWIISGRDQKFLNKWLGGKLPQLGLSAEHGCFMKDVSCQDWVNLTEKVDMSWQVRVNEVMEEFTTRTPGSFIERKKVALTWHYRRTVPELGEFHAKELKEKLLSFTDDFDLEVMDGKANIEVRPRFVNKGEIVKRLVWHQHGKPQDMLKGISEKLPKDEMPDFVLCLGDDFTDEDMFRQLNTIETCWKEKYPDQKNQWGNYGFYPVTVGSAKTVAKAHLTDPQQVLETLGLLVGDVSLFQSAGTVDLDSRGHVKNSESSLKSKLASKAYVMKRSASYTGAKV SEQ ID NO.189, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae TPS3, amino acid sequence List SEQ ID NO.190, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae TSL1, amino acid sequence List SEQ ID NO.191, derived from Saccharomyces cerevisiae (Saccharomyces cer Saccharomyces cerevisiae UTR4, amino acid sequence List MGDNYSTYLLDIEGTVCPISFVKETLSPYFTKKVPQLVQQDTRDSPVSNILSQFHIDDKEQLQAHILELVAKDVKDPILKQLQGYIWAQGYESGQIKAPVYADAIDFIRKKRVFIYSSGSVKAQKLLFGYVQDPNAPAHDSLDLNSYIDGYFDINTSGKKTETQSYANILRDIGAKASEVLFSDNPLELDAAAGVGIATGLASRPGNAPVPDGQKYQVYKDFETL SEQ ID NO.192, derived from Saccharomyces cerevisiae (Saccharomyces cer Saccharomyces cerevisiae VHS3, amino acid sequence List MTNKSSLKNNRKGVASNTLSGAEQANIGSSAMPDTNSTGPFSSVSSLDTPVVRKSTSPTGSQTKSIMNASGTSGAVVSNTPEPGLKRIPTVTFSDPKLGSLRSDVEQTPPNQVARQSSEKKATSVHIAAEGANQGRNLKDINTKVPKDGEASASSFSTPTSILSNADMGNNISSLAKKLSFTGGTDSILNSDNSSDSPRKEHPHFYVEDPLHTPSVRSRSNSTSPRPSVVVNTFNPINIEREGSISKTGEPTLLESVLEEAMSPNAVSNPLKRENIMTNMDPRLPQDDGKLHVLFGATGSLSVFKLKHMIRKLEEIYGRDKICIQVILTNSATKFF AMKYMRKNKKQHNSIDTSFNSTNSNAGNITGNKKKVASLEKFSIQKTSSNSAASQTNNKQEEEKQMASTTGFPSTLGGSRTYSNSSNVSQHPQIELPAHIQFWTDQDEWDVWRQRTDPVLHIELRRWADILVVAPLTANTLAKIALGLCDNLLTSVIRAWNPTFPIF LAPSMGSGTFNSIMTKKHFRIIQEEMPWVTVFKPSEKVMGINGDIGLSGMMDANEIVGKIVVKLGGYPVSAKGEEEEDEDNDEEDDNKKNDTGGKDEDNDDDDDDDDDDDDDDDDDDDDDDDDDDDDDDDDDDDDDDDDDDDDDEDEDEDDEGGKKKEDKGGLQRS SEQ ID NO.193, derived from Saccharomyces cerevisiae (Saccharomyces cer Saccharomyces cerevisiae VIP1, amino acid sequence List SEQ ID NO.194, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae VPS34, amino acids sequence MSLNNITFCVSQDLDVPLKVKIKSLEGHKPLLKPSQKILNPELMLIGSNVFPSDLIVSLQVFDKERNRNLTPYIPFRNSRTWDYWLTLPIRIKQLTFSSHLRIILWEYNGSKQIPFFNLETSIFNLKDCTLKRGFESLKFRYDVIDHCEVVTDNKDQENLNKYFQGEFTRLPWLDEITISKLRKQRENRTWPQGTFVLNLEFPMLELPVVFIEREINMNTQMNIPTLKNNPGLSTDLREPNRNDPQIKISLGDKYHSTLKFYDPDQPNNDPIEEKYRRLERASKNANLDKQVKPDIKKRDYLNKIINYPPGTKLTAHEKGSIWKYRYYLMNNKKALTKLLQSTNLREESERVEVLELMDSWAEIDIDDALELLGSTFKNLSVRSYAVNRLKKASDKELELYLLQLVEAVCFENLSTFSDKSNSSEFTIVDAVS SQKLSGDSMLLSTSHANQKLLKSISSESSTGTESLPIVISPLAEFLIRRALVNPRLGSFFYWYLKSESEDKPYLDQILSSFWSRLDKKSRNILNDQVRLINVLRECCETIKRLKDTTAKKMELLVHLLETKVRPLVKVRPIALPLDPDVLICDVCPETSKVFKSSLSPLKITFKTTLNQPYHLMFKVGDDLRQDQLVVQIISLMNELLKNENVDLKLTPYKILATGQEGAIEFIPNDTLASILSKYHGILGYLKLHYPDENATLGVQGWVLDNFVKSCAGYCVITYILGVGDRHLDNLLVTPDGHFFHADFGYILGQDPKPPFPPLMKLPPQIIEAFGGAESSNYDKFRSYCFVAYSILRRNAGLILNLFELMKTSNIPDIRIDPNGAILRVRERFNLNMSEEDATVHFQNLINDSVNALLPIVIDHLHNLAQYWRT SEQ ID NO.195, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae VPS74, amino acids sequenceMSTLQRRRVNRADSGDTSSIHSSANNTKGDKIANIAVDGDDDNGTNKKIAYDPEESKLRDNINIPTLTLMEEVLLMGLRDREGYLSFWNDSISYALRGCIIIELALRGKIRILDDSARKRFDLSERLIEVIDSSKTGEVLLDETLQLMKNDEPLSISNWIDLLSGETWNLLKINYQLKQVRERLAKGLVDKGVLRTEMKNFFLFDMATHPIADASCKEAIKRRVLSVLVSRNMELSYNEYFPETTSFKIIRTLALICGSYGANVLENVLTTLEYEKRDKAISRAEEIMAQFSQYPFDLEKETELGVSVNLNKEVKEEIENNPGHDLQLEVIAGVFEVFSRMDMLL SEQ ID NO.196, derived from Saccharomyces cerevisiae (Saccharomyces cer Saccharomyces cerevisiae WHI2, amino acid sequence List MDDIITQVSPDNAESAPILQEQQQQQNSQYEGNEEDYGDSLIHLNIQENHYFITRDQLMSLPESLLLCLFPSGVFLDRCGQVITNLTRDDEVYIVNFPPDCFEYIMEIYTKAHDDLYNHPVEKFFDRPSSSFVSNAKGFFGLSSNNSISSNNEQDILHQKPAIIVLREDLDYYCVPQEEFQFDSTNEENNEDLLRHFMAQVKMAAGSYLTSKTSIFQGLYSSNRLKQQQQQQKIEKGSNSSSNTKSTSKKLGPAEQHLMDMLCSSGFTKETCWGNRTQETGKTVISSLSLCRLANETTEGFRQKFNEAKAKWEAEHKPSQDNFITPMQSNISINSLSASKSNSTISTARNLTSGSTAPATARDKRKSRLSKLADNVRSHSSSRHSSQTRSKPPELPKLYDLVPKPNINAKLLLFWRKPARKCWWGEEDIELEVEVFGSWKDESKKIIELILPTNVDPEAELHKIIVPVRLHIRRVWTLELSVIGVQ SEQ ID NO.197, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae YAR068W, amino acid sequenceMPQVQSWFPVQKQPTLAVTFTPLPQLSHAHLPLPPSHLVTKTDAMFQHQLLPTQLQPFPPSHTPLLLLLTVTTMAVTPRLSLLNVLKKLQQPPFLQNHTLLLPLLTVTTTAVTPRLSLPRLPNKHHWPLAQSPSLLLQLLILLLPAPSLVLSFNPKVWLLV SEQ ID NO.198, derived from Saccharomyces cerevisiae (Saccharomyces cer Saccharomyces cerevisiae YBR242W, amino acid sequence MTATITNKKSCSGSVEAGKTRLTTEWKPESQVPQYVKNELSKPHPNYILAFLNVVQQLKIQRRTGYLDLGIKECESISDHMYRLSIITMLIKDSRVNRDKCVRIALVHDIAESLVGDITPVDPIGKEEKHRREWETIKYLCNALIKPYNEIAAKEIMDDWLAYENVTSLEARYVKDIDKYEMLVQCFEYEREYKGTKNFDDFFGAVASIKTDEVKGWTSDLVVQRQKYFADLTQSITK SEQ ID NO.199, derived from Saccharomyces cerevisiae (Saccharomyces cer Saccharomyces cerevisiae YCH1, amino acid sequence List MDSYSITNVKYLDPTELHRWMQEGHTTTLREPFQVVDVRGSDYMGGHIKDGWHYAYSRLKQDPEYLRELKHRLLEKQADGRGALNVIFHCMLSQQRGPSAAMLLLRSLDTAELSRCRLWVLRGGFSRWQSVYGDDESVTAGYLPDLWR SEQ ID NO.200, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae YER134C, amino acid sequence MTGYPDVAAFDLDYTIWPCYCDTHLHGPFKPVKSSNGEVLTIICRDGYELTIYKDIPRILGDLKDNGVKLMTASRTWAPEIAQEILKIFKVKYAGVVTPLANLFDEFQWGERSKIGHLRDGLKDLYNTSDLKSKKICLFDDESRNKEVEKYGVKFVYVRDPENGPSWKLYQDYLSGKV SEQ ID NO.201, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae YGK1, amino acid sequence ListMTAVNIWKPEDNIPREILAILSKPHPNYQLAFLNIIQLLKTQRRTGWVDHGIDPCESISDHMYRMGLTTMLITDKNVDRNKCIRIALVHDFAESLVGDITPNDPMTKEEKHRREFETVKYLCESIIRPCSESASREILDDWLAYEKQTCLEGRYVKDIDKYEMLVQCFEYEQKYNGKKDLKQFLGAINDIKTDEVKKWTQSLLEDRQAFFDSLKE SEQ ID NO.202, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae YIG1, amino acid sequence List MGIPMQIYQDGKGVQFYHTRYQNVFDERASKYGNYTVNNDYPQLPDTIKEHIDQLTFSNVGEDGGDVGNYSEEDDDGDEEKELEDVFRSNRGLEFVRINNYFTTHDLQSFKSFRNFNSKYWIFYSNQAEDKKLLLYDFNGQHLIFIKQQFYGQLNLLLSDAIICMDCNFGYNSNTIQILVGFQNGKLLKLNCDLNGNVNNHLLLKDPSTSSHQSHLSILNVWAGLLPHFVVSFSLKDGLLITSLDHQQSNGSFQSFHTNIDLPVDLRTTTNVKSVLNFPQFTLYKGNDMIFHCKNLLGSDASTLNKEINFMLKIDEDVQKIDYLLKTNHILLETNMRYLSIPTRDPIENSNSSPPVSDSEVYPIFYKTQELHVHASGTGRQIANNGKYIFITEQHLYGTALSVYKYSISFKRWLFVGYSDIRAKYGIRSVKDLFVGNCPSVNSPVLTILTDDNNIQTILLK SEQ ID NO.203, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae YJR142W, amino acid sequenceMKVEKSSKGLEVLVRTQEDDLEGFSFLEIMDRVDPLPLDFENYKNFKEGIYYMCTHDGTKIGFVLKFAINEMETVCSEIFEETFQLDESRHELRFKSEDFDHRNNLIDQLARKMYLESSLSGVKGWRNEKYAVWVNKKPYVLVERAVAGVLGIITYGIHINGYVLDPKSKKVQFWVPRRSKTKQTWPLMLDNIIAGGLGYPYGIYETVLKESMEEANLEKSVIEDNIKATGSVSYLYFTGDISVTKFNKESDFIVGEVQYVYDLKLSEDIIPKPNDGEVESFNLFSLQETINALRKKEFKPNCALVMVDFLIRHGYITPENEPNELEVTRMHRRLPFPTLN SEQ ID NO.204, derived from Saccharomyces cerevisiae (Saccharomyces cer Saccharomyces cerevisiae YKL033W-A, ammonia amino acid sequence MTHPVAVKACLFDMGLLINTEDIYTETLNETLAEFGKGPLTWDVKIKLQGLPGPEAGKRVIEHYKLPITLDEYDERNVALQSLKWGTCEFLPGALNLLKYLKLKNIPIALCTSSNKTKFRGKTSHLEEGFDLFDTIVTGDDPRIAKGRGKPFPDIWQLGLKELNEKFHTDIKPDECIVFEDGIPGVKSAKAFGAHVIWVPHPEAHAVLGDTEALLAGKGELLSSLEKLEMSKYGL SEQ ID NO.205, derived from Saccharomyces cerevisiae (Saccharomyces cer Saccharomyces cerevisiae YMR027W, amino acid sequenceMTIPGRFMTNDKGTFGEYTASTRWPIIIQNAIDDLSKHQETEKSNGTKFEQGEVIKKELKEFRQEIIDRVPLRPFTEEIKIANVPLSFNEYLKKHPEVNWGAVEWLFSEVYLYRRVNVLFQRQCEWAKFDIFNRLKQSTFESSFYGVVELALRYENLLPQLREMKQNPGNEIDDILKVLFKEFIEISLWGNATDLSLLTNATLEDIKIQGAKARAASESKIVVNDTEKAWEVLTKARADANSREIRVDFVLDNSGFELYADLMLAAFLLQSGLATKCIFHAKDIPYMVSDVMLKDFDILVHDLRDREFPSGEPSTKESRALDLFAGEMEKFVSSGKIEFREDSFWTTELDYWNLDANETKYHGSILHKDLQKSNLVIFKGDLNYRKLTGDRKWPRTTKWETAIGPLATNGITSLSLRTCKADVQVALPEGLDAKLSQEWEKENPGRGSWWCCSGKWAVICFCSGIHK SEQ ID NO.206, derived from Saccharomyces cerevisiae (Saccharomyces cer Saccharomyces cerevisiae YMR1, amino acid sequence ListMEYYIKIAKVSNVVLHRRGTATQGTLHLTTHHLIFESPQLSTEFWFPYPLIYGVHKNPGSTLLSKLTSTNQIQLEGTESQNYKLYQGKDLWSFVNIKVIGKDYAVFSLDFGDGDLHLQARKVYDSILNLTVLSNITQLYAFIYISNNLERKLPSPDSWDIYDPIKEFRRQGLDS KDETCPWRLSTVNEHYEFCPTYPSKLVPRSTSDILLKHASKFRSQKRIPVLTYHHKATDCNILRSSQPLPGLINQRSIQDEKLVWESFNSFCNKDIRRTKHVIDARPRTNALAQMALGGGTENMDNYNFLADNNMGVDKSLKLPTVTRLFLGIDNIHIVSNTAAYMTEV ICQGGDLNLPLEQNLIRSQKFSNWLKLNTLILKSVDMLLKSIIFNHSNVLVHCSDGWDRTSQVVSLLEICLDPFYRTFEGFMILVEKDWCSFGHRFLERSGHLNSDIRFHDNTMHSNFNDVDTNGDDLDIGVNTQDDYAEDDEGGEDETNLINLSRISKKFNENFKLNKKSLKFVSPVFQQFLDCVYQLLTQNPDLFEFNERFLRRLVYHLYSCQYGTFLSNSEKEKFQQNLPNKTKSVWDYFRSRRKQFINPNFIQRKRSGMNEHDQNLEEEEKVEWISPDLKKVQWWWQLYGRKDSEMNDELRHKRDSVPISVDKKSKEHSNSDGGKGLNLSIFGFDMFNRK SEQ ID NO.207, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae YND1, amino acid sequence ListMLIENTNDRFGIVIDAGSSGSRIHVFKWQDTESLLHATNQDSQSILQSVPHIHQEKDWTFKLNPGLSSFEKKPQDAYKSHIKPLLDFAKNIIPESHWSSCPVFIQATAGMRLLPQDIQSSILDGLCQGLKHPAEFLVEDCSAQIQVIDGETEGLYGWLGLNYLYGHFNDYNPEVSDHFTFGFMDMGGASTQIAFAPHDSGEIARHRDDIATIFLRSVNGDLQKWDVFVSTWLGFGANQARRRYLAQLINTLPENTNDYENDDFSTRNLNDPCMPRGSSTDFEFKDTIFHIAGSGNYEQCTKSIYPLLLKNMPCDDEPCLFNGVHAPRIDFANDKFIGTSEYWYTANDVFKLGGEYNFDKFSKSLREFCNSNWTQILANSDKGVYNSIPENFLKDACFKGNWVLNILHEGFDMPRIDVDAENVNDRPLFQSVEKVEERELSWTLGRILLYASGSILAGNDDFMVGIAPSERRTKLTGKKFIPGKLLESDQLRKQSSSLSNKGFLMWFAIICCIFYLIFHRSHIIRRRFSGLYNITKDFKTGIRRRLKFLRRSDPFSRLEEGELGTDVDGFKDVYRMKSSSMFDLGKSSATMQREHEPQRTASQSANLAPSNLRPAFSMADFSKFKDSRLYD SEQ ID NO.208, derived from Saccharomyces cerevisiae (Saccharomyces cer Saccharomyces cerevisiae YNL108C, amino acid sequence MAIENIYIARHGYRSNWLPKGPYPPPPTGIDNDVPLSEHGVEQAHELANYISKLDVKPEMIFSSPFYRCLETSKPTVEALKIPLYVDRGVGEWYKPDRPIIPEPATHEVMSKFFPSMISPDWEPSIIPSNKGETEEDIFERCHKFWPVFIDRVERKFPNVKTIMIVTHAATKSALGMNLLKFSSAKEPIDNKGTFIRNGSCAIDKFELVKGENESIPFEEREWKLTMNGNTSFLTNGEEMNWTFMNAFEAGSDADIKARRAAESGKLKME SEQ ID NO.209, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae YOR131C, amino acid sequenceMTKLQGLQGLKHIKAVVFDMDGTLCLPQPWMFPAMRNAIGLEDKSIDILHFIDTLPTEKEKKEAHDRIELVEAKAMKEMQPQPGLVDIMRYLTKNGISKNICTRNVGAPVETFVKRFIPSELSRFDYIVTREFRPTKPQPDPLLHIASKLNIRPLEMIMVGDSFDDMKSGRSAGCFTVLLKNHVNGHLLLEHKELVDVSVEDLSEIIELIQNMNKESF SEQ ID NO.210, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae YOR283W, amino acid sequence MTKEVPYYCDNDDNNIIRLFIIRHGQTEHNVKKILQGHKDTSINPTGEEQATKLGHYLRSRGIHFDKVVSSDLKRCRQTTALVLKHSKQENVPTSYTSGLRERYMGVIEGMQITEAEKYADKHGEGSFRNFGEKSDDFVARLTGCVEEEVAEASNEGVKNLALVSHGGAIRMILQWLKYENHQAHKIIVFNTSVTIVDYVKDSKQFIVRRVGNTQHLGDGEFVVSDLRLR SEQ ID NO.211, derived from Saccharomyces cerevisiae (Saccharomyces cer Saccharomyces cerevisiae YPD1, amino acid sequence List MSTIPSEIINWTILNEIISMDDDDSDFSKGLIIQFIDQAQTTFAQMQRQLDGEKNLTELDNLGHFLKGSSAALGLQRIAWVCERIQNLGRKMEHFFPNKTELVNTLSDKSIINGINIDEDDEEIKIQVDDKDENSIYLILIAKALNQSRLEFKLARIELSKYYNTNL SEQ ID NO.212, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae YPI1, amino acid sequence List MSGNQMAMGSEQQQTVGSRTVSVEEVPAVLQLRATQDPPRSQEAMPTRHNVRWEENVIDNENMNKKKTKICCIFHPQNEDEEECNHHSDDDGSSSSGSSSSESENEKDLDFNERRQRRLERRHRKLEKKRSYSPNAYEIQPDYSEYRRKQQEKKD SEQ ID NO.213, derived from Saccharomyces cerevisiae (Saccharomyces cer Saccharomyces cerevisiae YSR3, amino acid sequence ListMTIIQTVTELGVTEDTIKVQMAPSGGKHLLADPGNHPAEHFESQMSWLRFQTRQYLTRFTDNQSDFVHSLQKKHRTPFRDVYFKYTSLMGSHMFYVIVLPMPVWLGYRDLTRDMIYVLGYSIYLSGYLKDYWCLPRPKSPPVDRITLSEYTTKEYGAPSSHSANATAVSLLFFWRICLSDTLVWPTKLLLLSLVIFYYLTLVFGRVYCGMHGMLDLFSGAAVGAICFFIRIWVVHALRNFQIGEHLWFPLLSVAWGLFILFNHVRPIDECPCFEDSVAFIGVVSGLDCSDWLTERYGWNLVCSRYASCGSKVFLRPLVGVASVIVWKDVISKTAVYTLLIKLLRFHDDRSEKVHFHNETSEEEECLLYSGVSKVEIVGRFLIYAGIPTTVFLLCPVFFTWTNLR SEQ ID NO.214, derived from Saccharomyces cerevisiae (Saccharomyces cer Saccharomyces cerevisiae YSW1, amino acid sequence ListMSSLADTVEGSEAKRGRFSNNALTSDTGILQKNSTLRNWFLKPTADLKNSCEDRVEDDVNDVYLNDKNSQKSVEERKLGRKVRSFFKQTNSNKDESVLEDEDDALVWKKTSNKCAKKENSHDIQKGSFTKKIRNSIFKSANDVKEFRNENNLLLPVELSSDDENESHFTDANSHVMQSKSPEKIPSKDQCLTKGAKNKGLKKEYEKSFEEYSDDSDDEFSPATPPENVLEGPYKFVFQTPNTFTSQPNITVENDFHKGGRHVIDYLNKKLATMNIDIDLTSGGKQNVSWEEELDQLSDHVIESI TNHISKGRMHAQEKQDELEKLKLENLNLSTLKQENLQHKQEINSLKDNLESISKKNNDLILEMNKLKKKSTNNKTNEYISTDENENEEITKSNMGPGILELNVNETSKKLQQSTFKPSKYLPRETRNNENRLKHLEKRIFGLEKSKLKKKQVRADSVRLDLNRYTIDQFLTLLKSLESVLQFHNVYGNDLKENDDNIIKIETCCSALNMKNCFEDSSSFRLQENSFKRQLGPLFANINFSLIDQLTMNFRFYERSANFQKETIGGLRMMLQDKDNYIKTLMQHLKKKESTKLIKDSKNGASTLTS SEQ ID NO.215, derived from Saccharomyces cerevisiae (Saccharomyces cer Saccharomyces cerevisiae YVH1, amino acid sequence ListMAGNANSVDEEVTRILGGIYLGGIRPIIDHRPLGAEFNITHILSVIKFQVIPEYLIRKGYTLKNIPIDDDDVTDVLQYFDETNRFIDQCLFPNEVEYSPRLVDFKKKPQRGAVFAHCQAGLSRSVTFIVAYLMYRYGLSLSMAMHAVKRKKPSVEPNENFMEQLHLFEKMGGDFVDFDNPAYKQWKLKQSIKLDPSGSELVSNSGMFKDSESSQDLDKLTEAEKSKVTAVRCKKCRTKLALSTSFIAHDPPSKSESSEGHIKRAANSHRIIDIQESQANCSHFFIEPLKWMQPELQGKQELEGKFSCPGCSSKVGGYNWKGSRCSCGKWVIPAIHLQTSKVDQFPLQSTALPNMVNFESEKVNR SEQ ID NO.216, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae ZDS1, amino acid sequence ListMLRTTSSDKAIASQRDKRKSEVLIAAQSLDNEIRSVKNLKRLSIGSMDLLIDPELDIKFGGESSGRRSWSGTTSSSASMPSDTTTVNNTRYSDPTPLENLHGRGNSGTESSNKTKQGYYLGIKKKGVHSPSRKLNANALKKNLLWVPANQHPNVKPDNFLELVQDTLQNIQLSDNGEDNDGNSNENNDIEDNGEDKESQSYENKENNTINLNRGLSRHGNASLIRRPSTLRRSYTEFDDNEDDDNKGDSASETVNKVEERTSKIKERPVSLRDITEELTKISNSAGLTDNDAITLARTLSMAGSYSDKKDQPQPEGHYDEGDIGFSTSQANTLDDGEFASNMPINNTMTWPERSSLRRSRSFNTYRIRSQEQEKEVEQSVDEMKNDDEERLNLTKNTIKVEIDPHKSPFFRQQDEDSENMSSPGSIGDFQDIYNHYRQSSGEWEQEMGIEKAEEVPVKVR NDTVEQDLELREGTTDMVKPSATDDNKETKRHRRRNGWTWLNNKMSREDDNEENQGDDENEENVDSQRMELDNSKKHYISLFNGGEKTEVSNKEEMNNSSTSTATSQTRQKIEKTFANLFRRKPHHKHDASSSPSSSPSSSPSIPNNDAVHVRVRKTKKLGNKSGREPVEPIVLRNRPRPHRHHSRHGSQKISVKTLKDSQPQQQIPLQPQLEGAIEIEKKEESDSES LPQLQPAVSVSSTKSNSRDREEEAKKKKNRSNTTEISNQQHSKHAQKENTDEQKAQLQAPAQEQVQAQEQVQASVPVQASVPVQASAPVQTSAPVEASAQTQAPAAPPLKHTSILPPRKLTFADVKKPDKPNSPVQFTDSAFGPPLLTVSTVIMFDHRLPINVERAIYRLSHLKLSNSKRGLREQVLLSNFMYAYLNLVNHTLYMEQVAHDKEQQQQQQQQP SEQ ID NO. 217, derived from Escherichia coli ( Escherichia coli Ec.PgpA, amino acid sequenceMTILPRHKDVAKSRLKMSNPWHLLAVGFGSGLSPIVPGTMGSLAAIPFWYLMTFLPWQLYSLVVMLGICIGVYLCHQTAKDMGVHDHGSIVWDEFIGMWITLMALPTNDWQWVAAGFVIFRILDMWKPWPIRWFDRNVHGGMGIMIDDIVAGVISAGILYFIGHHWPLGILS SEQ ID NO. 218, derived from Escherichia coli ( Escherichia coli Ec.PgpB, amino acid sequence MRSIARRTAVGAALLLVMPVAVWISGWRWQPGEQSWLLKAAFWVTETVTQPWGVITHLILFGWFLWCLRFRIKAAFVLFAILAAAILVGQGVKSWIKDKVQEPRPFVIWLEKTHHIPVDEFYTLKRAERGNLVKEQLAEEKNIPQYLRSHWQKETGFAFPSGHTMFAASWALLAVGLLWPRRRTLTIAILLVWATGVMGSRLLLGMHWPRDLVVATLISWALVAVATWLAQRICGPLTPPAEENREIAQREQES SEQ ID NO. 219, derived from Escherichia coli ( Escherichia coli Ec.PgpC, amino acid sequence MATHERRVVFFDLDGTLHQQDMFGSFLRYLLRRQPLNALLVLPLLPIIAIALLIKGRAARWPMSLLLWGCTFGHSEARLQTLQADFVRWFRDNVTAFPLVQERLTTYLLSSDADIWLITGSPQPLVEAVYFDTPWLPRVNLIASQIQRGYGGWVLTMRCLGHEKVAQLERKIGTPLRLYSGYSDSNQDNPLLYFCQHRWRVTPRGELQQLE SEQ ID NO. 220, derived from Escherichia coli ( Escherichia coli The amino acid sequence of Ec.YbjG is as follows: MLENLNLSLFSLINATPDSAPWMISLAIFIAKDLITVVPLLAVVLWLWGLTAQRQLVIKIAIALAVSLFVSWTMGHLFPHDRPFVENIGYNFLHHAADDSFPSDHGTVIFTFALAFLCWHRLWSGSLLMVLAVVIAWSRVYLGVHWPLDMLGGLLAGMIGCLSAQIIWQAMGHKLYQRLQSWYRVCFALPIRKGWVRD SEQ ID NO.221, derived from human ( Homo sapiens Hs.DOLPP1, amino acid sequenceMAADGQCSLPASWRPVTLTHVEYPAGDLSGHLLAYLSLSPVFVIVGFVTLIIFKRELHTISFLGGLALNEGVNWLIKNVIQEPRPCGGPHTAVGTKYGMPSSHSQFMWFFSVYSFLFLYLRMHQTNNARFLDLLWRHVLSLGLLAVAFLVSYSRVYLLYHTWSQVLYGGIAGGLMAIAWFIFTQEVLTPLFPRIAAWPVSEFFLIRDTSLIPNVLWFEYTVTRAEARNRQRKLGTKLQ SEQ ID NO.222, derived from human ( Homo sapiens Hs.PLPP6, amino acid sequence MPSPRRSMEGRPLGVSASSSSSSPGSPAHGGGGGGSRFEFQSLLSSRATAVDPTCARLRASESPVHRRGSFPLAAAGPSQSPAPPLPEEDRMDLNPSFLGIALRSLLAIDLWLSKKLGVCAGESSSWGSVRPLMKLLEISGHGIPWLLGTLYCLCRSDSWAGREVLMNLLFALLLDLLLVALIKGLVRRRRPAHNQMDMFVTLSVDKYSFPSGHATRAALMSRFILNHLVLAIPLRVLVVLWAFVLGLSRVMLGRHNVTDVAFGFFLGYMQYSIVDYCWLSPHNAPVLFLLWSQR SEQ ID NO. 223, derived from Bacillus subtilis ( Bacillus subtilis Bs.yisP, amino acid sequence column MKEIKEAYQQCGQIVGEYAPACFKALSYLPLKQRQASWAVLSFCHTAASADEKVLPAFEAKADHVYQRTNNGKQHLWKAFDHAYRTFTLESEPFREFIAAQKEDAKPYDDLDELLMYAYRTGGAAGLMLLPILTRRKQDQLKQAAVSLGLAIQLVRFLSDLGTDQQKNRIPRQVMQQFGYTEADLQKGTVNKAFTMTWEYIAFEAEAYLEECQDALPLFPQYSQKTVKAALHLHRAVLEKIRAKQHDVFQYHFALTETEVKQILSDI SEQ ID NO.224, derived from moso bamboo ( Phyllostachys edulis Mo.TPS2, amino acid sequenceMAATPAVGSNNEDQGLRKAATFHPSLWGDFFLTYQPPTAPQSASMERRAGVLREEVRKIVKGSNEIPKILDLTLTLQRLGLDYHYENEIDELLRLVYNSGYNKDDLNLVSLRFYLLRKHGYDVSSNVFLKFKDKEGNFAADDTRSLLSLYNAAYLRTHGEKVLDKAIVFTRSLLERALAVHLESPLRDEVSLALETPLFRRVRILETRNYIPIYEKEATRDEAILELAKLNFNLLQLLYCEELKKVTLWWKQLNVKSNLSFVRDRIVETHFWM TGACSEPHCSLSRIIIIKMTACITILDDIFDTYGTTEESMMLAEAMYRWNENAASLLPEYMKDFYLYLLKTFDSCEDELGPNKSYRVLYLKELLKMLVRGYSQEIKWRDEHHVPKTIKEHLELSRVTIGAFQVACS SFVGMGDIITKGTLDWLLTYPELVKSFTTFVRLSNDIASTKREQTGEHHASTVQCYMLQHGTTMHDACEKIKELIEDSWKDMVKQYLTPTEQPTVVARTIVDFARTGDYIYKRTDAFTFSDTIKDMIASLYVESLPL SEQ ID NO.225, derived from corn ( Zea mays Zm.TPS1, amino acid sequenceMAMPVKLTPASLSLKAVCCRFSSGGHALRFGSSLPCWRRTPTQRSTSSSTTRPAAEVSSGKSKQHDQEASEATIRQQLQLVDVLENMGISRHFAAEIKCILDRTYRSWLQRHEEIMLDTMTCAMAFRILRLNGYNVSSDELYHVVEASGLHNSLGGYLNDTRTLLELHKASTVSISEDESILDSIGSRSRTLLREQLESGGALRKPSLFKEVEHALDGPFYTTLDRLHHRWNIENFNIIEQHMLETPYLSNQHTSRDILALSIRDFSSSQFTYQQELQHLESWVKECRLDQLQFARQKLAYFYLSAAGTMFSPELSDARTLWAKNGVLTTIVDDFFDVAGSKEELENLVMLVEMWDEHHKVEFYSEQVEIIFSSIYDSVNQLGEKASLVQDRSITKHLVEIWLDLLKSMMTEVEWRLSKYVPTEKEYMINASLTFGLGPIVLPALYFVGPKISESIVKDPEYDELFKLMSTCGRLLNDVQTFEREYNEGKLNSVSLLVLHGGSMSISDAKRKLQKPIDTCRRDLLSLVLREESVVPRPCKELFWKMCKVCYFFYSTTDGFSSQVERAKEVDAVINEPLKLQGSHTLVSDV SEQ ID NO.226, derived from japonica rice ( Oryza sativa subsp. japonica Os.TPS13, amino acid sequenceMAPAFHPAIFGDFFINNVQPSPKESDEWMEERVDQLVEEVGRMLEVCKDDVVKQMNLVDVLQRLGIDHHFEEQIDTILKNIHRAEFNSSDLYEVALRFRLLRKQGYWVSPDEFNKFKAEDGSFSSDDITNDPKGLLSLYNAAHLLTHNEKALEEAILFARHHLQLLRGNLAYPLDEQVTRALEIPLPRTMKRVEVLNYIFEYSAEEKMFNPSILELAVLDFNILQKVHQNELKEICQWWENLSSDIRLDYVRERVVECYFCAYAAYYEKEHARARMIFAKRCMLFSLLDDTYDVRATLEEARKFNDALQRWDKSDVSLLPEDLKRFFLSIISNFREFEDELEPHEKYRNSYNIKAFQILSSNFLQEAEWFHQNYIPCFTDHVTVSLQTGGAIELPVSLIVGMGDIATKEVLDWALANPDAGRAFAEVARFMDDLAASHSGRDKMDVASTVECYMNEHGVTREVAEAKIAGMAEDGWKSMNQIRFKHRAFLPFVQRIANLCMSATLLYHGKKNGFSNSLELKDMFESHFVNPIPLNHIDYD SEQ ID NO.227, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae ERG20, nucleotide sequence SEQ ID NO.228, derived from Saccharomyces cerevisiae (Saccharomyces cer Saccharomyces cerevisiae tHMG1, nucleotide sequence SEQ ID NO.229, derived from Saccharomyces cerevisiae (Saccharomyces cer Saccharomyces cerevisiae ERG10, nucleotide sequence SEQ ID NO.230, derived from Saccharomyces cerevisiae (Saccharomyces cer Saccharomyces cerevisiae ERG13, nucleotide sequence SEQ ID NO.231, derived from Saccharomyces cerevisiae (Saccharomyces cer Saccharomyces cerevisiae ERG12, nucleotide sequence SEQ ID NO.232, derived from Saccharomyces cerevisiae (Saccharomyces cer Saccharomyces cerevisiae ERG8, nucleotide sequence column SEQ ID NO.233, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae ERG19, nucleotides sequence SEQ ID NO.234, derived from Saccharomyces cerevisiae (Saccharomyces cer Saccharomyces cerevisiae IDI1, nucleotide sequence column ATGACTGCCGACAACAATAGTATGCCCCATGGTGCAGTATCTAGTTACGCCAAATTAGTGCAAAACCAAACACCTGAAGACATTTTGGAAGAGTTTCCTGAAATTATTCCATTACAACAAAGACCTAATACCCGATCTAGTGAGACGTCAAATGACGAAAGCGGAGAAACATGTTTTTCTGGTCATGATGAGGAGCAAATTAAGTTAATGAATGAAAATTGTATTGTTTTGGATTGGGACGATAATGCTATTGGTGCCGGTACCAAGAAAGTTTGTCATTTAATGGAAAATATTGAAAAGGGTTTACTACATCGTGCATTCTCCGTCTTTATTTTCAATGAACAAGGTGAATTACTTTTACAACAAAGAGCCACTGAAAAAAAATAACTTTCCCTGATCTTTTGGACTAACACATGCTGCTCTCATCCACTATGTA TTGATGACGAATTAGGTTTGAAGGGTAAGCTAGACGATAAGATTAAGGGCGCTATTACTGCGGCGTGAGAAAACTAGATCATGAATTAGGTATTCCAGAAGATGAAACTAAGACAAGGGGTAAGTTTCACTTTTTAAACAGAATCCATTACATGGCACCAAGCAATGAACCATGGGGTGAACATGAAATTGATTACATCCTATTTTATAAGATCAACGCTAAAGAAAACTTGACTGTCAACCCAAACGTCAATGAAGTTAGAGACTTCAAATGGGTTTCACCAAATGATTTGAAAACTATGTTTGCTGACCCAAGTTACAAGTTTACGCCTTGGTTTAAGATTATTTGCGAGAATTACTTATTCAACTGGTGGGAGCAATTAGATGACCTTTCTGAAGTGGAAAATGACAGGCAAATTCATAGAATGCTATAA SEQ ID NO.235, derived from Saccharomyces cerevisiae (Saccharomyces cer Saccharomyces cerevisiae BTS1, nucleotide sequence column SEQ ID NO.236, derived from Saccharomyces cerevisiae (Saccharomyces cer Saccharomyces cerevisiae tSsLPPS, nucleoside acid sequence SEQ ID NO.237, derived from Saccharomyces cerevisiae (Saccharomyces cer Saccharomyces cerevisiae ADR1, nucleotide sequence column SEQ ID NO.238, derived from Saccharomyces cerevisiae (Saccharomyces cer Saccharomyces cerevisiae APP1, nucleotide sequence column SEQ ID NO.239, derived from Saccharomyces cerevisiae (Saccharomyces cer Saccharomyces cerevisiae ARR2, nucleotide sequence column ATGGTAAGTTTCATAACGTCTAGGCAACTCAAGGGCCTAATTGAAAATCAGAGGAAGGATTTTCAAGTTGTTGATCTTCGAAGAGAAGATTTTGCACGTGATCATATTACAAACGCTTGGCATGTTCCAGTAACAGCACAGATTACAGAGAAGCAACTGAATCAATTAATTAAAGGTTTATCCGATACTTTCTCAAGTTCTCAATTCGTCAAAGTGATATTTCATTGTACTGGGTCCAAGAATAGGGGACCAAAAGTAGCTGCTAAATTCGAAACCTACTTACAAGAAGAAGATTACAAGTAAGTTTGAGTTGCATCCTCGTTGGAGGTTTTTACGCTTGGGAGACCCATTGTAGAGAGAGTAACCTTAAATTGATTGTTAGTGGTTGA SEQ ID NO.240, derived from Saccharomyces cerevisiae (Saccharomyces cer Saccharomyces cerevisiae BNI4, nucleotide sequence column SEQ ID NO.241, derived from Saccharomyces cerevisiae (Saccharomyces cer Saccharomyces cerevisiae BSP1, nucleotide sequence column SEQ ID NO.242, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae BUD14, nucleotides sequence SEQ ID NO.243, derived from Saccharomyces cerevisiae (Saccharomyces cer Saccharomyces cerevisiae CAX4, nucleotide sequence column ATGAATAGTACCGCCGCTGCAATAAATCCAAATCCAAATGTTATACCATTCGATGACACATACATTCTCTATGATTCGCATGACTTTCTATCATTCCTTAGTGCATATTTCTCGCTGATGCCCATCCTAGTGCTAGCTTTTTATTTGTCGTGGTTTATCATCACAAGAGAGTTAGAAGCCTGCATTGTAGCCTTTGGCCAATTGATGAACGAAATATTCAATAACGTGATCAAGAATATAATAAAACAGCCACGCCCCGTATCGTTCGGTGCGTCGTTCCAAAATGACACTATAAGATCCGGTTACGGGATGCCCAGTGCACACTCCCAATTCATGGGGTTTTGTTTTACCTATAACTCTCTGAAGATATACACTTCCTGGAAGAATCTAAACTTCTTAGAAAAATGCATTTTTTCTGGTGCATTGGCTTTATTATCGTTTTGCGTTTGCTTTTCCAGAGTTTACTTGCACTACCACAATTTAGATCAAGTAATCGTGGGATTCAGCGTGGGGGCACTGACTGGATCACTTTATTTTTTTATAGTTGGCATCATAAGAGAGCTTGGTTTAATCAATTGGTTTTTAAAACTACGTATTGTCAGATTATTTTACATGACAGATTCTTACAATCTGGCGCCTTTGACATTGAAAGAGAATTACGAGGCGTATTGGAAAAGAATAAATCAGCGATCTTTCAATGATAAATCCAAAAGGGATTAG SEQ ID NO.244, derived from Saccharomyces cerevisiae (Saccharomyces cer Saccharomyces cerevisiae CDC14, nucleotide sequence SEQ ID NO.245, derived from Saccharomyces cerevisiae (Saccharomyces cer Saccharomyces cerevisiae CDC48, nucleotide sequence SEQ ID NO.246, derived from Saccharomyces cerevisiae (Saccharomyces cer Saccharomyces cerevisiae CDC55, nucleotide sequence SEQ ID NO.247, derived from Saccharomyces cerevisiae (Saccharomyces cer Saccharomyces cerevisiae CET1, nucleotide sequence column SEQ ID NO.248, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae CMD1, nucleotide sequence column ATGTCCTCCAATCTTACCGAAGAACAAAATTGCTGAATTCAAAGAAGCCTTTGCCCTCTTTGATAAAGATAACAATGGCTCTATCTCATCAAGTGAATTGGCCACTGTGATGAGGTCATTGGGTCTTTCGCCCAGTGAAGCAGAAGTAAATGATTTGATGAACGAAATAGATGTTGATGGTAACCATCAAATCGAATTTAGTGAATTTTTGGCTCTGATGTCTCGTCAACTCAAATCAAATGACTCTGAACAAGAACTACTAGAAGCTTTTAAAGTATTCGATAAGAACGGTGATGGTTTAATCTCCGCCGCTGAGTTGAAACACGTGCTAACATCCATTGGTGAAAAATTGACTGATGCCGAAGTAGATGATATGCTAAGAGAGGTTAGTGATGGATCAGGCGAGATCAACATTCAACAATTCGCTGCTTTGTTATCTAAATAG SEQ ID NO.249, derived from Saccharomyces cerevisiae (Saccharomyces cer Saccharomyces cerevisiae CMP2, nucleotide sequence column SEQ ID NO.250, derived from Saccharomyces cerevisiae (Saccharomyces cer Saccharomyces cerevisiae CNA1, nucleotide sequence column SEQ ID NO.251, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae CNB1, nucleotide sequence column ATGGGTGCTGCTCCTTCCAAAATTGTGGATGGTCTTTTTAGAAGATACAAATTGTATGTACACTTCGGAGTGAGGAAAAGAAAGAAAGGGGAAATTAACCGATTTTACTAACACTGACACTTTGAACAGTTGATAGAGATGAAATTGAAAGGTTAAGGAAGAGATTCATGAAATTAGATAGAGATAGCTCAGGGTCTATTGATAAAAATGAATTTATGAGCATTCCTGGCGTTTCGTCAAACCCTCTTGCTGGACGTATAATGGGGTTTTCGATGCTGATAATAGTGGGGACGTGGATTTTC AAGAGTTCATCACAGGATTATCCATTTTCAGTGGGCGTGGGTCCAAGGACGAAAAGTTAAGATTCGCCTTCAAAATCTACGACATTGACAAGGACGGTTTCATATCCAATGGTGAGTTGTTCATCGTGTTGAAGATTATGGTAGGTTCTAA TCTGGACGATGAACAGCTGCAACAGATAGTAGATAGGACGATAGTGGAAAACGATAGCGACGGCGACGGACGTTTAAGTTTCGAGGAGGTTTAAGAATGCTATCGAAACCACAGAAGTGGCCAAGAGTCTGACATTGCAATACGATGTGTAA SEQ ID NO.252, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae CSS1, nucleotide sequence column SEQ ID NO.253, derived from Saccharomyces cerevisiae (Saccharomyces cer Saccharomyces cerevisiae CTK1, nucleotide sequence column SEQ ID NO.254, derived from Saccharomyces cerevisiae (Saccharomyces cer Saccharomyces cerevisiae CTK2, nucleotide sequence columnATGCCTAGCACGTTTGAATCCCAGCTTTTTTTTTCGAGACCGTTTCTGTCTAAAAGGCAAATTCAAAGAGCCCAAAAGAATACAATATCGGACTATCGAAATTACAACCAGAAAAAAACTTGCCGTGTTCAAATTTCTAAGTGACTTGTGTGTTCAGCTGAAATTTCCACGGAAGACTTTAGAAACAGCAGTATACTTTTACCAAAGATACCACCTCTTTAATCGCTTCGAGACCGAGGTTTGCTACACTGTAGCGACAAGCTGCCTGACTTTGGGCTGTAAAGAAGTTGAGACAATTAAAAAAACAAATGATATATGTACTTTGTCATTACGATTGAGGAATGTGGTTAAAATCAATACGGACATTTTGGAAAATTTTAAAAAAAGGGTATTTCAAATAGAACTTCGGATATTAGAGTCATGCTCATTCGATTATAGAGTCAACAATTACGGTTCATATTGATGAATATGTTATAAAAATTGGTAGG GAGCTATCCTTTGATTATAAGTTGTGCAATCTGGCTTGGGTAATTGCTTATGATGCTTTGAAGCTAGAAAACTATTTTAGTCATACCCCAACATTCCATTGCATTGGCCATTTTGAAAATAGCATATGAATTACTAGATAATAAGAATTGGTCAAGTAAAAGGTATTCTTTATTTGAAACAGACGAGAAATCCGTAAATGAAGCTTATTTTGATATAGTCAATTTTTACATCAATTCATTCGATATGTGCGATCTACAACGTCATTTACCGGCTGATTTGCTGCCGATTGGCGTTGAAAGGTTTATGGAACTGAAAAAAAACGCAGGACCAGAATCTGGATTGCCGCAAATACCAGATCACCTGTTGAATGCCGATCCTTATATCACTATTACTAGAGATAATAATGTCCAAGAAAGAAGATATGTACTTTCACTGGAGCTAATTAATGGCGAGTCCAGCATAAATAGTTCTACAAGACATGCATAG SEQ ID NO.255, derived from Saccharomyces cerevisiae (Saccharomyces cer Saccharomyces cerevisiae CTK3, nucleotide sequencecolumn ATGGACTCTCTTGAAGCTAGATTACAATTCATTCAGGTCCTGAAGAACCTGCAAAAGACGCTGCACAAGACCAGAGACTCTATCACATCATCGTCGACCACCACACCACCGTCATCGCAACAAAAGCTGAACAATGACCCTATACAGTTCTACTTGAGAAACTACAGACATCACTACGAGGACTTCCACCAATGTTTGTTCGATACAACCATGAAGATGGACCCACTAGATAGACTGGACGTAGTGATATACTATGTTAGAATAATAAGAAACTTATATCCGCATAGCCATTCCAATACCAATGTTACAAAAGTGTTAAACGAAGTGCTACTCATGGACATAGACTTGGTTTTTGAGCTTTGTCTGCCCTGCCAGGACTGGAAATCCCTCACGAATCAAGCCACCTGTAAAGAGCTATTCCTTGACTTATCCAAACTAATCCATTACGACGCCACCAGCGTCACGCACACACCATCAGACACCACACTCATAGACGCTACTACCTGGTACAGTGTCAAGACAGAGAGGACTACAAAGGACTATAAAGAATCATTGCAACGAACGGAGTCTCTGCTTAAGGACAGAGACTTGAAGAAATTGGCTTTCTTTCAGCAGTTCAATTCCGATACAACTGCGATCAACCCGGACTTACAGACGCAGCCAACCAATGCAAACATTTTGTTGCACAGGATGGAAGCAGACAGGGAACTGCACAAGAGGTCGAAAGAGACAAGTTGGTACATCGAAAGGCCCTCCAACGATATACTGGATGAATCCGAATTTAAAAGCTTGTGGACGCATTTTGAAACTACTGATTCCGGATTTGATAAGGACGATTACAAAAACATCAAGGCTTTAAATGACATTGCGAAGGCATCTTACATGTATTAG SEQ ID NO.256, derived from Saccharomyces cerevisiae (Saccharomyces cer Saccharomyces cerevisiae CTL1, nucleotide sequence columnATGTCTGACCAACCCGAGACTCCTTCCAATAGTAGAAATTCTCATGAAAATGTTGGCGCAAAGAAAGCTGACGCTAATGTTGCCTCGAAATTCAGAAGCTTGCATATCTCTGAAACCACTAAGCCATTAACATCAACTAGAGCTTTATACAAAACCACAAGAAACAATTCAAGAGGTGCGACAGAATTCCATAAACATGTTTGTAAGTTAGCATGGAAAATATCTTGCTTGTATTGATAAATCGTCGATATCACACATTGAAATCGAAATGAAATTTGGTGTTATAACAGACAAAAGGACACATCGCCAGGATGACACCACACAACAAGCCCTTTATTGTTCAAAACAGAAATGGCCGCTTAGTGTCTAACGTTCCTGAGCAAATGTTCTCGAGTTTCCAGGAGCTACTCCGCTCAAAATCGGAGAATCCAAGTAAATGTGCCCCAAGAGTAGTAAAACAGGTACAAAAGTATACGAAAGATT CTATATATAACTGCAACAATGCCTCGAAAGTTGGCAAATTAACTTCATGGCGTTGTTCGGAAGACCTTAGAAACAAAGAACTTAAACTTACTTACATCAAAAAAGGTCCGGGTCAAGGATTTTCTCATTCGCTATCCTCAAAGTTCATTAGACGCTAAAATTAGCATCAGCCTTGAAGTGCCTGAATACGAAACTTCTGCCGCTTTCAGGAATGGCTTTATTTTACAAAGAACCAAAAGCCGTTCCACCTACACCTTTAATGATAAAATGCCTTTACACTTGGATTTGACAAAGGTTACTACCACGCGAAGGAACTCCCATCAATACACGTCCCATGAAGTGGAGGTAGAAATGGATCCTATATTCAAGGAGACAATTTCCGCTAATGATAGGGAGAAGTTTAATGAGTATATGTGCTCGTTTTTGAATGCCAGCGACCTTATACGTAAGGCTGCAGAACGCGATAACATGTTAACGACATGA SEQ ID NO.257, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae CTO1, nucleotide sequence columnATGAAAACCATTATTATTTCAGATTTTGATGAAACAATCACAAGAGTTGACACAATCTGCACCATTGCTAAATTACCGTATCTACTGAACCCGCGGTTGAAACCTGAGTGGGGTCATTTTACCAAGACATATATGGACGGATACCATAAATACAAATACAATGGAACGAGATCACTGCCGTTGTTATCTTCAGGCGTACCTACGATAATTTCGCAGTCTAACTTCAATAAGTTGTTTGCGGACGAATTAAAATATCAAAATCATAACAGGGTTGTTGAGTTAAATAGTGTAAATGAAATTACAAAACAACAGATTTTTAAGTCGATTTCTTTGGATCAAATGAAAACGTTCGCCAGAGATCAGAATCACGAAGATTGTTTACTAAGAGATGGTTTCAAAACGTTTTGCTCTTCAGTTGTCAAAAATTTTGAAAGTGATTTTTTTACGTTTTATCTATAAATTGGTCAAAAGAGTTTATT CATGAAGTCATTGGTGACAGAAGACTTAAAAATAGTCATATTTTTTGTAACGATCTAAAAAAAGTTAGTGCAAAGTGTTCTCAAAGCTACAATGGTGAATTTGATTGTCGGTTATTGACAGGCTCTGATAAGGTCAAGATACTGGGTGAAATATTAGATAAGATCGACTCAGGTTGCAATAAAGAAGGAAATTCTTGCAGCTATTGGTATATAGGGGATAGTGAGACTGACTTGTTGTCCATATTACATCCATCTACTAATGGTGTACTGCTAATAAACCCGCAAGAAAATCCTTCCAAAATTCATAAAAATTACCGAAAAGATTATTGGTATCCCAAAGGATAAAATCTCGAGTTTTGAAGCTGATAATGGTCCAGCGTGGTTACAGTTTTGTGAAAAGGAAGGCGGTAAAGGTGCCTACCTTGTGAAATCCTGGGACTCTTTAAAAGATTTGATCATGCAGGTAACAAAAATGTAG SEQ ID NO.258, derived from Saccharomyces cerevisiae (Saccharomyces cer Saccharomyces cerevisiae DCR2, nucleotide sequence column SEQ ID NO.259, derived from Saccharomyces cerevisiae (Saccharomyces cer Saccharomyces cerevisiae DDP1, nucleotide sequence column ATGGGCAAAACCGCGGATAATCATGGTCCAGTACGTTCTGAGACAGCACGTGAAGGAAGAGAAAACCAGGTTTACTCACCCGTTACAGGTGCAAGATTAGTTGCTGGCTGCATATGTTTAACACCCGACAAGAAGCAAGTTCTCATGATTACTTCTTCTGCACACAAGAAAAGATGGATTGTCCCCAAAGGTGGCGTTGAGAAAGACGAGCCTAATTACGAGACGACTGCCCAACGAGAAACTTGGGAGGAAGCTGGTTGCATAGGTAAAATTGTCGCCAATTTGGGTACAGTTGAAGACATGAGACCCCCTAAGGACTGGAACAAAGACATTAAGCAATTCGAGAACTCTCGAAAAGATTCAGAAGTAGCAAAGCACCCGCCAAGAACCGAATTTCATTTTTATGAATTAGAGATTGAAAATCTCCTTGATAAATTTCCGGAATGTCACAAAAGACATAGAAAGCTATACTCTTATACAGAAGCTAAACAAAACTTGATAGACGCCAAGAGGCCTGAATTGTTGGAGGCCCTTAATAGGTCTGCTATCATTAAAGACGACAAATAG SEQ ID NO.260, derived from Saccharomyces cerevisiae (Saccharomyces cer Saccharomyces cerevisiae DET1, nucleotide sequence column SEQ ID NO.261, derived from Saccharomyces cerevisiae (Saccharomyces cer Saccharomyces cerevisiae DIA3, nucleotide sequence column SEQ ID NO.262, derived from Saccharomyces cerevisiae (Saccharomyces cer Saccharomyces cerevisiae DOG1, nucleotide sequence Column ATGGCAGAATTTTCAGCTGATCTATGTCTTTTTGACCTAGATGGTACCATAGTGAGTACAACAGTGGCCGCAGAGAAAGCATGGACCAAGTTGTGTTACGAATACGGTGTTGATCCTTCCGAGTTATTTAAGCATTCTCATGGTGCAAGAACACAAGAGGTTTTGAGAAGGTTTTTCCCTAAATTGGATGATACAGACAATAAAGGTGTTCTTGCTCTAGAAAAAGATATTGCCCATAGTTACTTGGACACAGTAAGCCTTATTCCTGGTGCAGAGAACTTACTGTTATCGTTAGATGTAGATACTGAGACTCAAAAAAAGTTACCTGAAAGGAAATGGGCTATCGTTACCTCTGGTTCTCCATATTTGGCATTTTCATGGTTCGAGACAATATTGAAAAATGTTGGAAAGCCCAAAGTTTTCATTACTGGGTTTGACGTGAAGAACGGTAAGCCTGATCCCGAGGGTTATTCAAGAGCTCGTGATTTATTGCGTCAAGATTTGCAATTAACTGGTAAACAGGATCTGAAGTATGTTGTCTTCGAAGATGCACCCGTGGGCATAAAGGCCGGCAAAGCAATGGGCGCCATTACTGTGGGTATAACATCCTCGTATGACAAGAGCGTTTTATTTGACGCAGGAGCAGATTATGTAGTCTGTGATTTGACACAGGTTTCCGTGGTTAAGAACAATGAAAACGGTATTGTCATCCAGGTAAACAACCCTTTGACAAGGGCCTGA SEQ ID NO.263, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae DOG2, nucleotide sequence ColumnATGCCACAATTTTCAGTAGATCTTTGTCTTTTTGACCTAGATGGGACTATTGTCAGCACAACAACTGCAGCGGAAAGTGCCTGGAAAAAATTATGCCGTCAGCATGGGGTTGATCCTGTTGAGTTATTCAAGCATTCCCATGGTGCAAGATCACAAGAAATGATGAAGAAATTTTTTCCAAAATTGGACAATACCGATAATAAAGGTGTTCTTGCGTTAGAAAAGGATATGGCAGATAATTATTTGGACACAGTAAGCCTTATCCCTGGTGCAGAGAATTTATTGTTATCGTTAGATGTAGATACTGAGACTCAAAAAAAGTTACCTGAAAGGAAATGGGCTATCGTTACCTCTGGTTCTCCATATTTGGCATTTTCATGGTTCGAGACAATATTGAAAAATGTTGGAAAGCCCAAAGTTTTCATTACTGGATTTGACGTGAAGAACGGTAAGCCTGATCCCGAGGGTTACTCAAGAGCTCGTGATTTATTGCGTCAAGATTTGCAATTAACTGGTAAACAGGATCTGAAGTATGTTGTCTTTGAAGATGCACCCGTGGGCATAAAGGCCGGCAAAGCAATGGGCGCAATTACTGTGGGTATAACATCCTCGTATGATAAGAGCGTTTTATTTGACGCAGGTGCAGATTATGTGGTCTGTGATTTGACACAGGTTTCCGTGGTTAAGAACAATGAGAACGGTATCGTTATCCAGGTAAACAACCCTTTGACGAGAGATTAA SEQ ID NO.264, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae DPP1, nucleotide sequence ColumnATGAACAGAGTTTCGTTTATTAAAACGCCTTTCAACATAGGGGCGAAATGGAGATTAGAAGATGTCTTTTTGCTCATTATCATGATACTTCTTAACTACCCAGTGTATTACCAACAACCGTTCGAACGTCAGTTTTACATTAACGATCTCACTATATCGCATCCTTATGCGACAACTGAACGTGTAAATAACAACATGTTGTTTGTTTATAGTTTTGTCGTGCCATCTTTAACCATATTGATAATTGGTTCCATTTTGGCCGATAGAAGACATTTGATTTTTATTTTGTACACATCTCTCCTTGGTTTATCACTCGCTTGGTTCAGTACGAGTTTCTTTACAAACTTCATCAAGAATTGGATTGGAAGACTAAGACCAGATTTTCTAGATCGTTGCCAACCTGTTGAAGGCTTGCCATTGGACACTTTATTTACTGCAAAAGATGTGTGTACGACTAAGAATCACGAACGTCTGTTGGATGGGTTTAGGACAACTCCGTCAGGTCATTCAAGTGAAAGCTTTGCAGGACTGGGTTATTTGTACTTCTGGCTATGTGGGCAACTTTTGACTGAATCACCGTTGATGCCTTTATGGAGAAAAATGGTGGCCTTTCTACCACTGTTAGGAGCTGCACTAATTGCTCTATCCAGAACTCAAGATTACAGACATCATTTCGTCGATGTAATTTTAGGGTCTATGTTGGGTTATATAATGGCACACTTTTTCTACAGAAGAATCTTCCCACCCATTGATGATCCTCTTCCGTTCAAACCATTGATGGACGATTCAGATGTCACCCTGGAGGAAGCAGTCACCCATCAGAGGATCCCGGATGAGGAATTACATCCTTTGTCCGATGAAGGTATGTAA SEQ ID NO.265, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae DSK2, nucleotide sequence Column SEQ ID NO.266, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae DUT1, nucleotide sequence Column ATGACTGCTACTAGCGACAAAGTACTAAAGATTCAATTGCGCTCAGCAAGCGCTACTGTACCTACCAAAGGTTCTGCCACTGCCGCGGGATACGACATTTATGCATCTCAGGATATTACCATTCCGGCTATGGGTCAAGGTATGGTTTCCACCGACATATCGTTCACCGTACCTGTTGGTACCTACGGTCGTATTGCGCCAAGGTCAGGCCTGGCAGTGAAAAACGGTATCCAAACCGGTGCTGGTGTTGTCGACAGAGATTACACCGGTGAAGTTAAAGTAGTTTTATTCAATCATTCACAGAGGGATTTCGCGATCAAAAAAGGTGATCGCGTAGCCCAATTGATTCTGGAAAAAATTGTCGATGATGCCCAGATCGTTGTTGTAGACTCTCTGGAAGAAAGTGCAAGAGGGGCCGGTGGCTTTGGTAGCACTGGTAACTAA SEQ ID NO.267, derived from Saccharomyces cerevisiae (Saccharomyces cer Saccharomyces cerevisiae FAB1, nucleotide sequence Column SEQ ID NO.268, derived from Saccharomyces cerevisiae (Saccharomyces cer Saccharomyces cerevisiae FBP1, nucleotide sequence Column SEQ ID NO.269, derived from Saccharomyces cerevisiae (Saccharomyces cer Saccharomyces cerevisiae FBP26, nucleotide Sequence SEQ ID NO.270, derived from Saccharomyces cerevisiae (Saccharomyces cer Saccharomyces cerevisiae FCP1, nucleotide sequence Column SEQ ID NO.271, derived from Saccharomyces cerevisiae (Saccharomyces cer Saccharomyces cerevisiae FIG4, nucleotide sequence Column SEQ ID NO.272, derived from Saccharomyces cerevisiae (Saccharomyces cer Saccharomyces cerevisiae FIN1, nucleotide sequence Column ATGAGCAATAAAAGCAACCGCAGGAGTTTACGTGACATAGGGAATACGATTGGTCGAAATAATATACCAAGTGACAAGGACAATGTCTTTGTGAGATTGAGCATGTCCCCTTCGAGGACGACAAGCCAAAAAGAGTTTTTGAAACCACCTATGAGGATGTCACCTAACAAGACAGATGGAATGGAATGAAGCATAGTATACAAGTAACACCAAGAAGGATAATGTCGCCGGAATGTCTGAAGGGCTATGTCTCCAAGGAAACTCAAAGCCTGGATAGGCCTCAGTTCAAAAATTCGAATAAAAATGTGAAGATCCAAAACTCAGATCATATAACTAATATAATATTCCCTACATCACCAACCAAACTGACATTCAGTAATGAAAATAAAATCGGGGGTGATGGTTCGTTAACGAGAATACGGGCCCCGGTTTAAGAATGGACTC ATGTCGCCTGAAAGGATACAGCAGCAACAGCAGCAACATATTCTCCCATCGGATGCCAAAAGCAACGCTGACCTCTGTTCTAATACTGAGCTCAAGGACGCCCCATTTGAGAATGACCTTCCTCGAGCTAAATTGAAAGGGAAGAATTTATTAGTTGAACTCAAAAAAGAAGAGGAAGACGTGGGAAATGGCATAGAATCCTTACTAAATCGAACACTAAACTGAATTCCATGCTGGCGAACGAAGGTAAAATACACAAAGCTAGTTTCCAGAAAAGTGTAAAATTTAAACTACCTGATAATATAGTGACTGAAGAAACCGTGGAACTTAAAGAAATAAAGGACTTGCTACTACAAATGTTGAGAAGACAGCGAGATTGAATCAAGATTATCCAATATGAACTTCAACTCACGGAAATATCGAAACATAAGTAA SEQ ID NO.273, derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae FPY1, nucleotide sequence ColumnATGGTGAAAGTAACTGCAGCTTGTATCATAATTGGTGATGAAGTGCTGAAATGGAAAAGTAGTTGATACAAATTCCACTTTTTTTGCGAAGTATTGCTTTGATCATGGAATTCAATTAAAA...

Claims

1. A method for producing compound of formula (I), R is H or a hydrocarbon group, which is cyclic or acyclic, straight or branched, saturated or unsaturated, and / or substituted or unsubstituted; The method includes the following steps: The precursor of compound (I) is catalyzed by a phosphorylase to generate compound (I); The precursor of compound (I) is compound (II) as shown below: ， The R in compound (II) is the same as the R in compound (I); and The phosphatases mentioned are derived from Mg(2+)-dependent phosphatidate phosphatase, phosphatidic acid phosphatase type 2, serine / threonine-protein phosphatase family, HAD-like hydrolase superfamily, phosphate (PA) phosphatase, polyphosphoinositide phosphatase, serine / threonine-protein kinases, alkaline phosphatase, phosphoprotein phosphatase family, SIT4 phosphatase-associated protein family, and TAP42 / TAP46 superfamily. TAP42 / TAP46-like superfamily, dual-specificity lipid and protein phosphatase, polynucleotide kinase 3 phosphatase, 5'-deoxynucleotidase, myosin family, histidine phosphatase superfamily, S-2-haloalkanoic acid dehalogenase, phosphoglycerate mutase, HAD-hydrolase superfamily, PA-phosphatase related phosphoesterase family, squalene / phytoene synthase family, terpene cyclase family, phosphate phosphatase App1 (phosphatidate)Phosphatase App1), Protein phosphatase 2A (PP2A), Protein phosphatase 2C (PP2C), Halide dehalogenase (HAD)-like sugar phosphate phosphatase, Fig4-like polyphosphoinositide phosphatase, Casein kinase 1 Ser / Thr protein kinase, Lipin family, PPZ / Ppq1 family, Clad-1 family, HAD-IA hydrolase family, HAD-IF subfamily, Dolichoyldiphosphatase family, or Haloperoxidase superfamily.

2. The method of claim 1, wherein the phosphatase is phosphatidylphosphatase (APP1), polyacyl-2-phosphatase (CAX4), PP2A protein phosphatase regulatory subunit B (CDC55), 2-deoxyglucose-6-phosphatase 1 (DOG1), diacylglycerol pyrophosphate phosphatase 1 (DPP1), inositol polyphosphate phosphatase (FIG4), 1-glycerol phosphate phosphatase 1 (GPP1), casein kinase I (HRR25), phosphatidylphosphatase (PAH1), alkaline phosphatase (PHO8), truncated alkaline phosphatase (PHO8^62aa), serine / threonine protein phosphatase (PPQ1), serine / threonine protein phosphatase (PPZ1), serine / threonine protein phosphatase (PTC3), serine / threonine protein phosphatase (RTS1), SIT4-associated protein SAP155, SIT4-associated protein SAP185, 2A Phosphatase-associated protein (TAP42), phosphatidylinositol 3,4,5-triphosphate 3-phosphatase (TEP1), polynucleotide 3'-phosphatase (TPP1), phosphatase (YAR068W), 5'-deoxynucleotidase (YBR242W), phosphatidylinositol 3-phosphatase, phosphatase (YNL108C), hydrolase (YOR131C), histidine phosphatase family phosphatases (YOR283W), phosphatidylglycerol phosphatase (PgpA), phosphatidylglycerol phosphatase (PgpB), phosphatidylglycerol phosphatase (PgpC), carbapenyl diphosphatase (YbjG), dihydroxy diphosphatase (DOLPP1), phosphatase (PLPP6), farnesyl diphosphatase (YisP), farnesol synthase (TPS2), acyclic sesquiterpene synthase (TPS1), or farnesol synthase (TPS13).

3. The method of claim 1 or 2, wherein the phosphatase is a phosphatase derived from a microorganism or a functional variant thereof, said microorganism comprising bacteria, yeast, or fungi, said bacteria being selected from Escherichia or Bacillus, said yeast being selected from Saccharomyces, or said phosphatase is derived from plants or humans (…). Homo sapiens Phosphohydrolases or their functional variants thereof; preferably, the phosphohydrolase is a phosphohydrolase or its functional variant derived from bacteria, yeast or fungi, wherein the bacteria are selected from *Escherichia coli* (…). Escherichia coli Bacillus subtilis ( Bacillus subtilis The yeast is brewer's yeast (Saccharomyces cerevisiae). Saccharomyces cerevisiae ), or the phosphorylase is derived from plants or humans ( Homo sapiens Phosphorylase or a functional variant thereof, wherein the plant is selected from moso bamboo ( Phyllostachys edulis ),corn( Zea mays ) or japonica rice ( Oryza sativa subsp. japonica More preferably, the phosphorylase is derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae ), Escherichia coli ( Escherichia coli ), human beings ( Homo sapiens Bacillus subtilis ( Bacillus subtilis ),bamboo( Phyllostachys edulis ),corn( Zea mays ) or japonica rice ( Oryza sativa subsp. japonica Phosphohydrolases or their functional variants.

4. The method according to any one of claims 1-3, wherein the phosphorylase comprises an amino acid sequence selected from SEQ ID NO. 11-226, or an amino acid sequence having at least 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with an amino acid sequence selected from SEQ ID NO. 12, SEQ ID NO. 17, SEQ ID NO. 20, SEQ ID NO. 36, SEQ ID NO. 38, SEQ ID NO. 45, SEQ ID NO. 58, SEQ ID NO. 63, SEQ ID NO. 45, SEQ ID NO. 58, SEQ ID NO. 63, SEQ ID NO. 64, SEQ ID NO.

226. ID NO.95, SEQ ID NO.106, SEQ ID NO.107, SEQ ID NO.122, SEQ ID NO.125, SEQ ID NO.133, SEQ ID NO.157, SEQ ID NO.159, SEQ ID NO.160, SEQ ID NO.180, SEQ ID NO.181, SEQ ID NO.186, SEQ ID NO.197, SEQ ID NO.198, SEQ ID NO.206, SEQ ID NO.208, SEQ ID NO.209, SEQ ID NO.210, SEQ ID NO.217, SEQ ID NO.218, SEQ ID NO.219, SEQ ID NO.220, SEQ ID NO.221, SEQ ID NO.222, SEQ ID NO.223, SEQ ID NO.224, SEQ ID The amino acid sequence of NO.225, SEQ ID NO.226, or selected from SEQ ID NO.12, SEQ ID NO.17, SEQ ID NO.20, SEQ ID NO.36, SEQ ID NO.38, SEQ ID NO.45, SEQ ID NO.58, SEQ ID NO.63, SEQ ID NO.95, SEQ ID NO.106, SEQ ID NO.107, SEQ ID NO.122, SEQ ID NO.125, SEQ ID NO.133, SEQ ID NO.157, SEQ IDNO.159, SEQ ID NO.

160. SEQ ID NO.180, SEQ ID NO.181, SEQ ID NO.186, SEQ ID NO.197, SEQ ID NO.198, SEQ ID NO.206, SEQ ID NO.208, SEQ ID NO.209, SEQ ID NO.210, SEQ ID NO.217, SEQ ID NO.218, SEQ ID NO.219, SEQ ID NO.220, SEQ ID NO.221, SEQ ID NO.222, SEQ ID NO.223, SEQ ID NO.224, SEQ ID NO.225, SEQ ID The amino acid sequence of NO. 226 has at least 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity.

5. The method according to any one of claims 1-4, wherein the phosphorylase is encoded by a nucleotide sequence selected from SEQ ID NO. 237-452, or by a nucleotide sequence having at least 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with a nucleotide sequence selected from SEQ ID NO. 238, SEQ ID NO. 243, SEQ ID NO. 246, SEQ ID NO. 262, SEQ ID NO. 264, SEQ ID NO. 271 ... NO.284, SEQ ID NO.289, SEQ ID NO.321, SEQ ID NO.332, SEQ ID NO.333, SEQ ID NO.348, SEQ ID NO.351, SEQ ID NO.359, SEQ ID NO.383, SEQ ID NO.385, SEQ ID NO.386, SEQ ID NO.406, SEQ ID NO.407, SEQ ID NO.412, SEQ ID NO.423, SEQ ID NO.424, SEQ ID NO.432, SEQ ID NO.434, SEQ ID NO.435, SEQ ID NO.436, SEQ ID NO.443, SEQ ID NO.444, SEQ ID NO.445, SEQ ID NO.446, SEQ ID NO.447, SEQ ID NO.448, SEQ ID The nucleotide sequence of NO.449, SEQ ID NO.450, SEQ ID NO.451, SEQ ID NO.452, or selected from the group consisting of SEQ ID NO.238, SEQ ID NO.243, SEQ ID NO.246, SEQ ID NO.262, SEQ ID NO.264, SEQ ID NO.271, SEQ ID NO.284, SEQ ID NO.289, SEQ ID NO.321, SEQ ID NO.332, SEQ ID NO.333, SEQ ID NO.348, SEQ ID NO.351, SEQ IDNO.359, SEQ ID NO.

383. SEQ ID NO.385, SEQ ID NO.386, SEQ ID NO.406, SEQ ID NO.407, SEQ ID NO.412, SEQ ID NO.423, SEQ ID NO.424, SEQ ID NO.432, SEQ ID NO.434, SEQ ID NO.435, SEQ ID NO.436, SEQ ID NO.443, SEQ ID NO.444, SEQ ID NO.445, SEQ ID NO.446, SEQ ID NO.447, SEQ ID NO.448, SEQ ID NO.449, SEQ ID NO.450, SEQ ID NO.451, SEQ IDNO. 452 encodes a nucleotide sequence with at least 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity.

6. The method according to any one of claims 1-5, wherein the compound of formula (I) is selected from farnesol, geraniol, lysinediol, or copalol; and / or the compound of formula (II) is selected from farnesyl pyrophosphate, geraniol pyrophosphate, or lysinediol pyrophosphate, or copalol pyrophosphate.

7. The method of any one of claims 1-6, wherein the catalysis is carried out extracellularly or intracellularly.

8. The method according to any one of claims 1-7, wherein the catalysis is to catalyze the compound of formula (II) to produce the compound of formula (I) using isolated phosphorylase, a mixture containing the phosphorylase, a microorganism containing the phosphorylase or its cell lysate or enzyme extract.

9. The method of claim 8, wherein the microorganism containing the phosphorylase is a recombinant engineered bacterium.

10. A recombinant engineered bacterium containing a phosphatase capable of catalyzing the precursor of a compound of formula (I) to produce the compound of formula (I). R is H or a hydrocarbon group, which is cyclic or acyclic, straight or branched, saturated or unsaturated, and / or substituted or unsubstituted; in, The precursor of compound (I) is compound (II) as shown below: ， The R in compound (II) is the same as the R in compound (I); and The phosphatases mentioned are derived from Mg(2+)-dependent phosphatidate phosphatase, phosphatidic acid phosphatase type 2, serine / threonine-protein phosphatase family, HAD-like hydrolase superfamily, phosphate (PA) phosphatase, polyphosphoinositide phosphatase, serine / threonine-protein kinases, alkaline phosphatase, phosphoprotein phosphatase family, SIT4 phosphatase-associated protein family, and TAP42 / TAP46 superfamily. TAP42 / TAP46-like superfamily, dual-specificity lipid and protein phosphatase, polynucleotide kinase 3 phosphatase, 5'-deoxynucleotidase, myosin family, histidine phosphatase superfamily, S-2-haloalkanoic acid dehalogenase, phosphoglycerate mutase, HAD-hydrolase superfamily, PA-phosphatase related phosphoesterase family, squalene / phytoene synthase family, terpene cyclase family, phosphate phosphatase App1 (phosphatidate)Phosphatase App1), Protein phosphatase 2A (PP2A), Protein phosphatase 2C (PP2C), Halide dehalogenase (HAD)-like sugar phosphate phosphatase, Fig4-like polyphosphoinositide phosphatase, Casein kinase 1 Ser / Thr protein kinase, Lipin family, PPZ / Ppq1 family, Clad-1 family, HAD-IA hydrolase family, HAD-IF subfamily, Dolichoyldiphosphatase family, or Haloperoxidase superfamily.

11. The recombinant engineered bacteria of claim 10, wherein the phosphatase is phosphatidylphosphatase (APP1), polyacyl-2-phosphatase (CAX4), PP2A protein phosphatase regulatory subunit B (CDC55), 2-deoxyglucose-6-phosphatase 1 (DOG1), diacylglycerol pyrophosphate phosphatase 1 (DPP1), inositol polyphosphate phosphatase (FIG4), 1-glycerol phosphate phosphatase 1 (GPP1), casein kinase I (HRR25), phosphatidylphosphatase (PAH1), alkaline phosphatase (PHO8), truncated alkaline phosphatase (PHO8^62aa), serine / threonine protein phosphatase (PPQ), serine / threonine protein phosphatase (PPZ1), serine / threonine protein phosphatase (PTC3), serine / threonine protein phosphatase (RTS1), SIT4-associated protein SAP155, SIT4-associated protein SAP185, 2A Phosphatase-associated protein (TAP42), phosphatidylinositol 3,4,5-triphosphate 3-phosphatase (TEP1), polynucleotide 3'-phosphatase (TPP1), phosphatase (YAR068W), 5'-deoxynucleotidase (YBR242W), phosphatidylinositol 3-phosphatase, phosphatase (YNL108C), hydrolase (YOR131C), histidine phosphatase family phosphatases (YOR283W), phosphatidylglycerol phosphatase (PgpA), phosphatidylglycerol phosphatase (PgpB), phosphatidylglycerol phosphatase (PgpC), carbapenyl diphosphatase (YbjG), dihydroxy diphosphatase (DOLPP1), phosphatase (PLPP6), farnesyl diphosphatase (YisP), farnesol synthase (TPS2), acyclic sesquiterpene synthase (TPS1), or farnesol synthase (TPS13).

12. The recombinant engineered bacteria of claim 10 or 11, wherein the phosphatase is a phosphatase derived from a microorganism or a functional variant thereof, wherein the microorganism includes bacteria, yeast, or fungi, wherein the bacteria are selected from Escherichia or Bacillus, the yeast is selected from Saccharomyces, or the phosphatase is derived from plants or humans (…). Homo sapiens Phosphohydrolases or their functional variants thereof; preferably, the phosphohydrolase is a phosphohydrolase or its functional variant derived from bacteria, yeast or fungi, wherein the bacteria are selected from *Escherichia coli* (…). Escherichia coli Bacillus subtilis ( Bacillus subtilis The yeast is brewer's yeast (Saccharomyces cerevisiae). Saccharomyces cerevisiae ), or the phosphorylase is derived from plants or humans ( Homo sapiens Phosphorylase or a functional variant thereof, wherein the plant is selected from moso bamboo ( Phyllostachys edulis ),corn( Zea mays ) or japonica rice ( Oryza sativa subsp. japonica More preferably, the phosphorylase is derived from Saccharomyces cerevisiae (Saccharomyces cerevisiae). Saccharomyces cerevisiae ), Escherichia coli ( Escherichia coli ), human beings ( Homo sapiens Bacillus subtilis ( Bacillus subtilis ),bamboo( Phyllostachys edulis ),corn( Zea mays ) or japonica rice ( Oryza sativa subsp. japonica Phosphohydrolases or their functional variants.

13. The recombinant engineered bacteria according to any one of claims 10-12, wherein the phosphate hydrolase comprises an amino acid sequence selected from SEQ ID NO. 11-226, or an amino acid sequence having at least 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the amino acid sequences selected from SEQ ID NO. 12, SEQ ID NO. 17, SEQ ID NO. 20, SEQ ID NO. 36, SEQ ID NO. 38, SEQ ID NO. 45, SEQ ID NO. 58, ... ID NO.63, SEQ ID NO.95, SEQ ID NO.106, SEQ ID NO.107, SEQ ID NO.122, SEQ ID NO.125, SEQ ID NO.133, SEQ ID NO.157, SEQ ID NO.159, SEQ ID NO.160, SEQ ID NO.180, SEQ ID NO.181, SEQ ID NO.186, SEQ ID NO.197, SEQ ID NO.198, SEQ ID NO.206, SEQ ID NO.208, SEQ ID NO.209, SEQ ID NO.210, SEQ ID NO.217, SEQ ID NO.218, SEQ ID NO.219, SEQ ID NO.220, SEQ ID NO.221, SEQ ID NO.222, SEQ ID NO.223, SEQ ID The amino acid sequence of NO.224, SEQ ID NO.225, SEQ ID NO.226, or selected from SEQ ID NO.12, SEQ ID NO.17, SEQ ID NO.20, SEQ ID NO.36, SEQ ID NO.38, SEQ ID NO.45, SEQ ID NO.58, SEQ ID NO.63, SEQ ID NO.95, SEQ ID NO.106, SEQ ID NO.107, SEQ ID NO.122, SEQ ID NO.125, SEQ ID NO.133, SEQ ID NO.157, SEQ ID NO.159, SEQ ID NO.

160. SEQ ID NO.180, SEQ ID NO.181, SEQ ID NO.186, SEQ ID NO.197, SEQ ID NO.198, SEQ ID NO.206, SEQ ID NO.208, SEQ ID NO.209, SEQ ID NO.210, SEQ ID NO.217, SEQ ID NO.218, SEQ ID NO.219, SEQ ID NO.220, SEQ ID NO.221, SEQ ID NO.222, SEQ ID NO.223, SEQ ID NO.224, SEQ ID NO.225, SEQ ID The amino acid sequence of NO. 226 has at least 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity.

14. The recombinant engineered bacteria according to any one of claims 10-13, wherein the phosphate hydrolase is encoded by a nucleotide sequence selected from SEQ ID NO. 237-452, or by a nucleotide sequence having at least 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with a nucleotide sequence selected from SEQ ID NO. 238, SEQ ID NO. 243, SEQ ID NO. 246, SEQ ID NO. 262, SEQ ID NO. 264, SEQ ID NO. 271, SEQ ID NO. 238, SEQ ID NO. 243, SEQ ID NO. 246, SEQ ID NO. 262, SEQ ID NO. 264, SEQ ID NO. 271, SEQ ID NO. 237-452. ID NO.284, SEQ ID NO.289, SEQ ID NO.321, SEQ ID NO.332, SEQ ID NO.333, SEQ ID NO.348, SEQ ID NO.351, SEQ ID NO.359, SEQ ID NO.383, SEQ ID NO.385, SEQ ID NO.386, SEQ ID NO.406, SEQ ID NO.407, SEQ ID NO.412, SEQ ID NO.423, SEQ ID NO.424, SEQ ID NO.432, SEQ ID NO.434, SEQ ID NO.435, SEQ ID NO.436, SEQ ID NO.443, SEQ ID NO.444, SEQ ID NO.445, SEQ ID NO.446, SEQ ID NO.447, SEQ ID NO.448, SEQ ID The nucleotide sequence of NO.449, SEQ ID NO.450, SEQ ID NO.451, SEQ ID NO.452, or the nucleotide sequence selected from SEQ ID NO.238, SEQ ID NO.243, SEQ ID NO.246, SEQ ID NO.262, SEQ ID NO.264, SEQ ID NO.271, SEQ ID NO.284, SEQ ID NO.289, SEQ ID NO.321, SEQ ID NO.332, SEQ ID NO.333, SEQ ID NO.348, SEQ ID NO.351, SEQ ID NO.359, SEQ ID NO.

383. SEQ ID NO.385, SEQ ID NO.386, SEQ ID NO.406, SEQ ID NO.407, SEQ ID NO.412, SEQ ID NO.423, SEQ ID NO.424, SEQ ID NO.432, SEQ ID NO.434, SEQ ID NO.435, SEQ ID NO.436, SEQ ID NO.443, SEQ ID NO.444, SEQ ID NO.445, SEQ ID NO.446, SEQ ID NO.447, SEQ ID NO.448, SEQ ID NO.449, SEQ ID NO.450, SEQ ID NO.451, SEQ ID The nucleotide sequence of NO. 452 encodes a nucleotide sequence with at least 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity.

15. The recombinant engineered bacteria according to any one of claims 10-14, wherein the compound of formula (I) is selected from farnesol, geraniol, lysinediol, or copal; and / or the compound of formula (II) is selected from farnesyl pyrophosphate, geraniol pyrophosphate, lysinediol pyrophosphate, or copal pyrophosphate.

16. The method of claim 9 or the recombinant engineered bacteria of any one of claims 10-15, wherein, The recombinant engineered bacteria also contain genes for the synthesis pathway of compound (II).

17. The method or recombinant engineered bacteria of claim 16, wherein the gene for the synthetic pathway of the compound of formula (II) comprises: (1) Genes involved in the farnesyl pyrophosphate (FPP) synthesis pathway. (2) Farnesyl pyrophosphate (FPP) synthesis pathway genes and gerany-gerany-gerany pyrophosphate synthase (GGPPS) genes, or, (3) Farnesyl pyrophosphate (FPP) synthesis pathway gene, geraniol geraniol pyrophosphate synthase (GGPPS) gene and lysine pyrophosphate diol ester synthase (LPPS) gene.

18. The method or recombinant engineered bacteria of claim 17, wherein the farnesyl pyrophosphate (FPP) synthesis pathway gene comprises one or more of the following: acetyl-CoA transferase gene, 3-methyl-3-hydroxyglutaryl-CoA synthase gene, 3-hydroxy-3-methylglutaryl-CoA reductase gene, mevalonate kinase gene, mevalonate-5-phosphate kinase gene, mevalonate-5-pyrophosphate decarboxylase gene, pentene pyrophosphate isomerase gene, or farnesyl pyrophosphate synthase gene.

19. The method or recombinant engineered bacteria according to any one of claims 9-18, wherein the recombinant engineered bacteria further comprises one or more of the following gene modifications: (1) At least one gene modification that enhances the activity of geraniol geraniol pyrophosphate synthase (GGPPS); and (2) At least one gene modification that enhances the activity of lysine pyrophosphate diol ester synthase (LPPS).

20. The method or recombinant engineered bacteria of claim 19, wherein, At least one gene modification that enhances the activity of gerany-gerany-gerany pyrophosphate synthase (GGPPS) includes: introducing an exogenous gerany-gerany-gerany pyrophosphate synthase (GGPPS) gene, increasing the gene copy number of the gerany-gerany-gerany pyrophosphate synthase (GGPPS) gene, and / or replacing the natural promoter of the endogenous gerany-gerany pyrophosphate synthase (GGPPS) with a promoter that has a higher expression level; and / or At least one gene modification that enhances the activity of lysandrindiol pyrophosphate synthase (LPPS) includes: introducing an exogenous lysandrindiol pyrophosphate synthase (LPPS) gene, increasing the gene copy number of the lysandrindiol pyrophosphate synthase (LPPS) gene, and / or replacing the natural promoter of the endogenous lysandrindiol pyrophosphate synthase (LPPS) with a promoter that has a higher expression level.

21. The method or recombinant engineered bacteria of claim 20, wherein, The exogenous gerany-gerany pyrophosphate synthase (GGPPS) comprises the amino acid sequence shown in SEQ ID NO. 9, preferably encoded by the nucleotide sequence of SEQ ID NO. 235; and / or The exogenous lysine pyrophosphate diol ester synthase (LPPS) gene encodes a truncated lysine pyrophosphate diol ester synthase (LPPS); preferably, the truncated lysine pyrophosphate diol ester synthase (LPPS) is a signal peptide with the first 63 amino acids removed; preferably, the exogenous lysine pyrophosphate diol ester synthase (LPPS) comprises the amino acid sequence shown in SEQ ID NO. 10, more preferably, the exogenous lysine pyrophosphate diol ester synthase (LPPS) is encoded by the nucleotide sequence of SEQ ID NO.

236.

22. The method or recombinant engineered bacteria according to any one of claims 9-21, wherein the recombinant engineered bacteria further comprises one or more of the following gene modifications: (1) At least one gene modification that enhances the function of acetyl-CoA transferase; (2) At least one gene modification that enhances the activity of 3-methyl-3-hydroxyglutaryl-CoA synthase; (3) At least one gene modification that enhances the activity of 3-hydroxy-3-methylglutaryl-CoA reductase; (4) At least one gene modification that enhances the activity of mevalonate kinase; (5) At least one gene modification that enhances the activity of mevalonate-5-phosphate kinase; (6) At least one gene modification that enhances the activity of mevalonate-5-pyrophosphate decarboxylase; (7) At least one gene modification that enhances the activity of pentylene pyrophosphate isomerase; and (8) At least one gene modification that enhances the activity of farnesyl pyrophosphate synthase.

23. The method or recombinant engineered bacteria as described in claim 22, wherein, At least one gene modification that enhances the function of acetyl-CoA transferase includes: introducing an exogenous acetyl-CoA transferase gene, increasing the gene copy number of the acetyl-CoA transferase gene, and / or replacing the natural promoter of endogenous acetyl-CoA transferase with a promoter that has a higher expression level. At least one gene modification that enhances the function of 3-methyl-3-hydroxyglutaryl-CoA synthase includes: introducing an exogenous 3-methyl-3-hydroxyglutaryl-CoA synthase gene, increasing the gene copy number of the 3-methyl-3-hydroxyglutaryl-CoA synthase gene, and / or replacing the natural promoter of endogenous 3-methyl-3-hydroxyglutaryl-CoA synthase with a promoter that has a higher expression level; At least one gene modification that enhances the activity of 3-hydroxy-3-methylglutaryl-CoA reductase includes: introducing an exogenous 3-hydroxy-3-methylglutaryl-CoA reductase gene, increasing the gene copy number of the 3-hydroxy-3-methylglutaryl-CoA reductase gene, and / or replacing the natural promoter of endogenous 3-hydroxy-3-methylglutaryl-CoA reductase with a promoter that has a higher expression level; At least one gene modification that enhances the activity of mevalonate kinase includes: introducing an exogenous mevalonate kinase gene, increasing the gene copy number of the mevalonate kinase gene, and / or replacing the natural promoter of endogenous mevalonate kinase with a promoter that has a higher expression level. At least one gene modification that enhances the activity of mevalonate-5-phosphokinase includes: introducing an exogenous mevalonate-5-phosphokinase gene, increasing the gene copy number of the mevalonate-5-phosphokinase gene, and / or replacing the natural promoter of endogenous mevalonate-5-phosphokinase with a promoter that has a higher expression level. At least one gene modification that enhances the activity of mevalonate-5-pyrophosphate decarboxylase includes: introducing an exogenous mevalonate-5-pyrophosphate decarboxylase gene, increasing the gene copy number of the mevalonate-5-pyrophosphate decarboxylase gene, and / or replacing the natural promoter of endogenous mevalonate-5-pyrophosphate decarboxylase with a promoter that has a higher expression level. At least one gene modification that enhances the activity of pentyrene pyrophosphate isomerase includes: introducing an exogenous pentyrene pyrophosphate isomerase gene, increasing the copy number of the pentyrene pyrophosphate isomerase gene, and / or replacing the natural promoter of the endogenous pentyrene pyrophosphate isomerase with a promoter that has a higher expression level; and / or At least one gene modification that enhances the activity of farnesyl pyrophosphate synthase includes: introducing an exogenous farnesyl pyrophosphate synthase gene, increasing the gene copy number of the farnesyl pyrophosphate synthase gene, and / or replacing the natural promoter of endogenous farnesyl pyrophosphate synthase with a promoter that has a higher expression level.

24. The method or recombinant engineered bacteria as described in claim 23, wherein: The exogenous acetyl-CoA transferase comprises the amino acid sequence shown in SEQ ID NO.3, preferably, the exogenous acetyl-CoA transferase is encoded by the nucleotide sequence of SEQ ID NO.229; The exogenous 3-methyl-3-hydroxyglutaryl-CoA synthase comprises the amino acid sequence shown in SEQ ID NO.4, preferably, the exogenous 3-methyl-3-hydroxyglutaryl-CoA synthase is encoded by the nucleotide sequence of SEQ ID NO.230; The exogenous 3-hydroxy-3-methylglutaryl-CoA reductase gene encodes a truncated 3-hydroxy-3-methylglutaryl-CoA reductase, wherein the truncated 3-hydroxy-3-methylglutaryl-CoA reductase is a truncated 3-hydroxy-3-methylglutaryl-CoA reductase with 528 amino acids removed from its N-terminus; preferably, the truncated 3-hydroxy-3-methylglutaryl-CoA reductase comprises the amino acid sequence shown in SEQ ID NO. 2, and preferably, the truncated 3-hydroxy-3-methylglutaryl-CoA reductase is encoded by the nucleotide sequence of SEQ ID NO. 228; The exogenous mevalonate kinase comprises the amino acid sequence shown in SEQ ID NO.5, preferably, the exogenous mevalonate kinase is encoded by the nucleotide sequence of SEQ ID NO.231; The exogenous mevalonate-5-phosphokinase comprises the amino acid sequence shown in SEQ ID NO. 6, preferably, the exogenous mevalonate-5-phosphokinase is encoded by the nucleotide sequence of SEQ ID NO. 232; The exogenous mevalonate-5-pyrophosphate decarboxylase comprises the amino acid sequence shown in SEQ ID NO.7, preferably, the exogenous mevalonate-5-pyrophosphate decarboxylase is encoded by the nucleotide sequence of SEQ ID NO.233; The exogenous pentene pyrophosphate isomerase comprises the amino acid sequence shown in SEQ ID NO. 8, preferably, the exogenous pentene pyrophosphate isomerase is encoded by the nucleotide sequence of SEQ ID NO. 234; and / or The exogenous farnesyl pyrophosphate synthase comprises the amino acid sequence shown in SEQ ID NO.1, preferably encoded by the nucleotide sequence of SEQ ID NO.

227.

25. The method or recombinant engineered bacteria according to any one of claims 9-24, wherein the engineered bacteria is a bacterium or yeast; preferably, the bacteria are selected from Escherichia, Corynebacterium, or Bacillus, and the yeast is selected from Saccharomyces, Pichia, Hansenula, Kluyveromyces, Phaffia, Schizosaccharomyces, Candida, Yarrowia, Hyphozyma, or Cryptococcus; more preferably, the bacteria are selected from Escherichia coli (…). Escherichia coli ), Corynebacterium glutamicum ( Corynebacterium glutamicum ), or Bacillus subtilis ( Bacillus subtilis The yeast is selected from brewer's yeast (Saccharomyces cerevisiae). Saccharomyces cerevisiae Pichia pastoris () Pichia pastoris ), Phaffia colomata ( Komagataellaphaffii) , Saccharomyces cerevisiae ( Schizosaccharomycespombe ), Candida albicans ( Candidaalbicans ), Candida utilis ( Candida utilis ), Yarrowia lipolytica ( Yarrowia lipolytica ), Hansenula polymorpha ( Hansenulapolymorpha Pichia pastoris (Canada) Pichia canadensis ), Max Kluyveromycin ( Kluyveromycesmarxianus Kluyveromycin (lactic acid yeast) Kluyveromyces lactis Hyphozyma roseoniger, Cryptococcus palea ( Cryptococcus albidus ) or Red Pavlova yeast ( Phaffia rhodozyma ).

26. A method for producing a compound of formula (I), comprising culturing the recombinant engineered bacteria as described in any one of claims 10-25 under suitable conditions.

27. The method according to any one of claims 1-9 and 16-26, wherein the culture medium for culturing the recombinant engineered bacteria contains at least one carbon source selected from glucose, fructose, sucrose, glycerol, maltose, acetic acid, lactic acid, and succinic acid.

28. The method according to any one of claims 1-9 and 16-27, further comprising: Separate the compound of formula (I).

29. The method according to any one of claims 1-9 and 16-28, further comprising: The compound of formula (I) is further converted into a derivative of the compound of formula (I) by chemical synthesis, biocatalysis, or a combination of both, wherein the derivative is a hydrocarbon, diol, triol, acetal, ketal, aldehyde, acid, ether, amide, ketone, epoxide, acetate, glycoside, and / or ester of the compound of formula (I); preferably, the derivative is perillyl glycol, perillyl lactone, ambroxol, or a derivative thereof.

30. Use of the recombinant engineered bacteria as described in any one of claims 10-25 in the production of compound (I).

31. The use as described in claim 30, wherein the compound of formula (I) is selected from farnesol, geraniol, lysine diol, or copalol.

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