(WO201914310) Biological methods for preparing terpenes 机翻标题: 暂无翻译,请尝试点击翻译按钮。

源语言标题
(WO201914310) Biological methods for preparing terpenes
公开号/公开日
WO2019/014310 WO2019/014310 / 2020-01-30 2019-01-17
申请号/申请日
WOUS2018/041579 / 2018-07-11
发明人
AELING KIMBELY;
申请人
VERDEZYNE ABC;
主分类号
IPC分类号
C07H-021/04 C07K-014/415 C12N-001/16 C12N-001/19 C12N-001/21 C12N-005/10 C12N-009/02 C12N-009/88 C12N-009/96 C12N-015/09 C12N-015/52
摘要
(WO2019/014310) The technology relates in part to biological methods for producing terpenes and to engineered cells and microorganisms capable of such production.
机翻摘要
暂无翻译结果,您可以尝试点击头部的翻译按钮。
地址
代理人
(WO201914310) SALVADORI, Silvia et al. ([US])
代理机构
;
优先权号
2017US-62532297
主权利要求
(WO2019/014310) What is claimed is: 1. A genetically modified microorganism, comprising:   one or more heterologous nucleic acids encoding one or more terpene biosynthesis polypeptides, wherein expression of at least one of the heterologous nucleic acids is regulated by a nucleic acid that provides for fatty acid or alkane induction of expression of the terpene biosynthesis polypeptide. 2. The microorganism of claim 1 , wherein the microorganism is a fungus. 3. The microorganism of claim 2, wherein the fungus is a yeast. 4. The microorganism of claim 3, wherein the yeast is chosen from Candida spp, Yarrowia spp, Rhodotorula spp, Rhodosporidium spp, Cryptococcus spp, Trichosporon spp, Lipomyces spp, and Blastobotrys spp. 5. The microorganism of any one of claims 1 to 4, wherein the one or more heterologous nucleic acids encode one or more terpene biosynthesis polypeptides chosen from terpene synthase, phytoene synthase, geranylgeranyl diphosphate synthase, phytoene desaturase, lycopene cyclase, bifunctional lycopene cyclase/phytoene synthase, β- carotene ketolase, β-carotene hydroxylase, astaxanthin synthase, zeaxanthin glucosyltransferase, valencene synthase, and cytochrome p450 reductase. 6. The microorganism of any one of claims 1 to 5, wherein the fatty acid is a saturated fatty acid or an unsaturated fatty acid. 7. The microorganism of any one of claims 1 to 6, wherein the fatty acid is chosen from one or more of oleic acid, palmitoleic acid, erucic acid, linoleic acid, palmitic acid, caproic acid, enanthic acid, caprylic acid pelargonic acid, capric acid, undecylic acid, lauric acid, myristic acid, pentadecanoic acid, margaric acid, stearic acid arachidic acid, behenic acid, tridecylic acid, and linolenic acid. 8. The microorganism of any one of claims 1 to 5, wherein the alkane is chosen from one or more of hexane, heptane, nonane, decane, undecane, dodecane, tridecane, tetradecane, pentadecane, hexadecane, heptadecane, and octadecane 9. The microorganism of any one of claims 1 to 8, wherein the nucleic acid that provides for fatty acid or alkane induction of expression of a terpene biosynthesis polypeptide comprises a fatty acid response element or an alkane response element. 10. The microorganism of claim 9, wherein the fatty acid response element comprises an oleic acid response element. 11. The microorganism of claim 9, wherein the alkane response element comprises an alkane response element 1 (ARE1) sequence. 12. The microorganism of any one of claims 1 to 11 , wherein the nucleic acid that provides for fatty acid induction of expression of a terpene biosynthesis polypeptide comprises a promoter region chosen from promoter regions of genes encoding hydratase-dehydrogenase-epimerase (HDE), acyl co-A oxidase (POX), acyl co-A thiolase (POT), peroxin (PEX) and peroxisomal adenine nucleotide transporter protein (ANT1). 13. The microorganism of any one of claims 1 to 12, wherein the microorganism is Candida viswanathii. 14. The microorganism of any one of claims 1 to 12, wherein the microorganism is Blastobotrys adeninivorans. 15. The microorganism of any one of claims 1 to 14, wherein the one or more heterologous nucleic acids encode phytoene synthase, geranylgeranyl diphosphate synthase and phytoene desaturase. 16. The microorganism of claim 15, wherein expression of the heterologous nucleic acids encoding phytoene synthase, geranylgeranyl diphosphate synthase and phytoene desaturase is regulated by a promoter region of the gene encoding a hydratase- dehydrogenase-epimerase (HDE). 17. The microorganism of claim 15, wherein expression of the heterologous nucleic acids encoding phytoene synthase, geranylgeranyl diphosphate synthase and phytoene desaturase is regulated by a promoter region of the gene encoding a Candida hydratase-dehydrogenase-epimerase (HDE). 18. The microorganism of claim 15, 16 or 17, wherein expression of the heterologous nucleic acids encoding phytoene synthase, geranylgeranyl diphosphate synthase and phytoene desaturase is regulated by a terminator region of the gene encoding an acyl co-A oxidase 4 (POX4). 19. The microorganism of claim 15, 16 or 17, wherein expression of the heterologous nucleic acids encoding phytoene synthase, geranylgeranyl diphosphate synthase and phytoene desaturase is regulated by a terminator region of the gene encoding a Candida acyl co-A oxidase 4 (POX4). 20. The microorganism of any one of claims 1 to 14, wherein the one or more heterologous nucleic acids encode valencene synthase. 21. The microorganism of claim 20, wherein expression of the heterologous nucleic acids encoding valencene synthase is regulated by a promoter region of the gene encoding a hydratase-dehydrogenase-epimerase (HDE). 22. The microorganism of claim 20, wherein expression of the heterologous nucleic acids encoding valencene synthase is regulated by a promoter region of the gene encoding a Candida hydratase-dehydrogenase-epimerase (HDE). 23. The microorganism of claim 20, 21 or 22, wherein expression of the heterologous nucleic acids encoding valencene synthase is regulated by a terminator region of the gene encoding an acyl co-A oxidase 4 (POX4). 24. The microorganism of claim 20, 21 or 22, wherein expression of the heterologous nucleic acids encoding valencene synthase is regulated by a terminator region of the gene encoding a Candida acyl co-A oxidase 4 (POX4). 25. The microorganism of any one of claims 1 to 14, wherein the one or more heterologous nucleic acids encode geranylgeranyl diphosphate synthase, phytoene desaturase and bifunctional lycopene cyclase/phytoene synthase. 26. The microorganism of claim 25, wherein expression of the heterologous nucleic acids encoding geranylgeranyl diphosphate synthase, phytoene desaturase and bifunctional lycopene cyclase/phytoene synthase is regulated by a promoter region of the gene encoding a hydratase-dehydrogenase-epimerase (HDE). 27. The microorganism of claim 25, wherein expression of the heterologous nucleic acids encoding geranylgeranyl diphosphate synthase, phytoene desaturase and bifunctional lycopene cyclase/phytoene synthase is regulated by a promoter region of the gene encoding a Candida hydratase-dehydrogenase-epimerase (HDE). 28. The microorganism of claim 25, 26 or 27, wherein expression of the heterologous nucleic acids encoding geranylgeranyl diphosphate synthase, phytoene desaturase and bifunctional lycopene cyclase/phytoene synthase is regulated by a terminator region of the gene encoding an acyl co-A oxidase 4 (POX4). 29. The microorganism of claim 25, 26 or 27, wherein expression of the heterologous nucleic acids encoding geranylgeranyl diphosphate synthase, phytoene desaturase and bifunctional lycopene cyclase/phytoene synthase is regulated by a terminator region of the gene encoding a Candida acyl co-A oxidase 4 (POX4). 30. The microorganism of any one of claims 1 to 29, wherein the one or more heterologous nucleic acids encoding the one or more terpene biosynthesis polypeptides are endogenously expressed in a microorganism chosen from Cronobacter spp, Callitropsis spp, Xanthophyllomyces spp, Agrobacterium spp, and Pantoea spp. 31. The microorganism of any one of claims 1 to 30, wherein the amount and/or activity of a Ras2 protein has been decreased. 32. The microorganism of any one of claims 1 to 31 , wherein the microorganism has been genetically modified to reduce or eliminate expression of an endogenous RAS2 gene. 33. The microorganism of any one of claims 1 to 32, wherein the amount and/or activity of an Faa1 protein has been decreased. 34. The microorganism of any one of claims 1 to 33, wherein the microorganism has been genetically modified to reduce or eliminate expression of an endogenous FAA1 gene. 35. The microorganism of any one of claims 1 to 34, wherein the amounts and/or activities of one or more proteins chosen from acetyl-CoA C-acetyltransferase, HMG- CoA synthase, HMG-CoA reductase, mevalonate kinase, phosphomevalonate kinase, diphosphomevalonate decarboxylase, and isopentyl diphosphate delta isomerase, have been increased. 36. The microorganism of any one of claims 1 to 35, wherein the microorganism has been genetically modified to increase expression of one or more endogenous genes chosen from ERG10, ERG13, HMG1, ERG12, ERG8, MVD1, and IDI1. 37. The microorganism of any one of claims 1 to 36, wherein the amount and/or activity of dimethylallyltranstransferase or farnesyl diphosphate synthetase has been increased. 38. The microorganism of any one of claims 1 to 37, wherein the microorganism has been genetically modified to increase expression of an endogenous ERG20 gene. 39. The microorganism of claim 36, wherein expression of ERG 10, ERG 13, HMG1, ERG 12, ERG8, MVD1, and/or IDI1 is regulated by a promoter region of the gene encoding oleate-induced peroxisomal protein (POX18). 40. The microorganism of claim 36 or 39, wherein expression of ERG10, ERG 13, HMG1, ERG12, ERG8, MVD1, and/or IDI1 is regulated by a terminator region of the gene encoding oleate-induced peroxisomal protein (POX18). 41. The microorganism of claim 38, wherein expression of ERG20 is regulated by a promoter region of the gene encoding oleate-induced peroxisomal protein (POX18). 42. The microorganism of claim 38 or 41 , wherein expression of ERG20 is regulated by a terminator region of the gene encoding oleate-induced peroxisomal protein (POX18). 43. A genetically modified microorganism, comprising:   one or more heterologous nucleic acids encoding one or more terpene biosynthesis polypeptides, and   a genetic modification that alters the expression of a polypeptide providing for transport of acetyl-carnitine in the microorganism. 44. The microorganism of claim 43, wherein expression of at least one of the heterologous nucleic acids is regulated by a nucleic acid that provides for fatty acid or alkane induction of expression of the terpene biosynthesis polypeptide. 45. The microorganism of claim 43, wherein expression of at least one of the heterologous nucleic acids is regulated by a nucleic acid that provides for glucose induction of expression of the terpene biosynthesis polypeptide. 46. The microorganism of claim 43, 44 or 45, wherein the microorganism is a fungus. 47. The microorganism of claim 46, wherein the fungus is a yeast. 48. The microorganism of claim 47, wherein the yeast is chosen from Candida spp, Yarrowia spp, Rhodotorula spp, Rhodosporidium spp, Cryptococcus spp, Trichosporon spp, Lipomyces spp, and Blastobotrys spp. 49. The microorganism of any one of claims 43 to 48, wherein the one or more heterologous nucleic acids encode one or more terpene biosynthesis polypeptides chosen from terpene synthase, phytoene synthase, geranylgeranyl diphosphate synthase, phytoene desaturase, lycopene cyclase, bifunctional lycopene   cyclase/phytoene synthase, β-carotene ketolase, β-carotene hydroxylase, astaxanthin synthase, zeaxanthin glucosyltransferase, valencene synthase, and cytochrome p450 reductase. 50. The microorganism of any one of claims 43 to 49, wherein the genetic modification reduces expression of the polypeptide providing for transport of acetyl-carnitine in the microorganism relative to a microorganism that does not have the genetic modification. 51. The microorganism of claim 50, wherein the genetic modification is a disruption, deletion or knockout of (i) a polynucleotide that encodes a polypeptide providing for transport of acetyl-carnitine, or (ii) a promoter operably linked to a polynucleotide that encodes a polypeptide providing for transport of acetyl-carnitine, whereby endogenous activity of a polypeptide providing for transport of acetyl-carnitine is reduced or abolished. 52. The microorganism of claim 50, further comprising a nucleic acid encoding a polypeptide providing for transport of acetyl-carnitine wherein expression of the nucleic acid encoding a polypeptide providing for transport of acetyl-carnitine is regulated by a promoter that provides for reduced expression relative to endogenous expression. 53. The microorganism of claim 52, wherein the genetic modification comprises replacing the promoter of an endogenous gene encoding the polypeptide providing for transport of acetyl-carnitine in the microorganism with a promoter that provides for reduced expression of the polypeptide in the microorganism relative to a microorganism that does not have the genetic modification. 54. The microorganism of claim 52 or 53, wherein the promoter that provides for reduced expression relative to endogenous expression is a promoter for a glucose-6-phosphate isomerase (G6PI) gene. 55. The microorganism of claim 52 or 53, wherein the promoter that provides for reduced expression relative to endogenous expression is a promoter for a Candida glucose-6- phosphate isomerase (G6PI) gene. 56. The microorganism of any one of claims 43 to 55, wherein the polypeptide providing for transport of acetyl-carnitine in the microorganism is an acetyl-carnitine translocase (CRC). 57. The microorganism of claim 56, wherein the acetyl-carnitine translocase (CRC) is acetyl-carnitine translocase 1 (CRC1). 58. The microorganism of any one of claims 43 to 57, wherein the microorganism is Candida viswanathii. 59. The microorganism of any one of claims 43 to 57, wherein the microorganism is Blastobotrys adeninivorans. 60. The microorganism of any one of claims 43 to 59, wherein the one or more heterologous nucleic acids encode phytoene synthase, geranylgeranyl diphosphate synthase and phytoene desaturase. 61. The microorganism of claim 60, wherein expression of the heterologous nucleic acids encoding phytoene synthase, geranylgeranyl diphosphate synthase and phytoene desaturase is regulated by a promoter region of the gene encoding a hydratase- dehydrogenase-epimerase (HDE). 62. The microorganism of claim 60, wherein expression of the heterologous nucleic acids encoding phytoene synthase, geranylgeranyl diphosphate synthase and phytoene desaturase is regulated by a promoter region of the gene encoding a Candida hydratase-dehydrogenase-epimerase (HDE). 63. The microorganism of claim 60, 61 or 62, wherein expression of the heterologous nucleic acids encoding phytoene synthase, geranylgeranyl diphosphate synthase and phytoene desaturase is regulated by a terminator region of the gene encoding an acyl co-A oxidase 4 (POX4). 64. The microorganism of claim 60, 61 or 62, wherein expression of the heterologous nucleic acids encoding phytoene synthase, geranylgeranyl diphosphate synthase and phytoene desaturase is regulated by a terminator region of the gene encoding a Candida acyl co-A oxidase 4 (POX4). 65. The microorganism of any one of claims 43 to 59, wherein the one or more heterologous nucleic acids encode geranylgeranyl diphosphate synthase, phytoene desaturase and bifunctional lycopene cyclase/phytoene synthase. 66. The microorganism of claim 65, wherein expression of the heterologous nucleic acids encoding geranylgeranyl diphosphate synthase, phytoene desaturase and bifunctional lycopene cyclase/phytoene synthase is regulated by a promoter region of the gene encoding a hydratase-dehydrogenase-epimerase (HDE). 67. The microorganism of claim 65, wherein expression of the heterologous nucleic acids encoding geranylgeranyl diphosphate synthase, phytoene desaturase and bifunctional lycopene cyclase/phytoene synthase is regulated by a promoter region of the gene encoding a Candida hydratase-dehydrogenase-epimerase (HDE). 68. The microorganism of claim 65, 66 or 67, wherein expression of the heterologous nucleic acids encoding geranylgeranyl diphosphate synthase, phytoene desaturase and bifunctional lycopene cyclase/phytoene synthase is regulated by a terminator region of the gene encoding an acyl co-A oxidase 4 (POX4). 69. The microorganism of claim 65, 66 or 67, wherein expression of the heterologous nucleic acids encoding geranylgeranyl diphosphate synthase, phytoene desaturase and bifunctional lycopene cyclase/phytoene synthase is regulated by a terminator region of the gene encoding a Candida acyl co-A oxidase 4 (POX4). 70. The microorganism of any one of claims 43 to 69, wherein the one or more heterologous nucleic acids encoding the one or more terpene biosynthesis polypeptides are endogenously expressed in a microorganism chosen from Cronobacter spp, Callitropsis spp, Xanthophyllomyces spp, Agrobacterium spp, and Pantoea spp. 71. The microorganism of any one of claims 43 to 70, wherein the amount and/or activity of a Ras2 protein has been decreased. 72. The microorganism of any one of claims 43 to 71 , wherein the microorganism has been genetically modified to reduce or eliminate expression of an endogenous RAS2 gene. 73. The microorganism of any one of claims 43 to 72, wherein the amount and/or activity of an Faa1 protein has been decreased. 74. The microorganism of any one of claims 43 to 73, wherein the microorganism has been genetically modified to reduce or eliminate expression of an endogenous FAA1 gene. 75. The microorganism of any one of claims 43 to 74, wherein the amounts and/or activities of one or more proteins chosen from acetyl-CoA C-acetyltransferase, HMG- CoA synthase, HMG-CoA reductase, mevalonate kinase, phosphomevalonate kinase, diphosphomevalonate decarboxylase, and isopentyl diphosphate delta isomerase, have been increased. 76. The microorganism of any one of claims 43 to 75, wherein the microorganism has been genetically modified to increase expression of one or more endogenous genes chosen from ERG10, ERG13, HMG1, ERG12, ERG8, MVD1, and IDI1. 77. The microorganism of any one of claims 43 to 76, wherein the amount and/or activity of dimethylallyltranstransferase or farnesyl diphosphate synthetase has been increased. 78. The microorganism of any one of claims 43 to 77, wherein the microorganism has been genetically modified to increase expression of an endogenous ERG20 gene. 79. The microorganism of claim 76, wherein expression of ERG10, ERG 13, HMG1, ERG 12, ERG8, MVD1, and/or IDI1 is regulated by a promoter region of the gene encoding oleate-induced peroxisomal protein (POX18). 80. The microorganism of claim 76 or 79, wherein expression of ERG 10, ERG 13, HMG1, ERG12, ERG8, MVD1, and/or \D\1 is regulated by a terminator region of the gene encoding oleate-induced peroxisomal protein (POX18). 81. The microorganism of claim 78, wherein expression of ERG20 is regulated by a promoter region of the gene encoding oleate-induced peroxisomal protein (POX18). 82. The microorganism of claim 78 or 81 , wherein expression of ERG20 is regulated by a terminator region of the gene encoding oleate-induced peroxisomal protein (POX18). 83. A genetically modified Candida viswanathii yeast, comprising one or more heterologous nucleic acids encoding one or more terpene biosynthesis polypeptides. 84. The genetically modified Candida viswanathii yeast of claim 83, wherein expression of at least one of the heterologous nucleic acids is regulated by a nucleic acid that provides for fatty acid or alkane induction of expression of the terpene biosynthesis polypeptide. 85. The genetically modified Candida viswanathii yeast of claim 83, wherein expression of at least one of the heterologous nucleic acids is regulated by a nucleic acid that provides for glucose induction of expression of the terpene biosynthesis polypeptide. 86. The genetically modified Candida viswanathii yeast of claim 83, 84 or 85, wherein the one or more heterologous nucleic acids encode one or more terpene biosynthesis polypeptides chosen from terpene synthase, phytoene synthase, geranylgeranyl diphosphate synthase, phytoene desaturase, lycopene cyclase, bifunctional lycopene cyclase/phytoene synthase, β-carotene ketolase, β-carotene hydroxylase, astaxanthin synthase, zeaxanthin glucosyltransferase, valencene synthase, and cytochrome p450 reductase. 87. The genetically modified Candida viswanathii yeast of any one of claims 83 to 86, wherein the one or more heterologous nucleic acids encode phytoene synthase, geranylgeranyl diphosphate synthase and phytoene desaturase 88. The genetically modified Candida viswanathii yeast of claim 87, wherein expression of the heterologous nucleic acids encoding phytoene synthase, geranylgeranyl diphosphate synthase and phytoene desaturase is regulated by a promoter region of the gene encoding a Candida hydratase-dehydrogenase-epimerase (HDE). 89. The genetically modified Candida viswanathii yeast of claim 88, wherein expression of the heterologous nucleic acids encoding phytoene synthase, geranylgeranyl diphosphate synthase and phytoene desaturase is regulated by a terminator region of the gene encoding a Candida acyl co-A oxidase 4 (POX4). 90. The genetically modified Candida viswanathii yeast of claim 87, wherein expression of the heterologous nucleic acids encoding phytoene synthase, geranylgeranyl diphosphate synthase and phytoene desaturase is regulated by a promoter region of the gene encoding a Candida glyceraldehyde-3-phosphate dehydrogenase (GPD). 91. The genetically modified Candida viswanathii yeast of any one of claims 83 to 86, wherein the one or more heterologous nucleic acids encode valencene synthase. 92. The genetically modified Candida viswanathii yeast of claim 91 , wherein expression of the heterologous nucleic acids encoding valencene synthase is regulated by a promoter region of the gene encoding a Candida hydratase-dehydrogenase-epimerase (HDE). 93. The genetically modified Candida viswanathii yeast of claim 92, wherein expression of the heterologous nucleic acids valencene synthase is regulated by a terminator region of the gene encoding a Candida acyl co-A oxidase 4 (POX4). 94. The genetically modified Candida viswanathii yeast of claim 91 , wherein expression of the heterologous nucleic acids encoding valencene synthase is regulated by a promoter region of the gene encoding a Candida glyceraldehyde-3-phosphate dehydrogenase (GPD). 95. The genetically modified Candida viswanathii yeast of any one of claims 83 to 86, wherein the one or more heterologous nucleic acids encode geranylgeranyl diphosphate synthase, phytoene desaturase and bifunctional lycopene cyclase/phytoene synthase. 96. The genetically modified Candida viswanathii yeast of claim 95, wherein expression of the heterologous nucleic acids encoding geranylgeranyl diphosphate synthase, phytoene desaturase and bifunctional lycopene cyclase/phytoene synthase is regulated by a promoter region of the gene encoding a Candida hydratase-dehydrogenase- epimerase (HDE). 97. The genetically modified Candida viswanathii yeast of claim 96, wherein expression of the heterologous nucleic acids encoding geranylgeranyl diphosphate synthase, phytoene desaturase and bifunctional lycopene cyclase/phytoene synthase is regulated by a terminator region of the gene encoding a Candida acyl co-A oxidase 4 (POX4). 98. The genetically modified Candida viswanathii yeast of claim 95, wherein expression of the heterologous nucleic acids encoding geranylgeranyl diphosphate synthase, phytoene desaturase and bifunctional lycopene cyclase/phytoene synthase is regulated by a promoter region of the gene encoding a Candida glyceraldehyde-3-phosphate dehydrogenase (GPD). 99. The genetically modified Candida viswanathii yeast of any one of claims 83 to 86, wherein the one or more heterologous nucleic acids encode geranylgeranyl diphosphate synthase, phytoene desaturase, bifunctional lycopene cyclase/phytoene synthase, β- carotene ketolase, β-carotene hydroxylase, astaxanthin synthase, and cytochrome p450 reductase. 100. The genetically modified Candida viswanathii yeast of claim 99, wherein expression of the heterologous nucleic acids encoding geranylgeranyl diphosphate synthase, phytoene desaturase, bifunctional lycopene cyclase/phytoene synthase, β- carotene ketolase, β-carotene hydroxylase, astaxanthin synthase, and cytochrome p450 reductase is regulated by a promoter region of the gene encoding a Candida hydratase- dehydrogenase-epimerase (HDE). 101. The genetically modified Candida viswanathii yeast of claim 100, wherein expression of the heterologous nucleic acids encoding geranylgeranyl diphosphate synthase, phytoene desaturase, bifunctional lycopene cyclase/phytoene synthase, β- carotene ketolase, β-carotene hydroxylase, astaxanthin synthase, and cytochrome p450 reductase is regulated by a terminator region of the gene encoding a Candida acyl co-A oxidase 4 (POX4). 102. The genetically modified Candida viswanathii yeast of claim 99, wherein expression of the heterologous nucleic acids encoding geranylgeranyl diphosphate synthase, phytoene desaturase, bifunctional lycopene cyclase/phytoene synthase, β- carotene ketolase, β-carotene hydroxylase, astaxanthin synthase, and cytochrome p450 reductase is regulated by a promoter region of the gene encoding a Candida   glyceraldehyde-3-phosphate dehydrogenase (GPD). 103. The genetically modified Candida viswanathii yeast of any one of claims 83 to 102, wherein the one or more heterologous nucleic acids encoding the one or more terpene biosynthesis polypeptides are endogenously expressed in a microorganism chosen from Cronobacter spp, Callitropsis spp, Xanthophyllomyces spp, Agrobacterium spp, and Pantoea spp. 104. The genetically modified Candida viswanathii yeast of any one of claims 83 to 103, further comprising a genetic modification that alters the expression of one or more nucleic acids encoding one or more endogenous polypeptides. 105. The genetically modified Candida viswanathii yeast of claim 104, wherein the one or more endogenous polypeptides are chosen from polypeptides having one or more of the following activities: acyl-CoA synthetase activity, acyl-CoA oxidase activity, ATP- binding cassette transporter activity, carnitine acetyltransferase activity, transport of acetyl-carnitine, acyl-CoA thioesterase activity, acyl-CoA hydrolase activity, aldehyde dehydrogenase activity, monooxygenase activity, or monooxgenase reductase activity. 106. The genetically modified Candida viswanathii yeast of any one of claims 83 to 105, wherein the amount and/or activity of a Ras2 protein has been decreased. 107. The genetically modified Candida viswanathii yeast of any one of claims 83 to 106, wherein the yeast has been genetically modified to reduce or eliminate expression of an endogenous RAS2 gene. 108. The genetically modified Candida viswanathii yeast of any one of claims 83 to 107, wherein the amount and/or activity of an Faa1 protein has been decreased. 109. The genetically modified Candida viswanathii yeast of any one of claims 83 to 108, wherein the yeast has been genetically modified to reduce or eliminate expression of an endogenous FAA 1 gene. 110. The genetically modified Candida viswanathii yeast of any one of claims 83 to 109, wherein the amounts and/or activities of one or more proteins chosen from acetyl-CoA C-acetyltransferase, HMG-CoA synthase, HMG-CoA reductase, mevalonate kinase, phosphomevalonate kinase, diphosphomevalonate decarboxylase, and isopentyl diphosphate delta isomerase, have been increased.   11 1. The genetically modified Candida viswanathii yeast of any one of claims 83 to 110, wherein the yeast has been genetically modified to increase expression of one or more endogenous genes chosen from ERG10, ERG13, HMG1, ERG12, ERG8, MVD1, and IDI1. 112. The genetically modified Candida viswanathii yeast of any one of claims 83 to 11 1 , wherein the amount and/or activity of dimethylallyltranstransferase or farnesyl diphosphate synthetase has been increased. 113. The genetically modified Candida viswanathii yeast of any one of claims 83 to 112, wherein the yeast has been genetically modified to increase expression of an   endogenous ERG20 gene. 114. The genetically modified Candida viswanathii yeast of claim 11 1 , wherein expression of ERG10, ERG13, HMG1, ERG12, ERG8, MVD1, and/or IDI1 is regulated by a promoter region of the gene encoding oleate-induced peroxisomal protein (POX18). 115. The genetically modified Candida viswanathii yeast of claim 11 1 or 1 14, wherein expression of ERG10, ERG13, HMG1, ERG12, ERG8, MVD1, and/or IDI1 is regulated by a terminator region of the gene encoding oleate-induced peroxisomal protein   (POX18). 116. The genetically modified Candida viswanathii yeast of claim 113, wherein expression of ERG20 is regulated by a promoter region of the gene encoding oleate- induced peroxisomal protein (POX18). 117. The genetically modified Candida viswanathii yeast of claim 113 or 1 16, wherein expression of ERG20 is regulated by a terminator region of the gene encoding oleate- induced peroxisomal protein (POX18). 118. A method for producing a terpene comprising:   contacting the genetically modified microorganism of any one of claims 1 to 42 with a feedstock comprising a carbon source, and   culturing the microorganism under conditions in which the terpenes are produced from the feedstock. 119. A method for producing a terpene comprising:   contacting the genetically modified microorganism of any one of claims 43 to 82 with a feedstock comprising a carbon source, and   culturing the microorganism under conditions in which the terpenes are produced from the feedstock. 120. A method for producing a terpene comprising:   contacting the genetically modified Candida viswanathii yeast of any one of claims 83 to 1 17 with a feedstock comprising a carbon source, and   culturing the microorganism under conditions in which the terpenes are produced from the feedstock. 121. The method of any one of claims 1 18 to 120, wherein the feedstock comprises one or more fatty acids. 122. The method of claim 121 , wherein the feedstock comprises one or more saturated fatty acids or one or more unsaturated fatty acids; or one or more saturated fatty acids and one or more unsaturated fatty acids. 123. (...)
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