Production of c6-c26 fatty alcohols from methanol
Recombinant microorganisms expressing TE, CAR, and ALDR genes produce C6-C26 fatty alcohols from methanol, addressing sustainability and environmental concerns in traditional plant oil-based production methods.
Patent Information
- Application Number
- PCT/EP2025/068121
- Authority / Receiving Office
- WO · WO
- Patent Type
- Applications
- Current Assignee / Owner
- Priority Date
- 2024-06-27
- Filing Date
- 2025-06-26
- Publication Date
- 2026-01-02
AI Technical Summary
Current methods for producing C6-C26 fatty alcohols, such as C12 and C14 fatty alcohols, from plant oils face sustainability and environmental issues, requiring large agricultural land use and high carbon footprints, and there is a need for more efficient and environmentally friendly production methods.
Development of recombinant microorganisms expressing thioesterase (TE), carboxylic acid reductase (CAR), and aldehyde reductase (ALDR) genes to produce fatty alcohols from methanol, which is a more sustainable feedstock.
The recombinant microorganisms enable the production of C6-C26 fatty alcohols, particularly C12 and C14 fatty alcohols, with reduced environmental impact and land use, offering a scalable and efficient alternative to traditional methods.
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Figure EP2025068121_02012026_PF_FP_ABST
Abstract
Description
[0001]Production of C6-C26 Fatty Alcohols from MethanolTechnical field of the inventionThe present invention relates to the field of biotechnology, microbiology, food ingredients and fatty alcohols. Inparticular the present invention relates to microorganisms capable of producing C6-C26 free fatty alcohols, such asC12, C14 or C16 free fatty alcohols, or a mixture thereof from methanol.BackgroundFatty alcohols are alcohols with aliphatic chains. The length of the aliphatic chain and presence, location or absenceof double bonds within the chain determines the physical properties and potential uses of the alcohol. Saturated fattyalcohols of lengths 12, 14 and 16 are commonly used in the chemical industry for detergents and various other marketsegments. Currently, they are primarily produced from fatty acids obtained from palm kernel oil the production of whichhas well known sustainability and environmental issues. Key market players are in search of alternative sources of this70 billion USD annual market feedstock. Microbial production of fatty alcohols is a promising alternative way forward.Since microbial production of fatty alcohols typically uses plant sugar as a feedstock, it is not inherently more efficientor environmentally friendly than using oil crops such as oil palm, sunflowers, soy, or rapeseed.Thus, there is a need for sustainable and alternative sources of C6-C26 free fatty alcohols, such as C12 and C14 freefatty alcohols, for e.g. the detergent industry. Also, there is a need for such alternative sources which can be exploitedin an environmentally sound way, e.g. not requiring vast areas of agricultural land and sugars as raw materials.In particular there is a need for a source of C6-C26 free fatty alcohols being amenable for effective production on alarge scale having acceptable environmental effects and climate footprint.Summary of the inventionThe present inventors have developed recombinant microorganisms comprising at least one gene enabling theexpression of a thioesterase (TE), at least one gene enabling the expression of at least one carboxylic acid reductase(CAR) and at least one gene enabling the expression of an aldehyde reductase (ALDR). These recombinantmicroorganisms surprisingly enable the industrial production of C6-C26 free fatty alcohols, such as C12, C14 or C16free fatty alcohols, or mixtures thereof from methanol.Methanol is a promising third generation feedstock that can be used for biotechnological production of various compounds. It can be produced from CO2 directly, bypassing agricultural crops and drastically decreasing the carbon footprint and land usage.In a first aspect the present invention provides a microorganism capable of producing at least one C6-C26 free fattyalcohol or a mixture thereof from methanol, said microorganism comprising: at least one gene enabling the expressionof a thioesterase (TE), at least one gene enabling the expression of at least one carboxylic acid reductase (CAR) andat least one gene enabling the expression of an aldehyde reductase (ALDR). The microorganism may be a recombinantmicroorganism. In various embodiments, the at least one gene enabling the expression of a thioesterase (TE) and / orthe at least one gene enabling the expression of at least one carboxylic acid reductase (CAR) and / or the at least onegene enabling the expression of an aldehyde reductase (ALDR) is heterologously expressed in said microorganism,i.e. at least one of these three genes, preferably two or all three, is / are a heterologous geneIn various embodiments, said TE is from Umbellularia californica (Uca-TE). Said TE may, in various embodiments, bea polypeptide that has at least 80% sequence identity to SEQ ID NO:6, at least 85% sequence identity to SEQ ID NO:6,at least 90% sequence identity to SEQ ID NO:6, at least 95% sequence identity to SEQ ID NO:6, or at least 98%sequence identity to SEQ ID NO:6 or at least 100% sequence identity to SEQ ID NO:6. In various embodiments, saidTE or Uca-TE comprises, consists essentially of or consists of SEQ ID NO:6.In various embodiments, the CAR is fromTsukamurella paurometabola (Tpa-CAR) or or from Mycobacterium tuberculosis (Mtu-CAR).In various embodiments,the CAR may be a polypeptide that has at least 80%, at least 85%, at least 90%, or at least 95%, or at least 98% or100% sequence identity to any one of SEQ ID NOs: 1-2, 4-5 and 20-29.In various embodiments, the ALDR may be a polypeptide that has at least 80%, at least 85%, at least 90%, or at least 95%, or at least 98% or 100% sequence identity to any one of SEQ ID NOs:7-18. In various embodiments, the above embodiments for TE, CAR and ALDR can be combined. In various embodiments, the TE is a polypeptide that has at least 80%, at least 85%, at least 90%, or at least 95%, or at least 98% or 100%sequence identity to SEQ ID NO:6 or 19 and / or the CAR is a polypeptide that has at least 80%, at least 85%, at least90%, or at least 95%, or at least 98% or 100% sequence identity to any one of SEQ ID NOs: 1-2, 4-5 and 20-29 and / orthe ALDR is a polypeptide that has at least 80%, at least 85%, at least 90%, or at least 95%, or at least 98% or 100% sequence identity to any one of SEQ ID NOs:7-18. In various embodiments, the TE is a polypeptide that has at least80%, at least 85%, at least 90%, or at least 95%, or at least 98% or 100% sequence identity to SEQ ID NO:6 or 19and the CAR is a polypeptide that has at least 80%, at least 85%, at least 90%, or at least 95%, or at least 98% or100% sequence identity to any one of SEQ ID NOs: 1-2, 4-5 and 20-29. In various embodiments, the TE is apolypeptide that has at least 80%, at least 85%, at least 90%, or at least 95%, or at least 98% or 100% sequenceidentity to SEQ ID NO:6 or 19 and the ALDR is a polypeptide that has at least 80%, at least 85%, at least 90%, or atleast 95%, or at least 98% or 100% sequence identity to any one of SEQ ID NOs:7-18. In various embodiments, the CAR is a polypeptide that has at least 80%, at least 85%, at least 90%, or at least 95%, or at least 98% or 100%sequence identity to any one of SEQ ID NOs: 1-2, 4-5 and 20-29 and the ALDR is a polypeptide that has at least 80%,at least 85%, at least 90%, or at least 95%, or at least 98% or 100% sequence identity to any one of SEQ ID NOs:7- 18. In various embodiments, the TE is a polypeptide that has at least 80%, at least 85%, at least 90%, or at least 95%,or at least 98% or 100% sequence identity to SEQ ID NO:6 or 19 and the CAR is a polypeptide that has at least 80%,at least 85%, at least 90%, or at least 95%, or at least 98% or 100% sequence identity to any one of SEQ ID NOs: 1-2, 4-5 and 20-29 and the ALDR is a polypeptide that has at least 80%, at least 85%, at least 90%, or at least 95%, orat least 98% or 100% sequence identity to any one of SEQ ID NOs:7-18.In various embodiments, the C6-C26 free fatty alcohol or a mixture thereof comprises at least one of C12, C14 andC16 free fatty alcohol.In various embodiments, the C12 free fatty alcohol comprises or is 1-dodecanol (lauric alcohol).In a second aspect the present invention provides a method for the manufacture of at least one C6-C26 free fattyalcohol or a mixture thereof comprising growing a microorganism as defined herein, for example in items 1 to 89 below,in a suitable medium, and isolation of said C6-C26 free fatty alcohol or a mixture thereof from the medium, such as the spent medium.In a third aspect the present invention provides a free fatty alcohol composition obtained by the method as definedabove.In a fourth aspect the present invention provides the use of a microorganism as defined herein, for example in items 1to 89 below, for the manufacture of a C6-C26 free fatty alcohol or a mixture thereof.The present invention is further characterized by the following items:1. Microorganism capable of producing at least one C6-C26 free fatty alcohol or a mixture thereof from methanol,said microorganism comprising:at least one gene enabling the expression of a thioesterase (TE),at least one gene enabling the expression of at least one carboxylic acid reductase (CAR) andat least one gene enabling the expression of an aldehyde reductase (ALDR).2. The microorganism according to item 1, wherein(1) said microorganism is a recombinant microorganism; (2) the at least one gene enabling the expression of a thioesterase (TE) and / or the at least one gene enabling the expression of at least one carboxylic acid reductase (CAR) and / or the at least one gene enabling the expression of an aldehyde reductase (ALDR)is heterologously expressed in said microorganism; and / or(3) said TE is from Umbellularia californica (Uca-TE).3. The microorganism according to item 2, wherein said Uca-TE has at least 80% sequence identity to SEQ IDNO:6, at least 85% sequence identity to SEQ ID NO:6, at least 90% sequence identity to SEQ ID NO:6, at least 95% sequence identity to SEQ ID NO:6, at least 98% sequence identity to SEQ ID NO:6, or 100% sequence identity to SEQ ID NO:6.4. The microorganism according to item 2 or 3, wherein said Uca-TE has at least 50% thioesterase activity ascompared to the activity of SEQ ID NO:6, at least 70% thioesterase activity as compared to the activity of SEQ ID NO:6, at least 80% thioesterase activity as compared to the activity of SEQ ID NO:6, at least 90% thioesterase activity as compared to the activity of SEQ ID NO:6, or at least 95% thioesterase activity as compared to the activity of SEQ ID NO:6.5. The microorganism according to any of items 2-4, wherein said Uca-TE is a truncated version of SEQ ID NO:6having at least 85% sequence identity to the corresponding sequence of SEQ ID NO:6, at least 90% sequence identity to the corresponding sequence of SEQ ID NO:6, at least 95% sequence identity to the corresponding sequence of SEQ ID NO:6.6. The microorganism according to item 5, wherein said Uca-TE is a truncated version of SEQ ID NO:6.7. The microorganism according to item 6, wherein said Uca-TE is SEQ ID NO: 19.8. The microorganism according to any of items 2-7, wherein said Uca-TE is SEQ ID NO:6 having 1, 2, 3, 4, 5, 6,7, 8, 9, or 10 substitutions, insertions, additions or deletions and retaining thioesterase activity.9. The microorganism according to any of items 2-8, wherein said Uca-TE comprises, consists essentially of, orconsists of SEQ ID NO:6 or SEQ ID NO:19.10. The microorganism according to any of items 2-9, wherein said Uca-TE is SEQ ID NO:6 or SEQ ID NO:19.11. The microorganism according to any one of the preceding items, wherein said at least one CAR comprises aCAR from Tsukamurella paurometabola (Tpa-CAR) or from Mycobacterium tuberculosis (Mtu-CAR).12. The microorganism according to any one of the preceding items, wherein said at least one CAR is a Tpa-CAR.13. The microorganism according to any of the preceding items, wherein the CAR is a Tpa-CAR having at least80% sequence identity to SEQ ID NO:5, at least 85% sequence identity to SEQ ID NO:5, at least 90% sequence identity to SEQ ID NO:5, at least 95% sequence identity to SEQ ID NO:5, at least 98% sequence identity to SEQ ID NO:5, or 100% sequence identity to SEQ ID NO:5.14. The microorganism according to any one of the preceding items, wherein the CAR is SEQ ID NO:5 having 1, 2,3, 4, 5, 6, 7, 8, 9, or 10 substitutions, insertions, additions or deletions and retaining CAR activity.15. The microorganism according to any one of the preceding items, wherein the CAR is a Tpa-CAR comprising,consisting essentially of or consisting of SEQ ID NO:5.16. The microorganism according to any one of the preceding items, wherein the CAR is a Tpa-CAR which is SEQID NO:5.17. The microorganism according to any one of the preceding items, wherein said at least one CAR is a Mtu-CAR.18. The microorganism according to any of the preceding items, wherein said at least one CAR is a Mtu-CAR havingat least 80% sequence identity to SEQ ID NO:4, at least 85% sequence identity to SEQ ID NO:4, at least 90% sequence identity to SEQ ID NO:4, at least 95% sequence identity to SEQ ID NO:4, at least 98% sequence identity to SEQ ID NO:4, or 100% sequence identity to SEQ ID NO:4.19. The microorganism according to any one of the preceding items, wherein the CAR is SEQ ID NO:4 having 1, 2,3, 4, 5, 6, 7, 8, 9, or 10 substitutions, insertions, additions or deletions and retaining CAR activity.20. The microorganism according to any one of the preceding items, wherein the CAR is a Mtu-CAR comprising,consisting essentially of, or consisting of SEQ ID NO:4.21. The microorganism according to any one of the preceding items, wherein the CAR is a Mtu-CAR which is SEQID NO:4.22. The microorganism according to any one of the preceding items, wherein the CAR is a polypeptide having atleast 80, 85, 90, 95, 98 or 100 % sequence identity to any one of SEQ ID NOs: 1-2 and 20-29.23. The microorganism according to any one of the preceding items, wherein the CAR is any one of SEQ ID NOs:1-2 and 20-29 having 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 substitutions, insertions, additions or deletions and retaining CARactivity.24. The microorganism according to any one of the preceding items, wherein the CAR is a polypeptide comprising,consisting essentially of, or consisting of any one of SEQ ID NOs: 1-2 and 20-29.25. The microorganism according to any one of the preceding items, wherein said at least one ALDR is apolypeptide having at least 80, 85, 90, 95, 98 or 100 % sequence identity to any one of SEQ ID NOs:7-18, preferablybeing selected from the group consisting of SEQ ID NO:7 to SEQ ID NO:18.26. The microorganism according to any one of the preceding items, wherein the ALDR is any one of SEQ IDNOs:7-18 having 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 substitutions, insertions, additions or deletions and retaining ALDRactivity.27. The microorganism according to any of the preceding items, wherein said at least one ALDR comprises,consists essentially of, or consists of or is SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17 or SEQ ID NO:18.28. The microorganism according to any of the preceding items, wherein said at least one ALDR is SEQ ID NO:7.29. The microorganism according to any of the preceding items, wherein said at least one ALDR is SEQ ID NO:8.30. The microorganism according to any of the preceding items, wherein said at least one ALDR is SEQ ID NO:9.31. The microorganism according to any of the preceding items, wherein said at least one ALDR is SEQ ID NO:10.32. The microorganism according to any of the preceding items, wherein said at least one ALDR is SEQ ID NO:11.33. The microorganism according to any of the preceding items, wherein said at least one ALDR is SEQ ID NO:12.34. The microorganism according to any of the preceding items, wherein said at least one ALDR is SEQ ID NO:13.35. The microorganism according to any of the preceding items, wherein said at least one ALDR is SEQ ID NO:14.36. The microorganism according to any of the preceding items, wherein said at least one ALDR is SEQ ID NO:15.37. The microorganism according to any of the preceding items, wherein said at least one ALDR is SEQ ID NO:16.38. The microorganism according to any of the preceding items, wherein said at least one ALDR is SEQ ID NO:17.39. The microorganism according to any one of the preceding items, wherein said at least one ALDR is fromProvidencia stuartii (Pst-ALDR).40. The microorganism according to any one of the preceding items, wherein said at least one ALDR is has at least80% sequence identity to SEQ ID NO:18, at least 85% sequence identity to SEQ ID NO:18, at least 90% sequence identity to SEQ ID NO:18, at least 95% sequence identity to SEQ ID NO:18, or at least 98% sequence identity to SEQ ID NO:18.41. The microorganism according to any one of the preceding items, wherein the ALDR is SEQ ID NO:18 having 1,2, 3, 4, 5, 6, 7, 8, 9, or 10 substitutions, insertions, additions or deletions and retaining ALDR activity.42. The microorganism according to any one of the preceding items, wherein the ALDR is a Pst-ALDR comprisingSEQ ID NO:18.43. The microorganism according to any one of the preceding items, wherein the ALDR is a Pst-ALDR which isSEQ ID NO:18.44. The microorganism according to any one of the preceding items, wherein the Tpa-CAR comprises SEQ ID NO:5and the ALDR comprises SEQ ID NO:18.45. The microorganism according to any one of the preceding items, wherein the Tpa-CAR is SEQ ID NO:5 andthe ALDR is SEQ ID NO:18.46. The microorganism according to any one of the preceding items, wherein the CAR comprises SEQ ID NO:4and the ALDR comprises SEQ ID NO:18.47. The microorganism according to any one of the preceding items, wherein the CAR is SEQ ID NO:4 and theALDR is SEQ ID NO:18.48. The microorganism according to any one of the preceding items, wherein the CAR comprises any one of SEQID NOs: 1-2 and 20-29and the ALDR comprises SEQ ID NO:18.49. The microorganism according to any one of the preceding items, wherein the CAR is any one of SEQ ID NOs:1-2 and 20-29 and the ALDR is SEQ ID NO:18.50. The microorganism according to any one of the preceding items, wherein the TE comprises SEQ ID NO:6, theCAR comprises any one of SEQ ID NOs:1, 2, 4, 5, 20-29 and the ALDR comprises SEQ ID NO:18.51. The microorganism according to any one of the preceding items, wherein the TE is SEQ ID NO:6, the CAR isany one of SEQ ID NOs: 1, 2, 4, 5, 20-29 and the ALDR is SEQ ID NO:18.52. The microorganism according to any one of the preceding items, wherein the TE comprises SEQ ID NO:19, theCAR comprises any one of SEQ ID NOs: 1, 2, 4, 5, 20-29 and the ALDR comprises SEQ ID NO:18.53. The microorganism according to any one of the preceding items, wherein the TE is SEQ ID NO:19, the CAR isany one of SEQ ID NOs: 1, 2, 4, 5, 20-29 and the ALDR is SEQ ID NO:18.54. The microorganism according to any one of the preceding items, wherein the hydroxyl group is in the primary(C1) position of said at least one C6-C26 free fatty alcohol.55. The microorganism according to any one of the preceding items, wherein said at least one C6-C26 free fattyalcohol is a C6, C8, C10, C12, C13, C14, C15, C16, C17 or C18 free fatty alcohol.56. The microorganism according to any one of the preceding items, wherein said at least one C6-C26 free fattyalcohol is an unsaturated free fatty alcohol.57. The microorganism according to item 56, wherein said unsaturated free fatty alcohol is C10:1, C12:1, C14:1,C16:1 or C18:1.58. The microorganism according to item 56 or 57, wherein said unsaturated free fatty alcohol is unsaturated atthe omega-7 position.59. The microorganism according to item 56, wherein said unsaturated free fatty alcohol comprises a cis doublebond.60. The microorganism according to any one of items 1 to 55, wherein said free fatty alcohol is a saturated freefatty alcohol.61. The microorganism according to any one of the preceding items, wherein said at least one C6-C26 free fattyalcohol or a mixture thereof comprises at least one C12, C14 or C16 free fatty alcohol or a mixture thereof.62. The microorganism according to any one of the preceding items, wherein said at least one C12, C14 or C16free fatty alcohol is a C12 free fatty alcohol.63. The microorganism according to item 62, wherein said at least one C12, C14 or C16 free fatty alcohol comprisesa saturated C12 free fatty alcohol.64. The microorganism according to item 62 or 63, wherein said at least one C12 free fatty alcohol comprises asaturated, unbranched C12 free fatty alcohol.65. The microorganism according to any one of the items 62 to 64, wherein said at least one C12 free fatty alcoholcomprises 1-dodecanol (lauryl alcohol).66. The microorganism according to any one of the items 62 to 65, wherein said at least one C12 free fatty alcoholis 1-dodecanol (lauryl alcohol).67. The microorganism according to any one of the items 61 to 63, wherein said at least one C12, C14 or C16free fatty alcohol comprises a C14 free fatty alcohol.68. The microorganism according to item 67, wherein said at least one C14 free fatty alcohol comprises a saturatedC14 free fatty alcohol.69. The microorganism according to item 67 or 68, wherein said at least one C14 free fatty alcohol comprises asaturated, unbranched C14 free fatty alcohol.70. The microorganism according to any one of the items 67 to 69, wherein said at least one C14 free fatty alcoholcomprises 1-tetradecanol (myristyl alcohol).71. The microorganism according to any one of the items 67 to 70, wherein said at least one C14 free fatty alcoholis 1-tetradecanol ( myristyl alcohol).72. The microorganism according to any one of the preceding items, which is a bacterium.73. The microorganism according to item 72, wherein the bacterium is selected from the group consisting ofEscherichia, Bacillus, Enterobacter Azotobacter, Erwinia, Pseudomonas, Klebsiella, Proteus, Salmonella, Serratia,Shigella, Rhizobia, Vitreoscilla and Paracoccus, Methylobacillus, Methylobacterium, Methylococcus, Methylophilus,Methylibium, Hyphomicrobium, Methylocella, Methylocapsa, and Methylocystis.74. The microorganism according to any one of items 1 to 71, which is a yeast.75. The microorganism according to item 74, wherein the yeast selected from the group consisting of Pichiapastoris, Hansenula polymorpha, Saccharomyces cerevisiae, Kluyveromyces lactis, Schwanniomyces occidentis,Schizosaccharomyces pombe, Trichoderma reesei and Yarrowia lipolytica.76. The microorganism according to any one of the preceding items, which does not express exopolysaccharides.77. The microorganism according to any of the preceding items, which has at least one EPS gene clusterinactivated.78. The microorganism according to any of the preceding items, which has both EPS gene clusters inactivated.79. The microorganism according to item 77 or 78, wherein said at least one EPS gene cluster or said both EPSgene clusters are entirely or partly deleted (absent).80. The microorganism according to any one of the preceding items, which has a decreased activity ofpolyphosphate kinase (PPK), inactivated PPK or deleted PPK gene.81. The microorganism according to any one of the preceding items, which has an inactivated PPK or a deletedPPK gene.82. The microorganism according to any one of the preceding items which has a decreased activity of Acyl-homoserine-lactone (AHL) synthase, inactivated AHL synthase or deleted AHL synthase.83. The microorganism according to any one of the preceding items which has an inactivated or deleted AHLsynthase.84. The microorganism according to any one of the items 1 to 73 and 76 to 83, which is selected from the groupconsisting of Methylobacillus, Methylobacterium, Methylococcus, Bacillus methanolicus, Methylophilus, Methylibium,Hyphomicrobium, Methylocella, Methylocapsa, and Methylocystis.85. The microorganism according to item 84 which is a Methylobacillus.86. The microorganism according to items 84 or 85, wherein said microorganism is selected from the groupconsisting of Methylobacillus flagellatus, Methylobacillus glycogenes, Methylobacillus pratensis, Methylobacillusrhizosphaerae, Methylobacillus gramineus, Methylobacillus arboreus, Methylobacillus caricics and Methylobacillusmethilovorans.87. The microorganism according to any one of items 84 to 86, wherein said microorganism is Methylobacillusflagellatus or Methylobacillus glycogenes.88. The microorganism according to any one of items 84 to 87, wherein said microorganism is Methylobacillusflagellatus.89. The microorganism according to any one of items 84 to 87, wherein said microorganism is Methylobacillusglycogenes.90. A method for the manufacture of at least one C6-C26 free fatty alcohol or a mixture thereof comprising growinga microorganism as defined in any one of items 1 to 77 in a suitable medium, and isolation of said C6-C26 free fattyalcohol or a mixture thereof from the medium, such as the spent medium.91. The method according to item 90, wherein the hydroxyl group is in the primary (C1) position of said at leastone C6-C26 free fatty alcohol.92. The method according to item 90 or 91, wherein said at least one C6-C26 free fatty alcohol is a C6, C8, C10,C12, C13, C14, C15, C16, C17 or C18 free fatty alcohol.93. The method according to any one of items 90 to 92, wherein said at least one C6-C26 free fatty alcohol is anunsaturated free fatty alcohol.94. The method according to item 93, wherein said unsaturated free fatty alcohol is C10:1, C12:1, C14:1, C16:1or C18:1.95. The method according to item 93 or 94, wherein said unsaturated free fatty alcohol is unsaturated at theomega-7 position.96. The method according to item 95, wherein said unsaturated free fatty alcohol comprises a cis double bond.97. The method according to any one of items 90 to 92, wherein said free fatty alcohol is a saturated free fattyalcohol.98. The method according to any one of items 90 to 97, wherein said at least one C6-C26 free fatty alcohol or amixture thereof comprises at least one C12, C14 or C16 free fatty alcohol or a mixture thereof.99. The method according to item 98, wherein said C12, C14 or C16 free fatty alcohol or a mixture thereof comprisesa C12 free fatty alcohol.100. The method according to item 98 or 99, wherein said C12 free fatty alcohol comprises dodecanol.101. The method according to item 98 or 99, wherein said C12 free fatty alcohol is dodecanol.102. The method according to item 100 or 101, wherein said C12 free fatty alcohol comprises 1-dodecanol (laurylalcohol).103. The method according to any one of items 100 to 101, wherein said C12 free fatty alcohol is 1-dodecanol (laurylalcohol).104. The method according to item 98, wherein said C12, C14 or C16 free fatty alcohol or a mixture thereof comprisesa C14 fatty alcohol.105. The method according to item 98 or 104, wherein said C14 free fatty alcohol is 1-tetradecanol (or commonlymyristyl alcohol).106. Free fatty alcohol composition obtained by the method as defined in any one of items 90 to 105.107. Use of a microorganism as defined in any one of items 1 to 89 for the manufacture of a C6-C26 free fatty alcoholor a mixture thereof.108. The use according to item 107, which is for the manufacture of a C12, C14 or C16 free fatty alcohol or a mixturethereof.109. The use according to item 107, wherein said C12, C14 or C16 free fatty alcohol or mixture thereof comprises aC12 free fatty alcohol.110. The use according to any one of items 108 to 109, wherein said C12 free fatty alcohol is dodecanol.111. The use according to any one of the items 108 to 110, wherein said C12 free fatty alcohol is 1-dodecanol.112. The use according to item 108, wherein said C12, C14 or C16 free fatty alcohol or mixture thereof comprises aC14 fatty alcohol.113. The use according to item 108 or 112, wherein said C14 free fatty alcohol is tetradecanol.114. The use according to any one of the items 108, 112 and 113, wherein said C14 free fatty alcohol is 1-tetradecanol (myristyl alcohol). Description of the figuresFigure 1. Schematic pathway representation of fatty alcohol synthesis from methanol and the enzymes involved.Figure 2. Titers of C12, C14 and C16 fatty alcohols produced from methanol heterologously expressing Umbellulariacalifornica thioesterase (Uca-TE), carboxylic acid reductase (CAR) and YjgB_Eco aldehyde reductase (YjgB_Eco-ALDR) in M. flagellatus ABBAg_2.Figure 3. Titers of C12, C14 and C16 fatty acids produced from methanol heterologously expressing Umbellulariacalifornica thioesterase (Uca-TE), carboxylic acid reductase (CAR) and YjgB_Eco aldehyde reductase (YjgB_Eco-ALDR) in M. flagellatus ABBAg_2.Figure 4. Titers of C12, C14 and C16 fatty alcohols produced from methanol heterologously expressing Umbellulariacalifornica thioesterase (Uca-TE), carboxylic acid reductase (CAR) and different heterologous aldehyde reductases,demonstrating that a novel aldehyde reductase can result in highest titers of C12 and C14 fatty alcohols from methanol so far. Figure 5. Titers of C12, C14 and C16 fatty acids produced from methanol heterologously expressing Umbellulariacalifornica thioesterase (Uca-TE), carboxylic acid reductase (CAR) and different heterologous aldehyde reductases,demonstrating that a novel aldehyde reductase which produces the highest titers of C12 and C14 fatty alcohols from methanol so far also achieves ~90 % conversion of fatty acids into fatty alcohols. Description Unless specifically defined herein, all technical and scientific terms used have the same meaning as commonly understood by a skilled artisan in the fields of biochemistry, genetics, and molecular biology. All methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, with suitable methods and materials being described herein. All publications, patent applications,patents, and other references mentioned herein are incorporated by reference in their entirety. In case of conflict, thepresent specification, including definitions, will prevail. Further, the materials, methods, and examples are illustrative only and are not intended to be limiting, unless otherwise specified. The practice of the present invention will employ, unless otherwise indicated, conventional techniques of cell biology, cell culture, molecular biology, transgenic biology, microbiology, fermentation technology, recombinant DNA, and food science, which are within the skill of the art. Such techniques are explained fully in the literature. A significant portion of all saturated, unbranched C12 fatty acids and C14 fatty acids in the global market are convertedinto C12 or C14 fatty alcohols, which are primarily used in surfactants. Currently, most C12 and C14 fatty alcoholsused in the industry are produced through chemical conversion of C12 or C14 fatty acids originating from palm kerneloil. Producing alcohols instead of acids directly would remove the need for a conversion step, improving the economics of the product.Microbial production of C12 fatty alcohols or C14 fatty alcohols from methanol would have a favourable environmentalimpact by replacing harmful oil palm farming. The present invention describes methylotroph bacteria comprising aparticular combination of heterologous enzymes that facilitate a surprising effect on production of C12 free fattyalcohols or C14 free fatty alcohols from methanol. Very many enzymes which appear suitable have been found not togive rise to C12 free fatty alcohols production. Expressing a thioesterase from Umbellularia californica (Uca-TE) in amethylotrophic bacterium leads to the secretion of low amounts of C12 free fatty acids. The Uca-TE enzyme has beendescribed before in the literature to preferentially cleave C12 fatty acids from ACP, compared to other lengths, so thisresult was to be expected. Surprisingly, when the Uca-TE enzyme was expressed in the methylotrophic bacterial hostin combination with an aldehyde reductase and either a CAR from Tsukamurella paurometabola (Tpa-CAR) or a CARfrom Mycobacterium tuberculosis (Mtu-CAR) then significantly increased C12 free fatty alcohol production.In a first aspect the present invention provides a microorganism capable of producing at least one C6-C26 free fattyalcohol or a mixture thereof from methanol, said microorganism comprising:at least one gene enabling the expression of a thioesterase (TE),at least one gene enabling the expression of at least one carboxylic acid reductase (CAR) andat least one gene enabling the expression of an aldehyde reductase (ALDR). It is understood that the term “at least one gene enabling the expression of” means genes that include a nucleotide sequence that encodes the respective enzyme but may additionally comprise regulatory sequences that facilitate the expression of the coding sequence in the host organism. A “gene enabling the expression of” includes thus a gene that comprise a nucleotide sequence that encodes the respective enzyme and can be expressed by the microorganism. In some embodiments said gene may be a nucleotide sequence that encodes the respective enzyme and can be expressed by the microorganism. The microorganism may be a recombinant microorganism in that it is genetically engineered to comprise and express a gene that it does not naturally comprise and expresses. In various embodiments of this aspect, at least one, preferably two or all three, of the at least one gene enabling the expression of a thioesterase (TE), the at least one gene enabling the expression of at least one carboxylic acidreductase (CAR), and the at least one gene enabling the expression of an aldehyde reductase (ALDR) is aheterologous gene. “Heterologous”, as used in this context, means that said gene does not naturally occur in the respective organism and may, for example, originate from a different species than the host organism or may be artificially generated or modified to differ from the genes naturally occurring in said organism. These heterologous genes are then heterologously expressed in the microorganisms of the invention. In various embodiments, the expression of both genes provides for a higher production of at least one C6-C26 freefatty alcohol or a mixture thereof, in particular C12, C14 and / or C16 fatty alcohol, more preferably C12 fatty alcohol,from methanol relative to the same microorganism that expresses none, only one or only two of these genes. Theproduction yield is preferably at least 5, 10, 15, 20, 25 or 30 % higher than the production achieved relative to the same microorganism that expresses none, one or two (but not all three) of these genes (in particular the reference that provides for the highest production, typically the microorganism only expressing the TE and the ALDR but not the CAR) under identical production conditions. In various embodiments, the invention thus refers to a microorganism capable of producing at least one C6-C26 free fatty alcohol or a mixture thereof from methanol, in particular C12, C14 and / orC16 fatty alcohol, more preferably C12 fatty alcohol, said microorganism comprising at least one gene enabling theexpression of a thioesterase (TE) and at least one gene enabling the expression of at least one carboxylic acidreductase (CAR) and at least one gene enabling the expression of an aldehyde reductase (ALDR), wherein saidmicroorganism provides for a higher production yield, preferably an at least 10 % higher production yield, relative tothe same microorganism that lacks one, two or all three of the TE, CAR and ALDR genes, in particular to amicroorganism that lacks the CAR gene. The terms “C6-C26“, “C12 free fatty alcohol” and “C14 free fatty alcohol” as used herein are intended to mean a fatty alcohol having the respective number of carbons and being in a free state, i.e. not chemically bound in oils and fats. Recombinant enzymes All recombinant enzymes referred to herein may be derived from a naturally occurring nucleotide sequence which has been codon-optimized for expression in the microorganism of choice. The respective enzymes are thus generally defined by reference to their amino acid sequence. Unless otherwise stated, percent sequence identity (% sequence identity) between two sequences is determined from a pairwise sequence alignment created by using program “Needle” (as implemented in the European Molecular Biology Open Software Suite (EMBOSS), version 6.3.1.2 or later (Trends in Genetics (2000) 16 (6), p.276-277) with applying a gap open penalty of 10, a gap extension penalty of 0.5, the matrix EBLOSUM62 (which is the “Needle” EMBOSS version of matrix BLOSUM62) for protein sequences, and the matrix EDNAFULL (which is the “Needle”EMBOSS version of matrix DNAFULL) for nucleotide sequences, by the following calculation: % sequence identity =(Identical Residues x 100) / (Length of Alignment - Total Number of Gaps in Alignment), which is also reported as“Longest_Identity” in the output of “Needle” EMBOSS when parameter “-nobrief” is applied. Program “Needle”EMBOSS has implemented the algorithm of Needleman & Wunsch (J. Mol. Biol. (1979) 48, p.443-453) for aligning oftwo sequences.The three enzymes that may be encoded by recombinant genes in the microorganisms of the present invention are athioesterase such as from Umbellularia californica (Uca-TE), a carboxylic acid reductase (CAR) such as from eitherTsukamurella paurometabola (Tpa-CAR) or from Mycobacterium tuberculosis, and an aldehyde reductase (ALDR).In an embodiment the microorganism comprises at least one gene enabling the expression of a TE which is fromUmbellularia californica (Uca-TE).In various embodiments, the (at least one) TE has at least 80%, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94,95, 96, 97, 98, 99 or 100 % sequence identity to SEQ ID NO:6, such as at least 85% sequence identity to SEQ IDNO:6, at least 90% sequence identity to SEQ ID NO:6, at least 95% sequence identity to SEQ ID NO:6, or at least 98%sequence identity to SEQ ID NO:6. It is understood that in an enumeration such as “at least 80, 81…”, the “at least”refers to all listed values.In various embodiments, the TE has at least 50% thioesterase activity as compared to the activity of SEQ ID NO:6,preferably at least 55, 60, 65, 70, 75, 80, 85, 90, 95 or 100 % thioesterase activity as compared to the activity of SEQID NO:6. Said activity can be determined in a suitable enzymatic activity assay, which are routinely known to thoseskilled in the art.The above definitions may be combined such that the TE has at least 80%, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91,92, 93, 94, 95, 96, 97, 98, or 99 % sequence identity to SEQ ID NO:6 and at least 50, 55, 60, 65, 70, 75, 80, 85, 90,95 or 100 % thioesterase activity as compared to the activity of SEQ ID NO:6.In various embodiments, the TE is a truncated version of SEQ ID NO:6, for example having at least 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, or 99 % sequence identity to the corresponding sequence of SEQ ID NO:6, for example at least 90% sequence identity to the corresponding sequence of SEQ ID NO:6, at least 95% sequence identity to the corresponding sequence of SEQ ID NO:6. If the N-terminus is truncated, the amino acid sequence may additionally comprise an N-terminal M residue. In suchtruncated versions, the enzymatic activity may be at least 50, 55, 60, 65, 70, 75, 80, 85, 90, 95 or 100 % thioesteraseactivity as compared to the activity of SEQ ID NO:6.In various embodiments, the TE comprises or is SEQ ID NO:19, which is a truncated 287 amino acid long C-terminalfragment of SEQ ID NO:6 (aa 97-382) that comprises an N-terminal methionine residue and has the following amino acid sequence: MDDHFGLHGLVFRRTFAIRSYEVGPDRSTSILAVMNHMQEATLNHAKSVGILGDGFGTTLEMSKRDLMWVVRRTHV AVERYPTWGDTVEVECWIGASGNNGMRRDFLVRDCKTGEILTRCTSLSVLMNTRTRRLSTIPDEVRGEIGPAFIDNVA VKDDEIKKLQKLNDSTADYIQGGLTPRWNDLDVNQHVNNLKYVAWVFETVPDSIFESHHISSFTLEYRRECTRDSVLR SLTTVSGGSSEAGLVCDHLLQLEGGSEVLRARTEWRPKLTDSFRGISVIPAEPRVIn various embodiments, the TE is SEQ ID NO:6 having 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 substitutions, insertions, additionsor deletions and retaining thioesterase activity. The activity may be as defined above, i.e. at least 50, 55, 60, 65, 70,75, 80, 85, 90, 95 or 100 % thioesterase activity as compared to the activity of SEQ ID NO:6.In various embodiments the TE comprises, consists essentially of, or consists of SEQ ID NO:6. In variousembodiments, the TE is SEQ ID NO:6. “Consists essentially of”, as used in relation to a given sequence, means thatthe respective enzyme consists of more than 50%, preferably more than 60, 70, 80, or 90 % of the given sequence, i.e. may comprise <50%, <40%, <30%, <20%, or <10% of additional amino acids in addition to the recited sequence,typically in form of flanking sequences that are extending the N- and / or C-terminus of the given sequence.In various embodiments, the at least one CAR comprises a CAR from Tsukamurella paurometabola (Tpa-CAR) or fromMycobacterium tuberculosis (Mtu-CAR).In various embodiments, the CAR is a Tpa-CAR.In various embodiments, the (at least one) CAR is a polypeptide having at least 80, 81, 83, 84, 85, 86, 87, 88, 89, 90,91, 92, 93, 94, 95, 96, 97, 98, 99 or 100% sequence identity to SEQ ID NO:5, for example at least 85% sequence identity to SEQ ID NO:5, at least 90% sequence identity to SEQ ID NO:5, at least 95% sequence identity to SEQ ID NO:5, or at least 98% sequence identity to SEQ ID NO:5.In various embodiments, the CAR has at least 50% activity as compared to the activity of SEQ ID NO:5, preferably atleast 55, 60, 65, 70, 75, 80, 85, 90, 95 or 100 % activity as compared to the activity of SEQ ID NO:5. Said activity canbe determined in a suitable enzymatic activity assay, which are routinely known to those skilled in the art.The above definitions may be combined such that the CAR has at least 80%, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91,92, 93, 94, 95, 96, 97, 98, or 99 % sequence identity to SEQ ID NO:5 and at least 50, 55, 60, 65, 70, 75, 80, 85, 90,95 or 100 % enzymatic activity as compared to the activity of SEQ ID NO:5.In yet another embodiment the CAR is a truncated version of SEQ ID NO:5, for example having at least 85, 86, 87, 88,89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99 % sequence identity to the corresponding sequence of SEQ ID NO:5. If theN-terminus is truncated, the amino acid sequence may additionally comprise an N-terminal M residue. In suchtruncated versions, the enzymatic activity may be at least 50, 55, 60, 65, 70, 75, 80, 85, 90, 95 or 100 % activity ascompared to the activity of SEQ ID NO:5.In various embodiments, the CAR is SEQ ID NO:5 having 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 substitutions, insertions, additionsor deletions and retaining CAR activity. The activity may be as defined above, i.e. at least 50, 55, 60, 65, 70, 75, 80,85, 90, 95 or 100 % activity as compared to the activity of SEQ ID NO:5.In various embodiments the CAR comprises, consists essentially of, or consists of SEQ ID NO:5. In variousembodiments, the CAR is SEQ ID NO:5.In various embodiments, the CAR is a Mtu-CAR.In various embodiments, the CAR is a polypeptide having at least 80, 81, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94,95, 96, 97, 98, 99 or 100% sequence identity to SEQ ID NO:4, for example at least 85% sequence identity to SEQ ID NO:4, at least 90% sequence identity to SEQ ID NO:4, at least 95% sequence identity to SEQ ID NO:4, or at least 98% sequence identity to SEQ ID NO:4.In various embodiments, the CAR has at least 50% activity as compared to the activity of SEQ ID NO:4, preferably atleast 55, 60, 65, 70, 75, 80, 85, 90, 95 or 100 % activity as compared to the activity of SEQ ID NO:4. Said activity canbe determined in a suitable enzymatic activity assay, which are routinely known to those skilled in the art.The above definitions may be combined such that the CAR has at least 80%, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91,92, 93, 94, 95, 96, 97, 98, or 99 % sequence identity to SEQ ID NO:4 and at least 50, 55, 60, 65, 70, 75, 80, 85, 90,95 or 100 % enzymatic activity as compared to the activity of SEQ ID NO:4.In yet another embodiment the CAR is a truncated version of SEQ ID NO:4, for example having at least 85, 86, 87, 88,89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99 % sequence identity to the corresponding sequence of SEQ ID NO:4. If theN-terminus is truncated, the amino acid sequence may additionally comprise an N-terminal M residue. In suchtruncated versions, the enzymatic activity may be at least 50, 55, 60, 65, 70, 75, 80, 85, 90, 95 or 100 % activity ascompared to the activity of SEQ ID NO:4.In various embodiments, the CAR is SEQ ID NO:4 having 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 substitutions, insertions, additionsor deletions and retaining CAR activity. The activity may be as defined above, i.e. at least 50, 55, 60, 65, 70, 75, 80,85, 90, 95 or 100 % activity as compared to the activity of SEQ ID NO:4.In various embodiments the CAR comprises, consists essentially of, or consists of SEQ ID NO:4. In variousembodiments, the CAR is SEQ ID NO:4.In various embodiments, the CAR is a polypeptide having at least 80, 81, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94,95, 96, 97, 98, 99 or 100% sequence identity to any one of SEQ ID NOs: 1, 2 and 20-29.In various embodiments, the CAR has at least 50% activity as compared to the activity of any one of SEQ ID NOs: 1,2 and 20-29, preferably at least 55, 60, 65, 70, 75, 80, 85, 90, 95 or 100 % activity as compared to the activity of anyone of SEQ ID NOs:1, 2 and 20-29. Said activity can be determined in a suitable enzymatic activity assay, which areroutinely known to those skilled in the art.The above definitions may be combined such that the CAR has at least 80%, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91,92, 93, 94, 95, 96, 97, 98, or 99 % sequence identity to any one of SEQ ID NOs:1, 2 and 20-29and at least 50, 55, 60,65, 70, 75, 80, 85, 90, 95 or 100 % enzymatic activity as compared to the activity of any one of SEQ ID NO:1, 2 and20-29.In yet another embodiment the CAR is a truncated version of any one of SEQ ID NOs:1, 2 and 20-29, for examplehaving at least 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99 % sequence identity to the correspondingsequence of any one of SEQ ID NOs:1, 2 and 20-29. If the N-terminus is truncated, the amino acid sequence mayadditionally comprise an N-terminal M residue. In such truncated versions, the enzymatic activity may be at least 50, 55, 60, 65, 70, 75, 80, 85, 90, 95 or 100 % activity as compared to the activity of any one of SEQ ID NOs:1, 2 and 20- 29.In various embodiments, the CAR is any one of SEQ ID NOs:1, 2 and 20-29 having 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10substitutions, insertions, additions or deletions and retaining CAR activity. The activity may be as defined above, i.e.at least 50, 55, 60, 65, 70, 75, 80, 85, 90, 95 or 100 % activity as compared to the activity of any one of SEQ ID NOs:1,2 and 20-29.In various embodiments the CAR comprises, consists essentially of, or consists of any one of SEQ ID NOs:1, 2 and20-29. In various embodiments, the CAR is any one of SEQ ID NOs:1, 2 and 20-29. In various embodiments the CARcomprises, consists essentially of, or consists of SEQ ID NO:34. In various embodiments, the CAR is of SEQ ID NO:34.In various embodiments, the (at least one) ALDR is a polypeptide having at least 80, 81, 83, 84, 85, 86, 87, 88, 89, 90,91, 92, 93, 94, 95, 96, 97, 98, 99 or 100% sequence identity to any one of SEQ ID NOs:7-18.In various embodiments, the ALDR has at least 50% activity as compared to the activity of any one of SEQ ID NOs:7-18, preferably at least 55, 60, 65, 70, 75, 80, 85, 90, 95 or 100 % activity as compared to the activity of any one of SEQID NOs:7-18. Said activity can be determined in a suitable enzymatic activity assay, which are routinely known to thoseskilled in the art.The above definitions may be combined such that the ALDR has at least 80%, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90,91, 92, 93, 94, 95, 96, 97, 98, or 99 % sequence identity to any one of SEQ ID NOs:7-18 and at least 50, 55, 60, 65,70, 75, 80, 85, 90, 95 or 100 % enzymatic activity as compared to the activity of any one of SEQ ID NO:7-18.In yet another embodiment the ALDR is a truncated version of any one of SEQ ID NOs:7-18, for example having atleast 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99 % sequence identity to the corresponding sequenceof any one of SEQ ID NOs:7-18. If the N-terminus is truncated, the amino acid sequence may additionally comprise anN-terminal M residue. In such truncated versions, the enzymatic activity may be at least 50, 55, 60, 65, 70, 75, 80, 85,90, 95 or 100 % activity as compared to the activity of any one of SEQ ID NOs:7-18.In various embodiments, the ALDR is any one of SEQ ID NOs:7-18 having 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 substitutions,insertions, additions or deletions and retaining ALDR activity. The activity may be as defined above, i.e. at least 50, 55,60, 65, 70, 75, 80, 85, 90, 95 or 100 % activity as compared to the activity of any one of SEQ ID NOs:7-18.In various embodiments the ALDR comprises, consists essentially of, or consists of any one of SEQ ID NOs:7-18.In various embodiments, the at least one ALDR is selected from the group consisting of SEQ ID NO:7 to SEQ IDNO:18.In various embodiments, the at least one ALDR is SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17 or SEQ ID NO:18.In various embodiments, the at least one ALDR is SEQ ID NO:7. In various embodiments, the at least one ALDR isSEQ ID NO:8. In various embodiments, the at least one ALDR is SEQ ID NO:9. In various embodiments, the at leastone ALDR is SEQ ID NO:10. In various embodiments, the at least one ALDR is SEQ ID NO:11. In variousembodiments, the at least one ALDR is SEQ ID NO:12. In various embodiments, the at least one ALDR is SEQ IDNO:13. In various embodiments, the at least one ALDR is SEQ ID NO:14. In various embodiments, the at least oneALDR is SEQ ID NO:15. In various embodiments, the at least one ALDR is SEQ ID NO:16. In various embodiments,the at least one ALDR is SEQ ID NO:17.In various embodiments, the ALDR is from Providencia stuartii (Pst-ALDR).In various embodiments, the ALDR is has at least 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97,98, 99, or 100% sequence identity to SEQ ID NO:18, for example at least 85% sequence identity to SEQ ID NO:18, at least 90% sequence identity to SEQ ID NO:18, at least 95% sequence identity to SEQ ID NO:18, or at least 98% sequence identity to SEQ ID NO:18.In various embodiments, the ALDR is SEQ ID NO:18 having 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 substitutions, insertions,additions or deletions and retaining ALDR activity.In various embodiments, the ALDR is a Pst-ALDR comprising, consisting essentially of or consisting of SEQ ID NO:18.In various embodiments, the ALDR is a Pst-ALDR which is SEQ ID NO:18.In various embodiments, the CAR comprises SEQ ID NO:2 and the ALDR comprises SEQ ID NO:18.In various embodiments, the CAR is SEQ ID NO:2 and the ALDR is SEQ ID NO:18.In various embodiments, the CAR comprises or is SEQ ID NO:1 and the ALDR comprises or is SEQ ID NO:18.In various embodiments, the CAR comprises or is SEQ ID NO:4 and the ALDR comprises or is SEQ ID NO:18.In various embodiments, the CAR comprises or is SEQ ID NO:5 and the ALDR comprises or is SEQ ID NO:18.In various embodiments, the CAR comprises or is SEQ ID NO:20 and the ALDR comprises or is SEQ ID NO:18.In various embodiments, the CAR comprises or is SEQ ID NO:21 and the ALDR comprises or is SEQ ID NO:18.In various embodiments, the CAR comprises or is SEQ ID NO:22 and the ALDR comprises or is SEQ ID NO:18.In various embodiments, the CAR comprises or is SEQ ID NO:23 and the ALDR comprises or is SEQ ID NO:18.In various embodiments, the CAR comprises or is SEQ ID NO:24 and the ALDR comprises or is SEQ ID NO:18.In various embodiments, the CAR comprises or is SEQ ID NO:25 and the ALDR comprises or is SEQ ID NO:18.In various embodiments, the CAR comprises or is SEQ ID NO:26 and the ALDR comprises or is SEQ ID NO:18.In various embodiments, the CAR comprises or is SEQ ID NO:27 and the ALDR comprises or is SEQ ID NO:18.In various embodiments, the CAR comprises or is SEQ ID NO:28 and the ALDR comprises or is SEQ ID NO:18.In various embodiments, the CAR comprises or is SEQ ID NO:29 and the ALDR comprises or is SEQ ID NO:18.In various embodiments, the TE comprises or is SEQ ID NO:6 and the ALDR comprises or is SEQ ID NO:18.In various embodiments, the CAR comprises or is SEQ ID NO:1 and the TE comprises or is SEQ ID NO:6.In various embodiments, the CAR comprises or is SEQ ID NO:2 and the TE comprises or is SEQ ID NO:6.In various embodiments, the CAR comprises or is SEQ ID NO:4 and the TE comprises or is SEQ ID NO:6.In various embodiments, the CAR comprises or is SEQ ID NO:5 and the TE comprises or is SEQ ID NO:6.In various embodiments, the CAR comprises or is SEQ ID NO:20 and the TE comprises or is SEQ ID NO:6.In various embodiments, the CAR comprises or is SEQ ID NO:21 and the TE comprises or is SEQ ID NO:6.In various embodiments, the CAR comprises or is SEQ ID NO:22 and the TE comprises or is SEQ ID NO:6.In various embodiments, the CAR comprises or is SEQ ID NO:23 and the TE comprises or is SEQ ID NO:6.In various embodiments, the CAR comprises or is SEQ ID NO:24 and the TE comprises or is SEQ ID NO:6.In various embodiments, the CAR comprises or is SEQ ID NO:25 and the TE comprises or is SEQ ID NO:6.In various embodiments, the CAR comprises or is SEQ ID NO:26 and the TE comprises or is SEQ ID NO:6.In various embodiments, the CAR comprises or is SEQ ID NO:27 and the TE comprises or is SEQ ID NO:6.In various embodiments, the CAR comprises or is SEQ ID NO:28 and the TE comprises or is SEQ ID NO:6.In various embodiments, the CAR comprises or is SEQ ID NO:29 and the TE comprises or is SEQ ID NO:6.In various embodiments, the following combinations of enzymes are encompassed as specific embodiments of the present invention, where “variants” refers to the above enzymes that have at least 80, 81, 82, 83, 84, 85, 86, 87, 88,89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99 % sequence identity to the reference sequence and optionally retain theactivity of the reference sequence to at least 50% or more as defined herein above. Embodiment TE CAR ALDR1 SEQ ID NO:6 or variants SEQ ID NO:1 or variants SEQ ID NO:7 or variants thereof thereof thereof 2 SEQ ID NO:6 or variants SEQ ID NO:1 or variants SEQ ID NO:8 or variants thereof thereof thereof 3 SEQ ID NO:6 or variants SEQ ID NO:1 or variants SEQ ID NO:9 or variants thereof thereof thereof 4 SEQ ID NO:6 or variants SEQ ID NO:1 or variants SEQ ID NO:10 or variants thereof thereof thereof 5 SEQ ID NO:6 or variants SEQ ID NO:1 or variants SEQ ID NO:11 or variants thereof thereof thereof 6 SEQ ID NO:6 or variants SEQ ID NO:1 or variants SEQ ID NO:12 or variants thereof thereof thereof 7 SEQ ID NO:6 or variants SEQ ID NO:1 or variants SEQ ID NO:13 or variants thereof thereof thereof 8 SEQ ID NO:6 or variants SEQ ID NO:1 or variants SEQ ID NO:14 or variants thereof thereof thereof 9 SEQ ID NO:6 or variants SEQ ID NO:1 or variants SEQ ID NO:15 or variants thereof thereof thereof 10 SEQ ID NO:6 or variants SEQ ID NO:1 or variants SEQ ID NO:16 or variants thereof thereof thereof 11 SEQ ID NO:6 or variants SEQ ID NO:1 or variants SEQ ID NO:17 or variants thereof thereof thereof 12 SEQ ID NO:6 or variants SEQ ID NO:1 or variants SEQ ID NO:18 or variants thereof thereof thereof 13 SEQ ID NO:6 or variants SEQ ID NO:2 or variants SEQ ID NO:7 or variants thereof thereof thereof 14 SEQ ID NO:6 or variants SEQ ID NO:2 or variants SEQ ID NO:8 or variants thereof thereof thereof 15 SEQ ID NO:6 or variants SEQ ID NO:2 or variants SEQ ID NO:9 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:2 or variants SEQ ID NO:10 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:2 or variants SEQ ID NO:11 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:2 or variants SEQ ID NO:12 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:2 or variants SEQ ID NO:13 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:2 or variants SEQ ID NO:14 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:2 or variants SEQ ID NO:15 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:2 or variants SEQ ID NO:16 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:2 or variants SEQ ID NO:17 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:2 or variants SEQ ID NO:18 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:4 or variants SEQ ID NO:7 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:4 or variants SEQ ID NO:8 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:4 or variants SEQ ID NO:9 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:4 or variants SEQ ID NO:10 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:4 or variants SEQ ID NO:11 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:4 or variants SEQ ID NO:12 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:4 or variants SEQ ID NO:13 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:4 or variants SEQ ID NO:14 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:4 or variants SEQ ID NO:15 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:4 or variants SEQ ID NO:16 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:4 or variants SEQ ID NO:17 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:4 or variants SEQ ID NO:18 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:5 or variants SEQ ID NO:7 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:5 or variants SEQ ID NO:8 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:5 or variants SEQ ID NO:9 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:5 or variants SEQ ID NO:10 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:5 or variants SEQ ID NO:11 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:5 or variants SEQ ID NO:12 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:5 or variants SEQ ID NO:13 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:5 or variants SEQ ID NO:14 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:5 or variants SEQ ID NO:15 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:5 or variants SEQ ID NO:16 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:5 or variants SEQ ID NO:17 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:5 or variants SEQ ID NO:18 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:20 or variants SEQ ID NO:7 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:20 or variants SEQ ID NO:8 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:20 or variants SEQ ID NO:9 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:20 or variants SEQ ID NO:10 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:20 or variants SEQ ID NO:11 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:20 or variants SEQ ID NO:12 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:20 or variants SEQ ID NO:13 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:20 or variants SEQ ID NO:14 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:20 or variants SEQ ID NO:15 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:20 or variants SEQ ID NO:16 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:20 or variants SEQ ID NO:17 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:20 or variants SEQ ID NO:18 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:21 or variants SEQ ID NO:7 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:21 or variants SEQ ID NO:8 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:21 or variants SEQ ID NO:9 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:21 or variants SEQ ID NO:10 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:21 or variants SEQ ID NO:11 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:21 or variants SEQ ID NO:12 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:21 or variants SEQ ID NO:13 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:21 or variants SEQ ID NO:14 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:21 or variants SEQ ID NO:15 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:21 or variants SEQ ID NO:16 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:21 or variants SEQ ID NO:17 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:21 or variants SEQ ID NO:18 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:22 or variants SEQ ID NO:7 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:22 or variants SEQ ID NO:8 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:22 or variants SEQ ID NO:9 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:22 or variants SEQ ID NO:10 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:22 or variants SEQ ID NO:11 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:22 or variants SEQ ID NO:12 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:22 or variants SEQ ID NO:13 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:22 or variants SEQ ID NO:14 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:22 or variants SEQ ID NO:15 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:22 or variants SEQ ID NO:16 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:22 or variants SEQ ID NO:17 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:22 or variants SEQ ID NO:18 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:23 or variants SEQ ID NO:7 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:23 or variants SEQ ID NO:8 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:23 or variants SEQ ID NO:9 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:23 or variants SEQ ID NO:10 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:23 or variants SEQ ID NO:11 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:23 or variants SEQ ID NO:12 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:23 or variants SEQ ID NO:13 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:23 or variants SEQ ID NO:14 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:23 or variants SEQ ID NO:15 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:23 or variants SEQ ID NO:16 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:23 or variants SEQ ID NO:17 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:23 or variants SEQ ID NO:18 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:24 or variants SEQ ID NO:7 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:24 or variants SEQ ID NO:8 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:24 or variants SEQ ID NO:9 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:24 or variants SEQ ID NO:10 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:24 or variants SEQ ID NO:11 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:24 or variants SEQ ID NO:12 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:24 or variants SEQ ID NO:13 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:24 or variants SEQ ID NO:14 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:24 or variants SEQ ID NO:15 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:24 or variants SEQ ID NO:16 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:24 or variants SEQ ID NO:17 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:24 or variants SEQ ID NO:18 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:25 or variants SEQ ID NO:7 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:25 or variants SEQ ID NO:8 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:25 or variants SEQ ID NO:9 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:25 or variants SEQ ID NO:10 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:25 or variants SEQ ID NO:11 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:25 or variants SEQ ID NO:12 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:25 or variants SEQ ID NO:13 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:25 or variants SEQ ID NO:14 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:25 or variants SEQ ID NO:15 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:25 or variants SEQ ID NO:16 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:25 or variants SEQ ID NO:17 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:25 or variants SEQ ID NO:18 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:26 or variants SEQ ID NO:7 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:26 or variants SEQ ID NO:8 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:26 or variants SEQ ID NO:9 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:26 or variants SEQ ID NO:10 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:26 or variants SEQ ID NO:11 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:26 or variants SEQ ID NO:12 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:26 or variants SEQ ID NO:13 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:26 or variants SEQ ID NO:14 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:26 or variants SEQ ID NO:15 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:26 or variants SEQ ID NO:16 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:26 or variants SEQ ID NO:17 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:26 or variants SEQ ID NO:18 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:27 or variants SEQ ID NO:7 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:27 or variants SEQ ID NO:8 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:27 or variants SEQ ID NO:9 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:27 or variants SEQ ID NO:10 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:27 or variants SEQ ID NO:11 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:27 or variants SEQ ID NO:12 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:27 or variants SEQ ID NO:13 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:27 or variants SEQ ID NO:14 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:27 or variants SEQ ID NO:15 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:27 or variants SEQ ID NO:16 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:27 or variants SEQ ID NO:17 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:27 or variants SEQ ID NO:18 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:28 or variants SEQ ID NO:7 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:28 or variants SEQ ID NO:8 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:28 or variants SEQ ID NO:9 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:28 or variants SEQ ID NO:10 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:28 or variants SEQ ID NO:11 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:28 or variants SEQ ID NO:12 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:28 or variants SEQ ID NO:13 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:28 or variants SEQ ID NO:14 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:28 or variants SEQ ID NO:15 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:28 or variants SEQ ID NO:16 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:28 or variants SEQ ID NO:17 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:28 or variants SEQ ID NO:18 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:29 or variants SEQ ID NO:7 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:29 or variants SEQ ID NO:8 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:29 or variants SEQ ID NO:9 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:29 or variants SEQ ID NO:10 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:29 or variants SEQ ID NO:11 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:29 or variants SEQ ID NO:12 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:29 or variants SEQ ID NO:13 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:29 or variants SEQ ID NO:14 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:29 or variants SEQ ID NO:15 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:29 or variants SEQ ID NO:16 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:29 or variants SEQ ID NO:17 or variants thereof thereof thereof SEQ ID NO:6 or variants SEQ ID NO:29 or variants SEQ ID NO:18 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:1 or variants SEQ ID NO:7 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:1 or variants SEQ ID NO:8 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:1 or variants SEQ ID NO:9 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:1 or variants SEQ ID NO:10 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:1 or variants SEQ ID NO:11 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:1 or variants SEQ ID NO:12 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:1 or variants SEQ ID NO:13 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:1 or variants SEQ ID NO:14 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:1 or variants SEQ ID NO:15 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:1 or variants SEQ ID NO:16 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:1 or variants SEQ ID NO:17 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:1 or variants SEQ ID NO:18 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:2 or variants SEQ ID NO:7 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:2 or variants SEQ ID NO:8 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:2 or variants SEQ ID NO:9 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:2 or variants SEQ ID NO:10 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:2 or variants SEQ ID NO:11 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:2 or variants SEQ ID NO:12 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:2 or variants SEQ ID NO:13 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:2 or variants SEQ ID NO:14 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:2 or variants SEQ ID NO:15 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:2 or variants SEQ ID NO:16 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:2 or variants SEQ ID NO:17 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:2 or variants SEQ ID NO:18 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:4 or variants SEQ ID NO:7 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:4 or variants SEQ ID NO:8 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:4 or variants SEQ ID NO:9 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:4 or variants SEQ ID NO:10 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:4 or variants SEQ ID NO:11 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:4 or variants SEQ ID NO:12 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:4 or variants SEQ ID NO:13 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:4 or variants SEQ ID NO:14 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:4 or variants SEQ ID NO:15 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:4 or variants SEQ ID NO:16 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:4 or variants SEQ ID NO:17 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:4 or variants SEQ ID NO:18 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:5 or variants SEQ ID NO:7 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:5 or variants SEQ ID NO:8 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:5 or variants SEQ ID NO:9 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:5 or variants SEQ ID NO:10 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:5 or variants SEQ ID NO:11 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:5 or variants SEQ ID NO:12 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:5 or variants SEQ ID NO:13 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:5 or variants SEQ ID NO:14 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:5 or variants SEQ ID NO:15 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:5 or variants SEQ ID NO:16 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:5 or variants SEQ ID NO:17 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:5 or variants SEQ ID NO:18 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:20 or variants SEQ ID NO:7 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:20 or variants SEQ ID NO:8 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:20 or variants SEQ ID NO:9 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:20 or variants SEQ ID NO:10 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:20 or variants SEQ ID NO:11 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:20 or variants SEQ ID NO:12 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:20 or variants SEQ ID NO:13 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:20 or variants SEQ ID NO:14 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:20 or variants SEQ ID NO:15 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:20 or variants SEQ ID NO:16 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:20 or variants SEQ ID NO:17 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:20 or variants SEQ ID NO:18 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:21 or variants SEQ ID NO:7 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:21 or variants SEQ ID NO:8 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:21 or variants SEQ ID NO:9 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:21 or variants SEQ ID NO:10 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:21 or variants SEQ ID NO:11 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:21 or variants SEQ ID NO:12 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:21 or variants SEQ ID NO:13 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:21 or variants SEQ ID NO:14 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:21 or variants SEQ ID NO:15 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:21 or variants SEQ ID NO:16 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:21 or variants SEQ ID NO:17 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:21 or variants SEQ ID NO:18 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:22 or variants SEQ ID NO:7 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:22 or variants SEQ ID NO:8 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:22 or variants SEQ ID NO:9 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:22 or variants SEQ ID NO:10 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:22 or variants SEQ ID NO:11 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:22 or variants SEQ ID NO:12 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:22 or variants SEQ ID NO:13 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:22 or variants SEQ ID NO:14 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:22 or variants SEQ ID NO:15 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:22 or variants SEQ ID NO:16 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:22 or variants SEQ ID NO:17 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:22 or variants SEQ ID NO:18 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:23 or variants SEQ ID NO:7 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:23 or variants SEQ ID NO:8 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:23 or variants SEQ ID NO:9 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:23 or variants SEQ ID NO:10 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:23 or variants SEQ ID NO:11 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:23 or variants SEQ ID NO:12 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:23 or variants SEQ ID NO:13 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:23 or variants SEQ ID NO:14 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:23 or variants SEQ ID NO:15 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:23 or variants SEQ ID NO:16 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:23 or variants SEQ ID NO:17 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:23 or variants SEQ ID NO:18 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:24 or variants SEQ ID NO:7 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:24 or variants SEQ ID NO:8 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:24 or variants SEQ ID NO:9 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:24 or variants SEQ ID NO:10 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:24 or variants SEQ ID NO:11 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:24 or variants SEQ ID NO:12 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:24 or variants SEQ ID NO:13 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:24 or variants SEQ ID NO:14 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:24 or variants SEQ ID NO:15 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:24 or variants SEQ ID NO:16 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:24 or variants SEQ ID NO:17 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:24 or variants SEQ ID NO:18 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:25 or variants SEQ ID NO:7 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:25 or variants SEQ ID NO:8 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:25 or variants SEQ ID NO:9 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:25 or variants SEQ ID NO:10 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:25 or variants SEQ ID NO:11 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:25 or variants SEQ ID NO:12 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:25 or variants SEQ ID NO:13 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:25 or variants SEQ ID NO:14 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:25 or variants SEQ ID NO:15 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:25 or variants SEQ ID NO:16 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:25 or variants SEQ ID NO:17 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:25 or variants SEQ ID NO:18 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:26 or variants SEQ ID NO:7 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:26 or variants SEQ ID NO:8 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:26 or variants SEQ ID NO:9 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:26 or variants SEQ ID NO:10 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:26 or variants SEQ ID NO:11 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:26 or variants SEQ ID NO:12 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:26 or variants SEQ ID NO:13 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:26 or variants SEQ ID NO:14 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:26 or variants SEQ ID NO:15 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:26 or variants SEQ ID NO:16 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:26 or variants SEQ ID NO:17 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:26 or variants SEQ ID NO:18 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:27 or variants SEQ ID NO:7 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:27 or variants SEQ ID NO:8 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:27 or variants SEQ ID NO:9 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:27 or variants SEQ ID NO:10 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:27 or variants SEQ ID NO:11 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:27 or variants SEQ ID NO:12 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:27 or variants SEQ ID NO:13 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:27 or variants SEQ ID NO:14 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:27 or variants SEQ ID NO:15 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:27 or variants SEQ ID NO:16 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:27 or variants SEQ ID NO:17 or variants thereof thereof thereof SEQ ID NO:19 or variants SEQ ID NO:27 or variants SEQ ID NO:18 or variants thereof thereof thereof 313 SEQ ID NO:19 or variants SEQ ID NO:28 or variants SEQ ID NO:7 or variants thereof thereof thereof 314 SEQ ID NO:19 or variants SEQ ID NO:28 or variants SEQ ID NO:8 or variants thereof thereof thereof 315 SEQ ID NO:19 or variants SEQ ID NO:28 or variants SEQ ID NO:9 or variants thereof thereof thereof 316 SEQ ID NO:19 or variants SEQ ID NO:28 or variants SEQ ID NO:10 or variants thereof thereof thereof 317 SEQ ID NO:19 or variants SEQ ID NO:28 or variants SEQ ID NO:11 or variants thereof thereof thereof 318 SEQ ID NO:19 or variants SEQ ID NO:28 or variants SEQ ID NO:12 or variants thereof thereof thereof 319 SEQ ID NO:19 or variants SEQ ID NO:28 or variants SEQ ID NO:13 or variants thereof thereof thereof 320 SEQ ID NO:19 or variants SEQ ID NO:28 or variants SEQ ID NO:14 or variants thereof thereof thereof 321 SEQ ID NO:19 or variants SEQ ID NO:28 or variants SEQ ID NO:15 or variants thereof thereof thereof 322 SEQ ID NO:19 or variants SEQ ID NO:28 or variants SEQ ID NO:16 or variants thereof thereof thereof 323 SEQ ID NO:19 or variants SEQ ID NO:28 or variants SEQ ID NO:17 or variants thereof thereof thereof 324 SEQ ID NO:19 or variants SEQ ID NO:28 or variants SEQ ID NO:18 or variants thereof thereof thereof 325 SEQ ID NO:19 or variants SEQ ID NO:29 or variants SEQ ID NO:7 or variants thereof thereof thereof 326 SEQ ID NO:19 or variants SEQ ID NO:29 or variants SEQ ID NO:8 or variants thereof thereof thereof 327 SEQ ID NO:19 or variants SEQ ID NO:29 or variants SEQ ID NO:9 or variants thereof thereof thereof 328 SEQ ID NO:19 or variants SEQ ID NO:29 or variants SEQ ID NO:10 or variants thereof thereof thereof 329 SEQ ID NO:19 or variants SEQ ID NO:29 or variants SEQ ID NO:11 or variants thereof thereof thereof 330 SEQ ID NO:19 or variants SEQ ID NO:29 or variants SEQ ID NO:12 or variants thereof thereof thereof 331 SEQ ID NO:19 or variants SEQ ID NO:29 or variants SEQ ID NO:13 or variants thereof thereof thereof 332 SEQ ID NO:19 or variants SEQ ID NO:29 or variants SEQ ID NO:14 or variants thereof thereof thereof 333 SEQ ID NO:19 or variants SEQ ID NO:29 or variants SEQ ID NO:15 or variants thereof thereof thereof 334 SEQ ID NO:19 or variants SEQ ID NO:29 or variants SEQ ID NO:16 or variants thereof thereof thereof 335 SEQ ID NO:19 or variants SEQ ID NO:29 or variants SEQ ID NO:17 or variants thereof thereof thereof 336 SEQ ID NO:19 or variants SEQ ID NO:29 or variants SEQ ID NO:18 or variants thereof thereof thereofIn various embodiments, the hydroxyl group is in the primary (C1) position of said at least one C6-C26 free fattyalcohol.In various embodiments, at least one C6-C26 free fatty alcohol is a C6, C8, C10, C12, C13, C14, C15, C16, C17 orC18 free fatty alcohol.In various embodiments, the at least one C6-C26 free fatty alcohol is an unsaturated free fatty alcohol.In various embodiments, the unsaturated free fatty alcohol is C10:1, C12:1, C14:1, C16:1 or C18:1.In various embodiments, the unsaturated free fatty alcohol is unsaturated at the omega-7 position.In various embodiments, the unsaturated free fatty alcohol comprises a cis double bond.In various embodiments, the free fatty alcohol is a saturated free fatty alcohol.In various embodiments, the at least one C6-C26 free fatty alcohol or a mixture thereof comprises at least one C12,C14 or C16 free fatty alcohol or a mixture thereof.In various embodiments, the at least one C6-C26 free fatty alcohol or a mixture thereof is at least one C12, C14 or C16free fatty alcohol or a mixture thereof.In various embodiments, the at least one C12, C14 or C16 free fatty alcohol comprises a saturated C12 free fattyalcohol.In various embodiments, the at least one C12, C14 or C16 free fatty alcohol is a saturated C12 free fatty alcohol.In various embodiments, the at least one C12, C14 or C16 free fatty alcohol is a saturated, unbranched C12 free fattyalcohol.In various embodiments, the at least one C12, C14 or C16 free fatty alcohol is 1-dodecanol (lauryl alcohol).Host cellThe host cell is a microorganism. In an embodiment the microorganism is a bacterium.In an embodiment the bacterium is selected from the group consisting of Escherichia, Bacillus, EnterobacterAzotobacter, Erwinia, Pseudomonas, Klebsiella, Proteus, Salmonella, Serratia, Shigella, Rhizobia, Vitreoscilla andParacoccus, Methylobacillus, Methylobacterium, Methylococcus, Methylophilus, Methylibium, Hyphomicrobium, Methylocella, Methylocapsa, and Methylocystis.In various embodiments, the microorganism is a yeast.In various embodiments, the yeast is selected from the group consisting of Pichia pastoris, Hansenula polymorpha,Saccharomyces cerevisiae, Kluyveromyces lactis, Schwanniomyces occidentis, Schizosaccharomyces pombe,Trichoderma reesei and Yarrowia lipolytica.In various embodiments, the microorganism is a methylotrophic bacterium. In an embodiment the methylotrophicbacterium is selected from the group consisting of Methylobacillus, Methylobacterium, Methylococcus, Bacillus methanolicus, Methylophilus, Methylibium, Hyphomicrobium, Methylocella, Methylocapsa, and Methylocystis.In various embodiments, the methylotrophic bacterium is a Methylobacillus.In various embodiments, the methylotrophic bacterium selected from the group consisting of Methylobacillusflagellatus, Methylobacillus glycogenes, Methylobacillus pratensis, Methylobacillus rhizosphaerae, Methylobacillusgramineus, Methylobacillus arboreus, Methylobacillus caricics and Methylobacillus methilovorans. In variousembodiments, the methylotrophic bacterium is Methylobacillus flagellatus or Methylobacillus glycogenes. In a furtherembodiment the methylotrophic bacterium is Methylobacillus flagellatus. In a further embodiment the methylotrophicbacterium is Methylobacillus glycogenes.In various embodiments, the methylotrophic bacterium does not express exopolysaccharides (EPS). In a furtherembodiment the methylotrophic bacterium has at least one EPS gene cluster inactivated. In various embodiments, themethylotrophic bacterium has both EPS gene clusters inactivated. In a further embodiment the at least one EPS genecluster or said both EPS gene clusters are entirely or partly deleted (absent).In various embodiments,, the microorganism has a decreased activity of polyphosphate kinase (PPK), inactivated PPKor deleted PPK gene. In various embodiments,, the methylotrophic bacterium has an inactivated PPK or a deleted PPKgene.In various embodiments, the microorganism has a decreased activity of Acyl-homoserine-lactone (AHL) synthase,inactivated AHL synthase or deleted AHL synthase.In various embodiments, the microorganism has an inactivated or deleted AHL synthase.Methyllobacillus strains having a decreased, inactivated or deleted polyphosphate kinase (PPK) and / or a decreased,inactivated or deleted Acyl-homoserine-lactone (AHL) synthase are disclosed in e.g. WO2023 / 139255. Method of manufactureIn a further aspect the invention provides a method for the manufacture of at least one C6-C26 free fatty alcohol or amixture thereof comprising growing a microorganism as defined by the present invention in a suitable medium, andisolation of said C6-C26 free fatty alcohol or a mixture thereof from the (spent) medium.In various embodiments, said at least one C6-C26 free fatty alcohol is a C6, C8, C10, C12, C13, C14, C15, C16, C17or C18 free fatty alcohol.In various embodiments, the at least one C6-C26 free fatty alcohol is an unsaturated free fatty alcohol.In various embodiments, the unsaturated free fatty alcohol is C10:1, C12:1, C14:1, C16:1 or C18:1.In various embodiments, the unsaturated free fatty alcohol is unsaturated at the omega-7 position.In various embodiments, the unsaturated free fatty alcohol comprises a cis double bond.In various embodiments, the free fatty alcohol is a saturated free fatty alcohol.In various embodiments, the at least one C6-C26 free fatty alcohol or a mixture thereof comprises at least one C12,C14 or C16 free fatty alcohol or a mixture thereof.In various embodiments, the C12, C14 or C16 free fatty alcohol or a mixture thereof comprises a C12 fatty alcohol.In various embodiments, the C12 free fatty alcohol comprises dodecanol. In various embodiments, the C12 free fattyalcohol is dodecanol.In various embodiments, the C12 free fatty alcohol comprises 1-dodecanol (lauryl alcohol). In various embodiments,the C12 free fatty alcohol is 1-dodecanol (lauryl alcohol).In various embodiments, the C12, C14 or C16 free fatty alcohol or a mixture thereof comprises a C14 fatty alcohol.In various embodiments, the C14 free fatty alcohol is 1-tetradecanol (myristyl alcohol).In a further aspect the present invention provides a free fatty alcohol composition obtained by the method as defined herein.In a further aspect the present invention provides the use of a methylotrophic bacterium as defined above for themanufacture of a C6-C26 free fatty alcohol or a mixture thereof.In various embodiments, the use is for the manufacture of a C12, C14 or C16 free fatty alcohol, such as C12 free fattyalcohol. In various embodiments, the use is for the manufacture of a C12 free fatty alcohol which is dodecanol. Invarious embodiments, the use is for the manufacture of a C12 free fatty alcohol which is 1-dodecanol.In various embodiments, the use is for the manufacture of a C14 free fatty alcohol. In various embodiments, the use isfor the manufacture of a C14 free fatty alcohol which is tetradecanol. In various embodiments, the use is for themanufacture of a C14 free fatty alcohol which is 1-tetradecanol (myristyl alcohol). Culture medium.The culture medium for growing microorganisms typically comprise carbon- and nitrogen sources as well as differentsalts to supply phosphorous, magnesium, potassium, sulphate, and some vitamins. Such culture media are well known in the art for many different microorganisms.For instance, the culture medium employed for growing the methylotrophic bacteria of the present invention may beany conventional medium suitable for culturing a bacterium cell in question, and may be composed according to the principles of the prior art. The medium will usually contain all nutrients necessary for the growth and survival of therespective bacterium, such as carbon and nitrogen sources and various inorganic salts. Suitable media, e.g. minimalor complex media, are available from commercial suppliers, or may be prepared according to published receipts, e.g. the American Type Culture Collection (ATCC) Catalogue of strains. Non-limiting standard medium well known to the skilled person include Luria Bertani (LB) broth, Sabouraud Dextrose (SD) broth, MS broth, Yeast Peptone Dextrose, BMMY, GM MY, or Yeast Malt Extract (YM) broth, which are all commercially available. A non-limiting example ofsuitable media for culturing methylotrophic bacteria, such as Methylobacillus, including minimal media and rich mediasuch as Luria Broth (LB), M9 media, M17 media, SA media, MOPS media, Terrific Broth, YT and others. The carbon source is preferably methanol but may be any suitable carbon substrate known in the art, and in particularly any carbon substrate commonly used in the cultivation of bacteria and / or fermentation. Non-limiting examples of suitable fermentable carbon substrates include carbohydrates (e.g., C5 sugars such as arabinose or xylose, or C6 sugars such as glucose), glycerol, glycerine, acetate, dihydroxyacetone, one-carbon source, methanol, methane, oils, animal fats, animal oils, plant oils, fatty acids, lipids, phospholipids, glycerolipids, monoglycerides, diglycerides, triglycerides, renewable carbon sources, polypeptides (e.g., a microbial or plant protein or peptide), yeast extract, component from a yeast extract, peptone, casaminoacids or any combination of two or more of the foregoing. According to some embodiments, the carbon substrate is selected from the group consisting of C5 sugars (such as arabinose or xylose), C6 sugars (such as glucose or fructose), lactose, sucrose, glycerol, glycerine, acetate, Corn steep liquor, yeast extract, component from a yeast extract, peptone, casaminoacids or combinations thereof. In the present case where the bacterium is a methylotrophic bacterium, the culture medium preferably comprises areduced one-carbon compound, such as methanol or methylamine, or a multi-carbon compound that contains nocarbon-carbon bonds, such as dimethylamine. Thus, according to some embodiments, the culture medium comprises methanol as a carbon source. The concentration of methanol in the culture medium may generally be in the range from about 0,5% w / v to about 4 % w / v, such as from about 2% w / v to about 4 % w / v. According to some embodiments, theconcentration of methanol in the culture medium is in the range from about 2,5% w / v to about 3,5% w / v.As the nitrogen source, various ammonium salts such as ammonia and ammonium sulfate, other nitrogen compounds such as amines, a natural nitrogen source such as peptone, soybeanhydrolysate, and digested fermentative microorganism can be used. As minerals, potassium monophosphate, magnesium sulfate, sodium chloride, ferrous sulfate, manganese sulfate, calcium chloride, and the like can be used. Suitably, the bacterium is cultivated under suitable conditions for growing the bacterium. Suitable conditions for culturing the respective bacterium are well known to the skilled person. Typically, a bacterium is cultured at a temperature ranging from about 20 to about 45°C, such as from about 30 to about 38°C, such as at about 37°C. The cultivation can be preferably performed under aerobic conditions, such as by a shaking culture, by a stirring culture or in a bioreactor with aeration, at a temperature of about 20 to about 45 °C, such as about 30 to 38 °C, preferably atabout 37°C. The pH of the culture is usually above 5, such as in a range from about 6 to about 8, preferably from about6.5 to about 7.5, more preferably from about 6.8 to about 7.2. The pH of the culture can be adjusted with ammonia, calcium carbonate, various acids, various bases, and buffers. The cultivation may be carried out for a period in the range from 10 to 70 h, preferably in a range from 24 to 60 h, more preferably in a range from 36 to 50 h. After cultivation, solids such as bacterial biomass can be removed from the culture medium by centrifugation ormembrane filtration. C6-C26 free fatty alcohols may be recovered from the (spent) fermentation medium and optionallypurified according to the intended application. The above written description provides a manner and process of making and using the invention such that any person skilled in the art is able to make and use the same, this enablement being provided in particular for the subject matter of the appended claims, which make up a part of the original description. Where a numerical limit or range is stated herein, the endpoints are included. Also, all values and subranges within a numerical limit or range are specifically included as if explicit written out. Having generally described this invention, a further understanding can be obtained by reference to certain specific examples, which are provided herein for the purposes of illustration only and are not intended to limit the scope of the claimed invention. Definitions A thioesterases (TE) according to this invention is an enzyme, which can hydrolyse a thioester bond, specifically the thioester bond of an acyl-ACP (Acyl Carrier Protein) complex to cleave free fatty acids from acyl-ACP / CoA.A carboxylic acid reductase (CAR) according to this invention is an enzyme, which can catalyse the ATP- and NADPH-dependent reduction of acids, specifically fatty acids to the corresponding aldehydes. An aldehyde reductase (ALDR) according to this invention is an enzyme, which can catalyze the NADPH-dependent reduction of aldehydes to alcohols, preferably fatty aldehydes to the corresponding alcohols.EPS according to this invention refers to exopolysaccharides produced by the bacteria used in this invention. EPS ina bioprocess increase viscosity of the broth and lead to increased emulsion formation, so removal of EPS production improves bioprocess performance, as described in WO2022069644A1. AHL according to this invention refers to the enzyme Acyl homoserine lactone synthase. The enzyme is used by some bacteria to synthesize cell signalling or quorum sensing molecules (acyl homoserine lactones). The signalling molecules can lead to a variety of responses, including programmed cell death. Removal of AHL activity from bacteria can prevent programmed cell death, which prevents premature bioprocess termination, as described in WO2023139255A1.PPK according to this invention refers to the enzyme polyphosphate kinase. The enzyme is involved in programmedcell death through an unknown mechanism programmed cell death. Removal of PPK activity from bacteria can prevent programmed cell death, which prevents premature bioprocess termination, as described in WO2023139255A1. Examples Example 1: Selection of genes.Fatty alcohols can be produced via two main pathways, one involving Fatty acyl reductase (FAR) which catalyzes theNADPH-dependent reduction of native fatty acyl-CoA or acyl-ACP metabolites to primary fatty alcohols and the otherwhich uses thioesterase (TE) to first cleave free fatty acids from acyl-ACP / CoA, followed by conversion of free fattyacids into aldehydes by the activity of carboxylic acid reductase (CAR) and finally converting fatty aldehydes to fattyalcohol by aldehyde reductase (ALDR) in two NADPH-dependent consequent reactions, see Figure 1. Thioesteraseenzymes have been shown to exhibit chain-length specificity multiple times. To achieve production of specific (C12and C14) fatty alcohols, C12 and C14 chain length specific acyl-ACP thioesterases can be employed to produce thecorresponding free fatty acids, which can then be converted into fatty alcohols via CAR and ALDR.Based on published literature, TE from Umbellularia californica (SEQ ID NO:6) was chosen as a suitable, C12 and C14chain length specific acyl-ACP thioesterase. Likewise, literature and sequence similarity bioinformatic searches wereemployed to select CAR enzymes (SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5; SEQ IDNos: 20-42).Aldehyde dehydrogenases YjgB_Eco-ALDR, Sce-ALDR, YahK_Eco-ALDR, Ybbo_Eco-ALDR were identified frompublished literature and chosen based on their characterization as long chain specific aldehyde reductase for enhancedfatty alcohol production in E. coli (SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9 and SEQ ID NO:10). Osp-ALDR wasfound by protein BLAST against the ALDR domain of the Marinobacter aquaeolei MAR FAR (only sequences shorterthan 600 aa) (SEQ ID NO:11). Nbo-ALDR, Ncy-ALDR, Ncy_1-ALDR, Gth-ALDR and Yli-ALDR were found by Uniprotkeyword search - aldehyde reductase, alcohol dehydrogenase in organisms that possess CAR enzymes (SEQ IDNO:12, SEQ ID NO:13 , SEQ ID NO:14 , SEQ ID NO:15 , SEQ ID NO:16).Ath-ALDR and Pst-ALDR were found by protein BLAST of long chain specific aldehyde reductases for enhanced fattyalcohol production in E. coli found in literature (SEQ ID NO:17, SEQ ID NO:18).Example 2: Construction of plasmids To achieve C12 and C14 fatty alcohol production, heterologous C12 and C14 chain length specific acyl-ACPthioesterases (TE), carboxylic acid reductase (CAR) and aldehyde reductase (ALDR) must be functionally expressedin the host organism.To test different CAR enzymes, TE from Umbellularia californica (Uca-TE) as a suitable and C12 / C14 chain lengthspecific acyl-ACP thioesterase was combined with the broad range E. coli aldehyde reductase enzyme YjgB (aldehydereductase capable of accepting a broad range of commercially available aldehydes with a selective preference forNADPH) and different carboxylic acid reductases. The CAR, TE and ALDR genes were codon harmonized forexpression in Methylobacillus flagellatus ABBAg2 and cloned into the expression vector. To test different ALDR enzymes, genes for heterologous C12 / C14 chain length specific acyl-ACP thioesterase (TE)from Umbellularia californica and carboxylic acid reductase (CAR) from Mycobacterium tuberculosis in combinationwith other, heterologous aldehyde reductases enzymes were tested.TE was placed under the control of the IPTG-inducible lacO / trc promotor, while CAR and ALDR were placed in an operon after the IPTG-inducible lacO / BBa_J23110 using the NEB Hi-Fi cloning kit according to manufacturer instructions. List of constructed plasmids is in Table 1. Table 1: Plasmids constructed to test whether C12 and C14 fatty alcohols can be produced in M. flagellatus, employing different carboxylic acid reductases and aldehyde reductases. Plasmid name TE ALDR CARUca-TE (SEQ ID YjgB_Eco-ALDR (SEQ IDpABBA_269 NO:6)NO:7) Mma-CAR (SEQ ID NO:1)Uca-TE (SEQ ID YjgB_Eco-ALDR (SEQ ID pABBA_270 NO:6)NO:7) Nio-CAR (SEQ ID NO:2)Uca-TE (SEQ ID YjgB_Eco-ALDR (SEQ ID pABBA_271 NO:6)NO:7) Ncr-CAR (SEQ ID NO:3)Uca-TE (SEQ ID YjgB_Eco-ALDR (SEQ ID pABBA_272 NO:6)NO:7) Mtu-CAR (SEQ ID NO:4)Uca-TE (SEQ ID YjgB_Eco-ALDR (SEQ ID pABBA_273 NO:6)NO:7) Tpa-CAR (SEQ ID NO:5)Uca-TE (SEQ IDSce-ALDR (SEQ IDpABBA_562 NO:6)NO:8) Mtu-CAR CAR (SEQ ID NO:4)Uca-TE (SEQ IDOsp-ALDR (SEQ IDpABBA_563 NO:6)NO:11) Mtu-CAR CAR (SEQ ID NO:4)Uca-TE (SEQ IDAth-ALDR (SEQ IDpABBA_564 NO:6)NO:17) Mtu-CAR CAR (SEQ ID NO:4)Uca-TE (SEQ IDPst-ALDR (SEQ IDpABBA_565 NO:6)NO:18) Mtu-CAR CAR (SEQ ID NO:4)Uca-TE (SEQ IDNbo-ALDR (SEQ IDpABBA_566 NO:6)NO:12) Mtu-CAR CAR (SEQ ID NO:4)Uca-TE (SEQ IDNcy-ALDR (SEQ IDpABBA_567 NO:6)NO:13) Mtu-CAR CAR (SEQ ID NO:4)Uca-TE (SEQ IDNcy_1-ALDR (SEQ IDpABBA_569 NO:6)NO:14) Mtu-CAR CAR (SEQ ID NO:4) Uca-TE (SEQ ID pABBA_573NO:6) Yli-ALDR (SEQ ID NO:16) Mtu-CAR CAR (SEQ ID NO:4)Uca-TE (SEQ IDGth-ALDR (SEQ IDpABBA_574 NO:6)NO:15) Mtu-CAR CAR (SEQ ID NO:4)Uca-TE (SEQ IDYahK-ALDR (SEQ IDpABBA_575 NO:6)NO:9) Mtu-CAR CAR (SEQ ID NO:4)Uca-TE (SEQ IDYbbo-ALDR (SEQ IDpABBA_576 NO:6)NO:10) Mtu-CAR CAR (SEQ ID NO:4)Example 3: Construction of strainsThe prepared plasmids shown in Table 1 above were checked by sequencing and transformed into M. flagellatusABBAg_2 via electroporation to create the strains shown in Table 2.Table 2: Plasmids constructed to test whether C12 and C14 fatty alcohols can be produced in M. flagellatus, employing different carboxylic acid reductases and aldehyde reductases. Strain Plasmid Viable transformants Y / NABBAg_2 / NAABBAg_432 pABBA_269 NABBAg_433 pABBA_270 NABBAg_434 pABBA_271 NABBAg_435 pABBA_272 YABBAg_436 pABBA_273 YABBAg_598 pABBA_562 YABBAg_599 pABBA_563 YABBAg_600 pABBA_564 YABBAg_601 pABBA_565 YABBAg_602 pABBA_566 YABBAg_603 pABBA_567 YABBAg_605 pABBA_569 YABBAg_608 pABBA_573 YABBAg_609 pABBA_574 YABBAg_610 pABBA_575 YABBAg_650 pABBA_576 YExample 4: Protocol for screening fatty alcohol production To test fatty alcohol production, the strains ABBAg_2, ABBAg_435, ABBAg_436, ABBAg_598, ABBAg_599, ABBAg_600, ABBAg_601, ABBAg_602, ABBAg_603, ABBAg_605, ABBAg_608, ABBAg_609, ABBAg_610 and ABBAg_650 were cultivated in 250 mL shake flasks in a mineral medium containing methanol, KH2PO4, Na2HPO4,MgSO4, NH4SO4, and trace elements. A dodecane overlay (20 %V / V) was used to extract the products duringfermentation. The shake flasks were inoculated with 10 %V / V liquid overnight culture. After 4 h of growth, 0.5 g / L IPTG was added to induce gene expression. After 24 hours 20 g / L of methanol was fed to the cultures. The cultures were sampled after 48 h of growth. Fatty alcohol content in the dodecane overlay was measured by GC-FID. Example 5: Screening of strains expressing CARInterestingly, transformations with plasmids pABBA_269, pABBA_270 and pABBA_271 did not yield any viabletransformant. Strains ABBAg_2, ABBAg_435 and ABBAg_436 were tested for fatty alcohol production. The strains ABBAg_435 and ABBAg_436 produced between 120 and 130 mg / L C12 fatty alcohols from methanol after48 h of cultivation (Figure 2). Under the same conditions, the control strain ABBAg_2, that did not contain the plasmidproduced 0 mg / L C12 and 0 C14 fatty alcohols. This confirmed that C12 and C14 fatty alcohols can successfully beproduced from methanol heterologously expressing Umbellularia californica thioesterase, carboxylic acid reductase(CAR) and YjgB_Eco aldehyde reductase (ALDR) in M. flagellatus ABBAg_2. However, conversion of free fatty acidsto fatty alcohols was incomplete, as evidenced by the free fatty acid titer (Figure 3).Example 6: Expression of heterologous aldehyde reductases enzymes in M. flagellatus together withthioesterase and carboxylic acid reductase Strains ABBAg_598, ABBAg_599, ABBAg_600, ABBAg_601, ABBAg_602, ABBAg_603, ABBAg_605, ABBAg_608, ABBAg_609, ABBAg_610 and ABBAg_650 produced between 60 and 160 mg / L C12 fatty alcohols from methanol after48 h of cultivation (Figure 4). Under the same conditions, the control strain that did not contain the plasmid, ABBAg_2,produced 0 mg / L C12 / C14 fatty alcohols. This confirmed that the C12 / C14 fatty alcohol titer can be increased by theexpression of a novel heterologous aldehyde reductase when expressed in combination with C12 and C14 chain lengthspecific acyl-ACP thioesterase (TE) from Umbellularia californica and carboxylic acid reductase (CAR) fromMycobacterium tuberculosis in M. flagellatus ABBAg_2. Furthermore, titers of remaining C12 and C14 fatty acidsmeasured in the same strains (Figure 5) demonstrated that a novel aldehyde reductase Pst-ALDR (corresponding toABBAg_601) which produces the highest titers of C12 and C14 fatty alcohols from methanol also achieves ~90 %conversion of fatty acids into fatty alcohols, which is the highest conversion ratio in all tested strains. This is highlysurprising, because this enzyme has never been shown to reduce fatty aldehydes into fatty alcohols. Example 7: Preparation of expression constructs For the CAR screen, each CAR gene (SEQ ID NOs: 1, 2, 4, 5, and 20-42) was codon harmonized for expression inMethylobacillus flagellatus ABBAg_2 using a proprietary Python algorithm and cloned into the expression vector underIPTG-inducible lacO / Trc promoter using the NEB Hi-Fi cloning kit according to manufacturer instructions. The following plasmids were obtained: pABBA_294, pABBA_1000, pABBA_1003, pABBA_1006, pABBA_1007, pABBA_1013, pABBA_1014, pABBA_1011, pABBA_1019, pABBA_1020, pABBA_1001, pABBA_1021, pABBA_1015, pABBA_1010, pABBA_1008, pABBA_1018, pABBA_1025, pABBA_1004, pABBA_551, pABBA_552, pABBA_553, pABBA_554,pABBA_555, pABBA_845, pABBA_846, pABBA_847, pABBA_1012 and pABBA_295. List of constructed plasmids isin Table 3. Table 3: Plasmids constructed to express CAR enzymes in M. flagellatus Plasmid CARpABBA_294 CAR_Mtu (SEQ ID NO: 4)pABBA_1000 CAR_107_BASF (SEQ ID NO:27)pABBA_1003 CAR_18_BASF (SEQ ID NO:24)pABBA_1006 CAR_8_BASF (SEQ ID NO:31)pABBA_1007 CAR_94_BASF (SEQ ID NO:32)pABBA_1013 CAR_87_BASF (SEQ ID NO:21)pABBA_1014 CAR_53_BASF (SEQ ID NO:33)pABBA_1011 CAR_51_BASF (SEQ ID NO:23)pABBA_1019 CAR_24_BASF (SEQ ID NO:34)pABBA_1020 CAR_77_BASF (SEQ ID NO:35)pABBA_1001 CAR_103_BASF (SEQ ID NO:20)pABBA_1021 CAR_96_BASF (SEQ ID NO:30)pABBA_1015 CAR_72_BASF (SEQ ID NO:36)pABBA_1010 CAR_59_BASF (SEQ ID NO:26)pABBA_1008 CAR_2_BASF (SEQ ID NO:22)pABBA_1018 CAR_37_BASF (SEQ ID NO:37)pABBA_1025 CAR_68_BASF (SEQ ID NO:38)pABBA_1004 CAR_65_BASF (SEQ ID NO:29)pABBA_551 CAR_Mar (SEQ ID NO:28)pABBA_552 CAR_Rsp (SEQ ID NO:39)pABBA_553 CAR_Ncy (SEQ ID NO:40)pABBA_554 CAR_Msp (SEQ ID NO:41)pABBA_555 CAR_Mab (SEQ ID NO:42)pABBA_845 CAR_Nio (SEQ ID NO:2)pABBA_846 CAR_Ncr (SEQ ID NO:3)pABBA_847 CAR_Mma (SEQ ID NO:1)pABBA_1012 CAR_15_BASF (SEQ ID NO:25)pABBA_295 CAR_Tpa (SEQ ID NO:5)Example 8: Preparation of strains The prepared plasmids pABBA_294, pABBA_1000, pABBA_1003, pABBA_1006, pABBA_1007, pABBA_1013, pABBA_1014, pABBA_1011, pABBA_1019, pABBA_1020, pABBA_1001, pABBA_1021, pABBA_1015, pABBA_1010, pABBA_1008, pABBA_1018, pABBA_1025, pABBA_1004, pABBA_551, pABBA_552, pABBA_553, pABBA_554,pABBA_555, pABBA_845, pABBA_846, pABBA_847, pABBA_1012 and pABBA_295 (see Table 4) were checked bysequencing and transformed into M. flagellatus ABBAg_983 via electroporation to create strains ABBAG_1160, ABBAG_1858, ABBAG_1859, ABBAG_1860, ABBAG_1861, ABBAG_1862, ABBAG_1863, ABBAG_1864, ABBAG_1865, ABBAG_1866, ABBAG_1871, ABBAG_1873, ABBAG_1874, ABBAG_1875, ABBAG_1876, ABBAG_1897, ABBAG_1909, ABBAG_1912, ABBAG_1358, ABBAG_1359, ABBAG_1360, ABBAG_1361, ABBAG_1362, ABBAG_1422, ABBAG_1443, ABBAG_1506, ABBAG_1923 and ABBAg_1932. Strain ABBAg_983 which was used as a control (no CAR) first transformed with linear fragment containingTE_Uca_H0_trUP (SEQ ID NO:19) flanked by genome homology regions to insert TE_Uca_H0_trUP on the genome.For the list of strains, see Table 4. Table 4: Strains constructed to screen carboxylic acid reductases. Strain Plasmid Genomic integrationABBAg_983 / TE_Uca_H0_trUPABBAg_1160 pABBA_294 TE_Uca_H0_trUPABBAg_1858 pABBA_1000 TE_Uca_H0_trUPABBAg_1859 pABBA_1003 TE_Uca_H0_trUPABBAg_1860 pABBA_1006 TE_Uca_H0_trUPABBAg_1861 pABBA_1007 TE_Uca_H0_trUPABBAg_1862 pABBA_1013 TE_Uca_H0_trUPABBAg_1863 pABBA_1014 TE_Uca_H0_trUPABBAg_1864 pABBA_1011 TE_Uca_H0_trUPABBAg_1865 pABBA_1019 TE_Uca_H0_trUPABBAg_1866 pABBA_1020 TE_Uca_H0_trUPABBAg_1871 pABBA_1001 TE_Uca_H0_trUPABBAg_1873 pABBA_1021 TE_Uca_H0_trUPABBAg_1874 pABBA_1015 TE_Uca_H0_trUPABBAg_1875 pABBA_1010 TE_Uca_H0_trUPABBAg_1876 pABBA_1008 TE_Uca_H0_trUPABBAg_1897 pABBA_1018 TE_Uca_H0_trUPABBAg_1909 pABBA_1025 TE_Uca_H0_trUPABBAg_1912 pABBA_1004 TE_Uca_H0_trUPABBAg_1358 pABBA_551 TE_Uca_H0_trUPABBAg_1359 pABBA_552 TE_Uca_H0_trUPABBAg_1360 pABBA_553 TE_Uca_H0_trUPABBAg_1361 pABBA_554 TE_Uca_H0_trUPABBAg_1362 pABBA_555 TE_Uca_H0_trUPABBAg_1442 pABBA_845 TE_Uca_H0_trUPABBAg_1443 pABBA_846 TE_Uca_H0_trUPABBAg_1506 pABBA_847 TE_Uca_H0_trUPABBAg_1923 pABBA_1012 TE_Uca_H0_trUPABBAg_1932 pABBA_295 TE_Uca_H0_trUP Example 9: Shaker-scale production assay set-up with overlay To test fatty alcohol production, the strains ABBAG_983 (no CAR control), ABBAG_1160, ABBAG_1858, ABBAG_1859, ABBAG_1860, ABBAG_1861, ABBAG_1862, ABBAG_1863, ABBAG_1864, ABBAG_1865, ABBAG_1866, ABBAG_1871, ABBAG_1873, ABBAG_1874, ABBAG_1875, ABBAG_1876, ABBAG_1897, ABBAG_1909, ABBAG_1912, ABBAG_1358, ABBAG_1359, ABBAG_1360, ABBAG_1361, ABBAG_1362, ABBAG_1422, ABBAG_1443, ABBAG_1506, ABBAG_1923, expressing genes encoding for CAR_Mtu, CAR_107, CAR_18, CAR_8, CAR_94, CAR_87, CAR_53, CAR_51, CAR_24, CAR_77, CAR_103, CAR_96, CAR_72, CAR_59, CAR_2, CAR_37, CAR_68, CAR_65, CAR_Mar, CAR_Rsp, CAR_Ncy, CAR_Msp, CAR_Mab, CAR_Nio, CAR_Ncr, CAR_Mma, CAR_15, CAR_Tpa respectively were cultivated in 250 mL shake flasks in a mineral medium containing methanol, KH2PO4, Na2HPO4, MgSO4, NH4SO4, and trace elements. A dodecane overlay (20% V / V) was used to extract the products during fermentation. The shake flasks were inoculated with 10% (V / V) liquid overnight culture. After 4 h of growth, g / L IPTG to the specified final concentration was added to induce gene expression. The cultureswere sampled after 24 h of growth. Fatty alcohol content in the dodecane overlay was measured by GC-FID.Example 10: Screening of CAR enzymes Strains strains ABBAG_983 (no CAR control), ABBAG_1160, ABBAG_1858, ABBAG_1859, ABBAG_1860, ABBAG_1861, ABBAG_1862, ABBAG_1863, ABBAG_1864, ABBAG_1865, ABBAG_1866, ABBAG_1871, ABBAG_1873, ABBAG_1874, ABBAG_1875, ABBAG_1876, ABBAG_1897, ABBAG_1909, ABBAG_1912, ABBAG_1358, ABBAG_1359, ABBAG_1360, ABBAG_1361, ABBAG_1362, ABBAG_1422, ABBAG_1443, ABBAG_1506, ABBAG_1923 each containing one CAR enzyme were tested for fatty alcohol production under three different IPTG induction levels. ABBAg_1160 expressing CAR_Mtu induced with 0.01 mM produced the highest concentration of fatty alcohols at a total of 387 mg / L. Strains ABBAg_1858, ABBAg_1859, ABBAg_1862, ABBAg_1864, ABBAg_1871, ABBAg_1875, ABBAg_1876, ABBAg_1912, ABBAg_1358, ABBAg_1442, ABBAg_1506, ABBAg_1923 and ABBAg_1932 also produced fatty alcohols titers above noise levels, suggesting CAR_Mtu, CAR_197, CAR18, CAR87, CAR_51, CAR_103, CAR59, CAR_2, CAR_65, CAR_Mar, CAR_Nio, CAR_Mma, CAR_15 and CAR_Tpa possess carboxylic acid reductase activity. The optimal IPTG level differed, but lower concentrations resulted in higher production in most cases. Table 5 CAR (on the IPTG induction SUM fatt SUM fatty Strain y SUM fatty acids plasmid) of CAR alcohols (mg / L) (mg / L) alcohols + fatty acids (mg / L) ABBAg_983 / / 2 507 5090.01mM 387 59 446ABBAg_1160 CAR_Mtu (SEQ ID NO:4)0.05mM 295 20 3150.5mM 193 16 209ABBAg_1858 CAR_107 (SEQ0.01mM 21 480 501ID NO:28)0.05mM 67 410 4770.5mM 79 228 3070.01mM 134 173 307ABBAg_1859 CAR_18 (SEQ ID NO:24)0.05mM 98 36 1340.5mM 24 24 480.01mM 2 534 536ABBAg_1860 CAR_8 (SEQ ID NO:31)0.05mM 2 513 5150.5mM 2 479 4810.01mM 2 638 640ABBAg_1861 CAR_94 (SEQ ID NO:31)0.05mM 1 460 4610.5mM 1 336 3370.01mM 184 109 293ABBAg_1862 CAR_87 (SEQ ID NO:21)0.05mM 101 18 1190.5mM 29 15 440.01mM 2 610 612ABBAg_1863 CAR_53 (SEQ ID NO:33)0.05mM 2 527 5290.5mM 2 454 4560.01mM 135 29 164ABBAg_1864 CAR_51 (SEQ ID NO:23)0.05mM 108 18 1260.5mM 48 11 590.01mM 2 634 636ABBAg_1865 CAR_24 (SEQ ID NO:34)0.05mM 6 547 5530.5mM 10 504 5140.01mM 2 517 519ABBAg_1866 CAR_77 (SEQ ID NO:35)0.05mM 2 364 3660.5mM 2 248 2500.01mM 233 31 264ABBAg_1871 CAR_103 (SEQ ID NO:20)0.05mM 141 12 1530.5mM 77 10 870.01mM 3 426 429ABBAg_1873 CAR_96 (SEQ ID NO:30)0.05mM 2 180 1820.5mM 2 111 1130.01mM 2 439 441ABBAg_1874 CAR_72 (SEQ ID NO:36)0.05mM 2 231 2330.5mM 2 156 1580.01mM 41 456 497ABBAg_1875 CAR_59 (SEQ ID NO:26)0.05mM 85 350 4350.5mM 104 290 3940.01mM 152 61 213ABBAg_1876 CAR_2 (SEQ ID NO:22)0.05mM 139 16 1550.5mM 10 255 2640.01mM 2 471 473ABBAg_1897 CAR_37 (SEQ ID NO:37)0.05mM 2 371 3730.5mM 2 241 2430.01mM 2 26 28ABBAg_1909 CAR_68 (SEQ ID NO:38)0.05mM 2 30 320.5mM 2 26 280.01mM 7 481 488ABBAg_1912 CAR_65 (SEQ ID NO:29)0.05mM 4 283 2870.5mM 3 171 1740.01mM 13 472 485ABBAg_1358 CAR_Mar (SEQ ID NO:28)0.05mM 17 390 4070.5mM 8 299 3070.01mM 2 413 415ABBAg_1359 CAR_Rsp (SEQ ID NO:39)0.05mM 1 145 1460.5mM 2 112 1140.01mM 2 27 29ABBAg_1360 CAR_Ncy (SEQ ID NO:40)0.05mM 2 27 290.5mM 2 26 280.01mM 2 477 479ABBAg_1361 CAR_Msp (SEQ ID NO:41)0.05mM 2 436 4380.5mM 1 376 3770.01mM 2 470 472ABBAg_1362 CAR_Mab (SEQ ID NO:42)0.05mM 2 215 2170.5mM 2 85 870.01mM 39 455 494ABBAg_1442 CAR_Nio (SEQ ID NO:2)0.05mM 140 325 4650.5mM 198 190 3880.01mM 1 31 32ABBAg_1443 CAR_Ncr (SEQ ID NO:3)0.05mM 2 30 320.5mM 2 29 310.01mM 14 493 507ABBAg_1506 CAR_Mma (SEQ ID NO:1)0.05mM 40 458 4980.5mM 94 373 4670.01mM 86 372 458ABBAg_1923 CAR_15 (SEQ ID NO:25)0.05mM 165 142 3070.5mM 111 54 1650.01mM 177 62 239ABBAg_1932 CAR_Tpa (SEQ ID NO:5)0.05mM 74 20 940.5mM 36 26 62
Claims
1. Claims1. Microorganism capable of producing at least one C6-C26 free fatty alcohol or a mixture thereof from methanol,said microorganism comprising: at least one gene enabling the expression of a thioesterase (TE),at least one gene enabling the expression of at least one carboxylic acid reductase (CAR) andat least one gene enabling the expression of an aldehyde reductase (ALDR).
2. The microorganism according to claim 1, wherein the microorganism is a recombinant microorganism.
3. The microorganism according to claim 1 or 2, wherein the at least one gene enabling the expression of athioesterase (TE) and / or the at least one gene enabling the expression of at least one carboxylic acid reductase (CAR)and / or the at least one gene enabling the expression of an aldehyde reductase (ALDR) is heterologously expressedby said microorganism.
4. The microorganism according to any one of the preceding claims wherein said microorganism provides for ahigher production yield of the at least one C6-C26 free fatty alcohol or a mixture thereof, preferably an at least 10 %higher production yield, relative to the same microorganism that lacks one, two or all three of the TE, the CAR and theALDR genes, in particular to a microorganism that lacks the CAR gene.
5. The microorganism according to any one of the preceding claims, wherein said TE is from Umbellulariacalifornica (Uca-TE).
6. The microorganism according to any one of the preceding claims, wherein said TE is a polypeptide that has atleast 80% sequence identity to SEQ ID NO:6, at least 85% sequence identity to SEQ ID NO:6, at least 90% sequence identity to SEQ ID NO:6, at least 95% sequence identity to SEQ ID NO:6, or at least 98% sequence identity to SEQ ID NO:6.
7. The microorganism according to any of the preceding claims, wherein said TE comprises, consists essentiallyof or consists of SEQ ID NO:6.
8. The microorganism according to any one of the preceding claims, wherein said at least one CAR is a Tpa-CARor a Mtu-CAR.
9. The microorganism according to any one of the preceding claims, wherein said at least one CAR is is apolypeptide that has at least 80%, at least 85%, at least 90%, at least 95% or at least 98% sequence identity to SEQ ID NO:4, SEQ ID NO:5 or any one of SEQ ID NOs:1, 2 and 20-29.
10. The microorganism according to any one of the preceding claims, wherein said at least one ALDR is apolypeptide that has at least 80%, at least 85%, at least 90%, at least 95% or at least 98% sequence identity to any one of SEQ ID NOs:7-18, preferably to SEQ ID NO:18.
11. The microorganism according to any one of the preceding claims, wherein (1) said TE is a polypeptide that hasat least 80%, at least 85%, at least 90%, at least 95% or at least 98% sequence identity to SEQ ID NO:6, (2) said atleast one CAR is is a polypeptide that has at least 80%, at least 85%, at least 90%, at least 95% or at least 98%sequence identity to SEQ ID NO:4, SEQ ID NO:5 or any one of SEQ ID NOs: 1, 2 and 20-29; and (3) said at least oneALDR is a polypeptide that has at least 80%, at least 85%, at least 90%, at least 95% or at least 98% sequence identityto any one of SEQ ID NOs:7-18, preferably to SEQ ID NO:18.
12. The microorganism according to any one of the preceding claims, wherein (1) said TE is a polypeptide that hasat least 80%, at least 85%, at least 90%, at least 95% or at least 98% sequence identity to SEQ ID NO:6, (2) said atleast one CAR is is a polypeptide that has at least 80%, at least 85%, at least 90%, at least 95% or at least 98%sequence identity to SEQ ID NO:4, SEQ ID NO:5 or any one of SEQ ID NOs: 1, 2 and 20-29; and (3) said at least oneALDR is a polypeptide that has at least 80%, at least 85%, at least 90%, at least 95% or at least 98% sequence identityto SEQ ID NO:18.
13. The microorganism according to any one of the preceding claims, wherein said at least one C6-C26 free fattyalcohol comprises at least one C12, C14 or C16 free fatty alcohol.
14. The microorganism according to claim 13, wherein said at least one C12, C14 or C16 free fatty alcohol is 1-dodecanol (lauryl alcohol).
15. The microorganism according to any one of claims 13 or 14, wherein said at least one C12, C14 or C16 freefatty alcohol comprises a C14 free fatty alcohol, in particular 1-tetradecanol (myristyl alcohol).
16. The microorganism according to any one of the preceding claims, which has at least one exopolysaccharide(EPS) gene cluster inactivated or does not express exopolysaccharides.
17. The microorganism according to any one of the preceding claims, which has a decreased activity ofpolyphosphate kinase (PPK), inactivated PPK or deleted PPK gene.
18. The microorganism according to any one of the preceding claims which has a decreased activity of Acyl-homoserine-lactone (AHL) synthase, inactivated AHL synthase or deleted AHL synthase.
19. The microorganism according to any one of the preceding claims, wherein said microorganism is a bacterium,in particular is a Methylobacillus, in particular Methylobacillus flagellatus or Methylobacillus glycogenes.
20. A method for the manufacture of at least one C6-C26 free fatty alcohol or a mixture thereof comprising growinga microorganism as defined in any one of claims 1 to 19 in a suitable medium, and isolation of said C6-C26 free fattyalcohol or a mixture thereof from the medium, for example the spent medium21. The method according to claim 20, wherein said at least one C6-C26 free fatty alcohol comprises at least oneC12, C14 or C16 free fatty alcohol or a mixture thereof, in particular 1-dodecanol (lauryl alcohol) or 1-tetradecanol(myristyl alcohol).
22. Free fatty alcohol composition obtained by the method as defined in claim 20 or 21.
23. Use of a microorganism as defined in any one of claims 1 to 19 for the manufacture of a C6-C26 free fattyalcohol or a mixture thereof.
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