Compositions and methods for the biosynthesis of 1,4-butanediol and its precursors
원문보기
IPC분류정보
국가/구분
United States(US) Patent
등록
국제특허분류(IPC7판)
C12P-007/18
C12N-001/21
C12P-007/42
C12N-009/04
C12N-009/02
C12N-009/88
C12N-009/00
C12P-007/52
C12P-017/04
출원번호
US-0717350
(2012-12-17)
등록번호
US-8969054
(2015-03-03)
발명자
/ 주소
Burk, Mark J.
Van Dien, Stephen J.
Burgard, Anthony P.
Niu, Wei
출원인 / 주소
Genomatica, Inc.
대리인 / 주소
Jones Day
인용정보
피인용 횟수 :
1인용 특허 :
95
초록▼
The invention provides a non-naturally occurring microbial biocatalyst including a microbial organism having a 4-hydroxybutanoic acid (4-HB) biosynthetic pathway having at least one exogenous nucleic acid encoding 4-hydroxybutanoate dehydrogenase, succinyl-CoA synthetase, CoA-dependent succinic semi
The invention provides a non-naturally occurring microbial biocatalyst including a microbial organism having a 4-hydroxybutanoic acid (4-HB) biosynthetic pathway having at least one exogenous nucleic acid encoding 4-hydroxybutanoate dehydrogenase, succinyl-CoA synthetase, CoA-dependent succinic semialdehyde dehydrogenase, or α-ketoglutarate decarboxylase, wherein the exogenous nucleic acid is expressed in sufficient amounts to produce monomeric 4-hydroxybutanoic acid (4-HB). Also provided is a non-naturally occurring microbial biocatalyst including a microbial organism having 4-hydroxybutanoic acid (4-HB) and 1,4-butanediol (BDO) biosynthetic pathways, the pathways include at least one exogenous nucleic acid encoding 4-hydroxybutanoate dehydrogenase, succinyl-CoA synthetase, CoA-dependent succinic semialdehyde dehydrogenase, 4-hydroxybutyrate:CoA transferase, 4-butyrate kinase, phosphotransbutyrylase, α-ketoglutarate decarboxylase, aldehyde dehydrogenase, alcohol dehydrogenase or an aldehyde/alcohol dehydrogenase, wherein the exogenous nucleic acid is expressed in sufficient amounts to produce 1,4-butanediol (BDO). Additionally provided are methods for the production of 4-HB and BDO.
대표청구항▼
1. A non-naturally occurring microbial organism having 4-hydroxybutanoic acid (4-HB) and 1,4-butanediol (1,4-BDO) biosynthetic pathways, said pathways comprising exogenous nucleic acids encoding a) an α-ketoglutarate decarboxylase; b) a 4-hydroxybutanoate dehydrogenase; c) a 4-hydroxybutyryl-CoA:ace
1. A non-naturally occurring microbial organism having 4-hydroxybutanoic acid (4-HB) and 1,4-butanediol (1,4-BDO) biosynthetic pathways, said pathways comprising exogenous nucleic acids encoding a) an α-ketoglutarate decarboxylase; b) a 4-hydroxybutanoate dehydrogenase; c) a 4-hydroxybutyryl-CoA:acetyl-CoA transferase, or a butyrate kinase and a phosphotransbutyrylase; d) an aldehyde dehydrogenase; and e) an alcohol dehydrogenase, wherein said exogenous nucleic acids are expressed in sufficient amounts to produce 1,4-butanediol (1,4-BDO). 2. The non-naturally occurring microbial organism of claim 1, wherein said pathways comprise a) an α-ketoglutarate decarboxylase; b) a 4-hydroxybutanoate dehydrogenase; c) a 4-hydroxybutyryl-CoA:acetyl-CoA transferase; d) an aldehyde dehydrogenase; and e) an alcohol dehydrogenase. 3. The non-naturally occurring microbial organism of claim 2, further comprising a CoA-dependent succinic semialdehyde dehydrogenase. 4. The non-naturally occurring microbial organism of claim 2, wherein said exogenous nucleic acids comprise at least one heterologous nucleic acid. 5. The non-naturally occurring microbial organism of claim 2, wherein the microbial organism is in a substantially anaerobic culture medium. 6. The non-naturally occurring microbial organism of claim 1, wherein said pathways comprise a) an α-ketoglutarate decarboxylase; b) a 4-hydroxybutanoate dehydrogenase; c) a butyrate kinase and a phosphotransbutyrylase; d) an aldehyde dehydrogenase; and e) an alcohol dehydrogenase. 7. The non-naturally occurring microbial organism of claim 6, further comprising a CoA-dependent succinic semialdehyde dehydrogenase. 8. The non-naturally occurring microbial organism of claim 6, wherein said exogenous nucleic acids comprise at least one heterologous nucleic acid. 9. The non-naturally occurring microbial organism of claim 6, wherein the microbial organism is in a substantially anaerobic culture medium. 10. A non-naturally occurring microbial organism having 4-hydroxybutanoic acid (4-HB) and 1,4-butanediol (1,4-BDO) biosynthetic pathways, said pathways comprising exogenous nucleic acids encoding a) an α-ketoglutarate dehydrogenase and a CoA-dependent succinic semialdehyde dehydrogenase; b) a 4-hydroxybutanoate dehydrogenase; c) a 4-hydroxybutyryl-CoA:acetyl-CoA transferase, or a butyrate kinase and a phosphotransbutyrylase; d) an aldehyde dehydrogenase; and e) an alcohol dehydrogenase, wherein said exogenous nucleic acids are expressed in sufficient amounts to produce 1,4-butanediol (1,4-BDO). 11. The non-naturally occurring microbial organism of claim 10, wherein said pathways comprise a) an α-ketoglutarate dehydrogenase and a CoA-dependent succinic semialdehyde dehydrogenase; b) a 4-hydroxybutanoate dehydrogenase; c) a 4-hydroxybutyryl-CoA:acetyl-CoA transferase; d) an aldehyde dehydrogenase; and e) an alcohol dehydrogenase. 12. The non-naturally occurring microbial organism of claim 11, wherein said exogenous nucleic acids comprise at least one heterologous nucleic acid. 13. The non-naturally occurring microbial organism of claim 11, wherein the microbial organism is in a substantially anaerobic culture medium. 14. The non-naturally occurring microbial organism of claim 10, wherein said pathways comprise a) an α-ketoglutarate dehydrogenase and a CoA-dependent succinic semialdehyde dehydrogenase; b) a 4-hydroxybutanoate dehydrogenase; c) a butyrate kinase and a phosphotransbutyrylase; d) an aldehyde dehydrogenase; and e) an alcohol dehydrogenase. 15. The non-naturally occurring microbial organism of claim 14, wherein said exogenous nucleic acids comprise at least one heterologous nucleic acid. 16. The non-naturally occurring microbial organism of claim 14, wherein the microbial organism is in a substantially anaerobic culture medium. 17. A non-naturally occurring microbial organism having 4-hydroxybutanoic acid (4-HB) and 1,4-butanediol (1,4-BDO) biosynthetic pathways, said pathways comprising exogenous nucleic acids encoding a) a glutamate:succinate semialdehyde transaminase and a glutamate decarboxylase; b) a 4-hydroxybutanoate dehydrogenase; c) a 4-hydroxybutyryl-CoA:acetyl-CoA transferase, or a butyrate kinase and a phosphotransbutyrylase; d) an aldehyde dehydrogenase; and e) an alcohol dehydrogenase, wherein said exogenous nucleic acids are expressed in sufficient amounts to produce 1,4-butanediol (1,4-BDO). 18. The microbial organism of claim 17, wherein said pathways comprise a) a glutamate: succinate semialdehyde transaminase and a glutamate decarboxylase; b) a 4-hydroxybutanoate dehydrogenase; c) a 4-hydroxybutyryl-CoA:acetyl-CoA transferase; d) an aldehyde dehydrogenase; and e) an alcohol dehydrogenase. 19. The non-naturally occurring microbial organism of claim 18, further comprising a CoA-dependent succinic semialdehyde dehydrogenase. 20. The non-naturally occurring microbial organism of claim 18, wherein said exogenous nucleic acids comprise at least one heterologous nucleic acid. 21. The non-naturally occurring microbial organism of claim 18, wherein the microbial organism is in a substantially anaerobic culture medium. 22. The non-naturally occurring microbial organism of claim 17, wherein said pathways comprise a) a glutamate:succinate semialdehyde transaminase and a glutamate decarboxylase; b) a 4-hydroxybutanoate dehydrogenase; c) a butyrate kinase and a phosphotransbutyrylase; d) an aldehyde dehydrogenase; and e) an alcohol dehydrogenase. 23. The non-naturally occurring microbial organism of claim 22, further comprising a CoA-dependent succinic semialdehyde dehydrogenase. 24. The non-naturally occurring microbial organism of claim 22, wherein said exogenous nucleic acids comprise at least one heterologous nucleic acid. 25. The non-naturally occurring microbial organism of claim 22, wherein the microbial organism is in a substantially anaerobic culture medium. 26. A method for the production of 1,4-BDO comprising, culturing the non-naturally occurring microbial organism of claim 1 under conditions and for a sufficient period of time to produce 1,4-BDO. 27. The method of claim 26, wherein said pathways comprise a) an α-ketoglutarate decarboxylase; b) a 4-hydroxybutanoate dehydrogenase; c) a 4-hydroxybutyryl-CoA:acetyl-CoA transferase; d) an aldehyde dehydrogenase; and e) an alcohol dehydrogenase. 28. The method of claim 27, wherein the microbial organism further comprises a CoA-dependent succinic semialdehyde dehydrogenase. 29. The method of claim 27, wherein said exogenous nucleic acids comprise at least one heterologous nucleic acid. 30. The method of claim 27, wherein the microbial organism is in a substantially anaerobic culture medium. 31. The method of claim 26, wherein said pathways comprise a) an α-ketoglutarate decarboxylase; b) a 4-hydroxybutanoate dehydrogenase; c) a butyrate kinase and a phosphotransbutyrylase; d) an aldehyde dehydrogenase; and e) an alcohol dehydrogenase. 32. The method of claim 31, wherein the microbial organism further comprises a CoA-dependent succinic semialdehyde dehydrogenase. 33. The method of claim 31, wherein said exogenous nucleic acids comprise at least one heterologous nucleic acid. 34. The method of claim 31, wherein the microbial organism is in a substantially anaerobic culture medium. 35. A method for the production of 1,4-BDO comprising, culturing the non-naturally occurring microbial organism of claim 10 under conditions and for a sufficient period of time to produce 1,4-BDO. 36. The method of claim 35, wherein said pathways comprise a) an α-ketoglutarate dehydrogenase and a CoA-dependent succinic semialdehyde dehydrogenase; b) a 4-hydroxybutanoate dehydrogenase; c) a 4-hydroxybutyryl-CoA:acetyl-CoA transferase; d) an aldehyde dehydrogenase; and e) an alcohol dehydrogenase. 37. The method of claim 36, wherein said exogenous nucleic acids comprise at least one heterologous nucleic acid. 38. The method of claim 36, wherein the microbial organism is in a substantially anaerobic culture medium. 39. The method of claim 35, wherein said pathways comprise a) an α-ketoglutarate dehydrogenase and a CoA-dependent succinic semialdehyde dehydrogenase; b) a 4-hydroxybutanoate dehydrogenase; c) a butyrate kinase and a phosphotransbutyrylase; d) an aldehyde dehydrogenase; and e) an alcohol dehydrogenase. 40. The method of claim 39, wherein said exogenous nucleic acids comprise at least one heterologous nucleic acid. 41. The method of claim 39, wherein the microbial organism is in a substantially anaerobic culture medium. 42. A method for the production of 1,4-BDO comprising, culturing the non-naturally occurring microbial organism of claim 17 under conditions and for a sufficient period of time to produce 1,4-BDO. 43. The method of claim 42, wherein said pathways comprise a) a glutamate:succinate semialdehyde transaminase and a glutamate decarboxylase; b) a 4-hydroxybutanoate dehydrogenase; c) a 4-hydroxybutyryl-CoA:acetyl-CoA transferase; d) an aldehyde dehydrogenase; and e) an alcohol dehydrogenase. 44. The method of claim 43, wherein the microbial organism further comprises a CoA-dependent succinic semialdehyde dehydrogenase. 45. The method of claim 43, wherein said exogenous nucleic acids comprise at least one heterologous nucleic acid. 46. The method of claim 43, wherein the microbial organism is in a substantially anaerobic culture medium. 47. The method of claim 42, wherein said pathways comprise a) a glutamate:succinate semialdehyde transaminase and a glutamate decarboxylase; b) a 4-hydroxybutanoate dehydrogenase; c) a butyrate kinase and a phosphotransbutyrylase; d) an aldehyde dehydrogenase; and e) an alcohol dehydrogenase. 48. The method of claim 47, wherein the microbial organisms further comprises a CoA-dependent succinic semialdehyde dehydrogenase. 49. The method of claim 47, wherein said exogenous nucleic acids comprise at least one heterologous nucleic acid. 50. The method of claim 47, wherein the microbial organism is in a substantially anaerobic culture medium.
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Huisman Gjalt W. ; Skraly Frank ; Martin David P. ; Peoples Oliver P., Biological systems for manufacture of polyhydroxyalkanoate polymers containing 4-hydroxyacids.
Huisman, Gjalt W.; Skraly, Frank; Martin, David P.; Peoples, Oliver P., Biological systems for manufacture of polyhydroxyalkanoate polymers containing 4-hydroxyacids.
Tobin Allan J. (Los Angeles CA) Erlander Mark G. (Tarzana CA) Kaufman Daniel L. (Santa Monica CA) Clare-Salzler Michael J. (Los Angeles CA), Cloned glutamic acid decarboxylase peptides.
Burdette Douglas S. ; Zeikus Joseph G., Cloning and expression of the gene encoding thermoanaerobacter ethanolicus 39E secondary-alcohol dehydrogenase and enzy.
Burk, Mark J.; Van Dien, Stephen J.; Burgard, Anthony P.; Niu, Wei, Compositions and methods for the biosynthesis of 1,4-butanediol and its precursors.
Frommer Wolf-Bernd (Berlin DEX) Riesmeier Jorg (Berlin DEX), DNA sequences with oligosaccharide transporter, plasmids, bacteria and plants containing a transporter as well as a proc.
Davis,S. Christopher; Grate,John H.; Gray,David R.; Gruber,John M.; Huisman,Gjalt W.; Ma,Steven K.; Newman,Lisa M.; Sheldon,Roger; Wang,Li A, Enzymatic processes for the production of 4-substituted 3-hydroxybutyric acid derivatives.
Davis,S. Christopher; Grate,John H.; Gray,David R.; Gruber,John M.; Huisman,Gjalt W.; Ma,Steven K.; Newman,Lisa M.; Sheldon,Roger; Wang,Li A, Enzymatic processes for the production of 4-substituted 3-hydroxybutyric acid derivatives and vicinal cyano, hydroxy substituted carboxylic acid esters.
Cao,Yongwei; Hinkle,Gregory J.; Slater,Steven C.; Chen,Xianfeng; Goldman,Barry S., Expression of microbial proteins in plants for production of plants with improved properties.
Rieping, Mechthild; Bastuck, Christine; Hermann, Thomas; Thierbach, Georg, Fermentation process for the preparation of L-amino acids using strains of the family Enterobacteriaceae.
Tobin Allan J. ; Erlander Mark G. ; Kaufman Daniel L., Hybridomas and monoclonal antibodies that specifically bind to glutamic acid decarboxylase peptides.
Broecker Franz Josef (Ludwigshafen DT) Schwarzmann Matthias (Limburgerhof DT), Manufacture of butanediol and/or tetrahydrofuran from maleic and/or succinic anhydride via g
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Tobin Allan J. ; Erlander Mark G. ; Kaufman Daniel L., Method for ameliorating glutamic acid decarboxylase associated autoimmune disorders.
Donnelly Mark I. ; Sanville-Millard Cynthia ; Chatterjee Ranjini, Method for construction of bacterial strains with increased succinic acid production.
Allan J. Tobin ; Mark G. Erlander ; Daniel L. Kaufman, Methods and kits useful for determining the status of and detecting pancreatic B-cell associated autoimmune diseases.
Gruys Kenneth James ; Mitsky Timothy Albert ; Kishore Ganesh Murthy ; Slater Steven Charles ; Padgette Stephen Rogers ; Stark David Martin, Methods of optimizing substrate pools and biosynthesis of poly-.beta.-hydroxybutyrate-co-poly-.beta.-hydroxyvalerate in.
Gruys Kenneth James ; Mitsky Timothy Albert ; Kishore Ganesh Murthy ; Slater Steven Charles ; Padgette Stephen Rogers ; Stark David Martin, Methods of optimizing substrate pools and biosynthesis of poly-.beta.-hydroxybutyrate-co-poly-.beta.-hydroxyvalerate in.
Timothy A. Mitsky ; Steven C. Slater ; Steven E. Reiser ; Ming Hao ; Kathryn L. Houmiel, Multigene expression vectors for the biosynthesis of products via multienzyme biological pathways.
Steinbuchel Alexander,DEX ; Liebergesell Mathias,DEX ; Valentin Henry ; Pries Andreas,DEX, PHA E and PHA C components of poly(hydroxy fatty acid) synthase from thiocapsa pfennigii.
Tobin Allan J. (Los Angeles CA) Erlander Mark G. (Tarzana CA) Kaufman Daniel L. (Santa Monica CA) Clare-Salzler Michael J. (Gainesville FL), Peptides derived from glutamic acid decarboxylase.
Cannon, Maura; Cannon, Francis C.; McCool, Gabriel J.; Valentin, Henry E.; Gruys, Kenneth J., Polyhydroxyalkanoate biosynthesis associated proteins and coding region in bacillus megaterium.
Matsuyama Akinobu (Niigata JPX) Nikaido Teruyuki (Niigata JPX) Kobayashi Yoshinori (Niigata JPX), Process for producing optically active 1,3-butanediol by reduction of 4-hydroxy-2-butanone.
Emptage,Mark; Haynie,Sharon L.; Laffend,Lisa A.; Pucci,Jeff P.; Whited,Gregory, Process for the biological production of 1,3-propanediol with high titer.
Emptage,Mark; Haynie,Sharon L.; Laffend,Lisa A.; Pucci,Jeff P.; Whited,Gregory Marshall, Process for the biological production of 1,3-propanediol with high titer.
Gottschalk G. (Nrtenhardenberg DEX) Averhoff Beate (Gottingen DEX), Process for the microbiological preparation of 1,3-propane-diol from glycerol by citrobacter.
Rieping,Mechthild; Hermann,Thomas, Process for the production of L-amino acids using strains of the family Enterobacteriaceae that contain an attenuated fruR gene.
Somerville Christopher R. (Portola Valley CA) Nawrath Christiane (Palo Alto CA) Poirier Yves (Palo Alto CA), Processes for producing polyhydroxybutyrate and related polyhydroxyalkanoates in the plastids of higher plants.
Jao Go Pan KR; Soo An Shin KR; Chan Kyu Park KR; Pil Kim KR; Dong Eun Chang KR; Jae Eun Kim KR, Pta LDHA double mutant Escherichia coli SS373 and the method of producing succinic acid therefrom.
Hespell Robert B. ; Wyckoff Herbert A. ; Dien Bruce S. ; Bothast Rodney J., Stabilization of pet operon plasmids and ethanol production in bacterial strains lacking lactate dehydrogenase and pyruvate formate lyase activities.
Somerville Christopher R. (Okemos MI) Poirier Yves (East Lansing MI) Dennis Douglas E. (Weyers Cave VA), Transgenic plants producing polyhydroxyalkanoates.
Burk, Mark J.; Van Dien, Stephen J.; Burgard, Anthony P.; Niu, Wei, Compositions and methods for the biosynthesis of 1,4-butanediol and its precursors.
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