Microorganisms for the production of 1,4-butanediol
원문보기
IPC분류정보
국가/구분
United States(US) Patent
등록
국제특허분류(IPC7판)
C12P-007/18
C12N-001/21
출원번호
US-0009813
(2011-01-19)
등록번호
US-8178327
(2012-05-15)
발명자
/ 주소
Burk, Mark J.
Burgard, Anthony P.
Osterhout, Robin E.
Sun, Jun
출원인 / 주소
Genomatica, Inc.
대리인 / 주소
Jones Day
인용정보
피인용 횟수 :
13인용 특허 :
93
초록▼
The invention provides non-naturally occurring microbial organisms comprising a 1,4-butanediol (BDO) pathway comprising at least one exogenous nucleic acid encoding a BDO pathway enzyme expressed in a sufficient amount to produce BDO. The invention additionally provides methods of using such microbi
The invention provides non-naturally occurring microbial organisms comprising a 1,4-butanediol (BDO) pathway comprising at least one exogenous nucleic acid encoding a BDO pathway enzyme expressed in a sufficient amount to produce BDO. The invention additionally provides methods of using such microbial organisms to produce BDO.
대표청구항▼
1. A non-naturally occurring microbial organism having nucleic acids encoding enzymes of a 1,4-butanediol (BDO) pathway, said microbial organism comprising at least one exogenous nucleic acid encoding a BDO pathway enzyme expressed in a sufficient amount to produce BDO, wherein said BDO pathway enzy
1. A non-naturally occurring microbial organism having nucleic acids encoding enzymes of a 1,4-butanediol (BDO) pathway, said microbial organism comprising at least one exogenous nucleic acid encoding a BDO pathway enzyme expressed in a sufficient amount to produce BDO, wherein said BDO pathway enzymes comprise glutamate dehydrogenase, said enzyme classified as EC 1.4.1.a and converting alpha-ketoglutarate to glutamate; glutamate decarboxylase, said enzyme classified as EC 4.1.1.a and converting glutamate to 4-aminobutyrate; 4-aminobutyrate oxidoreductase (deaminating), said enzyme classified as EC 1.4.1.a and converting 4-aminobutyrate to succinate semialdehyde; and 4-hydroxybutyrate dehydrogenase, said enzyme classified as EC 1.1.1.a and converting succinate semialdehyde to 4-hydroxybutyrate; and wherein said BDO pathway enzymes further comprise: (a) 4-hydroxybutyrate kinase, said enzyme classified as EC 2.7.2.a and converting 4-hydroxybutyrate to 4-hydroxybutyryl-phosphate; phosphotrans-4-hydroxybutyrylase, said enzyme classified as EC 2.3.1.a and converting 4-hydroxybutyryl-phosphate to 4-hydroxybutyryl-CoA; 4-hydroxybutyryl-CoA reductase, said enzyme classified as EC 1.2.1.b and converting 4-hydroxybutyryl-CoA to 4-hydroxybutanal; and 1,4-butanediol dehydrogenase, said enzyme classified as EC 1.1.1.a converting 4-hydroxybutanal to 1,4-butanediol;(b) 4-hydroxybutyryl-CoA transferase, said enzyme classified as EC 2.8.3.a and converting 4-hydroxybutyrate to 4-hydroxybutyryl-CoA, 4-hydroxybutyryl-CoA hydrolase, said enzyme classified as EC 3.1.2.a and converting 4-hydroxybutyrate to 4-hydroxybutyryl-CoA, or 4-hydroxybutyryl-CoA ligase, said enzyme classified as EC 6.2.1.a and converting 4-hydroxybutyrate to 4-hydroxybutyryl-CoA; 4-hydroxybutyryl-CoA reductase; and 1,4-butanediol dehydrogenase;(c) 4-hydroxybutyryl-CoA transferase, 4-hydroxybutyryl-CoA hydrolase, or 4-hydroxybutyryl-CoA ligase; and 4-hydroxybutyryl-CoA reductase (alcohol forming), said enzyme classified as EC 1.1.1.c and converting 4-hydroxybutyryl-CoA to 1,4-butanediol;(d) 4-hydroxybutyrate kinase; 4-hydroxybutanal dehydrogenase (phosphorylating), said enzyme classified as EC 1.2.1.d and converting 4-hydroxybutyryl-phosphate to 4-hydroxybutanal; and 1,4-butanediol dehydrogenase; or(e) 4-hydroxybutyrate kinase; phosphotrans-4-hydroxybutyrylase; and 4-hydroxybutyryl-CoA reductase (alcohol forming). 2. The non-naturally occurring microbial organism of claim 1, wherein said at least one exogenous nucleic acid is a heterologous nucleic acid. 3. The non-naturally occurring microbial organism of claim 1, wherein said BDO pathway enzymes comprise glutamate dehydrogenase; glutamate decarboxylase; 4-aminobutyrate oxidoreductase (deaminating); 4-hydroxybutyrate dehydrogenase; 4-hydroxybutyrate kinase; phosphotrans-4-hydroxybutyrylase; 4-hydroxybutyryl-CoA reductase; and 1,4-butanediol dehydrogenase. 4. The non-naturally occurring microbial organism of claim 1, wherein said BDO pathway enzymes comprise glutamate dehydrogenase; glutamate decarboxylase; 4-aminobutyrate oxidoreductase (deaminating); 4-hydroxybutyrate dehydrogenase; 4-hydroxybutyryl-CoA transferase, 4-hydroxybutyryl-CoA hydrolase, or 4-hydroxybutyryl-CoA ligase; 4-hydroxybutyryl-CoA reductase; and 1,4-butanediol dehydrogenase. 5. The non-naturally occurring microbial organism of claim 1, wherein said BDO pathway enzymes comprise glutamate dehydrogenase; glutamate decarboxylase; 4-aminobutyrate oxidoreductase (deaminating); 4-hydroxybutyrate dehydrogenase; 4-hydroxybutyryl-CoA transferase, 4-hydroxybutyryl-CoA hydrolase, or 4-hydroxybutyryl-CoA ligase; and 4-hydroxybutyryl-CoA reductase (alcohol forming). 6. The non-naturally occurring microbial organism of claim 1, wherein said BDO pathway enzymes comprise glutamate dehydrogenase; glutamate decarboxylase; 4-aminobutyrate oxidoreductase (deaminating); 4-hydroxybutyrate dehydrogenase; 4-hydroxybutyrate kinase; 4-hydroxybutanal dehydrogenase (phosphorylating); and 1,4-butanediol dehydrogenase. 7. The non-naturally occurring microbial organism of claim 1, wherein said BDO pathway enzymes comprise glutamate dehydrogenase; glutamate decarboxylase; 4-aminobutyrate oxidoreductase (deaminating); 4-hydroxybutyrate dehydrogenase; 4-hydroxybutyrate kinase; phosphotrans-4-hydroxybutyrylase; and 4-hydroxybutyryl-CoA reductase (alcohol forming). 8. A non-naturally occurring microbial organism having nucleic acids encoding enzymes of a 1,4-butanediol (BDO) pathway, said microbial organism comprising at least one exogenous nucleic acid encoding a BDO pathway enzyme expressed in a sufficient amount to produce BDO, wherein said BDO pathway enzymes comprise alpha-ketoglutarate decarboxylase, said enzyme classified as EC 4.1.1.a and converting alpha-ketoglutarate to succinate semialdehyde, or glutamate dehydrogenase, said enzyme classified as EC 1.4.1.a and converting alpha-ketoglutarate to glutamate, glutamate decarboxylase, said enzyme classified as EC 4.1.1.a and converting glutamate to 4-aminobutyrate, and 4-aminobutyrate transaminase, said enzyme classified as EC 2.6.1.a and converting 4-aminobutyrate to succinate semialdehyde; and 4-hydroxybutyrate dehydrogenase, said enzyme classified as EC 1.1.1.a and converting succinate semialdehyde to 4-hydroxybutyrate; and wherein said BDO pathway enzymes further comprise: (a) 4-hydroxybutyryl-CoA ligase, said enzyme classified as EC 6.2.1.a and converting 4-hydroxybutyrate to 4-hydroxybutyryl-CoA; 4-hydroxybutyryl-CoA reductase, said enzyme classified as EC 1.2.1.b and converting 4-hydroxybutyryl-CoA to 4-hydroxybutanal; and 1,4-butanediol dehydrogenase, said enzyme classified as EC 1.1.1.a converting 4-hydroxybutanal to 1,4-butanediol;(b) 4-hydroxybutyryl-CoA transferase, said enzyme classified as EC 2.8.3.a and converting 4-hydroxybutyrate to 4-hydroxybutyryl-CoA, 4-hydroxybutyryl-CoA hydrolase, said enzyme classified as EC 3.1.2.a and converting 4-hydroxybutyrate to 4-hydroxybutyryl-CoA, or 4-hydroxybutyryl-CoA ligase; and 4-hydroxybutyryl-CoA reductase (alcohol forming), said enzyme classified as EC 1.1.1.c and converting 4-hydroxybutyryl-CoA to 1,4-butanediol;(c) 4-hydroxybutyrate kinase, said enzyme classified as EC 2.7.2.a and converting 4-hydroxybutyrate to 4-hydroxybutyryl-phosphate; 4-hydroxybutanal dehydrogenase (phosphorylating), said enzyme classified as EC 1.2.1.d and converting 4-hydroxybutyryl-phosphate to 4-hydroxybutanal; and 1,4-butanediol dehydrogenase; or(d) 4-hydroxybutyrate kinase; phosphotrans-4-hydroxybutyrylase, said enzyme classified as EC 2.3.1.a and converting 4-hydroxybutyryl-phosphate to 4-hydroxybutyryl-CoA; and 4-hydroxybutyryl-CoA reductase (alcohol forming). 9. The non-naturally occurring microbial organism of claim 8, wherein said at least one exogenous nucleic acid is a heterologous nucleic acid. 10. The non-naturally occurring microbial organism of claim 8, wherein said BDO pathway enzymes comprise alpha-ketoglutarate decarboxylase, or glutamate dehydrogenase, glutamate decarboxylase, and 4-aminobutyrate transaminase; 4-hydroxybutyrate dehydrogenase; 4-hydroxybutyryl-CoA ligase; 4-hydroxybutyryl-CoA reductase; and 1,4-butanediol dehydrogenase. 11. The non-naturally occurring microbial organism of claim 8, wherein said BDO pathway enzymes comprise alpha-ketoglutarate decarboxylase, or glutamate dehydrogenase, glutamate decarboxylase, and 4-aminobutyrate transaminase; 4-hydroxybutyrate dehydrogenase; 4-hydroxybutyryl-CoA transferase, 4-hydroxybutyryl-CoA hydrolase, or 4-hydroxybutyryl-CoA ligase; and 4-hydroxybutyryl-CoA reductase (alcohol forming). 12. The non-naturally occurring microbial organism of claim 8, wherein said BDO pathway enzymes comprise alpha-ketoglutarate decarboxylase, or glutamate dehydrogenase, glutamate decarboxylase, and 4-aminobutyrate transaminase; 4-hydroxybutyrate dehydrogenase; 4-hydroxybutyrate kinase; 4-hydroxybutanal dehydrogenase (phosphorylating); and 1,4-butanediol dehydrogenase. 13. The non-naturally occurring microbial organism of claim 8, wherein said BDO pathway enzymes comprise alpha-ketoglutarate decarboxylase, or glutamate dehydrogenase, glutamate decarboxylase, and 4-aminobutyrate transaminase; 4-hydroxybutyrate dehydrogenase; 4-hydroxybutyrate kinase; phosphotrans-4-hydroxybutyrylase; and 4-hydroxybutyryl-CoA reductase (alcohol forming). 14. A non-naturally occurring microbial organism having nucleic acids encoding enzymes of a 1,4-butanediol (BDO) pathway, said microbial organism comprising at least one exogenous nucleic acid encoding a BDO pathway enzyme expressed in a sufficient amount to produce BDO, wherein said BDO pathway enzymes comprise alpha-ketoglutarate dehydrogenase, said enzyme classified as EC 1.2.1.c and converting alpha-ketoglutarate to succinyl-CoA; CoA-dependent succinic semialdehyde dehydrogenase, said enzyme classified as EC 1.2.1.b and converting succinyl-CoA to succinate semialdehyde; and 4-hydroxybutyrate dehydrogenase, said enzyme classified as EC 1.1.1.a and converting succinate semialdehyde to 4-hydroxybutyrate; and wherein said BDO pathway enzymes further comprise: (a) 4-hydroxybutyryl-CoA ligase, said enzyme classified as EC 6.2.1.a and converting 4-hydroxybutyrate to 4-hydroxybutyryl-CoA; 4-hydroxybutyryl-CoA reductase, said enzyme classified as EC 1.2.1.b and converting 4-hydroxybutyryl-CoA to 4-hydroxybutanal; and 1,4-butanediol dehydrogenase, said enzyme classified as EC 1.1.1.a converting 4-hydroxybutanal to 1,4-butanediol;(b) 4-hydroxybutyryl-CoA transferase, said enzyme classified as EC 2.8.3.a and converting 4-hydroxybutyrate to 4-hydroxybutyryl-CoA, 4-hydroxybutyryl-CoA hydrolase, said enzyme classified as EC 3.1.2.a and converting 4-hydroxybutyrate to 4-hydroxybutyryl-CoA, or 4-hydroxybutyryl-CoA ligase; and 4-hydroxybutyryl-CoA reductase (alcohol forming), said enzyme classified as EC 1.1.1.c and converting 4-hydroxybutyryl-CoA to 1,4-butanediol;(c) 4-hydroxybutyrate kinase, said enzyme classified as EC 2.7.2.a and converting 4-hydroxybutyrate to 4-hydroxybutyryl-phosphate; 4-hydroxybutanal dehydrogenase (phosphorylating), said enzyme classified as EC 1.2.1.d and converting 4-hydroxybutyryl-phosphate to 4-hydroxybutanal; and 1,4-butanediol dehydrogenase; or(d) 4-hydroxybutyrate kinase; phosphotrans-4-hydroxybutyrylase, said enzyme classified as EC 2.3.1.a and converting 4-hydroxybutyryl-phosphate to 4-hydroxybutyryl-CoA; and 4-hydroxybutyryl-CoA reductase (alcohol forming). 15. The non-naturally occurring microbial organism of claim 14, wherein said at least one exogenous nucleic acid is a heterologous nucleic acid. 16. The non-naturally occurring microbial organism of claim 14, wherein said BDO pathway enzymes comprise alpha-ketoglutarate dehydrogenase; CoA-dependent succinic semialdehyde dehydrogenase; 4-hydroxybutyrate dehydrogenase; 4-hydroxybutyryl-CoA ligase; 4-hydroxybutyryl-CoA reductase; and 1,4-butanediol dehydrogenase. 17. The non-naturally occurring microbial organism of claim 14, wherein said BDO pathway enzymes comprise alpha-ketoglutarate dehydrogenase; CoA-dependent succinic semialdehyde dehydrogenase; 4-hydroxybutyrate dehydrogenase; 4-hydroxybutyryl-CoA transferase, 4-hydroxybutyryl-CoA hydrolase, or 4-hydroxybutyryl-CoA ligase; and 4-hydroxybutyryl-CoA reductase (alcohol forming). 18. The non-naturally occurring microbial organism of claim 14, wherein said BDO pathway enzymes comprise alpha-ketoglutarate dehydrogenase; CoA-dependent succinic semialdehyde dehydrogenase; 4-hydroxybutyrate dehydrogenase; 4-hydroxybutyrate kinase; 4-hydroxybutanal dehydrogenase (phosphorylating); and 1,4-butanediol dehydrogenase. 19. The non-naturally occurring microbial organism of claim 14, wherein said BDO pathway enzymes comprise alpha-ketoglutarate dehydrogenase; CoA-dependent succinic semialdehyde dehydrogenase; 4-hydroxybutyrate dehydrogenase; 4-hydroxybutyrate kinase; phosphotrans-4-hydroxybutyrylase; and 4-hydroxybutyryl-CoA reductase (alcohol forming).
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