CPC C12P 7/18 (2013.01) [C12N 15/52 (2013.01)] | 15 Claims |
1. A non-naturally occurring microbial organism having a 1,3-butanediol (1,3-BDO) pathway, wherein said non-naturally occurring microbial organism comprises at least one exogenous nucleic acid encoding a 1,3-BDO pathway enzyme expressed in a sufficient amount to produce 1,3-BDO; said non-naturally occurring microbial organism further comprising:
at least one exogenous nucleic acid encoding an enzyme selected from the group consisting of a CO dehydrogenase, an H2 hydrogenase, and combinations thereof;
wherein said 1,3-BDO pathway comprises a pathway selected from the group consisting of:
(a) (1) a 2-amino-4-ketopentanoate (AKP) thiolase; (2) an AKP dehydrogenase; (3) a 2-amino-4-hydroxypentanoate aminotransferase or oxidoreductase (deaminating); (4) a 2-oxo-4-hydroxypentanoate decarboxylase; and (5) a 3-hydroxybutyraldehyde reductase;
(b) (1) an AKP thiolase; (2) an AKP aminotransferase or oxidoreductase (deaminating); (3) a 2,4-dioxopentanoate decarboxylase; (4) a 3-oxobutyraldehyde reductase (ketone reducing); and (5) a 3-hydroxybutyraldehyde reductase;
(c) (1) an AKP thiolase; (2) an AKP aminotransferase or oxidoreductase (deaminating); (3) a 2,4-dioxopentanoate decarboxylase; (4) a 3-oxobutyraldehyde reductase (aldehyde reducing); and (5) a 4-hydroxy-2-butanone reductase;
(d) (1) an AKP thiolase; (2) an AKP decarboxylase; (3) a 4-aminobutan-2-one aminotransferase or oxidoreductase (deaminating); (4) a 3-oxobutyraldehyde reductase (ketone reducing); and (5) a 3-hydroxybutyraldehyde reductase;
(e) (1) an AKP thiolase; (2) an AKP decarboxylase; (3) a 4-aminobutan-2-one aminotransferase or oxidoreductase (deaminating); (4) a 3-oxobutyraldehyde reductase (aldehyde reducing); and (5) a 4-hydroxy-2-butanone reductase;
(f) (1) an AKP thiolase; (2) an AKP decarboxylase; (3) a 4-aminobutan-2-one ammonia-lyase; (4) a butenone hydratase; and (5) a 4-hydroxy-2-butanone reductase;
(g) (1) an AKP thiolase; (2) an AKP ammonia-lyase; (3) an acetylacrylate decarboxylase; (4) a butenone hydratase; and (5) a 4-hydroxy-2-butanone reductase;
(h) (1) a 4-hydroxybutyryl-CoA dehydratase; (2) a crotonase; and (3) a 3-hydroxybutyryl-CoA reductase (alcohol forming); and
(i) (1) a 4-hydroxybutyryl-CoA dehydratase; (2) a crotonase; (3) a 3-hydroxybutyryl-CoA reductase (aldehyde forming); and (4) a 3-hydroxybutyraldehyde reductase;
(j) (1) a succinyl-CoA transferase, a succinyl-CoA synthetase or a succinyl-CoA ligase, (2) a succinyl-CoA reductase (aldehyde forming), (3) a 4-hydroxybutyrate dehydrogenase, (4) a 4-hydroxybutyrate kinase, (5) a phosphotrans-4-hydroxybutyrylase, (6) a 4-hydroxybutyryl-CoA dehydratase, (7) a crotonase, (8) a 3-hydroxybutyryl-CoA reductase (aldehyde forming), and (9) a 3-hydroxybutanal reductase;
(k) (1) (i) an alpha-ketoglutarate decarboxylase, or (ii) (a) a glutamate dehydrogenase and/or a glutamate transaminase, (b) a glutamate decarboxylase, and (c) a 4-aminobutyrate dehydrogenase and/or a 4-aminobutyrate transaminase, (2) a 4-hydroxybutyrate dehydrogenase, (3) a 4-hydroxybutyrate kinase, (4) a phosphotrans-4-hydroxybutyrylase, (5) a 4-hydroxybutyryl-CoA dehydratase; (6) a crotonase, (7) a 3-hydroxybutyryl-CoA reductase (aldehyde forming), and (8) a 3-hydroxybutanal reductase;
(l) (1)(i) an alpha-ketoglutarate decarboxylase, or (ii) (a) a glutamate dehydrogenase and/or a glutamate transaminase, (b) a glutamate decarboxylase, and (c) a 4-aminobutyrate dehydrogenase and/or a 4-aminobutyrate transaminase, (2) a 4-hydroxybutyrate dehydrogenase, (3) a 4-hydroxybutyryl-CoA transferase or 4-hydroxybutyryl-CoA synthetase, (4) a 4-hydroxybutyryl-CoA dehydratase, (5) a crotonase, (6) a 3-hydroxybutyryl-CoA reductase (aldehyde forming), and (7) a 3-hydroxybutanal reductase;
(m) (1) (i) an alpha-ketoglutarate decarboxylase, or (ii) (a) a glutamate dehydrogenase and/or a glutamate transaminase, (b) a glutamate decarboxylase, and (c) a 4-aminobutyrate dehydrogenase and/or a 4-aminobutyrate transaminase, (2) a 4-hydroxybutyrate dehydrogenase, (3) a 4-hydroxybutyrate kinase, (4) a phosphotrans-4-hydroxybutyrylase, (5) a 4-hydroxybutyryl-CoA dehydratase, (6) a crotonase, and (7) a 3-hydroxybutyryl-CoA reductase (alcohol forming);
(n) (1)(i) an alpha-ketoglutarate decarboxylase, or (ii) (a) a glutamate dehydrogenase and/or a glutamate transaminase, (b) a glutamate decarboxylase, and (c) a 4-aminobutyrate dehydrogenase and/or a 4-aminobutyrate transaminase, (2) a 4-hydroxybutyrate dehydrogenase, (3) a 4-hydroxybutyryl-CoA transferase or 4-hydroxybutyryl-CoA synthetase, (4) a 4-hydroxybutyryl-CoA dehydratase, (5) a crotonase, and (6) a 3-hydroxybutyryl-CoA reductase (alcohol forming);
(o) (1)(i) an alpha-ketoglutarate decarboxylase, or (ii) (a) a glutamate dehydrogenase and/or a glutamate transaminase, (b) a glutamate decarboxylase, and (c) a 4-aminobutyrate dehydrogenase and/or a 4-aminobutyrate transaminase, (2) a 4-hydroxybutyrate dehydrogenase, (3) a 4-hydroxybutyrate kinase, (4) a phosphotrans-4-hydroxybutyrylase, (5) a 4-hydroxybutyryl-CoA dehydratase, (6) a crotonase, (7) a 3-hydroxybutyryl-CoA hydrolase, transferase or synthetase, and (8) a 3-hydroxybutyrate reductase;
(p) (1)(i) an alpha-ketoglutarate decarboxylase, or (ii) (a) a glutamate dehydrogenase and/or a glutamate transaminase, (b) a glutamate decarboxylase, and (c) a 4-aminobutyrate dehydrogenase and/or a 4-aminobutyrate transaminase, (2) a 4-hydroxybutyrate dehydrogenase, (3) a 4-hydroxybutyryl-CoA transferase or 4-hydroxybutyryl-CoA synthetase, (4) a 4-hydroxybutyryl-CoA dehydratase, (5) a crotonase, (6) a 3-hydroxybutyryl-CoA hydrolase, transferase or synthetase, and (7) a 3-hydroxybutyrate reductase;
(q) (1) a succinate reductase, (2) a 4-hydroxybutyrate dehydrogenase, (3) a 4-hydroxybutyrate kinase, (4) a phosphotrans-4-hydroxybutyrylase, (5) a 4-hydroxybutyryl-CoA dehydratase, (6) a crotonase, (7) a 3-hydroxybutyryl-CoA reductase (aldehyde forming), and (8) a 3-hydroxybutanal reductase;
(r) (1) a succinate reductase, (2) a 4-hydroxybutyrate dehydrogenase, (3) a 4-hydroxybutyryl-CoA transferase or 4-hydroxybutyryl-CoA synthetase, (4) a 4-hydroxybutyryl-CoA dehydratase, (5) a crotonase, (6) a 3-hydroxybutyryl-CoA reductase (aldehyde forming), (7) a 3-hydroxybutanal reductase;
(s) (1) a succinate reductase, (2) a 4-hydroxybutyrate dehydrogenase, (3) a 4-hydroxybutyrate kinase, (4) a phosphotrans-4-hydroxybutyrylase, (5) a 4-hydroxybutyryl-CoA dehydratase, (6) a crotonase, and (7) a 3-hydroxybutyryl-CoA reductase (alcohol forming);
(t) (1) a succinate reductase, (2) a 4-hydroxybutyrate dehydrogenase, (3) a 4-hydroxybutyryl-CoA transferase or 4-hydroxybutyryl-CoA synthetase, (4) a 4-hydroxybutyryl-CoA dehydratase, (5) a crotonase, and (6) a 3-hydroxybutyryl-CoA reductase (alcohol forming);
(u) (1) a succinate reductase, (2) a 4-hydroxybutyrate dehydrogenase, (3) a 4-hydroxybutyrate kinase, (4) a phosphotrans-4-hydroxybutyrylase, (5) a 4-hydroxybutyryl-CoA dehydratase, (6) a crotonase, (7) a 3-hydroxybutyryl-CoA hydrolase, transferase or synthetase, and (8) a 3-hydroxybutyrate reductase;
(v) (1) a succinate reductase, (2) a 4-hydroxybutyrate dehydrogenase, (3) a 4-hydroxybutyryl-CoA transferase or 4-hydroxybutyryl-CoA synthetase, (4) a 4-hydroxybutyryl-CoA dehydratase, (5) a crotonase, (6) a 3-hydroxybutyryl-CoA hydrolase, transferase or synthetase, and (7) a 3-hydroxybutyrate reductase;
(w) (1) a succinyl-CoA transferase, succinyl-CoA synthetase or succinyl-CoA ligase, (2) a succinyl-CoA reductase (aldehyde forming), (3) a 4-hydroxybutyrate dehydrogenase, (5) a 4-hydroxybutyrate kinase, (6) a phosphotrans-4-hydroxybutyrylase, (7) a 4-hydroxybutyryl-CoA dehydratase, (8) a crotonase, and (9) a 3-hydroxybutyryl-CoA reductase (alcohol forming);
(x) (1) a succinyl-CoA transferase, succinyl-CoA synthetase or succinyl-CoA ligase, (2) a succinyl-CoA reductase (aldehyde forming), (3) a 4-hydroxybutyrate dehydrogenase, (4) a 4-hydroxybutyrate kinase, (5) a phosphotrans-4-hydroxybutyrylase, (6) a 4-hydroxybutyryl-CoA dehydratase, (7) a crotonase, (8) a 3-hydroxybutyryl-CoA hydrolase, transferase or synthetase, and (9) a 3-hydroxybutyrate reductase;
(y) (1) a succinyl-CoA transferase, succinyl-CoA synthetase or succinyl-CoA ligase, (2) a succinyl-CoA reductase (alcohol forming), (3) a 4-hydroxybutyrate kinase, (4) a phosphotrans-4-hydroxybutyrylase, (5) a 4-hydroxybutyryl-CoA dehydratase, (6) a crotonase, (7) a 3-hydroxybutyryl-CoA reductase (aldehyde forming), and (8) a 3-hydroxybutanal reductase;
(z) (1) a succinyl-CoA transferase, succinyl-CoA synthetase or succinyl-CoA ligase, (2) a succinyl-CoA reductase (alcohol forming), (3) a 4-hydroxybutyrate kinase, (4) a phosphotrans-4-hydroxybutyrylase, (5) a 4-hydroxybutyryl-CoA dehydratase, (6) a crotonase, and (7) a 3-hydroxybutyryl-CoA reductase (alcohol forming);
(aa) (1) a succinyl-CoA transferase, succinyl-CoA synthetase or succinyl-CoA ligase, (2) a succinyl-CoA reductase (alcohol forming), (3) a 4-hydroxybutyrate kinase, (4) a phosphotrans-4-hydroxybutyrylase, (5) a 4-hydroxybutyryl-CoA dehydratase, (6) a crotonase, (7) a 3-hydroxybutyryl-CoA hydrolase, transferase or synthetase, and (8) a 3-hydroxybutyrate reductase;
(bb) (1) a succinyl-CoA transferase, succinyl-CoA synthetase or succinyl-CoA ligase, (2) a succinyl-CoA reductase (aldehyde forming), (3) a 4-hydroxybutyrate dehydrogenase, (4) a 4-hydroxybutyryl-CoA transferase, or 4-hydroxybutyryl-CoA synthetase, (5) a 4-hydroxybutyryl-CoA dehydratase, (6) a crotonase, (7) a 3-hydroxybutyryl-CoA reductase (aldehyde forming), and (8) a 3-hydroxybutanal reductase;
(cc) (1) a succinyl-CoA transferase, succinyl-CoA synthetase or succinyl-CoA ligase, (2) a succinyl-CoA reductase (aldehyde forming), (3) a 4-hydroxybutyrate dehydrogenase, (4) a 4-hydroxybutyryl-CoA transferase or 4-hydroxybutyryl-CoA synthetase, (5) a 4-hydroxybutyryl-CoA dehydratase, (6) a crotonase, and (7) a 3-hydroxybutyryl-CoA reductase (alcohol forming);
(dd) (1) a succinyl-CoA transferase, succinyl-CoA synthetase or succinyl-CoA ligase, (2) a succinyl-CoA reductase (aldehyde forming), (3) a 4-hydroxybutyrate dehydrogenase, (4) a 4-hydroxybutyryl-CoA transferase or 4-hydroxybutyryl-CoA synthetase, (5) a 4-hydroxybutyryl-CoA dehydratase, (6) a crotonase, (7) a 3-hydroxybutyryl-CoA hydrolase, transferase or synthetase, (8) a 3-hydroxybutyrate reductase;
(ee) (1) a succinyl-CoA transferase, succinyl-CoA synthetase or succinyl-CoA ligase, (2) a succinyl-CoA reductase (alcohol forming), (3) a 4-hydroxybutyryl-CoA transferase or 4-hydroxybutyryl-CoA synthetase, (4) a 4-hydroxybutyryl-CoA dehydratase, (5) a crotonase, (6) a 3-hydroxybutyryl-CoA reductase (aldehyde forming), and (7) a 3-hydroxybutanal reductase;
(ff) (1) a succinyl-CoA transferase, succinyl-CoA synthetase or succinyl-CoA ligase, (2) a succinyl-CoA reductase (alcohol forming), (3) a 4-hydroxybutyryl-CoA transferase or 4-hydroxybutyryl-CoA synthetase, (4) a 4-hydroxybutyryl-CoA dehydratase, (5) a crotonase, and (6) a 3-hydroxybutyryl-CoA reductase (alcohol forming);
(gg) (1) a succinyl-CoA transferase, succinyl-CoA synthetase or succinyl-CoA ligase, (2) a succinyl-CoA reductase (alcohol forming), (3) a 4-hydroxybutyryl-CoA transferase or 4-hydroxybutyryl-CoA synthetase, (5) a 4-hydroxybutyryl-CoA dehydratase, (6) a crotonase, (7) a 3-hydroxybutyryl-CoA hydrolase, transferase or synthetase, and (8) a 3-hydroxybutyrate reductase;
(hh) (1)(i) an alpha-ketoglutarate decarboxylase, or (ii) (a) a glutamate dehydrogenase and/or a glutamate transaminase, (b) a glutamate decarboxylase, and (c) a 4-aminobutyrate dehydrogenase and/or a 4-aminobutyrate transaminase, (2) a 4-hydroxybutyrate dehydrogenase, (3) a 4-hydroxybutyryl-CoA transferase or 4-hydroxybutyryl-CoA synthetase, (4) a 4-hydroxybutyryl-CoA dehydratase, (5) a crotonase, (6) a 3-hydroxybutyryl-CoA reductase (aldehyde forming), and (7) 3-hydroxybutyraldehyde reductase, and
(ii) (1) a 4-hydroxybutyryl-CoA dehydratase, (2) a crotonase, (3) a 3-hydroxybutyryl-CoA hydrolase, transferase or synthetase, and (4) a 3-hydroxybutyrate reductase.
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