Methods and organisms with increased carbon flux efficiencies
AssigneeGenomatica, Inc.
InventorsAnthony P. Burgard, Robin E. Osterhout, Stephen J. Van Dien, Priti Pharkya, Tae Hoon Yang, Jungik Choi
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Abstract
The invention is directed to a non-naturally occurring microbial organism comprising a first attenuation of a succinyl-CoA synthetase or transferase and at least a second attenuation of a succinyl-CoA converting enzyme or a gene encoding a succinate producing enzyme within a multi-step pathway having a net conversion of succinyl-CoA to succinate.
Claims21
-75. (canceled)
A non-naturally occurring microbial organism comprising a gene disruption of a gene encoding YciA CoA hydrolase and a metabolically engineered pathway for producing a bioderived compound from a TCA cycle intermediate, wherein the microbial organism comprises one or more modifications selected from the group consisting of:
- (a) increased expression of a pyridine nucleotide transhydrogenase relative to a microbial organism lacking said modification;
- (b) a genetic alteration that increases expression of NADH dehydrogenase Ndh-I, cytochrome bo oxidase, or both NADH dehydrogenase Ndh-I and cytochrome bo oxidase relative to a microbial organism lacking said modification;
- (c) attenuation of one or more NAD(P)H dehydrogenases or NAD(P)H:quinine oxidoreductases, one or more NAD(P)H dehydrogenases, or one or more non-cytochrome bo ubiquinol oxidases;
- (d) a gene disruption of one or more endogenous nucleic acids encoding a menaquinol biosynthetic enzyme, or one or more nucleic acids encoding a dimethylmenaquinol biosynthetic enzyme;
- (e) attenuation of protein encoding ClpA, pyruvate kinase or glucose phosphotransferase system (PTS);
- and
- (f) a genetic alteration that increases expression of a phosphoenoylpyruvate carboxykinase (PEPCK), a phosphoenoylpyruvate carboxylase (PPC), or both a PEPCK and a PPC in said microbial organism relative to a microbial organism lacking said modification.
The non-naturally occurring microbial organism of claim 95, wherein:
- (i) said microbial organism comprises an exogenous nucleic acid encoding said PEPCK;
- or
- (ii) said microbial organism further comprises a genetic alteration that comprises attenuation of a phosphoenoylpyruvate carboxylase (PPC) in said microbial organism.
Dependencies are inferred from the claim text.