Methods and organisms with increased carbon flux efficiencies
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.
1. A non-naturally occurring microbial organism comprising
(i) a genetic alteration that attenuates a cytochrome oxidase encoded by cydA or cydB, or an orthologous gene thereof, and a genetic alternation that increases expression of a NAD(P) transhydrogenase encoded by pntAB or an orthologous gene thereof; and
(ii) a genetic alternation that attenuates a succinyl-CoA synthetase encoded by sucCD or an orthologous gene thereof, and a genetic alternation that attenuates a CoA hydrolase encoded by yciA or an orthologous gene thereof.
2. The non-naturally occurring microbial organism of claim 1 , further comprising a metabolically engineered pathway for producing a bioderived compound from a TCA cycle intermediate or a TCA cycle substrate.
3. A non-naturally occurring microbial organism of claim 1 , wherein said microbial organism is selected from the group consisting of bacteria, yeast, fungus or other microorganism applicable to a fermentation process.
4. The non-naturally occurring microbial organism of claim 2 , wherein the yield of the bioderived compound is increased relative to the absence of said genetic alteration.
5. A method of producing a bioderived compound comprising culturing a non-naturally occurring microbial organism of claim 2 for a sufficient period of time under conditions sufficient to produce said bioderived compound.
6. The non-naturally occurring microbial organism of claim 2 , wherein said bioderived compound is selected from the group consisting of 4-hydroxybutyrate (4HB), 1,4-butanediol (1,4-BDO), 1,3-butanediol (1,3-BDO), polyhydroxylbutanoate (PHB), butadiene, adipate, 6-aminocaproate, caprolactam, methacrylic acid, isopropanol, long chain alcohols, hexamethylenediamene, methyl methacrylate, butanol, 3-butene-1-ol, 3-butene-2-ol and crotyl-alcohol.
7. A non-naturally occurring microbial organism of claim 3 , wherein said microbial organism is Escherichia coli.