Methods and organisms with increased carbon flux efficiencies

Patent metadata

Field	Value
Publication number	US-10597684-B2
Application number	US-201415108259-A
Country	US
Kind code	B2
Filing date	Dec 23, 2014
Priority date	Dec 27, 2013
Publication date	Mar 24, 2020
Grant date	Mar 24, 2020

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.

First claim

What is claimed is:

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.

Assignees

• Genomatica Inc

Inventors

• Burgard Anthony P
• Osterhout Robin E
• Van Dien Stephen J
• Pharkya Priti
• Yang Tae Hoon
• Choi Jungik

Classifications

• C12N9/93

  Ligases (6) · CPC title

• C12P7/42

  Hydroxy-carboxylic acids · CPC title

• C07K14/245

  Escherichia (G) · CPC title

• C12N1/20

  Bacteria; Culture media therefor · CPC title

• C12Y401/01031

  Phosphoenolpyruvate carboxylase (4.1.1.31) · CPC title