skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Engineered microorganisms capable of producing target compounds under anaerobic conditions

Patent ·
OSTI ID:1034914

The present invention is generally provides recombinant microorganisms comprising engineered metabolic pathways capable of producing C3-C5 alcohols under aerobic and anaerobic conditions. The invention further provides ketol-acid reductoisomerase enzymes which have been mutated or modified to increase their NADH-dependent activity or to switch the cofactor preference from NADPH to NADH and are expressed in the modified microorganisms. In addition, the invention provides isobutyraldehyde dehydrogenase enzymes expressed in modified microorganisms. Also provided are methods of producing beneficial metabolites under aerobic and anaerobic conditions by contacting a suitable substrate with the modified microorganisms of the present invention.

Research Organization:
Gevo, Inc. (Englewood, CO)
Sponsoring Organization:
USDOE
DOE Contract Number:
FG02-07ER84893
Assignee:
Gevo, Inc. (Englewood, CO); California Institute of Technology (Pasadena, CA)
Patent Number(s):
8,097,440
Application Number:
13/269,937
OSTI ID:
1034914
Country of Publication:
United States
Language:
English

References (27)

Reversal of the Nucleotide Specificity of Ketol Acid Reductoisomerase by Site-Directed Mutagenesis Identifies the NADPH Binding Site1 journal February 1997
Expression of protein engineered NADP+-dependent xylitol dehydrogenase increases ethanol production from xylose in recombinant Saccharomyces cerevisiae journal November 2008
Manipulation of malic enzyme in Saccharomyces cerevisiae for increasing NADPH production capacity aerobically in different cellular compartments journal October 2004
Metabolic Engineering of Saccharomyces cerevisiae journal March 2000
Redesign of the coenzyme specificity of a dehydrogenase by protein engineering journal January 1990
Cofactor Regeneration by a Soluble Pyridine Nucleotide Transhydrogenase for Biological Production of Hydromorphone journal December 2000
The expression of aPichia stipitis xylose reductase mutant with higherKM for NADPH increases ethanol production from xylose in recombinantSaccharomyces cerevisiae journal January 2006
Ethanol production from xylose by recombinant Saccharomyces cerevisiae expressing protein-engineered NADH-preferring xylose reductase from Pichia stipitis journal September 2007
Improved synthesis of chiral alcohols with Escherichia coli cells co-expressing pyridine nucleotide transhydrogenase, NADP+-dependent alcohol dehydrogenase and NAD+-dependent formate dehydrogenase journal November 2004
Alcohol dehydrogenase gene of Drosophila melanogaster: relationship of intervening sequences to functional domains in the protein. journal May 1981
Complete Reversal of Coenzyme Specificity by Concerted Mutation of Three Consecutive Residues in Alcohol Dehydrogenase journal August 2003
Metabolic flux response to phosphoglucose isomerase knock-out in Escherichia coli and impact of overexpression of the soluble transhydrogenase UdhA journal November 2001
Novel Antioxidant Role of Alcohol Dehydrogenase E from Escherichia coli journal June 2003
Ethanol production from xylose by recombinant Saccharomyces cerevisiae expressing protein engineered NADP+-dependent xylitol dehydrogenase journal June 2007
Expression of a cytoplasmic transhydrogenase inSaccharomyces cerevisiae results in formation of 2-oxoglutarate due to depletion of the NADPH pool journal January 2000
Bioethanol production from xylose by recombinant Saccharomyces cerevisiae expressing xylose reductase, NADP+-dependent xylitol dehydrogenase, and xylulokinase journal March 2008
Metabolic engineering of Escherichia coli for 1-butanol production journal November 2008
Altering the coenzyme preference of xylose reductase to favor utilization of NADH enhances ethanol yield from xylose in a metabolically engineered strain of Saccharomyces cerevisiae journal January 2008
Metabolic engineering for advanced biofuels production from Escherichia coli journal October 2008
The Soluble and Membrane-bound Transhydrogenases UdhA and PntAB Have Divergent Functions in NADPH Metabolism of Escherichia coli journal December 2003
Metabolic engineering of Escherichia coli for 1-butanol and 1-propanol production via the keto-acid pathways journal November 2008
Expression of the Escherichia coli pntA andpntB Genes, Encoding Nicotinamide Nucleotide Transhydrogenase, in Saccharomyces cerevisiae and Its Effect on Product Formation during Anaerobic Glucose Fermentation journal January 1999
Metabolic engineering of microorganisms for biofuels production: from bugs to synthetic biology to fuels journal December 2008
Replacing Escherichia coli NAD-dependent glyceraldehyde 3-phosphate dehydrogenase (GAPDH) with a NADP-dependent enzyme from Clostridium acetobutylicum facilitates NADPH dependent pathways journal November 2008
Expression of Azotobacter vinelandii soluble transhydrogenase perturbs xylose reductase-mediated conversion of xylose to xylitol by recombinant Saccharomyces cerevisiae journal December 2003
Engineering the isobutanol biosynthetic pathway in Escherichia coli by comparison of three aldehyde reductase/alcohol dehydrogenase genes journal July 2009
In silico aided metabolic engineering of Saccharomyces cerevisiae for improved bioethanol production journal November 2005