Method for producing hydroxycarboxylic acid by enhancing synthesis of coenzyme

Abstract

Hydroxycarboxylic acids are produced by using a microorganism that is improved in ability to produce nicotinamide adenine dinucleotide by deleting, mutating or substituting nadR gene in the microorganism or introducing a gene encoding nicotinic acid phosphoribosyltransferase.

1 . A method for producing a hydroxycarboxylic acid from an aliphatic polyhydric alcohol having a hydroxyl group at the end by using a microorganism, the method comprising using the microorganism which has an enhanced ability to produce nicotinamide adenine dinucleotide. 
     
     
         2 . The production method as set forth in  claim 1 , wherein the microorganism is provided with enhanced ability to produce nicotinamide adenine dinucleotide by performing at least one genetic manipulation of the following (1) and (2):
 (1) deleting, mutating or substituting nadR gene in the microorganism;   (2) introducing into the microorganism a plasmid integrated with a gene of nicotinic acid phosphoribosyltransferase in the microorganism   
     
     
         3 . The production method as set forth in  claim 1 , wherein the microorganism has an enhanced ability to regenerate oxidized form of nicotinamide adenine dinucleotide. 
     
     
         4 . The production method as set forth in  claim 3 , wherein the microorganism is provided with enhanced ability to regenerate oxidized form of nicotinamide adenine dinucleotide by introducing a plasmid integrated with a gene of NADH dehydrogenase. 
     
     
         5 . The production method as set forth in  claim 1 , wherein the microorganism has enhanced activity of at least one enzyme of lactaldehyde reductase and lactaldehyde dehydrogenase. 
     
     
         6 . The production method as set forth in  claim 3 , wherein the microorganism has enhanced activity of at least one enzyme of lactaldehyde reductase and lactaldehyde dehydrogenase. 
     
     
         7 . The production method as set forth in any one of  claims 1 ,  3 ,  5  and  6 , wherein the microorganism has inactivated or lowered activity of glycolate oxidase as compared to the activity of existing microorganism. 
     
     
         8 . The production method as set forth in any one of  claims 1  to  6 , wherein the aliphatic polyhydric alcohol having a hydroxyl group at the end is ethylene glycol and the hydroxycarboxylic acid is glycolic acid. 
     
     
         9 . A microorganism, wherein an activity of at least one enzyme of lactaldehyde reductase and lactaldehyde dehydrogenase is enhanced, as well as an ability to produce nicotinamide adenine dinucleotide is enhanced by performing at least one gene manipulation of the following (1) and (2):
 (1) deleting, mutating or substituting nadR gene in the microorganism;   (2) introducing into the microorganism a plasmid integrated with a gene of nicotinic acid phosphoribosyltransferase in the microorganism.   
     
     
         10 . The microorganism as set forth in  claim 9 , wherein an ability to regenerate oxidized form of nicotinamide adenine dinucleotide is enhanced. 
     
     
         11 . A microorganism, wherein an activity of NADH dehydrogenase is enhanced, and an ability to produce nicotinamide adenine dinucleotide is enhanced by performing at least one gene manipulation of the following (1) and (2):
 (1) deleting, mutating or substituting nadR gene in the microorganism;   (2) introducing into the microorganism a plasmid integrated with a gene of nicotinic acid phosphoribosyltransferase in the microorganism.   
     
     
         12 . The microorganism as set forth in  claim 9  or  10 , wherein the activity of glycolate oxidase is inactivated, or lowered than the activity of the existing microorganism. 
     
     
         13 . The microorganism as set forth in  claim 11 , wherein the activity of glycolate oxidase is inactivated, or lowered than the activity of the existing microorganism. 
     
     
         14 . The production method as set forth in any one of  claims 1  to  6 , wherein the microorganism is any one of genus  Escherichia , genus  Shigella , genus  Salmonella , genus  Erwinia , genus  Yersinia  and genus  Photorhabdus.    
     
     
         15 . The production method as set forth in  claim 14 , wherein the microorganism is  Escherichia coli.    
     
     
         16 . The microorganism as set forth in  claims 9  or  10 , which is any one of genus  Escherichia , genus  Shigell , genus  Salmonella , genus  Erwinia , genus  Yersinia  and genus  Photorhabdus.    
     
     
         17 . The microorganism as set forth in  claim 11  or 13, which is any one of genus  Escherichia , genus  Shigella , genus  Salmonella , genus  Erwinia , genus  Yersinia  and genus  Photorhabdus.    
     
     
         18 . The microorganism as set forth in  claim 16 , which is  Escherichia coli.    
     
     
         19 . The microorganism as set forth in  claim 17 , which is  Escherichia coli.    
     
     
         20 . The production method as set forth in  claim 7 , wherein the aliphatic polyhydric alcohol having a hydroxyl group at the end is ethylene glycol and the hydroxycarboxylic acid is glycolic acid. 
     
     
         21 . The production method as set forth in  claim 7 , wherein the microorganism is any one of genus Escherichia, genus  Shigella , genus  Salmonella , genus  Erwinia , genus  Yersinia  and genus  Photorhabdus.    
     
     
         22 . The production method as set forth in  claim 8 , wherein the microorganism is any one of genus  Escherichia , genus  Shigella , genus  Salmonella , genus  Erwinia , genus  Yersinia  and genus  Photorhabdus.    
     
     
         23 . The microorganism as set forth in  claim 12 , which is any one of genus  Escherichia , genus  Shigell , genus  Salmonella , genus  Erwinia , genus  Yersinia  and genus  Photorhabdus.