Mutant phosphoribosylpyrophosphate synthetase and method for producing L-histidine

Abstract

The present invention relates to a mutant bacterial PRPP synthetase which is resistant to feedback by purine nucleotides, and a method for producing L-histidine using the bacterium of the Enterobacteriaceae family wherein the L-amino acid productivity of said bacterium is enhanced by use of the PRPP synthetase which is resistant to feedback by purine nucleotides, coded by the mutant prsA gene.

1 . A mutant bacterial phosphoribosylpyrophosphate synthetase (PRPP synthetase), wherein the aspartic acid at position 115 in a wild-type phosphoribosylpyrophosphate synthetase from  Escherichia coli  is substituted with another L-amino acid residue, and feedback inhibition by purine nucleotides is desensitized.  
     
     
         2 . The mutant PRPP synthetase of  claim 1 , wherein said aspartic acid residue at position 115 in a wild-type PRPP synthetase is substituted with an serine residue.  
     
     
         3 . The mutant PRPP synthetase of  claim 2 , which includes deletion, substitution, insertion, or addition of one or several amino acids at one or a plurality of positions other than position 115, and wherein feedback inhibition by purine nucleotides is desensitized.  
     
     
         4 . A DNA encoding said mutant PRPP synthetase of  claim 1 .  
     
     
         5 . A bacterium of the Enterobacteriaceae family, which contains the DNA of  claim 4  and has an ability to produce L-histidine.  
     
     
         6 . The bacterium of  claim 5 , wherein the activity of said mutant PRPP synthetase is enhanced.  
     
     
         7 . The bacterium of  claim 6 , wherein said bacterium belongs to the genus  Escherichia.    
     
     
         8 . The bacterium of  claim 6 , wherein the activity of said mutant PRPP synthetase is enhanced by increasing the expression of said mutant PRPP synthetase gene.  
     
     
         9 . The bacterium of  claim 8 , wherein the activity of said mutant PRPP synthetase is enhanced by increasing the copy number of said mutant PRPP synthetase gene, or modifying an expression control sequence of said gene so that the expression of said gene is enhanced.  
     
     
         10 . The bacterium of  claim 9 , wherein the copy number is increased by integration of additional copies of said mutant PRPP synthetase gene into the chromosome of the bacterium.  
     
     
         11 . A method for producing L-histidine comprising cultivating the bacterium of  claim 5  in a culture medium, allowing said L-histidine to accumulate in the culture medium, and collecting said L-histidine from the culture medium.  
     
     
         12 . The method of  claim 11 , wherein said bacterium has enhanced expression of the genes for histidine biosynthesis.