Method for increasing the production of small molecules in submerged corynebacterium culture

Abstract

Described are methods for increasing the production of small molecules in a submerged Corynebacterium culture by supplementing Corynebacterium growth medium with the non-enzymatic fraction of spent Trichoderma fermentation broth.

What is claimed is: 
     
         1 . A method for improving the production of small molecules in submerged  Corynebacterium  culture comprising adding to a submerged  Corynebacterium  culture a non-enzymatic fraction of spent  Trichoderma  fermentation broth, wherein the  Corynebacterium  grown in the presence of the non-enzymatic fraction of spent  Trichoderma  fermentation broth produce an increased amount of small molecules compared to  Corynebacterium  grown in an otherwise identical submerged culture in the absence of the non-enzymatic fraction of spent  Trichoderma  fermentation broth, wherein the increase in small molecule production is not due to enzymatic activity in the spent  Trichoderma  fermentation broth. 
     
     
         2 . The method of  claim 1 , wherein the non-enzymatic fraction of spent  Trichoderma  fermentation broth is produced by filtering whole or fractionated spent  Trichoderma  fermentation broth. 
     
     
         3 . The method of  claim 1 , wherein the non-enzymatic fraction of spent  Trichoderma  fermentation broth is produced by heat treating whole or fractionated spent  Trichoderma  fermentation broth. 
     
     
         4 . The method of  claim 1 , wherein the non-enzymatic fraction of spent  Trichoderma  fermentation broth used to increase small molecule production is a component of whole or fractionated spent  Trichoderma  fermentation broth that is added to the submerged  Corynebacterium  culture. 
     
     
         5 . The method of any of the preceding claims, wherein the non-enzymatic fraction of spent  Trichoderma  fermentation broth is a by-product of a fermentation that produces a recombinant enzyme. 
     
     
         6 . The method of  claim 5 , wherein the non-enzymatic fraction of  Trichoderma  fermentation broth used to increase small molecule production additionally comprises the recombinant enzyme. 
     
     
         7 . The method of  claim 5 , wherein the recombinant enzyme is removed from the non-enzymatic fraction of  Trichoderma  fermentation broth used to improve small molecule production. 
     
     
         8 . The method of any of  claims 5 - 7 , wherein the recombinant enzyme is a carbohydrate processing enzyme. 
     
     
         9 . The method of any of the preceding claims, wherein at least a portion of the spent fermentation broth is added at the time of inoculation of the  Corynebacterium  culture. 
     
     
         10 . The method of any of the preceding claims, wherein the spent fermentation broth is harvested from a  Trichoderma  growth culture at least 29 hours following inoculation of  Trichoderma  broth. 
     
     
         11 . The method of any of the preceding claims, wherein the spent fermentation broth is harvested from a  Trichoderma  growth culture prior to the expression of a protein of interest in the broth. 
     
     
         12 . The method of any of the preceding claims, wherein the small molecule is an amino acid. 
     
     
         13 . The method of  claim 12 , wherein the amino acid is glutamic acid or lysine. 
     
     
         14 . The method of any of the preceding claims, wherein the increase in small molecule production is not the result of increased cell mass in the  Corynebacterium  culture. 
     
     
         15 . A small molecule produced in submerged  Corynebacterium  culture produced by the method of any of  claims 1 - 14 . 
     
     
         16 . Use of a non-enzymatic fraction of spent  Trichoderma  fermentation broth to increase the amount of small molecules produced in a submerged  Corynebacterium  culture. 
     
     
         17 . Use of a non-enzymatic fraction of spent  Trichoderma  fermentation broth as in  claim 16  is combined with the features of any of  claims 1 - 14 .