L-valine biosynthesis during batch and fed-batch cultivations of Corynebacterium glutamicum:: Relationship between changes in bacterial growth rate and intracellular metabolism

A transition in the bacterial growth rate to below maximum was found to be an optimum parameter of cellular physiology to increase the activity of acetohydroxy acid synthase, a regulatory enzyme in L-valine synthesis, and amino acid overproduction by Corynebacterium glutamicum ATCC 13032 recombinants under batch and fed-batch cultivation conditions. An increase in L-valine synthesis under transient situations when cellular growth rate was downregulated was correlated to a decrease in the activity of aconitase, a key enzyme in the tricarboxylic acid cycle (TCA) of C. glutamicum, and, in contrast, to an increase in the activity of glucose-6-phosphate dehydrogenase, a key enzyme in the pentose phosphate pathway (PPP). The increase in amino acid synthesis was also directly related to a drastic increase in intracellular pyruvate concentration. Thus, an increase in intracellular pyruvate availability and NADPH(2) generation by PPP could be the metabolic origins of the increased L-valine overproduction by growth restrained C. glutamicum cell culture. (c) 2006 Elsevier Ltd. All rights reserved.