6533b852fe1ef96bd12ab539

RESEARCH PRODUCT

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

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Abstract 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.