To increase carbon flux to lysine, minimized production of amino acids that are biosynthetically related to lysine, for example, isoleucine and valine, is required. By limiting the supply of pantothenate, the precursor of coenzyme A, the carbon flux was redirected from isoleucine and valine to lysine in the recombinant of Corynebacterium lactofermentum ATCC 21799 containing the plasmid pGC77. The pGC77 contains hom(dr), thrB, and ilvA encoding feedback-deregulated homoserine dehydrogenase, homoserine kinase, and threonine dehydratase, respectively. At 250 microM of isopropyl-beta-d-thiogalactopyranoside, the recombinant (pGC77) produced lysine, valine, and isoleucine. Limiting the supply of pantothenate from 300 microg/l to 30 microg/l resulted in an increase in lysine (from 4.5 to 6.4 g/l) and decreases in valine (from 3.1 to 1.6 g/l) and isoleucine (from 0.9 to 0.3 g/l) production. The concentration of pyruvate was higher and that of acetate lower in the pantothenate-limited culture than in the control, suggesting that the limited supply of pantothenate delayed the conversion of pyruvate to acetyl-CoA. Increased availability of pyruvate by limiting the supply of pantothenate might favor the integration of pyruvate into the lysine branch. The results of this study are useful for the production of lysine with decreased concentrations of byproducts.
