Metabolic characterization of a L ‐lysine‐producing strain by continuous culture

Continuous culture experiments with the L ‐producer, Corynebacterium glutamicum, were carried out to characterize the effect of specific growth rate on fermentation yields, specific rates, productivities, and fluxes through the primary metabolism. The specific productivity of L ‐lysine exhibited a maximum with respect to specific growth rate, with an initial growth‐associated behavior up to specific growth rates of about 0.1 h −1 , and a constant specific productivity for specific growth rates in the range of about 0.1 to 0.2 h −1 . The productivity dropped at specific growth rates larger than about 0.2 h −1 . The yield of L −lysine on glucose increased approximately linearly with decreasing specific growth rate over the entire range studied, as did the respiratory quotient. A direct relationship was established between the culture respiratory quotient and the L ‐lysine yield. By explicitly accounting for glucose used for biomass synthesis, it was shown that the strain synthesizes L ‐lysine with an intrinsic yield, or efficiency, of about 0.41 mol L ‐lysine/mol glucose, compared with the theoretical yield of 0.75 mol/mol. Metabolic flux modeling based on the continuous culture data suggests that the production of ATP is not likely to be a limiting factor in L ‐lysine production, and that a high TCA cycle activity, coupled with a tightly controlled split of metabolite flow at the PEP node, is likely the cause of the large discrepancy between theoretical and actual yields in L ‐lysine fermentations.