Microaerobic lysine fermentations and metabolic flux analysis

Oxygen supply is known to have an important influence on microaerobic production of amino acids, and several researches have shown that the behavior of many l-lysine-producing microorganisms under various aeration conditions are different. In order to investigate the fermentative behavior under microaerobic condition using Corynebacterium glutamicum ATCC 21253, several experiments were carried out where dissolved oxygen concentration was controlled at either 1% or 5%, as well as fully aerated condition. The calculation of intracellular metabolic fluxes was made to illustrate two kinds of metabolic characteristics observed in microaerobic cultures. Evaluated flux distributions indicated that the activities of TCA cycle enzymes decreased with the decrease in oxygen supply, resulting in the amplified phosphoenol pyruvate (PEP) carboxylation which contributed to the 30% of increase in lysine yield for the microaerobic culture at 5% DO concentration as compared with the case of aerobic fermentation. Further analysis indicates that NADPH may not be the yield-limiting factor, while low split-ratio of PEP carboxylation at PEP or aspartate branch at oxaloacetate is considered to limit lysine production under microaerobic conditions.