Feeding Strategy of Required Components by Metabolic Engineering Approach in a Lysine Production Process

Abstract A metabolic reaction model was developed for on-line analysis of mole flux distribution in lysine metabolic pathway of Corynebacterium glutamicum AJ-3462 which was a leucine auxotroph mutant. The physiological states of the microorganisms were recognized based on the estimated mole flux distribution. In order to elongate the fermentation time keeping lysine productivity and production yield at high levels, effect of leucine addition on the mole flux distribution was analyzed. The intermittently addition strategy of leucine was developed based on the changes in the cell activities with respect to growth and lysine synthesis. Interval time of intermittent addition was changed from 30 h to 24 h when a decrease of cell activity was recognized. As the result, the fermentation time was elongated to 174 h, and lysine productivity and total molar production yield of lysine from glucose became 0.104 g/l/h and 29.2 %, respectively.