Metabolic Activity Control of the L‐Lysine Fermentation by Restrained Growth Fed‐Batch Strategies

Abstract
Batch and continuous culture experiments were conducted with the L‐lysine producer Corynebacterium glutamicum to characterize fermentation yields and rates, as well as the relationship between biomass catalytic activity toward L‐lysine production and online respiratory measurements. Experimental correlations suggested that improved fermentation performance (yield, productivity, and titer) could be achieved through fed‐batch cultivation of the organism under conditions of restrained growth, utilizing respiratory measurements as a metabolic activity indicator for feed rate control. Two different control schemes were developed for maximization of the fermentation yield and maximization of the fermentation productivity. Both strategies were successful in maintaining the yield and specific productivity at high levels for extended times, thus resulting in significant improvements in the overall fermentation yield, volumetric productivity, and titer. It was thus demonstrated that proper environmental control can be an effective means of manipulating microbial metabolism to favor metabolite overproduction.