Performance loss of Corynebacterium glutamicum cultivations under scale-down conditions using complex media

Substrate and oxygen gradients appear in industrial-scale fed-batch processes due to limitations in the achievable power input and concomitantly increased mixing times. In order to mimic these gradients at lab scale, scale-down reactors are applied. Previous studies in such reactor systems suggest that Corynebacterium glutamicum is robust against oscillatory oxygen and substrate availability in relation to growth and side product accumulation. Usually, defined mineral salt media are applied contrary to the industrial case, in which complex media containing different carbon sources are used. Therefore, this study investigated the cultivation performance using complex medium based on sucrose, molasses, and corn steep liquor in a three-compartment scale-down reactor. The reactor consisted of a stirred tank and two plug flow reactor modules. This approach was applied based on assumptions of gradient distributions in bottom-fed bioreactors. A drastic reduction of growth and volumetric product yield of a cadaverine producing strain was observed while several short chain fatty acids accumulated, among them l-lactate and acetate. Growth was depleted after several hours of cultivation, while the substrate uptake rate was reduced by 20%. Hence, the main carbon source sucrose accumulated after 10 h of fed-batch cultivation. Despite growth cessation, neither reduction of cell vitality nor increased cell lysis were observed