Substrate controlled fed-batch production of L-lysine with Corynebacterium glutamicum

A fed-batch process for the production of L-lysine with Corynebacterium glutamicum in a stirred tank reactor was developed up to a 150-L scale applying the general approach of reaction engineering: Experimental optimization of medium composition (13 components: mineral salts and biotin) in parallel shake-flask experiments using a Genetic Algorithm and the study of L-leucine, ammonia, and phosphate supply in glucose controlled fed-batch fermentations resulted in a volumetric L-lysine productivity of 8.3 mol/(m³·h), a L-lysine yield of 32% (mol/mol), and- a L-lysine concentration of 500 mM. The glucose concentration was controlled to 50 mM using on-line HPLC and semicontinuous extended Kalman-filter with a minimum variance controller. Nitrogen accumulation of the C. glutamicum cells in the early process phase for subsequent L-lysine formation was identified by means of a reaction engineering analysis. Glucose limitation in the inoculum (1-2 h) results in growth linked L-lysine production with a differential L-lysine selectivity of 38%(mol/mol) and a maximum cell specific L-lysine production rate of 1.1 mmol/(g·h). L-Lysine was not growth linked produced, if the inoculum was transferred at the exponential state.