원문정보
초록
영어
In this study, a methodology for the development of a chemically defined medium (CDM) using genome-scale metabolic network and flux balance analysis and its improvement by metabolic engineering technology are demonstrated. Two amino acids, cysteine and methionine, and four vitamins, nicotinic acid, pyridoxine HCl, thiamine, and Ca-pantothenate, were identified as non-substitutable essential compounds to be supplemented to a minimal medium for the sustainable growth of Mannheimia succiniciproducens by the genome-based in silico analysis. The in silico predictions were confirmed by cultivating the Mannheimia succiniciproducens on a CDM containing the six nonsubstitutable essential compounds, and it was further verified by observing no cell growth on the CDM lacking any one of the non-substitutable essentials. To enhance the cell growth and the succinic acid production, as a target product, an optimal CDM was developed with a single-addition technique. The fermentation on the optimal CDM increased the succinic acid productivity by 36%, the final succinic acid concentration by 17%, and the succinic acid yield on glucose by 15% compared to the cultivation using a complex medium. Moreover, metabolic engineering technologies were applied to improve the Mannheimia succiniciproducens for the further enhancement of CDM in an economical aspect.