Development of chemically defined medium for Mannheimia succiniciproducens based on its genome sequence

作者：Song Hyohak; Kim Tae Yong; Choi Bo Kyeong; Choi Seong Jun; Nielsen Lars K; Chang Ho Nam; Lee Sang Yup^*

来源：Applied Microbiology and Biotechnology, 2008, 79(2): 263-272.

DOI：10.1007/s00253-008-1425-2

• chemically defined medium
• Mannheimia succiniciproducens
• metabolic network
• flux balance analysis
• succinic acid

This study presents a novel methodology for the development of a chemically defined medium (CDM) using genome-scale metabolic network and flux balance analysis. The genome-based in silico analysis identified two amino acids and four vitamins as non-substitutable essential compounds to be supplemented to a minimal medium for the sustainable growth of Mannheimia succiniciproducens, while no substitutable essential compounds were identified. The in silico predictions were verified by cultivating the cells on a CDM containing the six non-substitutable essential compounds, and it was further demonstrated by observing no cell growth on the CDM lacking any one of the non-substitutable essentials. An optimal CDM for the enhancement of cell growth and succinic acid production, as a target product, was formulated 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. The optimal CDM also lowered the sum of the amounts of by-products (acetic, formic, and lactic acids) by 30%. The strategy reported in this paper should be generally applicable to the development of CDMs for other organisms, whose genome sequences are available.

• 出版日期2008-5