Development of chemically defined medium for Mannheimia succiniciproducens based on its genome sequence.
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.
Song
Hyohak
H
Department of Chemical and Biomolecular Engineering (BK21 Program), KAIST, 335 Gwahangno, Yuseong-gu, Daejeon 305-701, Republic of Korea.
Kim
Tae Yong
TY
Choi
Bo-Kyeong
BK
Choi
Seong Jun
SJ
Nielsen
Lars K
LK
Chang
Ho Nam
HN
Lee
Sang Yup
SY
D003470:Culture Media / Q000138:chemical synthesis / Q000737:chemistry*; D005285:Fermentation; D005818:Genetic Engineering / Q000379:methods; D016680:Genome, Bacterial; D031121:Mannheimia / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D053858:Metabolic Networks and Pathways / Q000235:genetics*; D019802:Succinic Acid / Q000378:metabolism*
D003470:Culture Media; D019802:Succinic Acid