Sunday, April 29, 2007

Deciphering metabolic flux of Mannheimia succiniciproducens MBEL55E by genome-scale constraints-base flux analysis

Tae Yong Kim, Hyun Uk Kim, Jong Myeong Park, Hyohak Song, and Sang Yup Lee. Metabolic and Biomolecular Engineering National Research Laboratory, Department of Chemical and Biomolecular Engineering, Korea Advanced Institute of Science and Technology, 373-1 Guseong-dong, Yuseong-gu, Daejeon, South Korea

Mannheimia succiniciproducens MBEL55E isolated from bovine rumen is a capnophilic gram-negative bacterium that efficiently produces succinic acid, an industrially important four carbon dicarboxylic acid. Here we report reconstruction of its genome-scale metabolic network consisting of 686 reactions and 520 metabolites based on reannotation and validation experiments. With the reconstructed model, the network structure was investigated to unravel key metabolites playing important roles in the metabolism of M. succiniciproducens allowing highly efficient production of succinic acid. All the simulations were performed using constraints-based flux analysis. It was, then, subjected to gene deletion studies in order to investigate the resulting physiological responses of M. succiniciproducens and its capability of succinic acid production. Such in silico analyses with a genome-scale model will contribute to the rational design of experiments for strain improvement.
[This work was supported by the Genome-based Integrated Bioprocess Project of the Ministry of Science and Technology. Further supports by the LG Chem Chair Professorship, IBM-SUR program, Microsoft, and the Center for Ultramicrochemical Process Systems sponsored by KOSEF are appreciated.]