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

  • Applied Microbial and Cell Physiology
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Abstract

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.

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Acknowledgments

This work was supported by the Genome-based Integrated Bioprocess Project of the Ministry of Science and Technology (No. 2005-01294) through the Korea Science and Engineering Foundation (KOSEF). Further supports by the LG Chem Chair Professorship and by the KOSEF through the Center for Ultramicrochemical Process Systems are appreciated.

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Authors and Affiliations

  1. Department of Chemical and Biomolecular Engineering (BK21 Program), KAIST, 335 Gwahangno, Yuseong-gu, Daejeon, 305-701, Republic of Korea

    Hyohak Song, Tae Yong Kim, Bo-Kyeong Choi, Seong Jun Choi, Ho Nam Chang & Sang Yup Lee

  2. BioProcess Engineering Research Center, KAIST, Daejeon, 305-701, Republic of Korea

    Hyohak Song, Tae Yong Kim, Bo-Kyeong Choi, Seong Jun Choi, Ho Nam Chang & Sang Yup Lee

  3. Metabolic and Biomolecular Engineering National Research Laboratory, Center for Systems and Synthetic Biotechnology, Institute for the BioCentury, KAIST, Daejeon, Republic of Korea

    Hyohak Song, Tae Yong Kim, Seong Jun Choi & Sang Yup Lee

  4. Department of Bio and Brain Engineering and Bioinformatics Research Center, KAIST, 335 Gwahangno, Yuseong-gu, Daejeon, 305-701, Republic of Korea

    Sang Yup Lee

  5. Australian Institute for Bioengineering and Nanotechnology, University of Queensland, Brisbane, Queensland, 4072, Australia

    Lars K. Nielsen

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  1. Hyohak Song
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  2. Tae Yong Kim
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  3. Bo-Kyeong Choi
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  4. Seong Jun Choi
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  5. Lars K. Nielsen
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  6. Ho Nam Chang
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  7. Sang Yup Lee
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Correspondence to Sang Yup Lee.

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Song, H., Kim, T.Y., Choi, BK. et al. Development of chemically defined medium for Mannheimia succiniciproducens based on its genome sequence. Appl Microbiol Biotechnol 79, 263–272 (2008). https://doi.org/10.1007/s00253-008-1425-2

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  • DOI: https://doi.org/10.1007/s00253-008-1425-2

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