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Fed-batch culture of Escherichia coli for L-valine production based on in silico flux response analysis

Authors

  • Jin Hwan Park,

    1. Metabolic and Biomolecular Engineering National Research Laboratory, Department of Chemical and Biomolecular Engineering (BK21 Program), KAIST, Daejeon 305-701, Republic of Korea; telephone: 82-42-869-3930; fax: 82-42-869-3910
    2. Center for Systems and Synthetic Biotechnology, Institute for the BioCentury, KAIST, Daejeon, Republic of Korea
    3. BioProcess Engineering Research Center, KAIST, Daejeon, Republic of Korea
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  • Tae Yong Kim,

    1. Metabolic and Biomolecular Engineering National Research Laboratory, Department of Chemical and Biomolecular Engineering (BK21 Program), KAIST, Daejeon 305-701, Republic of Korea; telephone: 82-42-869-3930; fax: 82-42-869-3910
    2. Center for Systems and Synthetic Biotechnology, Institute for the BioCentury, KAIST, Daejeon, Republic of Korea
    3. BioProcess Engineering Research Center, KAIST, Daejeon, Republic of Korea
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  • Kwang Ho Lee,

    1. Metabolic and Biomolecular Engineering National Research Laboratory, Department of Chemical and Biomolecular Engineering (BK21 Program), KAIST, Daejeon 305-701, Republic of Korea; telephone: 82-42-869-3930; fax: 82-42-869-3910
    Current affiliation:
    1. CJ CheilJedang, Icheon 467-812, Republic of Korea.
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  • Sang Yup Lee

    Corresponding author
    1. Metabolic and Biomolecular Engineering National Research Laboratory, Department of Chemical and Biomolecular Engineering (BK21 Program), KAIST, Daejeon 305-701, Republic of Korea; telephone: 82-42-869-3930; fax: 82-42-869-3910
    2. Center for Systems and Synthetic Biotechnology, Institute for the BioCentury, KAIST, Daejeon, Republic of Korea
    3. BioProcess Engineering Research Center, KAIST, Daejeon, Republic of Korea
    4. Department of Bio and Brain Engineering, Bioinformatics Research Center, KAIST, Daejeon, Republic of Korea
    5. Department of Biological Sciences, Bioinformatics Research Center, KAIST, Daejeon, Republic of Korea
    • Metabolic and Biomolecular Engineering National Research Laboratory, Department of Chemical and Biomolecular Engineering (BK21 Program), KAIST, Daejeon 305-701, Republic of Korea; telephone: 82-42-869-3930; fax: 82-42-869-3910.
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  • Jin Hwan Park and Tae Yong Kim contributed equally to this work.

Abstract

We have previously reported the development of a 100% genetically defined engineered Escherichia coli strain capable of producing L-valine from glucose with a high yield of 0.38 g L-valine per gram glucose (0.58 mol L-valine per mol glucose) by batch culture. Here we report a systems biological strategy of employing flux response analysis in bioprocess development using L-valine production by fed-batch culture as an example. Through the systems-level analysis, the source of ATP was found to be important for efficient L-valine production. There existed a trade-off between L-valine production and biomass formation, which was optimized for the most efficient L-valine production. Furthermore, acetic acid feeding strategy was optimized based on flux response analysis. The final fed-batch cultivation strategy allowed production of 32.3 g/L L-valine, the highest concentration reported for E. coli. This approach of employing systems-level analysis of metabolic fluxes in developing fed-batch cultivation strategy would also be applicable in developing strategies for the efficient production of other bioproducts. Biotechnol. Bioeng. 2011; 108:934–946. © 2010 Wiley Periodicals, Inc.

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