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Enhanced succinic acid production by Mannheimia employing optimal malate dehydrogenase

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  • Jung Ho Ahn

    (Institute for the BioCentury, Korea Advanced Institute of Science and Technology (KAIST)
    Systems Metabolic Engineering and Systems Healthcare Cross-Generation Collaborative Laboratory, KAIST
    Bioinformatics Research Center and BioProcess Engineering Research Center KAIST)

  • Hogyun Seo

    (KNU Creative BioResearch Group, Kyungpook National University
    Pohang University of Science and Technology)

  • Woojin Park

    (KNU Creative BioResearch Group, Kyungpook National University
    Kyungpook National University)

  • Jihye Seok

    (KNU Creative BioResearch Group, Kyungpook National University
    Kyungpook National University)

  • Jong An Lee

    (Institute for the BioCentury, Korea Advanced Institute of Science and Technology (KAIST)
    Systems Metabolic Engineering and Systems Healthcare Cross-Generation Collaborative Laboratory, KAIST
    Bioinformatics Research Center and BioProcess Engineering Research Center KAIST)

  • Won Jun Kim

    (Institute for the BioCentury, Korea Advanced Institute of Science and Technology (KAIST)
    Systems Metabolic Engineering and Systems Healthcare Cross-Generation Collaborative Laboratory, KAIST
    Bioinformatics Research Center and BioProcess Engineering Research Center KAIST)

  • Gi Bae Kim

    (Institute for the BioCentury, Korea Advanced Institute of Science and Technology (KAIST)
    Systems Metabolic Engineering and Systems Healthcare Cross-Generation Collaborative Laboratory, KAIST
    Bioinformatics Research Center and BioProcess Engineering Research Center KAIST)

  • Kyung-Jin Kim

    (KNU Creative BioResearch Group, Kyungpook National University
    Kyungpook National University)

  • Sang Yup Lee

    (Institute for the BioCentury, Korea Advanced Institute of Science and Technology (KAIST)
    Systems Metabolic Engineering and Systems Healthcare Cross-Generation Collaborative Laboratory, KAIST
    Bioinformatics Research Center and BioProcess Engineering Research Center KAIST)

Abstract

Succinic acid (SA), a dicarboxylic acid of industrial importance, can be efficiently produced by metabolically engineered Mannheimia succiniciproducens. Malate dehydrogenase (MDH) is one of the key enzymes for SA production, but has not been well characterized. Here we report biochemical and structural analyses of various MDHs and development of hyper-SA producing M. succiniciproducens by introducing the best MDH. Corynebacterium glutamicum MDH (CgMDH) shows the highest specific activity and least substrate inhibition, whereas M. succiniciproducens MDH (MsMDH) shows low specific activity at physiological pH and strong uncompetitive inhibition toward oxaloacetate (ki of 67.4 and 588.9 μM for MsMDH and CgMDH, respectively). Structural comparison of the two MDHs reveals a key residue influencing the specific activity and susceptibility to substrate inhibition. A high-inoculum fed-batch fermentation of the final strain expressing cgmdh produces 134.25 g L−1 of SA with the maximum productivity of 21.3 g L−1 h−1, demonstrating the importance of enzyme optimization in strain development.

Suggested Citation

  • Jung Ho Ahn & Hogyun Seo & Woojin Park & Jihye Seok & Jong An Lee & Won Jun Kim & Gi Bae Kim & Kyung-Jin Kim & Sang Yup Lee, 2020. "Enhanced succinic acid production by Mannheimia employing optimal malate dehydrogenase," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-15839-z
    DOI: 10.1038/s41467-020-15839-z
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