Enhanced succinic acid production by Mannheimia employing optimal malate dehydrogenase
Jung Ho Ahn,
Hogyun Seo,
Woojin Park,
Jihye Seok,
Jong An Lee,
Won Jun Kim,
Gi Bae Kim,
Kyung-Jin Kim () and
Sang Yup Lee ()
Additional contact information
Jung Ho Ahn: Institute for the BioCentury, Korea Advanced Institute of Science and Technology (KAIST)
Hogyun Seo: KNU Creative BioResearch Group, Kyungpook National University
Woojin Park: KNU Creative BioResearch Group, Kyungpook National University
Jihye Seok: KNU Creative BioResearch Group, Kyungpook National University
Jong An Lee: Institute for the BioCentury, Korea Advanced Institute of Science and Technology (KAIST)
Won Jun Kim: Institute for the BioCentury, Korea Advanced Institute of Science and Technology (KAIST)
Gi Bae Kim: Institute for the BioCentury, Korea Advanced Institute of Science and Technology (KAIST)
Kyung-Jin Kim: KNU Creative BioResearch Group, Kyungpook National University
Sang Yup Lee: Institute for the BioCentury, Korea Advanced Institute of Science and Technology (KAIST)
Nature Communications, 2020, vol. 11, issue 1, 1-12
Abstract:
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.
Date: 2020
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-15839-z
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DOI: 10.1038/s41467-020-15839-z
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