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Metabolic engineering of Corynebacterium glutamicum for L-arginine production

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  • Seok Hyun Park

    (Metabolic and Biomolecular Engineering National Research Laboratory, Center for Systems and Synthetic Biotechnology, Institute for the BioCentury, Korea Advanced Institute of Science and Technology (KAIST)
    Daesang Corporation Research Center)

  • Hyun Uk Kim

    (Metabolic and Biomolecular Engineering National Research Laboratory, Center for Systems and Synthetic Biotechnology, Institute for the BioCentury, Korea Advanced Institute of Science and Technology (KAIST)
    BioInformatics Research Center, KAIST)

  • Tae Yong Kim

    (Metabolic and Biomolecular Engineering National Research Laboratory, Center for Systems and Synthetic Biotechnology, Institute for the BioCentury, Korea Advanced Institute of Science and Technology (KAIST)
    BioInformatics Research Center, KAIST)

  • Jun Seok Park

    (Daesang Corporation Research Center)

  • Suok-Su Kim

    (Daesang Corporation Research Center)

  • Sang Yup Lee

    (Metabolic and Biomolecular Engineering National Research Laboratory, Center for Systems and Synthetic Biotechnology, Institute for the BioCentury, Korea Advanced Institute of Science and Technology (KAIST)
    BioInformatics Research Center, KAIST
    BioProcess Engineering Research Center, KAIST)

Abstract

L-Arginine is an important amino acid for diverse industrial and health product applications. Here we report the development of metabolically engineered Corynebacterium glutamicum ATCC 21831 for the production of L-arginine. Random mutagenesis is first performed to increase the tolerance of C. glutamicum to L-arginine analogues, followed by systems metabolic engineering for further strain improvement, involving removal of regulatory repressors of arginine operon, optimization of NADPH level, disruption of L-glutamate exporter to increase L-arginine precursor and flux optimization of rate-limiting L-arginine biosynthetic reactions. Fed-batch fermentation of the final strain in 5 l and large-scale 1,500 l bioreactors allows production of 92.5 and 81.2 g l−1 of L-arginine with the yields of 0.40 and 0.35 g L-arginine per gram carbon source (glucose plus sucrose), respectively. The systems metabolic engineering strategy described here will be useful for engineering Corynebacteria strains for the industrial production of L-arginine and related products.

Suggested Citation

  • Seok Hyun Park & Hyun Uk Kim & Tae Yong Kim & Jun Seok Park & Suok-Su Kim & Sang Yup Lee, 2014. "Metabolic engineering of Corynebacterium glutamicum for L-arginine production," Nature Communications, Nature, vol. 5(1), pages 1-9, December.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms5618
    DOI: 10.1038/ncomms5618
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    Cited by:

    1. Jiao Liu & Moshi Liu & Tuo Shi & Guannan Sun & Ning Gao & Xiaojia Zhao & Xuan Guo & Xiaomeng Ni & Qianqian Yuan & Jinhui Feng & Zhemin Liu & Yanmei Guo & Jiuzhou Chen & Yu Wang & Ping Zheng & Jibin Su, 2022. "CRISPR-assisted rational flux-tuning and arrayed CRISPRi screening of an l-proline exporter for l-proline hyperproduction," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    2. Charlotte Cautereels & Jolien Smets & Peter Bircham & Dries De Ruysscher & Anna Zimmermann & Peter De Rijk & Jan Steensels & Anton Gorkovskiy & Joleen Masschelein & Kevin J. Verstrepen, 2024. "Combinatorial optimization of gene expression through recombinase-mediated promoter and terminator shuffling in yeast," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

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