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Microbial production of multiple short-chain primary amines via retrobiosynthesis

Author

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  • Dong In Kim

    (Korea Advanced Institute of Science and Technology (KAIST)
    Systems Metabolic Engineering and Systems Healthcare Cross-Generation Collaborative Laboratory, KAIST)

  • Tong Un Chae

    (Korea Advanced Institute of Science and Technology (KAIST)
    Systems Metabolic Engineering and Systems Healthcare Cross-Generation Collaborative Laboratory, KAIST)

  • Hyun Uk Kim

    (Systems Metabolic Engineering and Systems Healthcare Cross-Generation Collaborative Laboratory, KAIST
    Systems Biology and Medicine Laboratory, Department of Chemical and Biomolecular Engineering, KAIST
    KAIST Institute for Artificial Intelligence, BioProcess Engineering Research Center and BioInformatics Research Center, KAIST)

  • Woo Dae Jang

    (Korea Advanced Institute of Science and Technology (KAIST)
    Systems Metabolic Engineering and Systems Healthcare Cross-Generation Collaborative Laboratory, KAIST)

  • Sang Yup Lee

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

Abstract

Bio-based production of many chemicals is not yet possible due to the unknown biosynthetic pathways. Here, we report a strategy combining retrobiosynthesis and precursor selection step to design biosynthetic pathways for multiple short-chain primary amines (SCPAs) that have a wide range of applications in chemical industries. Using direct precursors of 15 target SCPAs determined by the above strategy, Streptomyces viridifaciens vlmD encoding valine decarboxylase is examined as a proof-of-concept promiscuous enzyme both in vitro and in vivo for generating SCPAs from their precursors. Escherichia coli expressing the heterologous vlmD produces 10 SCPAs by feeding their direct precursors. Furthermore, metabolically engineered E. coli strains are developed to produce representative SCPAs from glucose, including the one producing 10.67 g L−1 of iso-butylamine by fed-batch culture. This study presents the strategy of systematically designing biosynthetic pathways for the production of a group of related chemicals as demonstrated by multiple SCPAs as examples.

Suggested Citation

  • Dong In Kim & Tong Un Chae & Hyun Uk Kim & Woo Dae Jang & Sang Yup Lee, 2021. "Microbial production of multiple short-chain primary amines via retrobiosynthesis," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-020-20423-6
    DOI: 10.1038/s41467-020-20423-6
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