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Reprogramming of the antimycin NRPS-PKS assembly lines inspired by gene evolution

Author

Listed:
  • Takayoshi Awakawa

    (The University of Tokyo
    The University of Tokyo)

  • Takuma Fujioka

    (The University of Tokyo)

  • Lihan Zhang

    (The University of Tokyo)

  • Shotaro Hoshino

    (The University of Tokyo)

  • Zhijuan Hu

    (The University of Tokyo)

  • Junko Hashimoto

    (Japan Biological Informatics Consortium)

  • Ikuko Kozone

    (Japan Biological Informatics Consortium)

  • Haruo Ikeda

    (Kitasato University)

  • Kazuo Shin-Ya

    (The University of Tokyo
    National Institute of Advanced Industrial Science and Technology (AIST))

  • Wen Liu

    (Chinese Academy of Sciences)

  • Ikuro Abe

    (The University of Tokyo
    The University of Tokyo)

Abstract

Reprogramming of the NRPS/PKS assembly line is an attractive method for the production of new bioactive molecules. However, it is usually hampered by the loss of intimate domain/module interactions required for the precise control of chain transfer and elongation reactions. In this study, we first establish heterologous expression systems of the unique antimycin-type cyclic depsipeptides: JBIR-06 (tri-lactone) and neoantimycin (tetra-lactone), and engineer their biosyntheses by taking advantage of bioinformatic analyses and evolutionary insights. As a result, we successfully accomplish three manipulations: (i) ring contraction of neoantimycin (from tetra-lactone to tri-lactone), (ii) ring expansion of JBIR-06 (from tri-lactone to tetra-lactone), and (iii) alkyl chain diversification of JBIR-06 by the incorporation of various alkylmalonyl-CoA extender units, to generate a set of unnatural derivatives in practical yields. This study presents a useful strategy for engineering NRPS-PKS module enzymes, based on nature’s diversification of the domain and module organizations.

Suggested Citation

  • Takayoshi Awakawa & Takuma Fujioka & Lihan Zhang & Shotaro Hoshino & Zhijuan Hu & Junko Hashimoto & Ikuko Kozone & Haruo Ikeda & Kazuo Shin-Ya & Wen Liu & Ikuro Abe, 2018. "Reprogramming of the antimycin NRPS-PKS assembly lines inspired by gene evolution," Nature Communications, Nature, vol. 9(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-05877-z
    DOI: 10.1038/s41467-018-05877-z
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    Cited by:

    1. Guifa Zhai & Yan Zhu & Guo Sun & Fan Zhou & Yangning Sun & Zhou Hong & Chuan Dong & Peter F. Leadlay & Kui Hong & Zixin Deng & Fuling Zhou & Yuhui Sun, 2023. "Insights into azalomycin F assembly-line contribute to evolution-guided polyketide synthase engineering and identification of intermodular recognition," Nature Communications, Nature, vol. 14(1), pages 1-12, December.

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