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Efficient biosynthesis of heterodimeric C3-aryl pyrroloindoline alkaloids

Author

Listed:
  • Wenya Tian

    (Wuhan University)

  • Chenghai Sun

    (Wuhan University)

  • Mei Zheng

    (Wuhan University)

  • Jeffrey R. Harmer

    (The University of Queensland)

  • Mingjia Yu

    (Beijing Institute of Technology)

  • Yanan Zhang

    (Wuhan University)

  • Haidong Peng

    (Wuhan University)

  • Dongqing Zhu

    (Wuhan University)

  • Zixin Deng

    (Wuhan University)

  • Shi-Lu Chen

    (Beijing Institute of Technology)

  • Mehdi Mobli

    (The University of Queensland)

  • Xinying Jia

    (The University of Queensland)

  • Xudong Qu

    (Wuhan University)

Abstract

Many natural products contain the hexahydropyrrolo[2, 3-b]indole (HPI) framework. HPI containing chemicals exhibit various biological activities and distinguishable structural arrangement. This structural complexity renders chemical synthesis very challenging. Here, through investigating the biosynthesis of a naturally occurring C3-aryl HPI, naseseazine C (NAS-C), we identify a P450 enzyme (NascB) and reveal that NascB catalyzes a radical cascade reaction to form intramolecular and intermolecular carbon–carbon bonds with both regio- and stereo-specificity. Surprisingly, the limited freedom is allowed in specificity to generate four types of C3-aryl HPI scaffolds, and two of them were not previously observed. By incorporating NascB into an engineered strain of E. coli, we develop a whole-cell biocatalysis system for efficient production of NAS-C and 30 NAS analogs. Interestingly, we find that some of these analogs exhibit potent neuroprotective properties. Thus, our biocatalytic methodology offers an efficient and simple route to generate difficult HPI framework containing chemicals.

Suggested Citation

  • Wenya Tian & Chenghai Sun & Mei Zheng & Jeffrey R. Harmer & Mingjia Yu & Yanan Zhang & Haidong Peng & Dongqing Zhu & Zixin Deng & Shi-Lu Chen & Mehdi Mobli & Xinying Jia & Xudong Qu, 2018. "Efficient biosynthesis of heterodimeric C3-aryl pyrroloindoline alkaloids," Nature Communications, Nature, vol. 9(1), pages 1-9, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-06528-z
    DOI: 10.1038/s41467-018-06528-z
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    Cited by:

    1. Garrett Deletti & Sajan D. Green & Caleb Weber & Kristen N. Patterson & Swapnil S. Joshi & Tushar M. Khopade & Mathew Coban & James Veek-Wilson & Thomas R. Caulfield & Rajesh Viswanathan & Amy L. Lane, 2023. "Unveiling an indole alkaloid diketopiperazine biosynthetic pathway that features a unique stereoisomerase and multifunctional methyltransferase," Nature Communications, Nature, vol. 14(1), pages 1-13, December.

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