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Discovery of non-squalene triterpenes

Author

Listed:
  • Hui Tao

    (The University of Tokyo)

  • Lukas Lauterbach

    (Kekulé-Institut für Organische Chemie und Biochemie, Rheinische Friedrich-Wilhelms-Universität Bonn)

  • Guangkai Bian

    (Wuhan University)

  • Rong Chen

    (Zhongnan Hospital of Wuhan University)

  • Anwei Hou

    (Kekulé-Institut für Organische Chemie und Biochemie, Rheinische Friedrich-Wilhelms-Universität Bonn)

  • Takahiro Mori

    (The University of Tokyo
    The University of Tokyo
    PRESTO, Japan Science and Technology Agency)

  • Shu Cheng

    (Wuhan University)

  • Ben Hu

    (Wuhan University)

  • Li Lu

    (Wuhan University)

  • Xin Mu

    (Wuhan University)

  • Min Li

    (Wuhan University)

  • Naruhiko Adachi

    (Structural Biology Research Center, Institute of Materials Structure Science, High Energy Accelerator Research Organization (KEK))

  • Masato Kawasaki

    (Structural Biology Research Center, Institute of Materials Structure Science, High Energy Accelerator Research Organization (KEK))

  • Toshio Moriya

    (Structural Biology Research Center, Institute of Materials Structure Science, High Energy Accelerator Research Organization (KEK))

  • Toshiya Senda

    (Structural Biology Research Center, Institute of Materials Structure Science, High Energy Accelerator Research Organization (KEK))

  • Xinghuan Wang

    (Zhongnan Hospital of Wuhan University)

  • Zixin Deng

    (Wuhan University)

  • Ikuro Abe

    (The University of Tokyo
    The University of Tokyo)

  • Jeroen S. Dickschat

    (Kekulé-Institut für Organische Chemie und Biochemie, Rheinische Friedrich-Wilhelms-Universität Bonn)

  • Tiangang Liu

    (Wuhan University
    Zhongnan Hospital of Wuhan University
    Wuhan University)

Abstract

All known triterpenes are generated by triterpene synthases (TrTSs) from squalene or oxidosqualene1. This approach is fundamentally different from the biosynthesis of short-chain (C10–C25) terpenes that are formed from polyisoprenyl diphosphates2–4. In this study, two fungal chimeric class I TrTSs, Talaromyces verruculosus talaropentaene synthase (TvTS) and Macrophomina phaseolina macrophomene synthase (MpMS), were characterized. Both enzymes use dimethylallyl diphosphate and isopentenyl diphosphate or hexaprenyl diphosphate as substrates, representing the first examples, to our knowledge, of non-squalene-dependent triterpene biosynthesis. The cyclization mechanisms of TvTS and MpMS and the absolute configurations of their products were investigated in isotopic labelling experiments. Structural analyses of the terpene cyclase domain of TvTS and full-length MpMS provide detailed insights into their catalytic mechanisms. An AlphaFold2-based screening platform was developed to mine a third TrTS, Colletotrichum gloeosporioides colleterpenol synthase (CgCS). Our findings identify a new enzymatic mechanism for the biosynthesis of triterpenes and enhance understanding of terpene biosynthesis in nature.

Suggested Citation

  • Hui Tao & Lukas Lauterbach & Guangkai Bian & Rong Chen & Anwei Hou & Takahiro Mori & Shu Cheng & Ben Hu & Li Lu & Xin Mu & Min Li & Naruhiko Adachi & Masato Kawasaki & Toshio Moriya & Toshiya Senda & , 2022. "Discovery of non-squalene triterpenes," Nature, Nature, vol. 606(7913), pages 414-419, June.
    • Handle: RePEc:nat:nature:v:606:y:2022:i:7913:d:10.1038_s41586-022-04773-3
    DOI: 10.1038/s41586-022-04773-3
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    Cited by:

    1. Zhong Li & Lilan Zhang & Kangwei Xu & Yuanyuan Jiang & Jieke Du & Xingwang Zhang & Ling-Hong Meng & Qile Wu & Lei Du & Xiaoju Li & Yuechan Hu & Zhenzhen Xie & Xukai Jiang & Ya-Jie Tang & Ruibo Wu & Re, 2023. "Molecular insights into the catalytic promiscuity of a bacterial diterpene synthase," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    2. Wei Yuan & Chenjian Jiang & Qin Wang & Yubo Fang & Jin Wang & Meng Wang & Han Xiao, 2022. "Biosynthesis of mushroom-derived type II ganoderic acids by engineered yeast," Nature Communications, Nature, vol. 13(1), pages 1-15, December.

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