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A gene cluster in Ginkgo biloba encodes unique multifunctional cytochrome P450s that initiate ginkgolide biosynthesis

Author

Listed:
  • Victor Forman

    (University of Copenhagen)

  • Dan Luo

    (University of Copenhagen)

  • Fernando Geu-Flores

    (University of Copenhagen)

  • René Lemcke

    (University of Copenhagen)

  • David R. Nelson

    (University of Tennessee)

  • Sotirios C. Kampranis

    (University of Copenhagen)

  • Dan Staerk

    (University of Copenhagen)

  • Birger Lindberg Møller

    (University of Copenhagen)

  • Irini Pateraki

    (University of Copenhagen)

Abstract

The ginkgo tree (Ginkgo biloba) is considered a living fossil due to its 200 million year’s history under morphological stasis. Its resilience is partly attributed to its unique set of specialized metabolites, in particular, ginkgolides and bilobalide, which are chemically complex terpene trilactones. Here, we use a gene cluster-guided mining approach in combination with co-expression analysis to reveal the primary steps in ginkgolide biosynthesis. We show that five multifunctional cytochrome P450s with atypical catalytic activities generate the tert-butyl group and one of the lactone rings, characteristic of all G. biloba trilactone terpenoids. The reactions include scarless C–C bond cleavage as well as carbon skeleton rearrangement (NIH shift) occurring on a previously unsuspected intermediate. The cytochrome P450s belong to CYP families that diversifies in pre-seed plants and gymnosperms, but are not preserved in angiosperms. Our work uncovers the early ginkgolide pathway and offers a glance into the biosynthesis of terpenoids of the Mesozoic Era.

Suggested Citation

  • Victor Forman & Dan Luo & Fernando Geu-Flores & René Lemcke & David R. Nelson & Sotirios C. Kampranis & Dan Staerk & Birger Lindberg Møller & Irini Pateraki, 2022. "A gene cluster in Ginkgo biloba encodes unique multifunctional cytochrome P450s that initiate ginkgolide biosynthesis," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32879-9
    DOI: 10.1038/s41467-022-32879-9
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    References listed on IDEAS

    as
    1. Zhang Bin & Horvath Steve, 2005. "A General Framework for Weighted Gene Co-Expression Network Analysis," Statistical Applications in Genetics and Molecular Biology, De Gruyter, vol. 4(1), pages 1-45, August.
    2. Zhiyan Zhou & Shaolin Zheng, 2003. "The missing link in Ginkgo evolution," Nature, Nature, vol. 423(6942), pages 821-822, June.
    3. Yun-Peng Zhao & Guangyi Fan & Ping-Ping Yin & Shuai Sun & Ning Li & Xiaoning Hong & Gang Hu & He Zhang & Fu-Min Zhang & Jing-Dan Han & Ya-Jun Hao & Qiwu Xu & Xianwei Yang & Wenjie Xia & Wenbin Chen & , 2019. "Resequencing 545 ginkgo genomes across the world reveals the evolutionary history of the living fossil," Nature Communications, Nature, vol. 10(1), pages 1-10, December.
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    Cited by:

    1. Jack Chun-Ting Liu & Ricardo De La Peña & Christian Tocol & Elizabeth S. Sattely, 2024. "Reconstitution of early paclitaxel biosynthetic network," Nature Communications, Nature, vol. 15(1), pages 1-11, December.

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