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Discovery and characterization of a terpene biosynthetic pathway featuring a norbornene-forming Diels-Alderase

Author

Listed:
  • Zuodong Sun

    (University of California, Los Angeles)

  • Cooper S. Jamieson

    (University of California, Los Angeles)

  • Masao Ohashi

    (University of California, Los Angeles)

  • K. N. Houk

    (University of California, Los Angeles
    University of California, Los Angeles)

  • Yi Tang

    (University of California, Los Angeles
    University of California, Los Angeles)

Abstract

Pericyclases, enzymes that catalyze pericyclic reactions, form an expanding family of enzymes that have biocatalytic utility. Despite the increasing number of pericyclases discovered, the Diels-Alder cyclization between a cyclopentadiene and an olefinic dienophile to form norbornene, which is among the best-studied cycloadditions in synthetic chemistry, has surprisingly no enzymatic counterpart to date. Here we report the discovery of a pathway featuring a norbornene synthase SdnG for the biosynthesis of sordaricin-the terpene precursor of antifungal natural product sordarin. Full reconstitution of sordaricin biosynthesis reveals a concise oxidative strategy used by Nature to transform an entirely hydrocarbon precursor into the highly functionalized substrate of SdnG for intramolecular Diels-Alder cycloaddition. SdnG generates the norbornene core of sordaricin and accelerates this reaction to suppress host-mediated redox modifications of the activated dienophile. Findings from this work expand the scopes of pericyclase-catalyzed reactions and P450-mediated terpene maturation.

Suggested Citation

  • Zuodong Sun & Cooper S. Jamieson & Masao Ohashi & K. N. Houk & Yi Tang, 2022. "Discovery and characterization of a terpene biosynthetic pathway featuring a norbornene-forming Diels-Alderase," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30288-6
    DOI: 10.1038/s41467-022-30288-6
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    References listed on IDEAS

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    1. Hak Joong Kim & Mark W. Ruszczycky & Sei-hyun Choi & Yung-nan Liu & Hung-wen Liu, 2011. "Enzyme-catalysed [4+2] cycloaddition is a key step in the biosynthesis of spinosyn A," Nature, Nature, vol. 473(7345), pages 109-112, May.
    2. Masao Ohashi & Cooper S. Jamieson & Yujuan Cai & Dan Tan & Daiki Kanayama & Man-Cheng Tang & Sarah M. Anthony & Jason V. Chari & Joyann S. Barber & Elias Picazo & Thomas B. Kakule & Shugeng Cao & Neil, 2020. "An enzymatic Alder-ene reaction," Nature, Nature, vol. 586(7827), pages 64-69, October.
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