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Structural insight on assembly-line catalysis in terpene biosynthesis

Author

Listed:
  • Jacque L. Faylo

    (Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania)

  • Trevor van Eeuwen

    (University of Pennsylvania
    University of Pennsylvania)

  • Hee Jong Kim

    (University of Pennsylvania
    University of Pennsylvania)

  • Jose J. Gorbea Colón

    (University of Pennsylvania
    University of Pennsylvania)

  • Benjamin A. Garcia

    (University of Pennsylvania)

  • Kenji Murakami

    (University of Pennsylvania)

  • David W. Christianson

    (Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania)

Abstract

Fusicoccadiene synthase from Phomopsis amygdali (PaFS) is a unique bifunctional terpenoid synthase that catalyzes the first two steps in the biosynthesis of the diterpene glycoside Fusicoccin A, a mediator of 14-3-3 protein interactions. The prenyltransferase domain of PaFS generates geranylgeranyl diphosphate, which the cyclase domain then utilizes to generate fusicoccadiene, the tricyclic hydrocarbon skeleton of Fusicoccin A. Here, we use cryo-electron microscopy to show that the structure of full-length PaFS consists of a central octameric core of prenyltransferase domains, with the eight cyclase domains radiating outward via flexible linker segments in variable splayed-out positions. Cryo-electron microscopy and chemical crosslinking experiments additionally show that compact conformations can be achieved in which cyclase domains are more closely associated with the prenyltransferase core. This structural analysis provides a framework for understanding substrate channeling, since most of the geranylgeranyl diphosphate generated by the prenyltransferase domains remains on the enzyme for cyclization to form fusicoccadiene.

Suggested Citation

  • Jacque L. Faylo & Trevor van Eeuwen & Hee Jong Kim & Jose J. Gorbea Colón & Benjamin A. Garcia & Kenji Murakami & David W. Christianson, 2021. "Structural insight on assembly-line catalysis in terpene biosynthesis," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
  • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-23589-9
    DOI: 10.1038/s41467-021-23589-9
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    Cited by:

    1. Michael P. Andreas & Tobias W. Giessen, 2024. "The biosynthesis of the odorant 2-methylisoborneol is compartmentalized inside a protein shell," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

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