Structural insight on assembly-line catalysis in terpene biosynthesis

Jacque L. Faylo, Trevor van Eeuwen, Hee Jong Kim, Jose J. Gorbea Colón, Benjamin A. Garcia, Kenji Murakami, David W. Christianson

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


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.

Original languageEnglish
Article number3487
JournalNature communications
Issue number1
StatePublished - Dec 1 2021


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