Structural insight on assembly-line catalysis in terpene biosynthesis.

Nature Communications
Jacque L FayloDavid W Christianson

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.

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Citations

Jul 14, 2021·Accounts of Chemical Research·Jacque L FayloDavid W Christianson
Oct 6, 2021·Biochemistry·Trey A RonnebaumDavid W Christianson

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Software Mentioned

Integrative Modeling Platform ( IMP )
Relion
IMP
xiView
Phenix
TurboRawToMGF
Prism
proSHADE
PaFS
e2boxer

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