Fusicoccadiene synthase from Phomopsis amygdali (PaFS) catalyzes the first committed step in the biosynthesis of Fusicoccin A, a diterpene glycoside and a a potential therapeutic agent. PaFS contains a C-terminal prenyltransferase domain that generates geranylgeranyl diphosphate (GGPP) and an N-terminal cyclase domain that utilizes GGPP to generate fusicoccadiene, which comprises the complex 5-8-5 tricyclic hydrocarbon skeleton of Fusicoccin A. The C-termimal domain octamerizes to form a central core, with the eight cyclase domains radiating outward via flexible linker segments with variable extended conformations. Crosslinking-mass spectrometry (XL-MS) experiments affirm and reveal inter-domain interactions, showing that compact conformations can be achieved. These studies, complemented by cryo-EM and functional studies, provide a framework for understanding substrate channeling between consecutive catalytic domains.