Terpene cyclase enzymes catalyze the most complex chemical reactions found in nature, forming products used as fragrances, biofuels and drugs. Most famously, taxadiene synthase and amorphadiene synthase catalyze principal chemical reactions in the biosynthesis of anti-cancer drug Taxol and anti-malarial artemisinin, respectively. Additionally: Fusicoccin A is a 5-8-5 tricyclic phytotoxin with anti-metastatic and axon regenerative properties; mangicdiene is a 5-5-6-5 tetracycle with antibiotic properties; ophiobolin F is a 25-carbon 5-8-5 tricycle with potential anti-tumor activities. The first committed steps of biosynthesis of these molecules are catalyzed by fusicoccadiene synthase (PaFS), mangicdiene synthase (FgMS), and ophiobolin F synthase (AcOS).Terpene cyclization is a major branch point in terpenoid biosynthetic pathway, following the condensation of 5-carbon substrates dimethylallyl diphosphate and isopentenyl diphosphate to form linear isoprenoid substrates. A small handful of fungal terpene synthase enzymes remarkably catalyze both prenyltransferase and cyclization reactions in independent catalytic domains of a single polypeptide chain. The elusive structural nature of these so-called bifunctional assembly-line terpene biosynthesis enzymes is described here. PaFS is the first assembly-line terpene synthase to be discovered; PaFS forms high-order oligomers and exhibits substrate channeling, in which the isoprenoid intermediate is transported to the cyclization domain without diffusion into bulk solution. While interactions between cyclase and prenyltransferase domains are transient, I use cryo-electron microscopy (cryo-EM) aided by combinatorial crosslinking studies to provide snapshots of condensed positions that occur at low abundance. I argue that these interactions, while wobbly, may be consequential to substrate channeling. I also consider orthologs of PaFS, including FgMS, and use cryo-EM and x-ray crystallography to study the extent to which properties of PaFS are conserved in assembly-line biosynthesis. I discuss ‘dynamic cluster channeling’ as a modified version of cluster channeling operative here, in which combined agglomeration of active sites and covalent tethering of consecutive domains enhances product flux at this metabolic branch point. These findings will inform the synthetic biological production of terpenoid-based drugs.