Figure 2.

Schematic overview of representative carbocation-driven reactions catalyzed by prenyl transferases (PTs) and diterpene synthases (TPSs). (A) PT catalyzed head-to-tail condensation of isopentenyl diphosphate (IPP) with its positional isomer dimethylallyl diphosphate (DMAPP) via ionization of the allylic diphosphate ester bond (OPP) and subsequent coupling between the resulting carbocation and the C3–C4 double bond of IPP. Deprotonation of the carbocation intermediate yields geranyl diphosphate (GPP). (B–C) Conversion of geranylgeranyl GGPP by class II diTPSs using protonation-initiated cyclization of GGPP to facilitate scaffold rearrangement into bicyclic prenyl diphosphates of ent-copalyl diphosphate (ent-CPP) (B) and related scaffolds of distinct stereochemistry and hydroxylation (C). (D–E) Class I diTPS-catalyzed conversion of bicyclic prenyl diphosphate intermediates via ionization of the diphosphate moiety and subsequent cyclization and rearrangement through various 1,2-hydride and methyl migrations to form, for example, ent-kaurene (D) and a range of other labdane diterpene scaffolds (E).