The precursor paradox for monoterpene biosynthesis in angiosperms

Monoterpenes are among the most widespread specialized metabolites in flowering plants and the main constituents of essential oils and aromas used in the food, cosmetic, and pharmaceutical industries. Their synthesis requires geranyl diphosphate (GPP), yet a dedicated GPP synthase (GPPS) is rare in angiosperms, though the geranylgeranyl diphosphate synthases (GGPPSs) that make C₂₀ GGPP are universally conserved. How, then, is GPP supplied? Here we review four solutions: heterodimeric GGPPS/small-subunit (SSU) complexes; Leu-Val to Val-Ala substitution in the GGPPS active site; recruitment of GPP-producing activity from SSU- and farnesyl diphosphate synthase-derived enzymes; and a cis-prenyltransferase route supplying neryl diphosphate. We propose that GPP-producing activity is best viewed not as a fixed enzyme identity conserved across the plant kingdom, but as a functional property that different plant lineages have achieved independently through modification of the prenyltransferase scaffold, and that matching the right GPP-supply module to the host is a general principle for engineering monoterpenoid flavors and aromas in plants and microbes.