Biosynthesis of Trichobisabolins Involves a UbiA-Type Terpene Cyclase for trans -Zingiberenol Generation and a Single Cytochrome P450 Catalyzing the γ-Butenolide Formation from an Isoprene Unit

Through genome mining, a conserved biosynthetic gene cluster from the biocontrol Trichoderma species was identified and characterized to be responsible for the biosynthesis of γ-butenolide-containing sesquiterpenoid trichobisabolin B. The biosynthetic pathway involves a UbiA-type terpene cyclase TbaA catalyzing the cyclization of farnesyl pyrophosphate to form (3S,6R,7S)-zingiberenol, a stink bug pheromone, and a multifunctional cytochrome P450 TbaB catalyzing the sequential oxidation on an isoprene unit of zingiberenol to generate the γ-butenolide moiety.