Identification and Cyclization Mechanism of Fungal (+)-β-Chamigrene Synthase.

Chamigranes are a unique class of sesquiterpenoids featuring a spiro[5.5]undecane framework, yet their biosynthesis in fungi has remained elusive for decades. In this study, we identify and characterize ChamTS, a sesquiterpene synthase from the basidiomycetous fungus Cerrena albocinnamomea, which specifically catalyzes the formation of (+)-β-chamigrane. In vitro isotope-labeling experiments unveiled the cyclization pathway of ChamTS, revealing an initial 1,6-cyclization followed by a 1,5-proton shift and spirocycle-forming rearrangement. This work provides a foundation for the biosynthetic production and further engineering of β-chamigrane-type terpenoids.