Biosynthesis of the Fully Saturated C16 Homosesquiterpene Descartane Through Deprotonation with Cyclopropanation.

Non-canonical terpene biosynthesis expands structural diversity beyond the classical C5n logic. Here we report the discovery of descartane, a C16 homosesquiterpene with an unprecedented scaffold produced by a bacterial type I terpene cyclase from Morganella morganii (MmTC). Unlike most terpene cyclase products, descartane is fully saturated and lacks both alkene and alcohol functions, while containing a cyclopropane ring formed in an unusual termination step. Functional characterisation demonstrated that MmTC converts α-presodorifen pyrophosphate (α-PSPP) into descartane. The cyclisation cascade was investigated by extensive isotopic labelling experiments and density functional theory (DFT) calculations, revealing a complex pathway involving fragmentation-recombination, multiple hydride shifts, and cyclopropane formation. Site-directed mutagenesis identified active site residues that control product formation and redirect the cascade towards related terpenes, including voltairene, malebranchene, de-beauvoirol, and pythagorene. These findings establish the biosynthetic origin of descartane and show how subtle changes in the active site can reprogram complex terpene cyclisation cascades.