Non-Canonical C Homoterpene Biosynthesis Widespread in Actinobacteria.

A novel biosynthetic pathway towards the rare and underexplored non-canonical family of homoterpenes was discovered in actinobacteria through targeted genome mining and enzymatic in vitro reconstitution. The pathway comprises initial methylation-induced double bond isomerization of farnesyl diphosphate (FPP) to (2E,7E)-6-methyl-farnesyl diphosphate, catalyzed by a novel family of methyltransferases with unique dual function. The resulting linear C double bond isomer of FPP constitutes the specific substrate for a distinct family of type I terpene cyclases, catalyzing diverse cyclization reactions.