Biosynthesis of Meroterpenoid Furanasperterpenes: Enzymatic Insights into a 6/6/6/6/5 Pentacyclic Skeleton

Furanasperterpenes are characterized by a novel 6/6/6/6/5 pentacyclic skeleton and demonstrate significant lipid-lowering activity. In this study, we elucidate the biosynthetic pathway of furanasperterpene B and the enzymatic basis for the formation of its distinctive pentacyclic scaffold. The pathway diverges at a key branching point through the action of Asp14, a novel NTF2-like isomerase that catalyzes D-ring rearrangement to direct biosynthesis toward furanasperterpenes instead of terretonins. Subsequently, α-ketoglutarate-dependent dioxygenase Asp7 catalyzes hydroxylation and facilitates furan ring formation to construct the 6/6/6/6/5 pentacyclic scaffold.