Biosynthesis of Terpenoid–Pyrrolobenzoxazine Hybrid Natural Product CJ‐12662

Abstract

The fungal natural product CJ‐12662 is a structurally complex terpene–amino acid hybrid, and is a potent anthelmintic compound. The biosynthetic pathway of CJ‐12662 is elucidated based on metabolite analysis from heterologous expression. We demonstrate the terpene portion is derived from successive P450‐catalyzed oxidations of amorpha‐4,11‐diene, while three flavin‐dependent enzymes are involved in morphing the esterified tryptophan into a chlorinated pyrrolobenzoxazine, utilizing a cascaded [1,2]‐Meisenheimer rearrangement.