Biosynthesis of (−)‐Vinigrol

Abstract (−)‐Vinigrol is one of the most complex and challenging molecules in total synthesis; however, the parallel biosynthetic strategy employed by nature for the synthesis of this compound has not yet been identified. In this study, we identified a minimal gene cluster encoding a diterpene cyclase (VniA) and a cytochrome P450 (VniB) which enables the synthesis of (−)‐vinigrol through three steps. VniA first cyclizes geranylgeranyl diphosphate to generate an unusual vinigrol‐type diterpene skeleton, and then VniB catalyzes the allylic C(sp 3 )−H iterative oxidation. Further genome mining investigation provides new fungal sources for this rare and valuable vinigrol‐type diterpene skeleton.