Concise Biosynthesis of Antifungal Papulacandins.

We report the complete biosynthesis of antifungal papulacandins through heterologous expression and enzymatic assays. The papulacandin biosynthesis follows a convergent five-component strategy, involving a linear polyketide chain that is synthesized and installed to the aryl-glucoside by a polyketide synthase fused with a C-terminal acyltransferase domain. The formation of the challenging tricyclic benzannulated spiroketal core is initiated by the C -glycosylation of 5-(hydroxymethyl)resorcinol, followed by spirocyclization catalyzed by a Fe(II)/α-ketoglutarate-dependent oxygenase PpcE.