Concise Biosynthesis of Antifungal Papulacandins

作者：Chao Yu, Niandi Zhang, Jinmei Li, Mingxin Zheng, Meihui Zhao, Lingyan Wang, Zhiqiang An, Gerald F. Bills, Zhuan Zhang · 发表于：Journal of the American Chemical Society · 年份：2025 · DOI：10.1021/jacs.4c13101 · 被引用次数：4 · 研究领域：Microbial Natural Products and Biosynthesis、Carbohydrate Chemistry and Synthesis、Plant biochemistry and biosynthesis

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.