Metabologenomics-Inspired Discovery and Combinatorial Biosynthesis-Based Diversification of Fungal O-Glycosylated Depsides

Abstract

Through metabologenomics mining, we prioritized Exophiala xenobiotica SDU 039, a deep-sea sediment-derived fungus producing Oglycosylated depsides (1−9), including seven new species with varying aliphatic chains. Heterologous expression validated the exo gene cluster, and in vitro enzyme assays elucidated the function of glycosyltransferase ExoC. The chemical diversity of O-glycosylated depsides is expanded by combinatorial biosynthesis using homologues depside biosynthetic genes and in vitro transformation with ExoC and different sugars as substrate.