Combinatorial Biosynthesis of Sulfated Benzenediol Lactones with a Phenolic Sulfotransferase from Fusarium Graminearum PH-1

The study identified and characterized FgSULT1, a phenolic sulfotransferase from Fusarium graminearum PH-1, which was expressed in Saccharomyces cerevisiae to sulfate benzenediol lactones and other compounds, enhancing their solubility. FgSULT1 was unique in its low similarity to known animal and plant sulfotransferases, forming a distinct clade with bacterial sulfotransferases. It demonstrated a broad substrate range, successfully sulfating 14 out of 49 model substrates, including benzenediol lactone congeners, but not anthraquinones, flavonoids, or simple phenols. The enzyme's large substrate binding cavity allowed for diverse phenolic compound binding, and no cytotoxicity was observed in tested cell lines. This research expanded the sulfotransferase superfamily to fungi and suggested potential applications in drug discovery, food safety, and environmental monitoring due to the improved solubility and drug-like properties of sulfated polyketides.