In this paper, we report the discovery of cryptic phosphorylation essential for the biosynthesis of nikkomycin and polyoxin class of antifungal peptidyl nucleoside natural products. Nikkomycins and polyoxins are an important class of antifungals currently used as agricultural fungicides and are clinically investigated to treat invasive fungal infections in humans. However, their biosynthesis has long remained poorly characterized. Our discovery of the cryptic phosphorylation allowed the characterization of all the downstream steps in these pathways and revealed a divergent mechanism of structurally related antifungal nucleosides. Furthermore, our study suggests that the cryptic phosphorylation is conserved in many other nucleoside biosynthetic pathways. Congratulations, Matthew and Jib!
Department of Biochemistry, Duke University School of Medicine
