Carbon extension in peptidylnucleoside biosynthesis by radical-SAM enzymes

Nikkomycins and polyoxins are antifungal peptidylnucleoside (PN) antibiotics active against human and plant pathogens. Here, we report that during PN biosynthesis in Streptomyces cacaoi and Streptomyces tendae, the C5′-extension of the nucleoside essential for downstream structural diversification is catalyzed by a conserved radical S-adenosyl-L-methionine (SAM) enzyme, PolH or NikJ. This is distinct from the nucleophilic mechanism reported for antibacterial nucleosides and represents a novel mechanism of nucleoside natural product biosynthesis.