Biosynthesis of the quinovosamycin nucleoside antibiotics diverges from that of tunicamycins by additional sugar processing genes

Nucleoside antibiotics tunicamycins and quinovosamycins are closely related microbial natural products with significant antibacterial and antifungal properties. In this study, we identify and elucidate the structure of a new quinovosamycin analogue, quinovosamycin Q4 (4), which displays potent activity against Cryptococcus neoformans (0.03 μg/mL), Candida albicans (0.5 μg/mL), and Bacillus subtilis (0.125 μg/mL). Bioinformatics analysis of the sequenced genome of the quinovosamycin producing Streptomyces strain PR-3G identified a biosynthetic gene cluster (BGC), encoding all of the enzymes needed for tunicamycin synthesis, as well as several new upstream genes likely responsible for synthesis and incorporation of the alternative N-acetylquinovosamine sugar needed for quinovosamycin production. The role of the upstream genes in quinovosamycins biosynthesis was confirmed by insertional mutagenesis.