Discovery of glycosylated naphthacemycins and elucidation of the glycosylation

Two glycosylated naphthacemycins (naphthacemycins D1 and D2) were identified in Streptomyces sp. N12W1565. These two compounds not only showed antimicrobial potential against bacteria but also exhibited more aqueous solubility than naphthacemycins. Furthermore, the whole genome of Streptomyces sp. N12W1565 has been sequenced, the natY gene, located outside the biosynthetic gene cluster encoding a D-glucose glycosyltransferase, was identified to mediate glycosylation in the phenolic hydroxyl of the naphthacemycin core scaffold. Glycosyltransferase was elucidated in vitro by using a homologous enzyme, which showed potential as a biocatalyst. •Isolation of two new glycosylated naphthacemycins from Streptomyces sp. N12W1565.•The genome of Streptomyces sp. N12W1565 was sequenced and the BGC gene cluster (nat) was revealed.•GtfE catalyzed O-glycosylation at C-9 of naphthacemycins in vitro using napthacemycins.•Glycosylation of naphthacemycins improved biological activities and aqueous solubilities.•Glycosylation of naphthacemycins indicated their potential for druggability.