Discovery of phenoxazine congeners as novel α-glucosidase inhibitors and identification of their biosynthetic gene cluster from Streptomyces sp. CB00316.

α-Glucosidase is considered an ideal target for the treatment of type 2 diabetes mellitus. Streptomyces species are known to produce a plethora of bioactive metabolites. On the basis of genomic information, the one strain many compounds (OSMAC) strategy and various chromatographic separation techniques, two compounds, bezerramycin A (1) and elloxazinone A (2), were identified from among Streptomyces sp. CB00316 metabolites. The α-glucosidase inhibitory activities of the isolated compounds were evaluated and compound 2 showed the strongest activity, with an IC50 value of 74.31 ± 3.74 µM. In silico molecular docking and molecular dynamics simulations confirmed the in vitro activities of these α-glucosidase inhibitors. In addition, we investigated the biosynthetic gene clusters and metabolic pathways of compounds 1 and 2. These findings highlight the potential of phenoxazines as lead compounds to combat the development of type 2 diabetes.