Generation of glucosylantimycins by heterologous expression of a promiscuous glycosyltransferase in a deepsea-derived Streptomyces.

Antimycins are a class of depsipeptide compounds that exhibit diverse bioactivities. However, their potential clinical applications are hampered by high cell toxicities. Glycosylation usually has profound impacts on the physicochemical properties, bioactivities and toxicities of natural products. In this study, we overexpressed an artificial glycosyltransferase (GT) gene sbmGT1 in deepsea-derived Streptomyces albus ZH66, leading to the discovery of three new antimycin derivatives glucosylantimycins A, B and C (1-3). Their structures were determined by a combination of spectroscopic methods, including high resolution electrospray ionisation mass spectrometry (HRESIMS) and nuclear magnetic resonance (NMR) analysis. The glycosylation remarkably improved the water solubility but simultaneously reduced the cytotoxicities of antimycins towards human cervix epidermoid carcinoma (HeLa) and human hepatic carcinoma (HepG2) cell lines.