Antibacterial and cytotoxic angucyclines discovered by heterologous expression of a type II polyketide gene cluster

Abstract

Three new aromatic polyketides, spirocyclione C (1) and angumycinones E and F (2 and3), were isolated from the heterologous expression of a type II gene cluster in the strain of Streptomyces coelicolor A3(2) assisted by the one strain many compounds (OSMAC) strategy. The structures and absolute configurations of these compounds were elucidated by extensive NMR, MS, theoretical NMR calculations, DP4+ probability analysis, and ECD analyses. Notably, compound 1 represents the first example of an angucycline structure with an unusual oxaspiro[5.4]undecane architecture. Directed by molecular docking and dynamics simulations, the bioactivities of compounds 1–3 were evaluated. Compounds 1 and 2 exhibited promising cytotoxic activity against a panel of human cancer cell lines, and compound 1 showed moderate antibacterial activity against clinical pathogenic strains of B. subtilis, P. vulgaris, B. cereus, M. phlei and MRSA.