Apoptolidin I: A new glycosylated macrocyclic lactone from wasp gut bacterium, Amycolatopsis sp

Apoptolidin I (1) was isolated along with previously reported apoptolidin A (2) from Amycolatopsis sp. DW02G, a bacterial strain isolated from the gut of Dolichovespula media media collected from Gwanak Mountain, Republic of Korea. 1 was identified as a new glycosylated macrolide in the apoptolidin family based on NMR spectroscopic, HRMS, and MS/MS data. Compound 1, which lacks the C-16 hydroxyl group of 2, is the first member of the apoptolidin family to possess a 2,6-dideoxy-β-d-arabino-hexopyranose moiety as a part of the disaccharide, instead of d-oleandrose. The full genome analysis of the producer strain DW02G identified the biosynthetic gene cluster responsible for apoptolidin production. The stereochemistry of 1 was proposed based on its CD spectrum and ketoreductase sequences relative to those of previously reported 2. The cytotoxicity evaluation of 1 and 2 indicated that the variation in the structure of the disaccharide moiety attached to C-27 could promote the inhibitory activity against cancer cell lines. [Display omitted]