Bathiapeptides: Polythiazole-Containing Peptides from a Marine Biofilm-Derived Bacillus sp.

Bacteria in marine biofilms are a rich reservoir of natural products. To facilitate novel secondary metabolite discovery, we investigated the metabolic profile of a marine biofilm-derived Bacillus sp. B19-2 by combining bioinformatics and LC-UV-MS analyses. After dereplication and purification of putatively unknown compounds, a new family of compounds 1-8 was uncovered and named bathiapeptides. Structural elucidation using NMR, HRESIMS, ozonolysis, advanced Marfey's analysis, and X-ray diffraction revealed that bathiapeptides are polypeptides that contain a rare polythiazole moiety. These compounds exhibited strong cytotoxicity against Hep G2, HeLa, MCF-7, and MGC-803 cell lines, and the lowest IC50 value was 0.5 mu M. An iterative biosynthesis logic in bathiapeptides' biosynthesis was proposed based on the identified chemical structures and putative gene cluster analysis.

Automated summary

Bacteria in marine biofilms are a valuable source of natural products. In this study, the metabolic profile of a Bacillus sp. B19-2 derived from a marine biofilm was investigated to discover novel secondary metabolites. A new family of compounds called bathiapeptides was identified and their structures, as well as cytotoxicity against different cell lines, were elucidated. An iterative biosynthesis logic for bathiapeptides was proposed based on the chemical structures and gene cluster analysis.