Discovery and Characterization of Marinsedin, a New Class II Lanthipeptide Derived from Marine Bacterium Marinicella sediminis F2 T .

Microbial natural products provide a large number of drug leads. It is believed that abundant unexploited marine microorganisms also exhibit great potential for discovering compounds with novel chemical scaffolds and bioactivities. Lanthipeptides are a group of ribosomally synthesized and post-translationally modified peptides exhibiting a variety of biological functionalities. They are characterized by the presence of the thioether-containing bis-amino acids lanthionine and methyllanthionine. However, marine-derived lanthipeptides remain underexplored. Here we identified, heterologously expressed, and structurally characterized the unprecedented class II lanthipeptide marinsedin from the rare marine bacterium Marinicella sediminis F2 T . Marinsedin consists of 19 amino acids and contains a rare 2-oxobutyryl group blocking the N-terminus of the peptide chain and two overlapping intramolecular thioether rings including an unusual 12-membered macro-thioether ring. Furthermore, we also evaluated the biological activity of marinsedin, demonstrating that it exhibits moderate cytotoxicity against HeLa cells and weak cytotoxicity against HCT-116 cell lines.