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

摘要

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.