Abstract
Analysis of the secondary metabolite biosynthesis gene cluster (BGC) from marine Streptomyces sp. SNJ102 revealed the presence of a noncanonical nonribosomal peptide synthetase (NRPS), predicted to produce a depsipeptide compound. The NRPS gene cluster was captured by transformation-associated recombination and heterologously expressed in Streptomyces albus. The production of the new compound was confirmed using high-resolution liquid chromatography-mass spectrometry, and its structure was elucidated using nuclear magnetic resonance spectroscopy. The structure of the new depsipeptide was more similar to the monomeric structure of cyclic depsipeptides derived from fungi than to other Streptomyces-derived depsipeptides. In addition, the bacterial depsipeptide, which we named jejumide, showed promising anti-inflammatory activity. These results demonstrate that genome mining and successful heterologous expression of cryptic nonlinear NRPS BGCs from marine bacteria will facilitate the discovery of novel nonribosomal peptides and understanding of the complicated biosynthetic mechanism of nonlinear NRPS. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s42995-025-00296-8.