Exploration of Chemical Diversity and Antitrypanosomal Activity of Some Red Sea-Derived Actinomycetes Using the OSMAC Approach Supported by LC-MS-Based Metabolomics and Molecular Modelling

Abstract

In the present study, we investigated the actinomycetes associated with the Red Sea-derived soft coral <i>Sarcophyton glaucum</i> in terms of biological and chemical diversity. Three strains were cultivated and identified to be members of genera <i>Micromonospora</i>, <i>Streptomyces</i>, and <i>Nocardiopsis</i>; out of them, <i>Micromonospora</i> sp. UR17 was putatively characterized as a new species. In order to explore the chemical diversity of these actinobacteria as far as possible, they were subjected to a series of fermentation experiments under altering conditions, that is, solid and liquid fermentation along with co-fermentation with a mycolic acid-containing strain, namely <i>Nocardia</i> sp. UR23. Each treatment was found to affect these actinomycetes differently in terms of biological activity (i.e., antitrypanosomal activity) and chemical profiles evidenced by LC-HRES-MS-based metabolomics and multivariate analysis. Thereafter, orthogonal projections to latent structures discriminant analysis (OPLS-DA) suggested a number of metabolites to be associated with the antitrypanosomal activity of the active extracts. The subsequent in silico screenings (neural networking-based and docking-based) further supported the OPLS-DA results and prioritized desferrioxamine B (<b>3</b>), bafilomycin D (<b>10</b>), and bafilomycin A1 (<b>11</b>) as possible antitrypanosomal agents. Our approach in this study can be applied as a primary step in the exploration of bioactive natural products, particularly those from actinomycetes.