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 Sarcophyton glaucum in terms of biological and chemical diversity. Three strains were cultivated and identified to be members of genera Micromonospora, Streptomyces, and Nocardiopsis; out of them, Micromonospora 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 Nocardia 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 (3), bafilomycin D (10), and bafilomycin A1 (11) 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.

Time-Dependent Analysis of Plasmalogens in the Hippocampus of an Alzheimer’s Disease Mouse Model: A Role of Ethanolamine Plasmalogen

“…Statistical significance was assessed using the Student’s t -test (paired, two-tailed). After applying autoscaling, a supervised orthogonal partial least square discriminant analysis (OPLS-DA) [ 35 ] and an unsupervised principal component analysis (PCA) [ 36 ] were performed using online MetaboAnalyst 5.0 software ( (accessed on 6 September 2021)). In the PCA, a score plot of the first and second principal components was generated.…”

Anti-Cancer and Anti-Inflammatory Potential of the Green Synthesized Silver Nanoparticles of the Red Sea Sponge Phyllospongia lamellosa Supported by Metabolomics Analysis and Docking Study

“…Accordingly, we subjected the metabolites (1-25) identified in the P. lamellosa-derived extracts (i.e., CE and EE) to the neural networking-based prediction software PASS. This software has shown very good success rate in its predictions, particularly for predictions higher than Pa = 0.5 [27][28][29][30][31][32][33].…”

“…Moreover, they showed a number of hydrophobic interactions with LEU-5, MET-21, HIS-46, TYR-50, and LYS-6 (Figure 6). sPLA2 has been reported to have a crucial role in the growth and development of different types of human cancers (e.g., breast, prostate, liver, and skin), and identified to be a promising target to control these types of tumors [24][25][26][27][28][29][30][31][32][33][34][35].…”

“…It is worth noting that the compounds 1-15 have also shown to be COX inhibitors according to PASS prediction; however, their scoring was poor (Pa < 0.5) (Figure 7). sPLA2 has been reported to have a crucial role in the growth and development of different types of human cancers (e.g., breast, prostate, liver, and skin), and identified to be a promising target to control these types of tumors [22,[24][25][26][27][28][29][30][31][32][33][34].…”

A Glossary for Chemical Approaches towards Unlocking the Trove of Metabolic Treasures in Actinomycetes

“…The co-cultivation has already been applied for the production of foods, food additives, enzymes and chemicals, but is not widely used for antibiotic production. On the other hand, the manipulation of fermentation conditions, or “one strain many compounds” “OSMAC” [ 16 ], represents a potential strategy for activating poorly expressed metabolic pathways, with the disadvantage of producing a low yield [ 17 ].…”