Abstract Description

The constant increase in multi-resistance has necessitated bioprospecting of actinomycetes from microorganisms untapped habitats such as marine for potent antibacterial compounds. Thus, this study aimed to explore antibacterial effect and mode of action of secondary metabolites from marine actinomycetes. Actinomycetes with capability to produce antibacterials were isolated from the sand beach and identified using 16S rRNA gene sequence analysis. Antibacterial potential of the secondary metabolites of the most producing isolate was evaluated using a microdilution assay and their effect on cell membrane integrity was assessed spectrophotometrically. Bioactive compounds were identified by gas chromatography–mass spectrometry. Network pharmacology analysis was employed to predict protein targets (SwissTargetPrediction) and bacterial infection–related genes (GeneCards), with overlapping targets analysed using STRING and Cytoscape. Gene Ontology and KEGG pathway enrichment analyses were performed using ShinyGO. Molecular docking and molecular dynamics simulations were conducted using SwissDock and Desmond. Among 14 actinomycete isolates, Streptomyces koyangensis (A2) exhibited the strongest antibacterial activity, with minimum inhibitory concentration values ranging from 19.5 to 625 µg/mL. Its extract disrupted bacterial cell membranes, leading to pathogen inhibition. Network analysis identified 39 overlapping genes, with key hub proteins (AKT1 and JAK1/2/3) involved in kinase activity and major signalling pathways. The identified ligands showed moderate to strong binding affinities (–5.55 to –8.60 kcal/mol) toward the targets. All ligand-protein complexes showed stabilities, with root mean square deviation values and root mean square fluctuations less than 2 Å. In conclusion, the findings demonstrated the antibacterial potential of marine actinomycete-derived compounds and support their promise as candidates for novel antibacterial drug development.