Bioactive Metabolites from Marine-derived Aspergillus flavor-furcatis: Optimization of Fermentation Conditions for Enhanced Antibacterial and Anticancer Activities

Introduction: Tam Giang Lagoon in Central Vietnam is a highly productive ecosystem with substantial microbial diversity, offering promising sources of bioactive secondary metabolites from fungi. This study aimed to isolate and characterize bioactive secondary metabolites from the marine-derived fungus Aspergillus flavo-furcatis, evaluate their cytotoxic and antibacterial activities, and identify optimal fermentation conditions for enhanced metabolite production. Methods: A. flavo-furcatis isolated from lagoon sediments was cultured in four media (PDW, Czapek, Sabouraud, YPD) supplemented with sea salt (2.5%). Extracts were evaluated against human cancer cell lines (MCF-7, HepG2) and standard bacterial pathogens. Metabolites were isolated using chromatographic techniques and structurally elucidated by NMR and MS spectroscopy. Results: Extracts from Sabouraud medium exhibited superior cytotoxicity (cell survival: MCF- 7, 43.7 ± 0.2%; HepG2, 44.1 ± 0.1%) and potent antibacterial activity, particularly against Staphylococcus aureus (31.7 ± 0.6 mm inhibition zone) and Pseudomonas putida (30.8 ± 0.3 mm). Among the isolated compounds, 6,8-dihydroxy-3,7-dimethylisocoumarin demonstrated significant anticancer activity (IC₂⁽: MCF-7, 14.57 ± 1.36 μM; HepG2, 13.28 ± 1.26 μM). Limited quantities prevented testing of trichodermin and 2,3-dihydrobenzofuran, although previous studies report strong bioactivities for these compounds. Discussion: This study highlights the chemotherapeutic potential of metabolites from Aspergillus flavo-furcatis and the need for further research on their production, optimization, and biological applications. Conclusion: Sabouraud medium supplemented with sea salt optimally supported bioactive metabolite production. The metabolites exhibited substantial anticancer and antibacterial potential, warranting further investigation for drug development.