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

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. 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. 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. 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. 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.