Identification and Screening of Natural Compounds with Cancer Chemoprevention Activity from Fungi and Bacteria Isolatedfrom The South Coast of Jember

Abstract

Marine microorganisms represent an invaluable yet underexplored source of bioactive natural products with potential applications in cancer chemoprevention. This study aimed to identify, characterize, and screen natural compounds with chemopreventive activity from culturable fungi and bacteria isolated from the south coast of Jember, Indonesia. To enhance culturability, enrichment strategies were employed by mimicking natural marine habitat conditions—adjusting nutrients, pH, temperature, and salinity using artificial seawater to ensure consistency and minimize interference from environmental pollutants. Biodiversity analysis revealed that all 17 culturable fungal isolates belonged to the phylum Ascomycota, dominated by Penicillium (47.06%), Scopulariopsis, and Curvularia. Meanwhile, bacterial isolates identified through 16S rRNA gene sequencing represented six genera (Bacillus, Vibrio, Pseudoalteromonas, Fictibacillus, Sphingomonas, and Morganella), with Bacillus (43.75%) and Vibrio (31.25%) as the dominant taxa. The majority were nonpathogenic and exhibited diverse metabolite profiles. Bioactivity screening demonstrated that the ethyl acetate extract of Aspergillus stromatoides strain SaH 1 exhibited selective cytotoxicity toward breast cancer cells, while Vibrio orientalis strain WaN 2 displayed potent and selective cytotoxicity (IC₅₀ < 100 μg/mL; 1.00 < SI < 3.00) against WiDr, T47D, and HeLa cells by inducing G₂/M phase arrest and apoptosis. UHPLC–HRMS metabolite profiling revealed 606 molecular features in A. stromatoides strain SaH 1 and 3,211 in V. orientalis strain WaN 2, with 76% and 80.54% of features, respectively, remaining unannotated—indicating the presence of potentially novel metabolites. To the best of our knowledge, this is the first report of V. orientalis isolated from Indonesia and the first evidence of its cancer chemopreventive activity. These findings establish the south coast of Jember as a new bioprospecting hotspot and underscore the vast untapped potential of Indonesia’s tropical marine microbiota for natural product discovery. Future research should aim not only to identify the 80.54% of currently unidentified compounds in V. orientalis strain WaN 2, but also to screen the 19.46% of identified ones for their potential cancer chemopreventive activity, supported by genomic, metabolomic, and in vivo validation approaches.