Marine endophytic fungi from mangroves: Chemical diversity, biosynthetic pathways, and therapeutic potential

Marine endophytic fungi from mangrove ecosystems represent valuable sources of bioactive secondary metabolites with pharmaceutical potential. This review examines the diversity, chemical profiles, and therapeutic applications of endophytic fungi isolated from mangrove plants. Studies consistently report that Ascomycota represents the majority of described isolates, with Aspergillus and Penicillium often cited as dominant genera in mangrove endophyte research. These fungi synthesize diverse compounds including polyketides, alkaloids, terpenoids, and peptides through polyketide synthases, non-ribosomal peptide synthetases, and hybrid biosynthetic systems. Recent discoveries include rhizoaspergillin A with novel orsellinic acid–ribose–pyridazinone–N-oxide architecture and fuscoposides with neuroprotective activity. Therapeutic applications encompass anticancer effects (cytochalasin H inhibiting cancer cell migration via YAP/TAZ signaling), antimicrobial activity against resistant pathogens, and antidiabetic properties. The extreme conditions of mangrove habitats salinity stress, anaerobic environments, and microbial competition drive evolutionary adaptations producing unique metabolites. Co-cultivation and OSMAC approaches have revealed additional chemical diversity by activating silent gene clusters. Mangrove endophytic fungi represent a promising source for natural product drug discovery, addressing antimicrobial resistance, cancer, and metabolic diseases. Our analysis provides an overview of current knowledge regarding bioactive metabolites from mangrove endophytic fungi and their potential applications in drug discovery.