Abdullah M. Nagib, Mahmoud H. Sultan, Hussein H. El-sheikh, Amr H. Hashem
Endophytic fungi residing within medicinal plants represent a rich and sustainable source of bioactive secondary metabolites with diverse pharmacological applications. These symbiotic microorganisms establish mutualistic relationships with their host plants, contributing to enhanced stress tolerance, growth promotion, and defense against pathogens. In recent years, endophytic fungi have gained considerable attention as alternative biofactories for the production of valuable compounds such as alkaloids, terpenoids, phenolics, lignans, and polysaccharides. These metabolites exhibit a wide range of biological activities, including antimicrobial, antiviral, anticancer, antioxidant, anti-inflammatory, and antidiabetic effects. Advances in cultivation strategies, such as OSMAC, co-culture, and epigenetic modification, have significantly improved metabolite yield and diversity. Moreover, the integration of genomics, transcriptomics, and metabolomics has revolutionized the understanding of biosynthetic gene clusters and metabolic pathways, enabling the discovery of novel compounds and optimization of production processes. Despite these advances, challenges such as low yield, silent gene clusters, and difficulties in large-scale production remain significant barriers. Nevertheless, continued progress in multi-omics technologies, synthetic biology, and biotechnological tools holds great promise for unlocking the full potential of endophytic fungi. Herein, endophytic fungi represent a powerful and eco-friendly platform for the development of new therapeutic agents and sustainable pharmaceutical applications.