Esther Ugo Alum, Olisa Alfred Nwuruku, Daniel Ejim Uti, Darlington Arinze Echegu, Okechukwu Paul-Chima Ugwu, Simeon Ikechukwu Egba, Peter Chinedu Agu, Patrick Maduabuchi Aja
Plant secondary metabolites (PSMs) are vital bioactive compounds with wide pharmaceutical, agricultural, and industrial applications. However, their commercial production faces challenges due to low yields, environmental variability, and high extraction costs. Endophytes, microorganisms living within plant tissues, have emerged as key regulators of plant metabolism, enhancing PSM production through activation of biosynthetic gene clusters, secretion of precursor molecules, and modulation of plant stress responses. This narrative review explores recent advances in understanding endophyte-plant interactions, focusing on their mechanisms for stimulating metabolite production. It highlights biotechnological applications, including metabolic engineering, genome editing, and co-cultivation strategies, for optimizing endophyte-mediated biosynthesis. The review also identifies challenges in large-scale application and proposes recommendations for integrating endophytes into sustainable agriculture and pharmaceutical production. Harnessing endophytes offers an eco-friendly, cost-effective approach for scalable natural product biosynthesis, with significant potential for addressing global health, agricultural sustainability, and industrial needs. • Endophytes activate plant genes to boost secondary metabolite production. • Genome editing enhances metabolite yield in engineered endophytes. • Co-cultivation strategies generate novel plant-derived bioactive compounds. • Endophytes modulate plant stress to trigger metabolite biosynthesis. • Eco-friendly endophyte methods offer scalable metabolite production.