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Abstract

Endophytic actinobacteria are a diverse group of Gram-positive bacteria with high G+C content, which inhabit plants’ internal tissues, and represent a significant yet underexplored reservoir of bioactive secondary metabolites. In host plants, a remarkable repertoire of metabolites, including broad-spectrum antibiotics, anticancer, antiviral, antifungal, antioxidant, and immunomodulatory compounds, is synthesized by these microbial allies, carrying significant medicinal and agricultural potential. These endophytes, in contrast to their soil relatives, have developed unique biosynthetic gene clusters (BGCs) strongly influenced by plant-associated factors, leading to the production of structurally novel metabolites. In recent years, the advances in genome mining, metagenomics, and metabolomics have accelerated the identification of cryptic BGCs, offering opportunities to discover new pharmacophores. This review summarizes current knowledge on the medicinal and industrial potential of endophytic actinobacteria, including their capability to yield enzymes, pigments, organic acids, bio surfactants, and natural preservatives with sustainable industrial applications. It also highlights advances in synthetic biology, co-culture strategies, and CRISPR-mediated editing that can awaken silent metabolic pathways. Yet, culturing difficulties and the absence of robust in-vivo models continue to be major challenges in transforming in-silico predictions into validated metabolites. Finally, in this review we highlighted the key research gaps and emphasized on future directions including extensive exploration of rare actinobacterial taxa, targeted isolation from extreme niches, and integration of “multi-omics” to optimize translational potential. Collectively, endophytic actinobacteria represent a promising new frontier in natural product discovery, offering solutions to antibiotic resistance, agricultural sustainability, and industrial innovation.

Article History

Received: Oct 2, 2025; Accepted: Mar 4, 2026; Published: June 30, 2026.


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