Harnessing the bioactive potential of endophytic Xylaria species: a comprehensive review on natural drug discovery and biotechnological applications

The genus Xylaria (family Xylariaceae) represents a taxonomically complex and ecologically versatile group of endophytic fungi, well known for their ability to colonize diverse hosts in terrestrial and aquatic ecosystems. Beyond their ecological roles, Xylaria species are prolific producers of structurally diverse secondary metabolites, including terpenoids, polyketides, cytochalasins, alkaloids, lactones, and volatile organic compounds. These metabolites exhibit a wide range of biological activities such as antimicrobial, cytotoxic, antioxidant, anti-inflammatory, and enzyme-inhibitory effects, underscoring their potential in drug discovery and sustainable agriculture. However, despite the expanding catalogue of compounds, most studies remain descriptive with limited efforts toward comparative evaluation, ecological integration, or translational application. Contradictory findings, poor reproducibility of bioactivity assays, and unresolved taxonomic issues further constrain their exploitation. This review critically synthesizes advances in the chemistry, biology, and ecology of Xylariaderived metabolites, evaluating their pharmacological and agronomic significance. We highlight methodological strengths and limitations in isolation, structural elucidation, and pathway activation strategies such as OSMAC (One Strain Many Compounds), co-culture, and genome mining, and discuss how emerging omics-integrated and synthetic biology approaches can overcome current bottlenecks. Importantly, we propose a framework linking metabolite diversity to ecological function and outline priority research directions for translating Xylaria metabolites into viable therapeutic and agricultural innovations. By moving beyond cataloguing, this synthesis positions Xylaria as a model genus for bridging fungal chemical ecology with applied biotechnology.