Abstract
Plant-associated endophytes define an important symbiotic association in nature and are established bio-reservoirs of plant-derived natural products. Endophytes colonize the internal tissues of a plant without causing any disease symptoms or apparent changes. Recently, there has been a growing interest in endophytes because of their beneficial effects on the production of novel metabolites of pharmacological significance. Studies have highlighted the socio-economic implications of endophytic fungi in agriculture, medicine, and the environment, with considerable success. Endophytic fungi-mediated biosynthesis of well-known metabolites includes taxol from Taxomyces andreanae, azadirachtin A and B from Eupenicillium parvum, vincristine from Fusarium oxysporum, and quinine from Phomopsis sp. The discovery of the billion-dollar anticancer drug taxol was a landmark in endophyte biology/research and established new paradigms for the metabolic potential of plant-associated endophytes. In addition, endophytic fungi have emerged as potential prolific producers of antimicrobials, antiseptics, and antibiotics of plant origin. Although extensively studied as a “production platform” of novel pharmacological metabolites, the molecular mechanisms of plant–endophyte dynamics remain less understood/explored for their efficient utilization in drug discovery. The emerging trends in endophytic fungi-mediated biosynthesis of novel bioactive metabolites, success stories of key pharmacological metabolites, strategies to overcome the existing challenges in endophyte biology, and future direction in endophytic fungi-based drug discovery forms the underlying theme of this article.
Highlights
Accepted: 1 February 2022Endophytes represent biological reservoirs of novel natural products, opening new avenues in the frontiers of drug discovery
Plant-associated endophytes serve as “biosynthetic platforms” of pharmaceutically important secondary metabolites, challenges exist in terms of the limited knowledge of endophyte biology and decreased production of secondary metabolites due to repeated sub-culturing of endophytic strains, projecting a need to adopt a more integrated and systematic approach towards the exploitation of endophytes in drug discovery and research
Literature reviews have provided key insights into the existing and emerging significance of endophytes in drug discovery and research—a few articles worth mentioning include Discussion on biodiversity of endophytes and its exploitation in drug discovery [1], Bioactive metabolites, and their pharmaceutical design in drug development [2], Emerging roles and applications of actinomycetes endophytes [13], Chemical ecology of endophytes and its role in bioactive metabolite production [43], The process of horizontal gene transfer and its implications in the transfer of novel traits in production of bioactive metabolites [56], and comprehensive insight on the diverse metabolites produced by fungal endophytes and their biological functions, among others
Summary
Endophytes represent biological reservoirs of novel natural products, opening new avenues in the frontiers of drug discovery. The low pace of discovery and indiscriminate use of the existing antibiotics have further necessitated the exploration of novel antimicrobial entities to compensate for the drying. Further necessitated the exploration of novel antimicrobial entities to compensate for the drying drug pipeline [2,6,7,8]. The rich yet less-explored diversity of endophytic entities anddrug theirpipeline considerable to impact the pharmaceutical industry haveand facilitated [2,6,7,8]. The rich yet less-explored diversity of endophytic entities their considerable potentialmetabolites to impact the industry have facilitated the the discovery of secondary of pharmaceutical therapeutic significance
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