Endophytic Fungi: Key Insights, Emerging Prospects, and Challenges in Natural Product Drug Discovery

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.

Endophytic Fungi Associated with Dusty Miller (Centaurea cineraria L.) and Judean Wormwood (Artemisia judaica L.) and Evaluation of their Antifungal Activities

“…In recent years the increase of microbial infections and the development of microbial resistance to synthetic drugs led to renewed interest to investigate natural sources of bioactive substances for therapy against infectious pathogens [36]. Endophytic fungi isolated from medicinal plants are well known to be valuable sources of a wide range of bioactive metabolites, with antimicrobial, cytotoxic, anticancer, antioxidant, antimalarial, and antiviral activities [37].…”

Endophytes in Lignin Valorization: A Novel Approach

“…Due to overwhelming incredibility and demands of enzymes, the global market value of enzymes is expected to hike at a compound annual growth rate of 6.1% until 2027, which was USD 5.6 billion in 2019 ( Fungal Enzymes Market Report, 2021 ). Hence, for the maximum utilization of endophytic enzymes and their contribution in enhancing the global economy, the bottlenecks regarding the endophytic growth, purity, maintenance/sub-culturing, and enzyme secretion should be addressed ( Tiwari and Bae, 2022 ). Research is required to explore the ways which could overcome these hurdles without enhancing the production costs.…”

Broad-Spectrum Antimicrobial Action of Cell-Free Culture Extracts and Volatile Organic Compounds Produced by Endophytic Fungi Curvularia Eragrostidis

“…In this study, an ethnomedicinally valuable plant H. isora from East Indian Forest is selected for an endophyte-related study, and an endophytic Curvularia eragrostidis HelS1 has been isolated from the leaf tissues of the host plant. H. isora as a whole or its different parts like stem-bark, leaves, fruits, seeds, and roots possess potent antimicrobial, anti-oxidant, hepato-protective, anti-plasmodial, anti-cancer, anti-nociceptive action and are randomly used as Ayurvedic and Unani medicines (Srinivasa et al, 2022;Tiwari and Bae, 2022). The secondary metabolites extracted from HelS1 endophyte are found to be effective antibacterial agents restricting the growth of pathogenic MRSA, and Vibrio parahaemolyticus, causing lethal leakage of necessary macromolecules, blocking bio-film formation, and hampering the central carbohydrate metabolism.…”