Fungal Endophytes as Efficient Sources of Plant-Derived Bioactive Compounds and Their Prospective Applications in Natural Product Drug Discovery: Insights, Avenues, and Challenges

Abstract

Fungal endophytes are well-established sources of biologically active natural compounds with many producing pharmacologically valuable specific plant-derived products. This review details typical plant-derived medicinal compounds of several classes, including alkaloids, coumarins, flavonoids, glycosides, lignans, phenylpropanoids, quinones, saponins, terpenoids, and xanthones that are produced by endophytic fungi. This review covers the studies carried out since the first report of taxol biosynthesis by endophytic Taxomyces andreanae in 1993 up to mid-2020. The article also highlights the prospects of endophyte-dependent biosynthesis of such plant-derived pharmacologically active compounds and the bottlenecks in the commercialization of this novel approach in the area of drug discovery. After recent updates in the field of ‘omics’ and ‘one strain many compounds’ (OSMAC) approach, fungal endophytes have emerged as strong unconventional source of such prized products.

Susceptibility Studies of Vancomycin Resistant Staphylococcus aureus (VRSA), Extended ?-lactamase Producing Escherichia coli and P. falciparum to Ethylacetate Extract of Endophytic Fungal Metabolites from Annona senegalensis

“…Endophytes are known to be valuable source of pharmacologically active plant-related compounds. [27][28][29][30] The antibacterial activities observed from the endophytic fungal metabolites from Annona senegalensis can be attributed to the synergy from the various compounds present in the ethyl acetate extract. It has been reported earlier that ethyl acetate has high extraction capacity for flavonoids, tannins, alkaloids and saponins which had been adjudged to have high antimicrobial activities.…”

Biotransformation ability of endophytic fungi: from species evolution to industrial applications

“…The gene clusters mediating the synthesis of some of these “shared” metabolites have been proposed to be endophytic fungal origin, having been transferred to host plants through their long co-evolutionary history (Glenn et al 2016 ). Currently, paclitaxel (an antineoplastic) (Shao et al 2021 ), camptothecin (for antitumor) (Kaur et al 2020 ), cinchonine (for treatment of malaria disease) (Maehara et al 2011 ), and podophyllotoxin (inhibit herpes virus) (Vasundhara et al 2016 ) can be synthesized by endophytic fungi and more than 90 high medicinal value metabolites (Archana et al 2021 ). However, in other cases, the biosynthetic pathway mediating the synthesis of similar bioactive metabolites found in both endophytic fungi and their plant hosts has been found to be completely different.…”

Endophytes of Brazilian Medicinal Plants With Activity Against Phytopathogens

“…Endophytes are microorganisms that reside within the internal tissues of living plants, without visibly harming the host ( Quiroga et al, 2001 ; Hardoim et al, 2015 ). These microorganisms, when associated with medicinal plants, possess high potential to produce new bioactive metabolites ( Savi et al, 2018 , 2019a ; Singh et al, 2021 ). Microorganisms have been regarded as a promising source with the most potential for structurally novel antifungal metabolites because of the isolation of many natural fungicides from the microbial resource ( Copping and Duke, 2007 ; Pham et al, 2019 ).…”