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.

Highlights

  • Quinones are biosynthesized through several pathways; for example, isoprenoid quinones are synthesized by the shikimate pathway using chorismite-derived compounds as precursors, terrequinone by nonribosomal peptide synthetases (NRPS) from L-tryptophan, dopaquinone by tyrosinase from tyrosine, and benzoquinone by catechol oxidase/polyketide synthase (PKS) from catechol [24]

  • Xanthatin exerts its trypanocidal activity by inhibiting both prostaglandin E2 (PGE2) synthesis and 5-lipoxygenase activity, thereby avoiding unwanted inflammation commonly observed in trypanosomiasis

  • After screening a large spectrum of articles dedicated to endophyte research, natural product drug discovery, combinatorial chemistry, genomics, metabolomics ethnobotany, modern medicine, and multidisciplinary science, we curated 101 specific plantderived medicinal compounds efficiently biosynthesized by hundreds of endophytic fungi

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Summary

Introduction

Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. The opportunity to find new potential bioactive metabolites from cryptic endophytic microorganisms of nearly 374,000–400,000 plant species congruently occupying millions of biological niches is considered high [5,10] This opportunity has increased further with the innovative discovery of biosynthesis of Taxus derived anticancer compound ‘taxol’ from its endophytic fungus T. andreanae in 1993 by Stierle et al [11]. It is an established fact that endophytes can co-/produce, induce, and/or modify a plethora of “specific plant-derived” metabolites in-/outside of host plants [12,14,17] Such discoveries opened the new horizons for the up-scaled production of plant-derived medicinal compounds from endophytes. Its outcome would certainly lead to strategize the use of endophytes as an efficient novel source for plant-derived metabolites

Plant-Derived Bioactive Natural Products from Fungal Endophytes
Plant-Derived Alkaloids from Fungal Endophytes
Aconitine
Berberine
Camptothecin
Capsaicin
Huperzine A
Peimisine and Imperialine-3β-D-glucoside
Piperine
Quinine
2.1.10. Rohitukine
2.1.11. Sanguinarine
2.1.12. Solamargine
2.1.13. Swainsonine
2.1.14. Vinblastine and Vincristine
2.1.15. Vincamine
Bergapten and Meranzin
Isofraxidin
Marmesin
Mellein
Scopoletin and Umbelliferone
Plant-Derived Flavonoids from Fungal Endophytes
Apigenin
Cajanol
Chrysin
Curcumin
Kaempferol
Luteolin
Quercetin
Silymarin
2.3.10. Vitexin
Plant-Derived Lignans from Fungal Endophytes
Plant-Derived Saponins from Fungal Endophytes
Plant-Derived Terpenes from Fungal Endophytes
Artemisinin
Bilobalide and Ginkgolides
Paclitaxel
Xanthatin
Plant-Derived Quinones and Xanthones from Fungal Endophytes
Hypericin
Pachybasin
Plumbagin and Shikonin
Tanshinones
Miscellaneous Plant-Derived Compounds from Fungal Endophytes
Digoxin
Avenues and Challenges in Application of Endophyte as Alternative Sources of
Conclusions
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