Submitted Successfully!
To reward your contribution, here is a gift for you: A free trial for our video production service.
Thank you for your contribution! You can also upload a video entry or images related to this topic.
Version Summary Created by Modification Content Size Created at Operation
1 + 2046 word(s) 2046 2021-02-20 03:51:13 |
2 format change -1060 word(s) 986 2021-02-24 13:38:06 | |
3 format change + 779 word(s) 1765 2021-02-25 06:39:22 |

Video Upload Options

Do you have a full video?

Confirm

Are you sure to Delete?
Cite
If you have any further questions, please contact Encyclopedia Editorial Office.
White, J. Fungal Endophytes: Sources of Medicines. Encyclopedia. Available online: https://encyclopedia.pub/entry/7551 (accessed on 18 April 2024).
White J. Fungal Endophytes: Sources of Medicines. Encyclopedia. Available at: https://encyclopedia.pub/entry/7551. Accessed April 18, 2024.
White, James. "Fungal Endophytes: Sources of Medicines" Encyclopedia, https://encyclopedia.pub/entry/7551 (accessed April 18, 2024).
White, J. (2021, February 24). Fungal Endophytes: Sources of Medicines. In Encyclopedia. https://encyclopedia.pub/entry/7551
White, James. "Fungal Endophytes: Sources of Medicines." Encyclopedia. Web. 24 February, 2021.
Fungal Endophytes: Sources of Medicines
Edit

Fungal endophytes are well-established sources of biologically active natural compounds with many producing pharmacologically valuable specific plant-derived products.

Fungal Endophytes

1. Introduction

Several recent reports suggest that natural products may play a substantial role in the drug discovery and development process as a source of diverse and novel templates for future drugs[1][2][3][4]. With the rapidly evolving recognition that significant numbers of natural products are either produced by microbes or a result of microbial interactions with their hosts, the area of endophyte research for natural products is positioned to take the drug discovery and development process to the next level [5][6]. In the backdrop of the past 25 years of studies, endophytes may be defined as a polyphyletic group of unique microorganisms residing in healthy living internal tissues of the plants with covert and/or overt positive effects on their hosts. They establish a variety of intricate biological intra- and inter-relationships among them and with their hosts, respectively. Endophytes are able to produce a multitude of secondary metabolites with diverse biological activities[7][8][9]. However, merely 0.75–1.50% of known plant species has been explored for their endophytes yet. So, 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]. This discovery leads to renewed attention in endophytic fungi for isolating plant-derived medicinal compounds [12][13][14]. Later, a series of works revealed that a reasonable number of plant-derived compounds are synthesized by endophytes rather than hosts[9][15]. However, there are unsettled and contradictory reports regarding the phylogenetic origin of genes related to the biosynthesis pathway of such plant-derived compounds in host plants and their microbial endophytes [16]. The above facts prompted us to use the word “plant/host-derived” rather than “plant/host-origin” for such compounds. Nevertheless, it is now an established fact that endophytes can co-/produce, induce, and/or modify a plethora of “specific plant-derived” metabolites in-/outside of host plants[17][12][14]. Such discoveries opened the new horizons for the up-scaled production of plant-derived medicinal compounds from endophytes. The recent increase in demand for natural products and difficulties in accessing them from plants make endophytes interesting targets for the assessment and isolation of typical host-derived compounds[18][19]. Since medicinal plants are an inherent source of many therapeutic compounds, it is vital to explore their endophytes to isolate such compounds. The current review aims to provide an up-to-date overview on the globally isolated specific plant-derived bioactive compounds synthesized by fungal endophytes from the period 1993 to mid-2020. It will also focus on applications and modes of actions of such compounds. This review will also provide insights about different challenges in employing endophytes as an alternative source for the synthesis of plant-derived bioactive compounds and their application in drug discovery. Its outcome would certainly lead to strategize the use of endophytes as an efficient novel source for plant-derived metabolites. 

2. Plant-Derived Bioactive Natural Products from Fungal Endophytes

A wide array of secondary metabolites in fungi is biosynthesized from very few key precursor compounds by slight variations in basic biosynthetic pathways and can be classified into nonribosomal peptides, polyketides, terpenes, and alkaloids. Nonribosomal peptides are biosynthesized by multimodular nonribosomal peptide synthetases (NRPS) enzymes using both proteinogenic and nonproteinogenic amino acids. Polyketides are biosynthesized by polyketide synthase (PKS) enzymes from acetyl-CoA and malonyl-CoA units. Terpenes consisting of isoprene subunits are biosynthesized from the mevalonate pathway catalyzed by terpene cyclase enzymes. Alkaloids are nitrogen-containing organic compounds biosynthesized as complex mixtures through the shikimic acid and the mevalonate pathways, as they are usually derived from aromatic amino acids and dimethlyallyl pyrophosphate[20]. Other classes of fungal secondary metabolites are linked with the above four groups of compounds. For ease and better understanding, we have classified different fungal secondary metabolites as alkaloids, coumarins, flavonoids, lignans, saponins, terpenes, quinones, and xanthones, and miscellaneous compounds. Coumarins are a class of lactones consisting of a benzene ring fused to a α-pyrone ring and are mainly biosynthesized by the shikimic acid pathway from cinnamic acid. Flavonoids are synthesized by the phenylpropanoid pathway from phenylalanine using enzymes phenylalanine ammonia lyase (PAL), chalcone synthase, chalcone isomerase, and flavonol reductase [21]. Lignans are low molecular weight polyphenols biosynthesized by enzymes pinoresinol-lariciresinol reductase (PLR), PAL, cinnamoyl-CoA reductase (CCR), and cinnamyl-alcohol dehydrogenase (CAD)[22]. Saponins are glycosides containing a non-sugar triterpene or steroid aglycone (sapogenin) attached to the sugar moiety. Saponins are derived from intermediates of the phytosterol pathway using enzymes oxidosqualene cyclases (OSCs), cytochromes P450 (P450s), and UDP-glycosyltransferases (UGTs) [23]. Quinones are biosynthesized through several pathways; for example, isoprenoid quinones are synthesized by the shikimate pathway using chorismite-derived compounds as precursors, terrequinone by NRPS from L-tryptophan, dopaquinone by tyrosinase from tyrosine, and benzoquinone by catechol oxidase/PKS from catechol[24]. Xanthones comprise an important class of oxygenated heterocyclics biosynthesized through the polyacetate/polymalonate pathway by the internal cyclization of a single folded polyketide chain[25].

2.1. Plant-Derived Alkaloids from Fungal Endophytes

After a systematic literature survey, we enlisted 19 plant-derived medicinal alkaloids that have been produced by different endophytic fungi (Table 1), and some important alkaloids are described below.

Table 1. Plant-derived alkaloids produced by endophytic fungi.

2.2. Plant-Derived Coumarins (Benzopyrones) from Fungal Endophytes

Coumarins have been routinely employed as herbal remedies since the onset of herbal medicine. It was first isolated as a natural product from seeds of Dipteryx odorata (Coumarouna odorata) [102]. A total of seven medicinally important specific plant-derived coumarins are produced by fungal endophytes (Table 2).

Table 2. Plant-derived coumarins produced by endophytic fungi.

2.3. Plant-Derived Flavonoids from Fungal Endophytes

Flavonoids are pigments of edible plants consisting of two benzene rings at either side of a three-carbon ring. Multiple substitutions in this basic structure produce several classes of derivatives, such as flavones, isoflavones, flavonols, flavanones, catechins, and anthocyanins. We found 12 different biologically active plant-derived flavonoids (Table 3) recovered from fungal endophytes and important flavonoids are described below.

Table 3. Plant-derived flavonoids produced by endophytic fungi.

 

References

  1. Shen, B. A new golden age of natural products drug discovery. Cell 2015, 163, 1297–1300.
  2. Newman, D.J.; Cragg, G.M. Natural products as sources of new drugs from 1981 to 2014. J. Nat. Prod. 2016, 79, 629–661.
  3. Calixto, J.B. The role of natural products in modern drug discovery. An. Acad. Bras. Cienc. 2019, 91, e20190105.
  4. Wilson, B.A.; Thornburg, C.C.; Henrich, C.J.; Grkovic, T.; O’Keefe, B.R. Creating and screening natural product libraries. Nat. Prod. Rep. 2020, 37, 893–918.
  5. Strobel, G. The emergence of endophytic microbes and their biological promise. J. Fungi 2018, 4, 57.
  6. Abdul-Razek, A.S.; El-Nagar, M.E.; Allam, A.; Morsy, O.M.; Othman, S.I. Microbial natural products in drug discovery. Processes 2020, 8, 470.
  7. Uzma, F.; Mohan, C.D.; Hashem, A.; Konappa, N.M.; Rangappa, S.; Kamath, P.V.; Singh, B.P.; Mudili, V.; Gupta, V.K.; Siddaiah, C.N.; et al. Endophytic fungi—Alternative sources of cytotoxic compounds: A review. Front. Pharmacol. 2018, 9, 309.
  8. Hyde, K.D.; Xu, J.; Rapior, S.; Jeewon, R.; Lumyong, S.; Niego, A.G.T.; Abeywickrama, P.D.; Aluthmuhandiram, J.V.S.; Brahamanage, R.S.; Brooks, S.; et al. The amazing potential of fungi: 50 ways we can exploit fungi industrially. Fungal Divers. 2019, 97, 1–136.
  9. Newman, D.J.; Cragg, G.M. Plant endophytes and epiphytes: Burgeoning sources of known and “unknown” cytotoxic and antibiotic agents? Planta Med. 2020, 86, 1095–1111.
  10. Christenhusz, M.J.M.; Byng, J.W. The number of known plants species in the world and its annual increase. Phytotaxa 2016, 261, 201–217.
  11. Stierle, A.; Strobel, G.; Stierle, D. Taxol and taxane production by Taxomyces andreanae, an endophytic fungus of Pacific yew. Science 1993, 260, 214–216.
  12. Aly, A.H.; Debbab, A.; Proksch, P. Fungal endophytes—Secret producers of bioactive plant metabolites. Pharmazie 2013, 68, 499–505.
  13. Nicoletti, R.; Fiorentino, A. Plant bioactive metabolites and drugs produced by endophytic fungi of Spermatophyta. Agriculture 2015, 5, 918–970.
  14. Venieraki, A.; Dimou, M.; Katinakis, P. Endophytic fungi residing in medicinal plants have the ability to produce the same or similar pharmacologically active secondary metabolites as their hosts. Hell. Plant Protect. J. 2017, 10, 51–66.
  15. Cook, D.; Gardner, D.R.; Pfister, J.A. Swainsonine-containing plants and their relationship to endophytic fungi.J. Agric. Food Chem. 2014, 62, 7326–7334.
  16. Naik, S.; Shaanker, R.U.; Ravikanth, G.; Dayanandan, S. How and why do endophytes produce plant secondary metabolites? Symbiosis 2019, 78, 193–201.
  17. Ludwig-Müller, J. Plants and endophytes: Equal partners in secondary metabolite production? Biotechnol. Lett. 2015, 37, 1325–1334.
  18. Knox, R. Introduction to medicinal plants. In Medicinal Plant Biotechnology; Knox, R., Ed.; Scientific e-Resources, ED-Tech Press: Essex, UK, 2019; pp. 32–60.
  19. Staniek, A.; Bouwmeester, H.; Fraser, P.D.; Kayser, O.; Martens, S.; Tissier, A.; Warzecha, H. Natural products–learning chemistry from plants. Biotechnol. J. 2014, 9, 326–336.
  20. Zeilinger, S.; García-Estrada, C.; Martín, J.F. Fungal secondary metabolites in the “OMICS” Era. In Biosynthesis and Molecular Genetics of Fungal Secondary Metabolites; Zeilinger, S.; Martín, J.F.; García-Estrada, C., Eds.; Springer: New York, NY, USA, 2015; Volume 2, pp. 1–12.
  21. Mohanta, T.K. Fungi contain genes associated with flavonoid biosynthesis pathway. J. Funct. Foods. 2020, 68, 103910.
  22. Esmaeilzadeh Bahabadi, S.; Sharifi, M.; Behmanesh, M.; Safaie, N.; Murata, J.; Araki, R.; Yamagaki, T.; Satake, H. Time-course changes in fungal elicitor-induced lignan synthesis and expression of the relevant genes in cell cultures of Linum album. J. Plant Physiol. 2012, 169, 487–491.
  23. Augustin, J.M.; Kuzina, V.; Andersen, S.B.; Bak, S. Molecular activities, biosynthesis and evolution of triterpenoid saponins. Phytochemistry 2011, 72, 435–457.
  24. Feng, P.; Shang, Y.; Cen, K.; Wang, C. Fungal biosynthesis of the bibenzoquinone oosporein to evade insect immunity. Proc. Nat. Acad. Sci. USA 2015, 112, 11365–11370.
  25. Le Pogam, P.; Boustie, J. Xanthones of lichen source: A 2016 update. Molecules 2016, 21, 294.
More
Information
Subjects: Plant Sciences
Contributor MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register :
View Times: 373
Revisions: 3 times (View History)
Update Date: 25 Feb 2021
1000/1000