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Oszako, T.K. Secondary Metabolites of Endophytic Fungi. Encyclopedia. Available online: https://encyclopedia.pub/entry/17938 (accessed on 05 December 2025).
Oszako TK. Secondary Metabolites of Endophytic Fungi. Encyclopedia. Available at: https://encyclopedia.pub/entry/17938. Accessed December 05, 2025.
Oszako, Tomasz Krzysztof. "Secondary Metabolites of Endophytic Fungi" Encyclopedia, https://encyclopedia.pub/entry/17938 (accessed December 05, 2025).
Oszako, T.K. (2022, January 10). Secondary Metabolites of Endophytic Fungi. In Encyclopedia. https://encyclopedia.pub/entry/17938
Oszako, Tomasz Krzysztof. "Secondary Metabolites of Endophytic Fungi." Encyclopedia. Web. 10 January, 2022.
Secondary Metabolites of Endophytic Fungi
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This entry is adapted from the peer-reviewed paper 10.3390/f12121784

Plant–microbe interactions range from symbiotic to pathogenic; in the symbiotic relationship, microbes are called ‘endophytes’. Endophytes are conventionally known as microbes existing in all plant endospheric tissues (roots, shoots, fruits, leaves, flowers, seeds, etc.) without causing harmful consequences to the host plant. These microorganisms are usually more abundant in roots and they can be transferred horizontally and vertically. Particularly, endophytic fungi constitute an extremely large community, reaching up to three million species worldwide. These eukaryotic organisms are known to harbor a large variety of secondary metabolites valuable to mankind, plants and the environment. They constitute an excellent substitute for exploring whole plants, thereby gaining time, facilitating the process of isolation and protecting the ecosystem. The scientific community has approved the excellent roles of the fungal bioactive compounds in several vital fields including medicine, pharmacy, agriculture, industry and bioremediation.

fungal endophytes secondary metabolites extracellular enzymes biotechnological applications

1. History of Fungal Production of Secondary Metabolites

Bioactive secondary metabolites are natural organic and low-molecular-weight compounds synthesized by almost all microorganisms and used as a means of defense against external aggressions [1][2]. Particularly, secondary metabolites produced by endophytic fungi possess different interesting activities applicable in several fields [3][4]. Fungi have attracted scientific researchers since the discovery of the wonder antibiotic penicillin from Penicillium notatum fungus back in 1928 [5][6]. In 1993, Stierle et al. discovered another bioactive metabolite, Taxol (paclitaxel), from the endophytic fungus Taxomyces andreanae, inhabiting the Taxus brevifolia tree. This potent drug is mainly used for chemotherapy against cancer diseases [7][8][9]. These two lead compounds have paved the way towards exploring novel drugs from endophytic fungi. Such natural products are prominent, affordable, environmentally friendly and could be applied for commercial use [10]. The bioprospecting of bioactive compounds from fungal endophytes expanded in the 1990s and is still thriving. This is confirmed by hundreds of articles and patents describing novel or existing natural products and their possible applications in multiple domains [11][12][13]. Nowadays, studies have revealed that almost 70% of the existing bioactive compounds originate from microorganisms [8].

2. Processes of Fungal Secondary Metabolite Production

Fungal endophytes are an abundant and natural treasury of drugs with simple and complex molecular structures. The operation of drug production is executed by the endophytic fungus and influenced by the host plant and by other competing endophytes. The biosynthetic pathways of secondary metabolites are manipulated by a group of arranged genes, named biosynthetic gene clusters (BGCs), encoding tandem enzymatic reactions [14][15]. The acyl-coenzyme A enzyme represents the initial point of synthesis of diverse classes of biomolecules including alkaloids, terpenoids, cyclohexanes, peptides, polyketides, flavonoids, hydrocarbons, steroids, monoterpenoids, xanthones, tetralones, quinones and several other compounds endowed with significant activities in vital fields of life [16][17][18][19][20][21]. The regulation of fungal BGCs occurs at the transcriptional and the epigenetic levels [22]. Transcriptional regulation ranges from cluster-specific regulators to global transcriptional complexes [23]. Keller [22] suggests that up to 50% of fungal BGCs contain a cluster-specific transcription factor recognizing palindromic motifs in cluster gene promoters. Epigenetic regulation occurs through DNA methylation and histone acetylation among other epigenetic mechanisms used to control gene expression. Epigenetic manipulation is actually an effective strategy for unlocking the chemical diversity encoded by fungal endophyte genomes [24].

3. Biotechnological Applications of Secondary Metabolites Produced by Endophytic Fungi

The trend of using biological (herbal and microbial) drugs encouraged the scientific community to prospect the natural products synthesized by endophytic fungi [25][26]. These endophytes produce unique compounds and also compounds similar to those produced by their host plants making them an easy alternative to plants to avoid ecological distortion [27]. The produced compounds may be directly or indirectly applied in several biotechnological fields such as medicine, pharmacy, agriculture, bioremediation and industry. Some of these natural products are discussed along with their functions in the following sections [28][29] (Figure 1).
Forests 12 01784 g002 550
Figure 1. Biotechnological applications of secondary metabolites and enzymes produced by endophytic fungi.

3.1. Medicinal and Pharmaceutical Applications

Global human health is threatened by the development of various chronic and infectious diseases, the emergence of pathogens resistant to commercial antibiotics and the harmful side effects engendered by the prolonged utilization of chemical drugs [30][31]. These shortcomings require the search for novel bioactive compounds from natural sources, such as fungal endophytes, to develop new pharmaceutical drugs for human diseases [2][32][33]. For instance, cancer constitutes a major health problem despite the continuous development of new medicines [34]. It is a disease caused by abnormal cell division (leading to tumors), which could invade all human body parts and engender elevated mortality rates in humans all over the world. This harmful disease is reported to be the second leading cause of death in the world, behind cardiovascular disease [7]. For instance, Taxol is a clinically approved fungal anticancer drug blocking the proliferation and migration of cancer cells [32][33][34][35][36]. Various other biological compounds, such as antibacterial, antifungal, antidiabetic, immunosuppressant, antihypertension, antiviral, antiprotozoal, antiparasitic, antimutagenic, insecticidal, antioxidant, anti-inflammatory, anticancer, etc., were exhibited by endophytic fungi and constitute alternative biological remedies for several human diseases [37][38][39][40][41][42][43][44].

3.2. Agricultural Applications

The plant–endophytic fungi interaction is a mutual association helping plants to cope with both biotic and abiotic stresses [45][46][47][48], promoting plant growth by assimilating essential nutrients (potassium, nitrogen and phosphorus) and producing ammonia, siderophores, hormones (auxins, gibberellins and cytokinins) and enzymes [49][50][51][52]. Particularly, secondary metabolites produced by beneficial fungi play a very interesting role in protecting and ameliorating the quality and yield of agricultural crops [53][54]. In recent years, the biocontrol of plant diseases using beneficial endophytes and their secreted compounds has been studied intensively due to the endless benefits to plants, human health and the environment [55][56][57].

3.3. Industrial Applications

Extracellular enzymes are the most common and searched compounds extracted from endophytic fungi for industrial and/or commercial purposes [28]. They include chitinases, cellulases, amylases, xylanases, pectinases, hydrolases, laccases, proteases, lipases, etc. [58][59]. Enzymes are used to degrade complex compounds into small ones that are easy to degrade or assimilate [60]. Various types of industries prefer using microbial hydrolytic enzymes due to their high stability, broad availability, cost-effectiveness and eco-friendliness [61][62]. For instance, protease dominates the global enzymes market and is responsible for hydrolyzing proteins and their derivatives into simple constituents (amino acids and oligopeptides). Fungal proteases are preferred for their high stability [59], and thus they are mostly used in pharmaceutical, therapeutic [63][64], food [65], detergent [66], waste management [67], leather and textile [68] industries. The cellulolytic enzyme is used to degrade cellulose and its related polysaccharides. It is applied in the human food, animal feed, agriculture, paper, laundry, wine and textile industries [69]. Xylanase works in synergy with esterase to hydrolyze xylan, which is a plant polysaccharide. Such organic carbon is mainly utilized in food-related industries (baking, drinking, etc.) [70][71]. In addition, it has been extensively documented that bacteria and fungi appear to be the dominant chitin decomposers due to the production of highly active and thermostable chitinase enzymes [72]. The application of chitinase is concentrated in seafood industries, since the catalyzation of chitin increases the nutritional benefits of seafood [73][74], human health improvements, due to its antioxidant, anti-inflammatory, antimicrobial and antitumor properties [75][76], and the biocontrol of phytopathogenic fungi and pests [77]. In addition, fungal pectinase is used to hydrolyze plant pectin. This enzyme is widely known in multiple industries for its versatile applications in fruit juice processing [78], breaking down pectin from agronomic and industrial wastes [79], textile industries [80], paper recycling [81] and many other applications [82]. Lipase is a serine hydrolase responsible for breaking down fats and oils; thus, it is essential in the food industry [83]. Lipases extracted from fungi are able to withstand extreme conditions [84]. Phytase enzyme is used to degrade phytates. It is especially used in the environmental, nutritional, and biotechnological fields [85][86]. Last but not least, amylase is responsible for converting starch into different types of sugars, and amylases originating from fungi are known to be thermostable: this is a redeeming feature for starch-producing industries [87].

3.4. Bioremediation Applications

Natural source contamination is mainly caused by uncontrolled industrial discharges and anthropogenic activities [51], leading to the accumulation of recalcitrant pollutants, heavy metals, herbicides, pesticides, chlorinated products, etc. [88][89]. Bioremediation has arisen in the last two decades as a biological alternative for remediating environmental pollution [90][91]. It is based on the use of bacteria and fungi and their secreted compounds to degrade, transform or accumulate targeted pollutants, converting them into non-toxic compounds [92][93][94]. Bioremediation could occur by endogenous microbes living within the contaminated area [95], or by exogenous microbes (having high bioremediation capacities) induced artificially [96][97].

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