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 [69,70]. These shortcomings require the search for novel bioactive compounds from natural sources, such as fungal endophytes, to develop new pharmaceutical drugs for human diseases [47,71,72]. For instance, cancer constitutes a major health problem despite the continuous development of new medicines [73]. 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 [20]. For instance, Taxol is a clinically approved fungal anticancer drug blocking the proliferation and migration of cancer cells [71,72,73,74,75]. 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 [76,77,78,79,80,81,82,83].

The plant–endophytic fungi interaction is a mutual association helping plants to cope with both biotic and abiotic stresses [31,42,84,85], promoting plant growth by assimilating essential nutrients (potassium, nitrogen and phosphorus) and producing ammonia, siderophores, hormones (auxins, gibberellins and cytokinins) and enzymes [12,13,17,86]. Particularly, secondary metabolites produced by beneficial fungi play a very interesting role in protecting and ameliorating the quality and yield of agricultural crops [40,87]. 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 [88,89,90].

Extracellular enzymes are the most common and searched compounds extracted from endophytic fungi for industrial and/or commercial purposes [9]. They include chitinases, cellulases, amylases, xylanases, pectinases, hydrolases, laccases, proteases, lipases, etc. [91,92]. Enzymes are used to degrade complex compounds into small ones that are easy to degrade or assimilate [93]. Various types of industries prefer using microbial hydrolytic enzymes due to their high stability, broad availability, cost-effectiveness and eco-friendliness [94,95]. 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 [92], and thus they are mostly used in pharmaceutical, therapeutic [26,96], food [97], detergent [98], waste management [99], leather and textile [100] 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 [101]. 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.) [102,103]. 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 [104]. The application of chitinase is concentrated in seafood industries, since the catalyzation of chitin increases the nutritional benefits of seafood [105,106], human health improvements, due to its antioxidant, anti-inflammatory, antimicrobial and antitumor properties [107,108], and the biocontrol of phytopathogenic fungi and pests [109]. 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 [110], breaking down pectin from agronomic and industrial wastes [111], textile industries [112], paper recycling [113] and many other applications [114]. Lipase is a serine hydrolase responsible for breaking down fats and oils; thus, it is essential in the food industry [115]. Lipases extracted from fungi are able to withstand extreme conditions [116]. Phytase enzyme is used to degrade phytates. It is especially used in the environmental, nutritional, and biotechnological fields [117,118]. 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 [119].

Natural source contamination is mainly caused by uncontrolled industrial discharges and anthropogenic activities [17], leading to the accumulation of recalcitrant pollutants, heavy metals, herbicides, pesticides, chlorinated products, etc. [120,121]. Bioremediation has arisen in the last two decades as a biological alternative for remediating environmental pollution [122,123]. 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 [124,125,126]. Bioremediation could occur by endogenous microbes living within the contaminated area [34], or by exogenous microbes (having high bioremediation capacities) induced artificially [27,127].