Fungal Endophytes: A Promising Frontier for Discovery of Novel Bioactive Compounds

Abstract

For years, fungi have served as repositories of bioactive secondary metabolites that form the backbone of many existing drugs. With the global rise in infections associated with antimicrobial resistance, in addition to the growing burden of non-communicable disease, such as cancer, diabetes and cardiovascular ailments, the demand for new drugs that can provide an improved therapeutic outcome has become the utmost priority. The exploration of microbes from understudied and specialized niches is one of the promising ways of discovering promising lead molecules for drug discovery. In recent years, a special class of plant-associated fungi, namely, fungal endophytes, have emerged as an important source of bioactive compounds with unique chemistry and interesting biological activities. The present review focuses on endophytic fungi and their classification, rationale for selection and prioritization of host plants for fungal isolation and examples of strategies that have been adopted to induce the activation of cryptic biosynthetic gene clusters to enhance the biosynthetic potential of fungal endophytes.

Keywords: bioactive compounds; endophytic fungi; natural products; secondary metabolites.

Figure 1

Some bioactive compounds isolated from fungal endophytes grouped according to their bioactivities.

Figure 2

Some approaches that have been employed to enhance secondary metabolites biosynthesis in fungal endophytes.

Figure 3

Number of journal articles published between 2002–2020 containing the phrase “one strain many compounds”, “one strain-many compounds” or “OSMAC” within the title, abstract or as a keyword (data based on a search from the Web of Science, 14 January 2021).

Figure 4

Some of the new compounds that have been isolated as a result of co-cultures of endophytic fungi with bacteria or with other fungal strains.

Figure 5

Some chemical epigenetic modifiers that have been used in fungal natural products research: DNA. methyltransferase inhibitors (25–27) and histone deacetylase inhibitors (28–34).

Figure 6

New compounds and those whose quantities have been reported to be enhanced by the growth of fungal endophytes in the presence of chemical epigenetic modifiers.