The seminal discovery of paclitaxel from endophytic fungus Taxomyces andreanae was a milestone in recognizing the immense potential of endophytic fungi as prolific producers of bioactive secondary metabolites of use in medicine, agriculture, and food industries. Following the discovery of paclitaxel, the research community has intensified efforts to harness endophytic fungi as putative producers of lead molecules with anticancer, anti-inflammatory, antimicrobial, antioxidant, cardio-protective, and immunomodulatory properties. Endophytic fungi have been a valuable source of bioactive compounds over the last three decades. Compounds such as taxol, podophyllotoxin, huperzine, camptothecin, and resveratrol have been effectively isolated and characterized after extraction from endophytic fungi. These findings have expanded the applications of endophytic fungi in medicine and related fields. In the present review, we systematically compile and analyze several important compounds derived from endophytic fungi, encompassing the period from 2011 to 2022. Our systematic approach focuses on elucidating the origins of endophytic fungi, exploring the structural diversity and biological activities exhibited by these compounds, and giving special emphasis to the pharmacological activities and mechanism of action of certain compounds. We highlight the tremendous potential of endophytic fungi as alternate sources of bioactive metabolites, with implications for combating major global diseases. This underscores the significant role that fungi can play in the discovery and development of novel therapeutic agents that address the challenges posed by prevalent diseases worldwide.

/pdf/fungal-endophytes-microfactories-of-novel-bioactive-1rv9dhkh.pdf

Fungal Endophytes: Microfactories of Novel Bioactive Compounds with Therapeutic Interventions; A Comprehensive Review on the Biotechnological Developments in the Field of Fungal Endophytic Biology over the Last Decade

Genomic analysis has demonstrated that many fungi possess essential gene clusters for the production of previously unobserved secondary metabolites; however, these genes are normally reduced or silenced under most conditions. These cryptic biosynthetic gene clusters have become treasures of new bioactive secondary metabolites. The induction of these biosynthetic gene clusters under stress or special conditions can improve the titers of known compounds or the production of novel compounds. Among the inducing strategies, chemical-epigenetic regulation is considered a powerful approach, and it uses small-molecule epigenetic modifiers, which mainly act as the inhibitors of DNA methyltransferase, histone deacetylase, and histone acetyltransferase, to promote changes in the structure of DNA, histones, and proteasomes and to further activate cryptic biosynthetic gene clusters for the production of a wide variety of bioactive secondary metabolites. These epigenetic modifiers mainly include 5-azacytidine, suberoylanilide hydroxamic acid, suberoyl bishydroxamic acid, sodium butyrate, and nicotinamide. This review gives an overview on the method of chemical epigenetic modifiers to trigger silent or low-expressed biosynthetic pathways to yield bioactive natural products through external cues of fungi, mainly based on the research progress in the period from 2007 to 2022. The production of about 540 fungal secondary metabolites was found to be induced or enhanced by chemical epigenetic modifiers. Some of them exhibited significant biological activities such as cytotoxic, antimicrobial, anti-inflammatory, and antioxidant activity.

/pdf/recent-advances-in-search-of-bioactive-secondary-metabolites-5h1vtoof.pdf

Recent Advances in Search of Bioactive Secondary Metabolites from Fungi Triggered by Chemical Epigenetic Modifiers

Secondary metabolism is one of the important mechanisms by which fungi adapt to their living environment and promote survival and reproduction. Recent studies have shown that epigenetic regulation, such as DNA methylation, histone modifications, and non-coding RNAs, plays key roles in fungal secondary metabolism and affect fungal growth, survival, and pathogenicity. This review describes recent advances in the study of epigenetic regulation of fungal secondary metabolism. We discuss the way in which epigenetic markers respond to environmental changes and stimulate the production of biologically active compounds by fungi, and the feasibility of these new findings applied to develop new antifungal strategies and optimize secondary metabolism. In addition, we have deliberated on possible future directions of research in this field. A deeper understanding of epigenetic regulatory networks is a key focus for future research. 

Epigenetic Regulation of Fungal Secondary Metabolism

Three new compounds phomtersines A-C (1-3) together with nine known compounds were isolated from the marine-derived fungus Phomopsis tersa FS441. Their structures were sufficiently established by spectroscopic methods, including extensive 1D and 2D NMR techniques and modified Snatzke's method. Moreover, compounds 1-12 were evaluated for cytotoxic and anti-inflammatory activities. As a result, phomtersine B (2) and the known compound 10 showed moderate cytotoxic activity against the four tested cell lines with IC50 values ranging from 20.21 to 36.53 μM, and phomtersine A (1) exhibited moderate inhibitory activity against LPS-induced NO production. 

3-Carboxy-indole derivatives from the deep-sea-derived fungus Phomopsis tersa FS441

Endophytic fungi of Cynodon dactylon: a treasure trove of bioactive compounds.

Chemical epigenetic modifiers enhance the production of immunosuppressants from the endophytic fungus Aspergillus fumigatus isolated from Cynodon dactylon.

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Chemical epigenetic modifiers enhance the production of immunosuppressants from the endophytic fungus Aspergillus fumigatus isolated from Cynodon dactylon.