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Review

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

by
Mengyao Xue
,
Xuwen Hou
,
Jiajin Fu
,
Jiayin Zhang
,
Jiacheng Wang
,
Zhitong Zhao
,
Dan Xu
,
Daowan Lai
and
Ligang Zhou
*
State Key Laboratory of Agrobiotechnology, Department of Plant Pathology, College of Plant Protection, China Agricultural University, Beijing 100193, China
*
Author to whom correspondence should be addressed.
J. Fungi 2023, 9(2), 172; https://doi.org/10.3390/jof9020172
Submission received: 23 November 2022 / Revised: 20 January 2023 / Accepted: 21 January 2023 / Published: 28 January 2023
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Abstract

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.
Keywords: fungal biosynthetic gene cluster; cryptic secondary metabolite; chemical epigenetic modification; biosynthetic regulation; DNA methyltransferase; histone deacetylase; biological activities fungal biosynthetic gene cluster; cryptic secondary metabolite; chemical epigenetic modification; biosynthetic regulation; DNA methyltransferase; histone deacetylase; biological activities

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MDPI and ACS Style

Xue, M.; Hou, X.; Fu, J.; Zhang, J.; Wang, J.; Zhao, Z.; Xu, D.; Lai, D.; Zhou, L. Recent Advances in Search of Bioactive Secondary Metabolites from Fungi Triggered by Chemical Epigenetic Modifiers. J. Fungi 2023, 9, 172. https://doi.org/10.3390/jof9020172

AMA Style

Xue M, Hou X, Fu J, Zhang J, Wang J, Zhao Z, Xu D, Lai D, Zhou L. Recent Advances in Search of Bioactive Secondary Metabolites from Fungi Triggered by Chemical Epigenetic Modifiers. Journal of Fungi. 2023; 9(2):172. https://doi.org/10.3390/jof9020172

Chicago/Turabian Style

Xue, Mengyao, Xuwen Hou, Jiajin Fu, Jiayin Zhang, Jiacheng Wang, Zhitong Zhao, Dan Xu, Daowan Lai, and Ligang Zhou. 2023. "Recent Advances in Search of Bioactive Secondary Metabolites from Fungi Triggered by Chemical Epigenetic Modifiers" Journal of Fungi 9, no. 2: 172. https://doi.org/10.3390/jof9020172

APA Style

Xue, M., Hou, X., Fu, J., Zhang, J., Wang, J., Zhao, Z., Xu, D., Lai, D., & Zhou, L. (2023). Recent Advances in Search of Bioactive Secondary Metabolites from Fungi Triggered by Chemical Epigenetic Modifiers. Journal of Fungi, 9(2), 172. https://doi.org/10.3390/jof9020172

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