Post‐translational modifications drive secondary metabolite biosynthesis in <scp><i>Aspergillus</i></scp>: a review

Yang, Kunlong; Tian, Jun; Keller, Nancy P.

doi:10.1111/1462-2920.16034

Cited by 23 publications

(17 citation statements)

References 205 publications

(294 reference statements)

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“…Chemical epigenetic and molecular epigenetic modifications are two strategies used to convert a heterochromatic structure to euchromatin in order to induce the expression of biosynthetic gene clusters for the secondary metabolism [ 157 ]. If a certain type of chemical epigenetic modifier, such as histone deacetylase inhibitors, was found to be very effective for secondary metabolism to a certain fungus, it may guide us to either knock out or overexpress histone acetyltransferase genes in order to activate the production of fungal secondary metabolites.…”

Section: Discussionmentioning

confidence: 99%

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

Xue

Hou

et al. 2023

JoF

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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.

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Section: Discussionmentioning

confidence: 99%

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

Xue

Hou

et al. 2023

JoF

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“…Histone post-translational modifications play an important role in various cellular progress. In the past decade, advances in mass spectrometry-based proteomics provides new insights into the regulatory scope of post-translational modifications of non-histone proteins, which links to the regulation of pivotal pathways related to cellular response and protein functions ( Buuh et al, 2017 ; Narita et al, 2019 ; Yang et al, 2022 ). SntB is a kind of epigenetic reader protein that assists in the recognition of histone tails.…”

Section: Discussionmentioning

confidence: 99%

Potential antifungal targets based on histones post-translational modifications against invasive aspergillosis

Song²,

Wang³

et al. 2022

Front. Microbiol.

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As a primary cause of death in patients with hematological malignancies and transplant recipients, invasive aspergillosis (IA) is a condition that warrants attention. IA infections have been increasing, which remains a significant cause of morbidity and mortality in immunocompromised patients. During the past decade, antifungal drug resistance has emerged, which is especially concerning for management given the limited options for treating azole-resistant infections and the possibility of failure of prophylaxis in those high-risk patients. Histone posttranslational modifications (HPTMs), mainly including acetylation, methylation, ubiquitination and phosphorylation, are crucial epigenetic mechanisms regulating various biological events, which could modify the conformation of histone and influence chromatin-associated nuclear processes to regulate development, cellular responsiveness, and biological phenotype without affecting the underlying genetic sequence. In recent years, fungi have become important model organisms for studying epigenetic regulation. HPTMs involves in growth and development, secondary metabolite biosynthesis and virulence in Aspergillus. This review mainly aims at summarizing the acetylation, deacetylation, methylation, demethylation, and sumoylation of histones in IA and connect this knowledge to possible HPTMs-based antifungal drugs. We hope this research could provide a reference for exploring new drug targets and developing low-toxic and high-efficiency antifungal strategies.

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“…Histone modifying enzymes, such as histone acetyltransferases and methyltransferases, can place or remove post-translational modifications on histone tails which influence how tight or relaxed the chromatin is, impacting the transcription of mycotoxin BGCs [ 41 ]. This literature is vast and we cannot cover all of the studies but highlighted a few below and recommend the reader to refer to other reviews on this topic [ 132 , 133 ].…”

Section: Regulation Mechanism Of Mycotoxin Biosynthesismentioning

confidence: 99%

Genetic Regulation of Mycotoxin Biosynthesis

Wang

Liang

et al. 2022

JoF

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Mycotoxin contamination in food poses health hazards to humans. Current methods of controlling mycotoxins still have limitations and more effective approaches are needed. During the past decades of years, variable environmental factors have been tested for their influence on mycotoxin production leading to elucidation of a complex regulatory network involved in mycotoxin biosynthesis. These regulators are putative targets for screening molecules that could inhibit mycotoxin synthesis. Here, we summarize the regulatory mechanisms of hierarchical regulators, including pathway-specific regulators, global regulators and epigenetic regulators, on the production of the most critical mycotoxins (aflatoxins, patulin, citrinin, trichothecenes and fumonisins). Future studies on regulation of mycotoxins will provide valuable knowledge for exploring novel methods to inhibit mycotoxin biosynthesis in a more efficient way.

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Post‐translational modifications drive secondary metabolite biosynthesis in Aspergillus: a review

Cited by 23 publications

References 205 publications

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

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

Potential antifungal targets based on histones post-translational modifications against invasive aspergillosis

Genetic Regulation of Mycotoxin Biosynthesis

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