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The Penicillium brasilianum Histone Deacetylase Clr3 Regulates Secondary Metabolite Production and Tolerance to Oxidative Stress.

التفاصيل البيبلوغرافية
العنوان: The Penicillium brasilianum Histone Deacetylase Clr3 Regulates Secondary Metabolite Production and Tolerance to Oxidative Stress.
المؤلفون: Akiyama DY; Department of Organic Chemistry, Institute of Chemistry, State University of Campinas, Campinas 13083-970, SP, Brazil., Rocha MC; Department of Genetic and Evolution, Federal University of São Carlos, São Carlos 13565-905, SP, Brazil., Costa JH; Department of Organic Chemistry, Institute of Chemistry, State University of Campinas, Campinas 13083-970, SP, Brazil., Teles CB; Department of Biochemistry and Tissue Biology, Institute of Biology, State University of Campinas, Campinas 13083-970, SP, Brazil., da Silva Zuccoli G; Department of Biochemistry and Tissue Biology, Institute of Biology, State University of Campinas, Campinas 13083-970, SP, Brazil., Malavazi I; Department of Genetic and Evolution, Federal University of São Carlos, São Carlos 13565-905, SP, Brazil., Fill TP; Department of Organic Chemistry, Institute of Chemistry, State University of Campinas, Campinas 13083-970, SP, Brazil.
المصدر: Journal of fungi (Basel, Switzerland) [J Fungi (Basel)] 2022 May 17; Vol. 8 (5). Date of Electronic Publication: 2022 May 17.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: MDPI AG Country of Publication: Switzerland NLM ID: 101671827 Publication Model: Electronic Cited Medium: Internet ISSN: 2309-608X (Electronic) Linking ISSN: 2309608X NLM ISO Abbreviation: J Fungi (Basel) Subsets: PubMed not MEDLINE
أسماء مطبوعة: Original Publication: Basel, Switzerland : MDPI AG, [2015]-
مستخلص: Most of the biosynthetic gene clusters (BGCs) found in microbes are silent under standard laboratory cultivation conditions due to the lack of expression triggering stimuli, representing a considerable drawback in drug discovery. To access the full biosynthetic potential, studies towards the activation of cryptic BGCs are essential. Histone acetylation status is an important regulator of chromatin structure, which impacts cell physiology and the expression of BGCs. In this study, clr3 , a gene encoding a histone deacetylase in Penicillium brasilianum LaBioMMi 136, is deleted and associated phenotypic and metabolic changes are evaluated. The results indicate reduced growth under oxidative stress conditions in the ∆ clr3 strain, higher intracellular reactive oxygen species (ROS) levels, and a different transcriptional profile of 13 ROS-related genes of both strains under basal and ROS-induced conditions. Moreover, the production of 14 secondary metabolites, including austin-related meroterpenoids, brasiliamides, verruculogen, penicillic acid, and cyclodepsipeptides was evaluated in the ∆ clr3 strain, most of them being reduced. Accordingly, the addition of epigenetic modulators responsible for HDAC inhibition into P. brasilianum 's growth media also culminated in the reduction in secondary metabolite production. The results suggest that Clr3 plays an essential role in secondary metabolite biosynthesis in P. brasilianum , thus offering new strategies for the regulation of natural product synthesis by assessing chromatin modification.
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معلومات مُعتمدة: 2016/07870-9, 2017/19694-3, 2017/25055-3, 2018/00315-5, 2018/13027-8, 2018/14666-4, 2019/06359-7 São Paulo Research Foundation
فهرسة مساهمة: Keywords: epigenetic modulation; natural product biosynthesis regulation; reactive oxygen species
تواريخ الأحداث: Date Created: 20220528 Latest Revision: 20220716
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC9146837
DOI: 10.3390/jof8050514
PMID: 35628769
قاعدة البيانات: MEDLINE
الوصف
تدمد:2309-608X
DOI:10.3390/jof8050514