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基于蛋白质组学分析的黄曲霉中 laeA 的全球调控作用研究。

Insight into the global regulation of laeA in Aspergillus flavus based on proteomic profiling.

机构信息

College of Biological Engineering, Henan University of Technology, Zhengzhou, PR China.

College of Biological Engineering, Henan University of Technology, Zhengzhou, PR China.

出版信息

Int J Food Microbiol. 2018 Nov 2;284:11-21. doi: 10.1016/j.ijfoodmicro.2018.06.024. Epub 2018 Jul 2.

DOI:10.1016/j.ijfoodmicro.2018.06.024
PMID:29990635
Abstract

In Aspergillus flavus, laeA affects cell morphology and contributes to the production of secondary metabolites (SMs) production including aflatoxin, cyclopiazonic acid, and aflatrem. Here, we investigated the function of this transcription factor by performing proteomics analysis of the wild-type (WT) and ΔlaeA mutant growing on corn. Notably, our proteomics profile confirmed the functions of extracellular hydrolases, conidial hydrophobin, and response to oxidative stress during the induction of aflatoxin biosynthesis regulated by laeA. Unexpectedly, deletion of laeA resulted in the significant upregulation of the NAD-dependent histone deacetylase sirA involved in silencing SM clusters via chromatin remodeling. Accompanying the chromatin modification, enzymes participating in SM, including aflatoxin and cyclopiazonic acid biosynthesis, were drastically decreased. Another unexpected finding was that enzymes in the recently identified ustiloxin B biosynthesis pathway might be regulated by laeA. These data provided novel insights into the complex regulation of laeA and suggested a potential link between laeA deletion, NAD-dependent histone deacetylation, and SM production in A. flavus.

摘要

在黄曲霉中,laeA 影响细胞形态,并有助于次级代谢产物(SMs)的生产,包括黄曲霉毒素、环匹罗嗪酸和黄曲霉烯。在这里,我们通过对在玉米上生长的野生型(WT)和ΔlaeA 突变体进行蛋白质组学分析,研究了这个转录因子的功能。值得注意的是,我们的蛋白质组学图谱证实了 laeA 调控的黄曲霉毒素生物合成诱导过程中细胞外水解酶、分生孢子疏水性蛋白和对氧化应激的反应等功能。出乎意料的是,laeA 的缺失导致 NAD 依赖的组蛋白去乙酰化酶 sirA 的显著上调,该酶通过染色质重塑参与 SM 簇的沉默。伴随着染色质修饰,参与 SM 合成的酶,包括黄曲霉毒素和环匹罗嗪酸生物合成,急剧减少。另一个意外的发现是,最近发现的 ustiloxin B 生物合成途径中的酶可能受 laeA 调控。这些数据为 laeA 的复杂调控提供了新的见解,并表明 laeA 缺失、NAD 依赖的组蛋白去乙酰化和黄曲霉中 SM 生产之间可能存在潜在联系。

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