Lab of Biosystems and Microanalysis, State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, PR China.
Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou 310014, Zhejiang, PR China.
Microbiology (Reading). 2017 Nov;163(11):1702-1710. doi: 10.1099/mic.0.000553. Epub 2017 Oct 23.
N-Lysine acetylation is a dynamic, reversible and regulatory post-translational modification (PTM) in prokaryotes, which integrates and coordinates metabolisms responding to environmental clues. However, the molecular mechanism underlying the signalling pathway from nutrient sensing to protein acetylation remains incompletely understood in micro-organisms. Here we found that global nitrogen regulator GlnR directly controls transcription of genes encoding lysine deacetylases in Actinobacteria. Electrophoretic mobility shift assays and real-time PCR (RT-PCR) in three Actinobacteria species (Saccharopolyspora erythraea, Streptomyces coelicolor and Mycobacterium smegmatis) revealed that GlnR regulator protein is able to interact with the promoter regions of these genes and activate their transcription. Furthermore, it was demonstrated that cellular acetylation status (acetylome) is modulated by extracellular nitrogen availability. Our results present an example of the novel complete signal transduction mechanism of regulating protein deacetylation through a nutrient-sensing pleiotropic regulator in response to nutrient availability.
N-赖氨酸乙酰化是原核生物中一种动态、可逆和调节性的翻译后修饰(PTM),它整合并协调了对环境线索的代谢反应。然而,在微生物中,从营养感应到蛋白质乙酰化的信号通路的分子机制仍不完全清楚。在这里,我们发现全局氮调节因子 GlnR 直接控制放线菌中编码赖氨酸去乙酰化酶的基因的转录。在三种放线菌(红色糖多孢菌、变铅青链霉菌和耻垢分枝杆菌)中的电泳迁移率变动分析和实时 PCR(RT-PCR)显示,GlnR 调节蛋白能够与这些基因的启动子区域相互作用并激活它们的转录。此外,还证明了细胞乙酰化状态(乙酰组)可通过细胞外氮的可用性进行调节。我们的结果提供了一个通过感应营养物质的多效调节因子响应营养物质可用性来调节蛋白质去乙酰化的新型完整信号转导机制的实例。