The Mechanism Of Protein Deacetylation And Pressure Response Mediated By Nitrogen Regulator GlnR In Actinomycetes

Nitrogen regulator GlnR is a wide-area regulatory protein that can sense changes in extracellular availability of nitrogen sources and regulate many of the genes involved in nitrogen metabolism,thereby regulating intracellular relevant physiological processes.Recent studies have found that GlnR can regulate post-translational modification,phosphorus metabolism,ABC transport,polysaccharide degradation,and carbon metabolism.In this study,we further expand the regenon of the regulatory protein GlnR of actinomycetes through bioinformatics and molecular biology methods,and two new target genes were identified---the genes encoding lysine deacetylases and whiB3.Our research contents are as follows:(1)Nitrogen regulator GlnR directly controls transcription of genes encoding lysine deacetylases in actinobacteria.In enzyme-catalyzed acetylation,lysine acetyltransferases are responsible for catalyzing the transfer of acetyl groups from acetyl-CoA to the s-decylamino group of lysine side chains.Deacetylases,also known as histone deacetylases(HDACs),can catalyze the deacetylation of lysine.Lysine acetylation is an important post-translational modification(PTM)in prokaryotes,which integrates and coordinates metabolisms responding to environmental clues.In this study,we found that GlnR binds to the promoters of genes encoding lysine deacetylases and regulates their transcription in S.erythraea,S.coelicolor,and M.smegmatis.The cellular acetylation status(acetylome)is modulated by extracellular nitrogen availability.This study provides a new molecular mechanism for the metabolic regulation of nutrition perception and the lysine acetylation of protein in actinomycetes.GlnR can directly activate or inhibit the transcription of the genes encoding lysine deacetylases.(2)Nitrogen regulator GlnR directly regulates transcription of whiB3 in Mycobacterium smegmatis.The expression level of whiB3 increased significantly in M.tuberculosis at low pH and redox pressure.And WhiB3 regulates the synthesis of mycobacterial virulence lipids in a redox-dependent manner,which can affect the interaction of pathogenic bacteria with host cells.In this study,using M.smegmatis as a model,we found that GlnR could bind to the promoter of whiB3 through bioinformatica analysis,and GlnR could regulate whiB3 gene at the transcription level in response to changes in extracellular nitrogen sources,thereby affecting its resistance to environmental stress.This study has great significance for understanding the role of whiB3 in physiological and pathological activities.