title: Sirtuin-dependent reversible lysine acetylation of glutamine synthetases reveals an autofeedback loop in nitrogen metabolism.
abstract: In cells of all domains of life, reversible lysine acetylation modulates the function of proteins involved in central cellular processes such as metabolism. In this study, we demonstrate that the nitrogen regulator GlnR of the actinomycete Saccharopolyspora erythraea directly regulates transcription of the acuA gene (SACE_5148), which encodes a Gcn5-type lysine acetyltransferase. We found that AcuA acetylates two glutamine synthetases (GlnA1 and GlnA4) and that this lysine acetylation inactivated GlnA4 (GSII) but had no significant effect on GlnA1 (GSI-β) activity under the conditions tested. Instead, acetylation of GlnA1 led to a gain-of-function that modulated its interaction with the GlnR regulator and enhanced GlnR-DNA binding. It was observed that this regulatory function of acetylated GSI-β enzymes is highly conserved across actinomycetes. In turn, GlnR controls the catalytic and regulatory activities (intracellular acetylation levels) of glutamine synthetases at the transcriptional and posttranslational levels, indicating an autofeedback loop that regulates nitrogen metabolism in response to environmental change. Thus, this GlnR-mediated acetylation pathway provides a signaling cascade that acts from nutrient sensing to acetylation of proteins to feedback regulation. This work presents significant new insights at the molecular level into the mechanisms underlying the regulation of protein acetylation and nitrogen metabolism in actinomycetes.
authors.affiliation: Laboratory of Biosystems and Microanalysis, State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China;
authors.forename: Di
authors.initials: D
authors.lastname: You
authors.affiliation: Laboratory of Biosystems and Microanalysis, State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China;
authors.forename: Bin-Cheng
authors.initials: BC
authors.lastname: Yin
authors.affiliation: Laboratory of Biosystems and Microanalysis, State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China;
authors.forename: Zhi-Hai
authors.initials: ZH
authors.lastname: Li
authors.affiliation: Laboratory of Biosystems and Microanalysis, State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China;
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Laboratory of Biosystems and Microanalysis, State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China;
authors.forename: Wen-Bang
authors.initials: WB
authors.lastname: Yu
authors.affiliation: Laboratory of Biosystems and Microanalysis, State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China;
authors.forename: Peng
authors.initials: P
authors.lastname: Zuo
authors.affiliation: Laboratory of Biosystems and Microanalysis, State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China; School of Chemistry and Chemical Engineering, Shihezi University, Xinjiang 832000, China bcye@ecust.edu.cn.
authors.forename: Bang-Ce
authors.initials: BC
authors.lastname: Ye
mesh_terms: D000107:Acetylation; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D005974:Glutamate-Ammonia Ligase / Q000235:genetics / Q000378:metabolism*; D008239:Lysine / Q000235:genetics / Q000378:metabolism*; D009584:Nitrogen / Q000378:metabolism*; D016930:Saccharopolyspora / Q000235:genetics / Q000378:metabolism*; D037761:Sirtuins / Q000235:genetics / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D037761:Sirtuins; D005974:Glutamate-Ammonia Ligase; D008239:Lysine; D009584:Nitrogen
keywords: actinomycetes; chaperone; glutamine synthetase; nitrogen metabolism; protein acetylation