Protein acetylation affects acetate metabolism, motility and acid stress response in Escherichia coli

• DOI: 10.15252/msb.20145227
• Publication Date: 2014-12-02T18:12:47Z
• Authors: Sara Castaño‐Cerezo; Vicente Bernal; Harm Post; Tobias Fuhrer; Salvatore Cappadona; Nerea C Sánchez‐Díaz; Uwe Sauer; Albert JR Heck; AF Maarten Altelaar; Manuel Cánovas
• Keywords: Proteomics; Isocitrate lyase; 0301 basic medicine; Medicine (General); [SDV]Life Sciences [q-bio]; Acetates; SACCHAROMYCES-CEREVISIAE; LYSINE ACETYLATION; Sirtuins; Biology (General); Oligonucleotide Array Sequence Analysis; 0303 health sciences; Flagella biosynthesis; Isocitrate lyase; Metabolic regulation; Sirtuin; Glutamate Decarboxylase; TRANSCRIPTIONAL REGULATION; Escherichia coli Proteins; Chromosome Mapping; Glyoxylates; Acetylation; Articles; OVERFLOW METABOLISM; SUBSTRATE-SPECIFICITY; 3. Good health; DNA-Binding Proteins; sirtuin; flagella biosynthesis; 570; QH301-705.5; Acetate-CoA Ligase; Microbiology; 03 medical and health sciences; R5-920; COA SYNTHETASE; Bacterial Proteins; Acetyltransferases; Stress, Physiological; Metabolic regulation; SALMONELLA-ENTERICA; Escherichia coli; Sirtuin; Proteolysis & Proteomics; sirtuin Subject Categories Post-translational Modifications; RHODOPSEUDOMONAS-PALUSTRIS; Gene Expression Regulation, Bacterial; isocitrate lyase; Virology & Host Pathogen Interaction; ACETYLTRANSFERASE PAT; metabolic regulation; ISOCITRATE DEHYDROGENASE; Protein Processing, Post-Translational; Flagella biosynthesis

AbstractAlthough protein acetylation is widely observed, it has been associated with few specific regulatory functions making it poorly understood. To interrogate its functionality, we analyzed the acetylome in Escherichia coli knockout mutants of cobB, the only known sirtuin‐like deacetylase, and patZ, the best‐known protein acetyltransferase. For four growth conditions, more than 2,000 unique acetylated peptides, belonging to 809 proteins, were identified and differentially quantified. Nearly 65% of these proteins are related to metabolism. The global activity of CobB contributes to the deacetylation of a large number of substrates and has a major impact on physiology. Apart from the regulation of acetyl‐CoA synthetase, we found that CobB‐controlled acetylation of isocitrate lyase contributes to the fine‐tuning of the glyoxylate shunt. Acetylation of the transcription factor RcsB prevents DNA binding, activating flagella biosynthesis and motility, and increases acid stress susceptibility. Surprisingly, deletion of patZ increased acetylation in acetate cultures, which suggests that it regulates the levels of acetylating agents. The results presented offer new insights into functional roles of protein acetylation in metabolic fitness and global cell regulation.