title: Protein acetylation affects acetate metabolism, motility and acid stress response in Escherichia coli.
abstract: Although 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.
authors.affiliation: Departamento de Bioquímica y Biología Molecular B e Inmunología, Facultad de Química, Universidad de Murcia Campus de Excelencia Mare Nostrum, Murcia, Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: Castaño-Cerezo
authors.affiliation: Departamento de Bioquímica y Biología Molecular B e Inmunología, Facultad de Química, Universidad de Murcia Campus de Excelencia Mare Nostrum, Murcia, Spain vicente.bernal@gmail.com mcanovas@um.es.
authors.forename: Vicente
authors.initials: V
authors.lastname: Bernal
authors.affiliation: Biomolecular Mass Spectrometry and Proteomics Group, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands Netherlands Proteomics Center, Utrecht, The Netherlands.
authors.forename: Harm
authors.initials: H
authors.lastname: Post
authors.affiliation: Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland.
authors.forename: Tobias
authors.initials: T
authors.lastname: Fuhrer
authors.affiliation: Biomolecular Mass Spectrometry and Proteomics Group, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Cappadona
authors.affiliation: Departamento de Bioquímica y Biología Molecular B e Inmunología, Facultad de Química, Universidad de Murcia Campus de Excelencia Mare Nostrum, Murcia, Spain.
authors.forename: Nerea C
authors.initials: NC
authors.lastname: Sánchez-Díaz
authors.affiliation: Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland.
authors.forename: Uwe
authors.initials: U
authors.lastname: Sauer
authors.affiliation: Biomolecular Mass Spectrometry and Proteomics Group, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands Netherlands Proteomics Center, Utrecht, The Netherlands.
authors.forename: Albert J R
authors.initials: AJ
authors.lastname: Heck
authors.affiliation: Biomolecular Mass Spectrometry and Proteomics Group, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands Netherlands Proteomics Center, Utrecht, The Netherlands.
authors.forename: A F Maarten
authors.initials: AF
authors.lastname: Altelaar
authors.affiliation: Departamento de Bioquímica y Biología Molecular B e Inmunología, Facultad de Química, Universidad de Murcia Campus de Excelencia Mare Nostrum, Murcia, Spain vicente.bernal@gmail.com mcanovas@um.es.
authors.forename: Manuel
authors.initials: M
authors.lastname: Cánovas
mesh_terms: D000106:Acetate-CoA Ligase / Q000235:genetics / Q000378:metabolism; D000085:Acetates / Q000378:metabolism*; D000107:Acetylation; D000123:Acetyltransferases / Q000235:genetics / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D002874:Chromosome Mapping; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics / Q000502:physiology*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D005968:Glutamate Decarboxylase / Q000235:genetics / Q000378:metabolism; D006038:Glyoxylates / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D011499:Protein Processing, Post-Translational; D040901:Proteomics; D037761:Sirtuins / Q000235:genetics / Q000378:metabolism; D013312:Stress, Physiological
chemical_list: D000085:Acetates; D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins; D006038:Glyoxylates; C074889:RcsB protein, Bacteria; D000123:Acetyltransferases; C062782:protein acyltransferase; D037761:Sirtuins; C483998:cobB protein, E Coli; D005968:Glutamate Decarboxylase; D000106:Acetate-CoA Ligase; C031150:glyoxylic acid
keywords: flagella biosynthesis; isocitrate lyase; metabolic regulation; sirtuin