title: MurAA, catalysing the first committed step in peptidoglycan biosynthesis, is a target of Clp-dependent proteolysis in Bacillus subtilis.
abstract: The carboxyvinyl transfer from phosphoenolpyruvate to UDP-N-acetylglucosamine is the first committed step in the pathway of peptidoglycan formation. This crucial reaction for bacterial cell growth is catalysed by the MurA enzymes. Gram-negative bacteria carry one murA gene, whereas in a subgroup of Gram-positive bacteria two separate paralogues, MurAA and MurAB, exist. This study provides evidence that in the Gram-positive bacterium Bacillus subtilis, the MurAA protein is specifically degraded by the ClpCP protease. This Clp-dependent degradation is especially enhanced upon entry into stationary phase, thus ensuring an immediate growth arrest due to stalled murein biosynthesis. The MurAA protein can therefore be addressed as a target of Clp-dependent regulatory proteolysis such as the transcriptional regulators CtsR, ComK, Spx in B. subtilis, CtrA in Caulobacter crescentus or RpoS in Escherichia coli. Taking into account all other known regulatory targets of ATP-dependent proteases, MurAA of B. subtilis represents the first example of a metabolic enzyme which is a unique regulatory substrate of Clp-dependent proteolysis. Its function as a regulatory metabolic checkpoint resembles that of homoserine trans-succinylase (MetA) in E. coli which is similarly ATP-dependently degraded.
authors.affiliation: Ernst-Moritz-Arndt-Universität Greifswald, Institut für Mikrobiologie und Molekularbiologie, Germany. Holger.Kock@uni-greifswald.de
authors.forename: Holger
authors.initials: H
authors.lastname: Kock
authors.forename: Ulf
authors.initials: U
authors.lastname: Gerth
authors.forename: Michael
authors.initials: M
authors.lastname: Hecker
mesh_terms: D049069:ATP-Dependent Proteases; D000251:Adenosine Triphosphatases / Q000378:metabolism*; D019883:Alkyl and Aryl Transferases / Q000235:genetics / Q000378:metabolism*; D001412:Bacillus subtilis / Q000201:enzymology / Q000254:growth & development / Q000378:metabolism*; D001426:Bacterial Proteins / Q000096:biosynthesis / Q000378:metabolism*; D015180:Electrophoresis, Gel, Two-Dimensional; D049071:Endopeptidase Clp; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial; D006207:Half-Life; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006868:Hydrolysis; D009154:Mutation; D010457:Peptidoglycan / Q000096:biosynthesis; D020543:Proteome / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D012697:Serine Endopeptidases / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D001426:Bacterial Proteins; C087481:ClpC protein, Bacteria; D006360:Heat-Shock Proteins; D010457:Peptidoglycan; D020543:Proteome; D012333:RNA, Messenger; D019883:Alkyl and Aryl Transferases; C022566:UDP-N-acetylglucosamine 1-carboxyvinyltransferase; D049069:ATP-Dependent Proteases; D012697:Serine Endopeptidases; D049071:Endopeptidase Clp; D000251:Adenosine Triphosphatases