The biosynthesis of peptidoglycan lipid-linked intermediates.
The biosynthesis of bacterial cell wall peptidoglycan is a complex process involving many different steps taking place in the cytoplasm (synthesis of the nucleotide precursors) and on the inner and outer sides of the cytoplasmic membrane (assembly and polymerization of the disaccharide-peptide monomer unit, respectively). This review summarizes the current knowledge on the membrane steps leading to the formation of the lipid II intermediate, i.e. the substrate of the polymerization reactions. It makes the point on past and recent data that have significantly contributed to the understanding of the biosynthesis of undecaprenyl phosphate, the carrier lipid required for the anchoring of the peptidoglycan hydrophilic units in the membrane, and to the characterization of the MraY and MurG enzymes which catalyze the successive transfers of the N-acetylmuramoyl-peptide and N-acetylglucosamine moieties onto the carrier lipid, respectively. Enzyme inhibitors and antibacterial compounds interfering with these essential metabolic steps and interesting targets are presented.
Bouhss
Ahmed
A
Laboratoire des Enveloppes Bactériennes et Antibiotiques, Institut de Biochimie et Biophysique Moléculaire et Cellulaire, UMR 8619 CNRS, Univ Paris-Sud, Orsay, France.
Trunkfield
Amy E
AE
Bugg
Timothy D H
TD
Mengin-Lecreulx
Dominique
D
D001419:Bacteria / Q000737:chemistry / Q000378:metabolism; D001425:Bacterial Outer Membrane Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D007700:Kinetics; D008055:Lipids / Q000096:biosynthesis* / Q000737:chemistry; D009005:Monosaccharides / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D017351:N-Acetylglucosaminyltransferases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D010457:Peptidoglycan / Q000096:biosynthesis*; D011106:Polyisoprenyl Phosphates / Q000737:chemistry / Q000378:metabolism; D013379:Substrate Specificity; D013729:Terpenes / Q000378:metabolism; D014166:Transferases / Q000037:antagonists & inhibitors / Q000302:isolation & purification / Q000378:metabolism; D017855:Transferases (Other Substituted Phosphate Groups); D014538:Uridine Diphosphate N-Acetylmuramic Acid / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism
D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D008055:Lipids; D009005:Monosaccharides; D009842:Oligopeptides; D010457:Peptidoglycan; D011106:Polyisoprenyl Phosphates; D013729:Terpenes; D014538:Uridine Diphosphate N-Acetylmuramic Acid; C438940:lipid I; C069249:muramyl-NAc-(pentapeptide)pyrophosphoryl-undecaprenol; C017788:undecaprenol; C009621:undecaprenyl phosphate; C088139:undecaprenyl pyrophosphate; D014166:Transferases; D017351:N-Acetylglucosaminyltransferases; C064057:UDP-N-acetylglucosamine-N-acetylmuramyl-(pentapeptide)pyrophosphoryl-undecaprenol N-acetylglucosamine transferase; D017855:Transferases (Other Substituted Phosphate Groups); C079803:mraY protein, Bacteria