| PW691615 | DAP-type peptidoglycan biosynthesis | Reaction compounds not found | | Peptidoglycan, a vital structural polymer in bacterial cell walls, comprises long chains of alternating N-acetylglucosamine (GlcNAc) and N-acetylmuramic acid (MurNAc) residues. Each MurNAc unit is linked to a short peptide chain, typically containing amino acids like L-alanine, D-glutamic acid, and meso-diaminopimelic acid (mDAP). These peptide chains cross-link adjacent glycan strands, forming a mesh-like sacculus that provides mechanical strength and maintains cell shape. The biosynthesis of peptidoglycan initiates in the cytoplasm with the formation of UDP-GlcNAc, which is converted to UDP-MurNAc through the actions of MurA and MurB enzymes. Subsequent enzymatic steps add a pentapeptide chain to UDP-MurNAc, producing UDP-MurNAc-pentapeptide. This precursor is then linked to a lipid carrier, undecaprenyl phosphate, forming lipid I, which is further modified by the addition of a GlcNAc residue to generate lipid II. The flippase MurJ transports lipid II across the cytoplasmic membrane into the periplasmic space. In the periplasm, transglycosylase enzymes polymerize the glycan chains, while transpeptidase enzymes cross-link the peptide side chains, solidifying the peptidoglycan matrix. This process is tightly regulated and coordinated with cell growth and division. Notably, the insertion of new peptidoglycan material requires the cleavage of existing cross-links by endopeptidases, creating space for expansion. In Escherichia coli, for instance, the endopeptidases MepS, MepM, and MepH perform this function, and their absence leads to cell lysis due to the inability to remodel the cell wall. Understanding the intricacies of peptidoglycan biosynthesis has significant implications for antibiotic development, as many antibiotics target various stages of this pathway. Recent studies have provided deeper insights into the enzymes involved and their regulation, offering potential avenues for novel antimicrobial strategies . |
