Undecaprenyl pyrophosphate-associated peptidoglycan biosynthesis enzyme complex

The undecaprenyl pyrophosphate-associated peptidoglycan biosynthesis enzyme complex is a vital multi-step pathway in bacteria responsible for the assembly and transport of cell wall building blocks across the cytoplasmic membrane (Bouhss et al., 2008). This complex utilizes the C55-isoprenyl lipid carrier, undecaprenyl phosphate (also known as bactoprenol), to shuttle sugar-peptide building blocks from the cytoplasm to the cell wall assembly site. Key enzymes within this functional complex include MraY and MurG, which synthesize the lipid-linked intermediates Lipid I and Lipid II, and undecaprenyl pyrophosphate phosphatase (UppP/BacA), which recycles the lipid carrier by dephosphorylating undecaprenyl pyrophosphate (Manat et al., 2014). Because this pathway is essential for bacterial survival and lacks a human homolog, it is a major target for various antibiotics. For instance, bacitracin exerts its bactericidal effect by binding to the undecaprenyl pyrophosphate substrate, thereby preventing its recycling and halting cell wall synthesis (Stone & Strominger, 1971; StatPearls, 2023). Other potent agents like vancomycin and teixobactin target the lipid-linked products of this complex, such as Lipid II, to inhibit the final stages of peptidoglycan polymerization and cause cell lysis (Ling et al., 2015).

Other names

Bactoprenol pyrophosphate-associated peptidoglycan biosynthesis enzyme complexLipid II cycleUndecaprenyl phosphate cycleC55-isoprenyl pyrophosphate metabolism complexBactoprenol cycle

Inhibition of undecaprenyl pyrophosphate dephosphorylation, sequestration of Lipid II precursors, and inhibition of peptidoglycan polymerization/cross-linking