Undecaprenyl-diphospho-N-acetylmuramoyl-pentapeptide (Lipid I)

Lipid I is an essential membrane-anchored intermediate in the bacterial peptidoglycan biosynthetic pathway [1.2.1]. It consists of a MurNAc-pentapeptide moiety linked to an undecaprenyl carrier lipid via a pyrophosphate bridge [1.2.3]. Synthesized on the inner leaflet of the cytoplasmic membrane by the enzyme MraY, Lipid I serves as the direct precursor to Lipid II, which is formed when the glycosyltransferase MurG adds an N-acetylglucosamine residue [1.1.1]. Because Lipid I is vital for cell wall assembly and is unique to bacteria, it is a highly attractive target for antibiotic development [1.2.2]. Several potent antimicrobial agents, including ramoplanin, teixobactin, and clovibactin, exert their effects by binding to Lipid I and/or Lipid II, thereby sequestering these precursors and halting the synthesis of the peptidoglycan layer [1.2.4]. This disruption leads to the loss of structural integrity, osmotic instability, and eventual bacterial lysis [1.1.3]. Since peptidoglycan is absent in human cells, drugs targeting Lipid I typically exhibit high selectivity and low host toxicity, although challenges such as poor oral bioavailability and potential resistance must be addressed [1.1.1, 1.4.1].

Other names

Undecaprenyl-pyrophosphoryl-N-acetylmuramoyl-pentapeptideUndecaprenyl-diphospho-MurNAc-pentapeptideC55-PP-MurNAc-pentapeptideBactoprenyl-pyrophosphoryl-MurNAc-pentapeptide

Inhibition of peptidoglycan synthesis by binding to the Lipid I precursor, preventing its conversion to Lipid II or its incorporation into the cell wall, leading to bacterial cell death.