Undecaprenyl phosphate (C55-P) (C55-P)

Undecaprenyl phosphate (C55-P), also known as bactoprenol, is an essential 55-carbon isoprenoid lipid that serves as the primary carrier for transporting hydrophilic cell wall precursors across the bacterial cytoplasmic membrane (Manat et al., 2014, PMID: 25100554). In the peptidoglycan synthesis pathway, it sequentially binds N-acetylmuramic acid (MurNAc) and N-acetylglucosamine (GlcNAc) to form Lipid I and Lipid II, which are then flipped to the periplasmic space for incorporation into the growing cell wall (Typas et al., 2011, PMID: 21301474). Following the release of the precursor, the carrier remains in the form of undecaprenyl diphosphate (C55-PP) and must be dephosphorylated by specific phosphatases to regenerate the active C55-P form (Bouhss et al., 2008, PMID: 18614014). This recycling process is a critical bottleneck in bacterial metabolism, as the total pool of undecaprenyl phosphate is extremely limited, with approximately 10^5 molecules per cell. Drugs such as bacitracin target this cycle by binding to C55-PP in a metal-dependent manner, preventing its dephosphorylation and effectively halting cell wall synthesis (Stone and Strominger, 1971, PMID: 4328831). Other antibiotics, like friulimicin B, bind directly to the C55-P form, while newer agents like teixobactin target the lipid-linked precursors themselves (Ling et al., 2015, PMID: 25561178). Because this lipid carrier system is unique to bacteria and lacks a human homolog, it is a highly attractive target for antimicrobial therapy with low potential for cross-kingdom toxicity.

Other names

BactoprenolUndecaprenyl diphosphateC55-isoprenyl phosphateUndecaprenyl pyrophosphateC55-PPUndecaprenyl diphosphate lipid carrier

Inhibition of the lipid carrier cycle through the sequestration of undecaprenyl phosphate or undecaprenyl diphosphate, which prevents the transport of peptidoglycan precursors across the membrane or the regeneration of the active carrier (Stone and Strominger, 1971; Manat et al., 2014).