Undecaprenyl pyrophosphate (UPP) (UPP)

Undecaprenyl pyrophosphate (UPP), also known as C55-isoprenyl pyrophosphate, is an essential lipid carrier required for the synthesis of the bacterial cell wall (Manat et al., 2014, FEMS Microbiol Rev). It plays a pivotal role in transporting hydrophilic building blocks, such as peptidoglycan and teichoic acid precursors, across the hydrophobic cytoplasmic membrane to the external site of assembly (Scheffers & Pinho, 2005, Microbiol Mol Biol Rev). After delivering its cargo, UPP must be dephosphorylated into undecaprenyl phosphate (UP) by membrane-bound phosphatases to be recycled for further transport cycles (Siewert & Strominger, 1967, PNAS). This recycling step is the specific target of the antibiotic bacitracin, which forms a complex with UPP in the presence of divalent metal ions, effectively sequestering the carrier and halting cell wall production (Stone & Strominger, 1971, PNAS). Because the UPP cycle is indispensable for bacterial viability and lacks a direct human homolog, it is a highly validated target for antimicrobial drug development (Ling et al., 2015, Nature). Targeting this molecule is particularly effective against Gram-positive pathogens, though systemic use of drugs like bacitracin is limited by significant nephrotoxicity (Gallagher et al., 2011, Bioorg Med Chem). Other antibiotics, such as teixobactin, also target the lipid-linked intermediates of this pathway, highlighting its vulnerability as a therapeutic target.

Other names

C55-isoprenyl pyrophosphateUndecaprenyl diphosphateBactoprenol pyrophosphateC55-PPLipid pyrophosphate

Inhibition of undecaprenyl pyrophosphate dephosphorylation and sequestration of lipid-linked cell wall precursors