Undecaprenyl pyrophosphate carrier cycle (UPP cycle)

The undecaprenyl pyrophosphate carrier cycle, also known as the Lipid II cycle, is a fundamental pathway in bacteria responsible for transporting cell wall precursors across the cytoplasmic membrane (Müller et al., 2017, Nature Communications). It utilizes a C55-isoprenoid lipid carrier, undecaprenyl phosphate (bactoprenol), to shuttle hydrophilic peptidoglycan building blocks from the cytoplasm to the periplasmic space. Key enzymatic steps include the formation of Lipid I and Lipid II intermediates, which are then translocated across the membrane by flippases such as MurJ (Sham et al., 2014, Science). Following the incorporation of the precursors into the peptidoglycan layer, the lipid carrier is released as undecaprenyl pyrophosphate and must be dephosphorylated by enzymes like UppP (BacA) to be recycled (El Ghachi et al., 2004, JBC). This cycle is a major target for antibiotics; for instance, bacitracin inhibits the dephosphorylation step, while glycopeptides like vancomycin and novel agents like teixobactin bind directly to the lipid-linked intermediates to halt cell wall assembly (Stone & Strominger, 1971, PNAS; Ling et al., 2015, Nature). Because this pathway is essential for bacterial survival and lacks a direct human counterpart, it remains a high-priority target for the development of new antimicrobial therapies.

Other names

Lipid II cycleBactoprenol cycleC55-isoprenoid cyclePeptidoglycan precursor transport cycleUndecaprenyl phosphate recycling pathway

Inhibition of undecaprenyl pyrophosphate dephosphorylation, sequestration of lipid-linked peptidoglycan precursors (Lipid I and Lipid II), and inhibition of flippase-mediated translocation across the cytoplasmic membrane.