Lipid II peptidoglycan precursor (Lipid II)

Lipid II is the universally conserved membrane-bound precursor for bacterial peptidoglycan biosynthesis. Its structure consists of a hydrophobic undecaprenyl lipid tail linked by pyrophosphate to a disaccharide unit of N-acetylglucosamine and N-acetylmuramic acid, which carries a pentapeptide stem. Synthesized on the inner leaflet of the bacterial cytoplasmic membrane, Lipid II is translocated (“flipped”) across the membrane by the MurJ flippase (or, controversially, FtsW), exposing its moiety for polymerization and cross-linking into peptidoglycan. It is essential for bacterial growth, division, and maintenance of cell shape. Numerous classes of antibiotics—including vancomycin, teicoplanin, ramoplanin, nisin, and plectasin—kill bacteria by binding to and sequestering Lipid II, thereby blocking cell wall synthesis. Because Lipid II and the enzymes and transporters associated with its metabolism are unique to bacteria, targeting these molecules avoids toxicity to mammalian cells and has become a major strategy for the development of antimicrobial agents.

Other names

Lipid IIUndecaprenyl pyrophosphoryl disaccharide-pentapeptidePeptidoglycan precursor lipid IIBacterial cell wall lipid IIShuttle carrier of peptidoglycan building blocks

Inhibition of cell wall biosynthesis by sequestering lipid II (vancomycin, teicoplanin, ramoplanin, nisin, plectasin); Interference with the translocation of lipid II across the membrane (various antibiotics inhibit flippases/MurJ); Blockage of peptidoglycan polymerization and crosslinking