Bacterial cell wall. MurJ is the flippase of lipid-linked precursors for peptidoglycan biogenesis

Science. 2014 Jul 11;345(6193):220-2. doi: 10.1126/science.1254522.


Peptidoglycan (PG) is a polysaccharide matrix that protects bacteria from osmotic lysis. Inhibition of its biogenesis is a proven strategy for killing bacteria with antibiotics. The assembly of PG requires disaccharide-pentapeptide building blocks attached to a polyisoprene lipid carrier called lipid II. Although the stages of lipid II synthesis are known, the identity of the essential flippase that translocates it across the cytoplasmic membrane for PG polymerization is unclear. We developed an assay for lipid II flippase activity and used a chemical genetic strategy to rapidly and specifically block flippase function. We combined these approaches to demonstrate that MurJ is the lipid II flippase in Escherichia coli.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Wall / metabolism*
  • Escherichia coli / genetics
  • Escherichia coli / metabolism*
  • Escherichia coli Proteins / antagonists & inhibitors
  • Escherichia coli Proteins / chemistry
  • Escherichia coli Proteins / physiology*
  • Mesylates / pharmacology
  • Models, Molecular
  • Peptidoglycan / biosynthesis*
  • Peptidoglycan / chemistry
  • Phospholipid Transfer Proteins / antagonists & inhibitors
  • Phospholipid Transfer Proteins / chemistry
  • Phospholipid Transfer Proteins / physiology*
  • Protein Conformation
  • Uridine Diphosphate N-Acetylmuramic Acid / analogs & derivatives*
  • Uridine Diphosphate N-Acetylmuramic Acid / metabolism


  • Escherichia coli Proteins
  • Mesylates
  • MurJ protein, E coli
  • Peptidoglycan
  • Phospholipid Transfer Proteins
  • Uridine Diphosphate N-Acetylmuramic Acid
  • muramyl-NAc-(pentapeptide)pyrophosphoryl-undecaprenol
  • (2-sulfonatoethyl)methanethiosulfonate