Deciphering the Metabolism of Undecaprenyl-Phosphate: The Bacterial Cell-Wall Unit Carrier at the Membrane Frontier

Microb Drug Resist. 2014 Jun;20(3):199-214. doi: 10.1089/mdr.2014.0035. Epub 2014 May 5.

Abstract

During the biogenesis of bacterial cell-wall polysaccharides, such as peptidoglycan, cytoplasmic synthesized precursors should be trafficked across the plasma membrane. This essential process requires a dedicated lipid, undecaprenyl-phosphate that is used as a glycan lipid carrier. The sugar is linked to the lipid carrier at the inner face of the membrane and is translocated toward the periplasm, where the glycan moiety is transferred to the growing polymer. Undecaprenyl-phosphate originates from the dephosphorylation of its precursor undecaprenyl-diphosphate, with itself generated by de novo synthesis or by recycling after the final glycan transfer. Undecaprenyl-diphosphate is de novo synthesized by the cytosolic cis-prenyltransferase undecaprenyl-diphosphate synthase, which has been structurally and mechanistically characterized in great detail highlighting the condensation process. In contrast, the next step toward the formation of the lipid carrier, the dephosphorylation step, which has been overlooked for many years, has only started revealing surprising features. In contrast to the previous step, two unrelated families of integral membrane proteins exhibit undecaprenyl-diphosphate phosphatase activity: BacA and members of the phosphatidic acid phosphatase type 2 super-family, raising the question of the significance of this multiplicity. Moreover, these enzymes establish an unexpected link between the synthesis of bacterial cell-wall polymers and other biological processes. In the present review, the current knowledge in the field of the bacterial lipid carrier, its mechanism of action, biogenesis, recycling, regulation, and future perspective works are presented.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alkyl and Aryl Transferases / metabolism
  • Biological Transport
  • Cell Membrane / chemistry
  • Cell Membrane / metabolism*
  • Cell Wall / chemistry
  • Cell Wall / metabolism*
  • Escherichia coli / chemistry
  • Escherichia coli / metabolism*
  • Escherichia coli Proteins / metabolism
  • Lipid Metabolism
  • Peptidoglycan / metabolism
  • Phosphatidate Phosphatase / metabolism
  • Phosphoric Monoester Hydrolases / metabolism
  • Polyisoprenyl Phosphates / metabolism*

Substances

  • Escherichia coli Proteins
  • Peptidoglycan
  • Polyisoprenyl Phosphates
  • undecaprenyl phosphate
  • undecaprenyl pyrophosphate
  • Alkyl and Aryl Transferases
  • undecaprenyl pyrophosphate synthetase
  • BacA protein, E coli
  • phosphatidic acid phosphatase type 2
  • Phosphoric Monoester Hydrolases
  • Phosphatidate Phosphatase