Undecaprenyl Phosphate Synthesis

Abstract

Undecaprenyl phosphate (C55-P) is an essential 55-carbon long-chain isoprene lipidinvolved in the biogenesis of bacterial cell wall carbohydrate polymers: peptidoglycan, O antigen, teichoic acids, and other cell surface polymers. It functions as a lipid carrier that allows the traffic of sugar intermediates across the plasma membrane, towards the periplasm,where the polymerization of the different cellwall components occurs. At the end of these processes, the lipid is released in a pyrophosphate form (C55-PP). C55-P arises from the dephosphorylation of C55-PP, which itself originates from either a recycling event or a de novo synthesis. In Escherichia coli , the formation of C55-PP is catalyzed by the essential UppS synthase, a soluble cis-prenyltransferase, whichadds eight isoprene units ontofarnesyl pyrophosphate. Severalapo- and halo-UppSthree-dimensional structures have provided a high level of understanding of this enzymatic step. The following dephosphorylationstep is required before the lipid carrier can accept a sugar unit at the cytoplasmic face of the membrane. Four integralmembrane proteins have been shown to catalyzethis reaction in E. coli:BacA and three members of the PAP2 super-family:YbjG, LpxT, and PgpB. None of these enzymes is essential,but the simultaneous inactivation of bacA , ybjG , and pgpB genes gave rise to a lethal phenotype, raising the question of the relevance of such a redundancy of activity. It was alsorecently shown that LpxTcatalyzes the specific transfer of the phosphate group arising from C55-PP to the lipidA moiety of lipopolysaccharides, leading to a lipid-A 1-diphosphate form whichaccounts for one-third of the total lipidA in wild-type E. coli cells. The active sites of LpxT, PgpB,andYbjG were shown to face the periplasm, suggesting that PAP2 enzymes arerather involved in C55-PP recycling. These recent discoveries have opened the way to the elucidation of the functional and structural characterization of these different phosphatases.