Abstract

An isoprenoid named undecaprenyl phosphate (Und-p) is the only known lipid carrier in bacteria. It is involved in the translocation of hydrophilic intermediates of cell wall components across the hydrophobic phospholipid bilayer of the cell membrane for subsequent polymerization in cell wall synthesis. Und-p is made available by both de novosynthesis and recycling. Evidences are emerging that in addition to dephosphorylation of undecaprenyl pyrophosphate (Und-pp), the phosphorylation of undecaprenol (Und-OH) into Und-p exists as an alternative pathway in Gram-positive bacteria but not in Gram-negative bacteria. This review gives an overview of the current knowledge in the synthesis of Und-p. It also hypothesizes the presence of yet to be identified Und-pp phosphatases at the inner cytoplasmic membrane that function in addition to a known phosphatase, named undecaprenyl pyrophosphate phosphatase (Upp-P) in de novo synthesis of Und-p. As the processes involved in cell wall synthesis remains the most promising antimicrobial therapeutic means, a more thorough understanding of the synthesis of the bacterial lipid carrier will not only improve the knowledge of cell wall synthesis but may also lead to the identification of potential drug targets and vaccine candidates.   Key words: Lipid carrier, undecaprenyl phosphate, undecaprenol, undecaprenol kinase, cell wall synthesis.

Highlights

  • Polyisoprenoids are polymers of five carbon isoprene units used as lipid carriers across the three domains of life (Jones et al, 2009)

  • Since UppP is absent, the dephosphorylation of undecaprenyl pyrophosphate (Und-pp) into functional undecaprenyl phosphate (Und-p) may be performed by other enzymes in T. pallidum and Rickettsia sp if the active sites of YbjG or PgpB present in these bacteria are in the periplasmic space as demonstrated in E. coli

  • In addition to the lack of outer cell membrane, the hypersensitivity of S. aureus and S. pneumoniae ∆uppP mutants to only bacitracin among other antibiotics may be attributed to the lack of Und-pp phosphatase activity required to compete with bacitracin for resistance

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Summary

INTRODUCTION

Polyisoprenoids are polymers of five carbon isoprene units used as lipid carriers across the three domains of life (Jones et al, 2009). At the centre of the synthesis of bacterial cell wall is an isoprenoid lipid carrier named undecaprenyl phosphate (Und-p). It is involved in the translocation of glycan biosynthetic intermediates of carbohydrate polymers across the hydrophobic phospholipid bilayer of bacteria cell membrane to the externally located site of polymerization during cell growth, and division. Und-p has long been known to be derived from dephosphorylation of its precursor, undecaprenyl pyrophosphate (Und-pp) by the action of Und-pp phosphatases. These phosphatases have drawn much attention lately because of the essential role they play in the availability of the lipid carrier.

DXP DXR
Biosynthesis of undecaprenyl phosphate
Recycling of undecaprenyl phosphate
More enzymes to be discovered
Contribution of undecaprenol kinase to the pool of the lipid carrier
Lipid I
Possible involvement of UppP in vaccine or drug target screening
Role in virulence
Role in antibiotic resistance
Findings
CONCLUSION AND OPEN RESEARCH
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