Current understanding of de novo synthesis of bacterial lipid carrier (undecaprenyl phosphate): More enzymes to be discovered

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.