Undecaprenyl-diphosphate phosphatase (UppP)

Undecaprenyl-diphosphate phosphatase (UppP), also known as BacA, is an essential integral membrane enzyme in bacteria that catalyzes the dephosphorylation of undecaprenyl diphosphate (UPP) to undecaprenyl phosphate (UP) [1][2]. This enzymatic step is a critical bottleneck in the peptidoglycan biosynthesis pathway, as UP serves as the vital C55-lipid carrier that transports sugar-peptide precursors across the cytoplasmic membrane to the growing cell wall [3]. By recycling UPP—which is generated both de novo and as a byproduct of peptidoglycan polymerization—UppP maintains the steady-state levels of UP necessary for continuous cell wall assembly [2][4]. Inhibition of this process leads to the depletion of the lipid carrier pool, resulting in the cessation of cell wall synthesis and subsequent bacterial cell death [3]. While the classic antibiotic bacitracin targets this pathway by sequestering the UPP substrate, UppP itself is a primary target for developing new antimicrobial strategies to combat multi-drug resistant pathogens [1][4]. Because the peptidoglycan synthesis machinery is unique to bacteria, UppP offers a high degree of selectivity with minimal potential for off-target effects in human hosts [2].

Other names

BacAUndecaprenyl pyrophosphate phosphataseC55-isoprenyl pyrophosphate phosphataseUPP phosphataseUndecaprenyl-diphosphatase

Inhibition of undecaprenyl phosphate recycling by preventing the dephosphorylation of undecaprenyl diphosphate, thereby halting peptidoglycan precursor transport and cell wall synthesis.