UppP

UppP, short for undecaprenyl pyrophosphate phosphatase, is an essential membrane-associated enzyme found in many bacteria. It catalyzes the dephosphorylation of undecaprenyl pyrophosphate (Und-PP) to undecaprenyl phosphate (Und-P), a critical step in the lipid carrier cycle that delivers cell-wall precursors to the site of peptidoglycan synthesis. Und-P is reused to shuttle disaccharide-peptide units across the cytoplasmic membrane, and the activity of UppP helps sustain peptidoglycan assembly and, in some organisms, teichoic acid and O-antigen biosynthesis. Because Und-P recycling is central to cell-wall biogenesis, UppP is often essential for viability and is conserved across Gram-positive and Gram-negative bacteria. In Escherichia coli, UppP is commonly referred to as BacA; other Und-PP phosphatases such as PgpB and YbjG provide redundant activity in some species.

UppP proteins are multi-pass inner membrane proteins, typically predicted to contain several transmembrane helices. The catalytic mechanism is not completely resolved, but UppP-family phosphatases are thought to use conserved acidic residues to coordinate metal ions and facilitate pyrophosphate hydrolysis. The exact topology and active-site arrangement vary among family members, but all share the general role of converting Und-PP to Und-P to sustain lipid carrier recycling.

Clinical and research relevance: Because Und-P recycling underpins cell-wall synthesis, UppP and related phosphatases are of interest as potential antimicrobial targets. Inhibitors that block UppP activity could impair peptidoglycan assembly and increase susceptibility to cell-wall–targeting antibiotics such as bacitracin. Ongoing research seeks to clarify structure–function relationships and to identify selective inhibitors.