upps

UppS, or undecaprenyl pyrophosphate synthase, is a bacterial enzyme that catalyzes the biosynthesis of undecaprenyl pyrophosphate (UPP), a key lipid carrier used in the assembly of cell wall precursors. The enzyme typically mediates the iterative head-to-tail condensation of eight isopentenyl pyrophosphate (IPP) units onto farnesyl pyrophosphate (FPP) to form C55 undecaprenyl pyrophosphate, which is subsequently dephosphorylated to undecaprenyl phosphate and incorporated into the peptidoglycan synthesis pathway.

Biochemical role and mechanism: UppS belongs to the trans-prenyltransferase family and requires divalent metal ions, commonly magnesium, for activity. It features conserved aspartate-rich motifs that coordinate substrates and determine the reaction. In many bacteria, UppS functions as a dimer, with the active site formed at the subunit interface. The product serves as a universal lipid carrier that transports glycan precursors across the cytoplasmic membrane for cell wall assembly.

Distribution and significance: UppS is widely distributed among bacteria and is essential for viability in most species, making it a potential target for antibiotic development. Its essential role links isoprenoid biosynthesis to cell envelope biogenesis, connecting metabolic pathways to structural integrity.

Structure and variation: While the core mechanism is conserved, UppS can exhibit species-specific variations in length and substrate tolerance. The enzyme’s activity is intimately tied to the proper generation and handling of the C55 lipid carrier, a cornerstone of bacterial cell wall synthesis.

Overall, UppS is a compact, essential polyprenyl pyrophosphate synthase that links isoprenoid metabolism to peptidoglycan production, with ongoing interest as a target for antimicrobial strategies.