Transfer of palmitate from phospholipids to lipid A in outer membranes of gram-negative bacteria

EMBO J. 2000 Oct 2;19(19):5071-80. doi: 10.1093/emboj/19.19.5071.


Regulated covalent modifications of lipid A are implicated in virulence of pathogenic Gram-negative bacteria. The Salmonella typhimurium PhoP/PhoQ-activated gene pagP is required both for biosynthesis of hepta-acylated lipid A species containing palmitate and for resistance to cationic anti-microbial peptides. Palmitoylated lipid A can also function as an endotoxin antagonist. We now show that pagP and its Escherichia coli homolog (crcA) encode an unusual enzyme of lipid A biosynthesis localized in the outer membrane. PagP transfers a palmitate residue from the sn-1 position of a phospholipid to the N-linked hydroxymyristate on the proximal unit of lipid A (or its precursors). PagP bearing a C-terminal His(6)-tag accumulated in outer membranes during overproduction, was purified with full activity and was shown by cross-linking to behave as a homodimer. PagP is the first example of an outer membrane enzyme involved in lipid A biosynthesis. Additional pagP homologs are encoded in the genomes of Yersinia and Bordetella species. PagP may provide an adaptive response toward both Mg(2+) limitation and host innate immune defenses.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acylation
  • Acyltransferases / genetics*
  • Acyltransferases / isolation & purification
  • Acyltransferases / metabolism
  • Animals
  • Bacterial Outer Membrane Proteins / genetics*
  • Bacterial Outer Membrane Proteins / isolation & purification
  • Bacterial Outer Membrane Proteins / metabolism
  • Bacterial Proteins / metabolism
  • Carbohydrate Sequence
  • Cell Membrane
  • Electrophoresis, Polyacrylamide Gel
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Lipid A / biosynthesis
  • Lipid A / metabolism*
  • Molecular Sequence Data
  • Palmitates / metabolism*
  • Phospholipids / metabolism*
  • Salmonella typhimurium / enzymology
  • Salmonella typhimurium / genetics*
  • Salmonella typhimurium / metabolism
  • Sequence Homology, Amino Acid


  • Bacterial Outer Membrane Proteins
  • Bacterial Proteins
  • Lipid A
  • Palmitates
  • PhoQ protein, Bacteria
  • Phospholipids
  • Acyltransferases