Shortened hydroxyacyl chains on lipid A of Escherichia coli cells expressing a foreign UDP-N-acetylglucosamine O-acyltransferase

Timna J. Odegaard, Igor A. Kaltashov, Robert J. Cotter, Liana Steeghs, Peter Van Der Ley, Shahid Khan, Duncan J. Maskell, Christian R.H. Raetz

Research output: Contribution to journalArticlepeer-review

55 Scopus citations


The first reaction of lipid A biosynthesis in Gram-negative bacteria is catalyzed by UDP-N-acetylglucosamine (UDP-GlcNAc) O-acyltransferase, the product of the lpxA gene. The reaction involves the transfer of an acyl chain from hydroxyacyl-acyl carrier protein (ACP) to the glucosamine 3-OH position of UDP-GlcNAc. The lipid A isolated from Escherichia coli contains (R)-3- hydroxymyristate at the 3 and 3' positions. Accordingly, LpxA of E. coli is highly selective for (R)-3-hydroxymyristoyl-ACP over ACP thioesters of longer or shorter acyl chains. We now demonstrate that the lpxA gene from Neisseria meningitidis encodes a similar acyltransferase that selectively utilizes 3- hydroxylauroyl-ACP. Strains of E. coli harboring the temperature-sensitive lpxA2 mutation make very little lipid A and lose viability rapidly at 42 °C. We have created an E. coli strain in which the chromosomal lpxA2 mutation is complemented by the N. meningitidis lpxA gene introduced on a plasmid. This strain, RO138/pTO6, grows similarly to wild type cells at 42°C and produces wild type levels of lipid A. However, the lipid A isolated from RO138/pTO6 contains mostly hydroxylaurate and hydroxydecanoate in the 3 and 3' positions. The strain RO138/pTO6 is more susceptible than wild type to certain antibiotics at 42°C. This is the first report of an E. coli strain growing with shortened hydroxyacyl chains on its lipid A. The lpxA gene product appears to be a critical determinant of the length of the ester- linked hydroxyacyl chains found on lipid A in living cells.

Original languageEnglish (US)
Pages (from-to)19688-19696
Number of pages9
JournalJournal of Biological Chemistry
Issue number32
StatePublished - Aug 8 1997
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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