Isolation and characterization of the Neisseria meningitidis lpxD-fabZ-lpxA gene cluster involved in lipid A biosynthesis.
The lpxD-fabZ-lpxA gene cluster involved in lipid A biosynthesis in Neisseria meningitidis has been cloned and sequenced. By complementation of a temperature-sensitive E. coli lpxD mutant, we first cloned a meningococcal chromosomal fragment that carries the lpxD homologue. Cloning and sequence analysis of chromosomal DNA downstream of lpxD revealed the presence of the fabZ and lpxA genes. This gene cluster shows high homology to the corresponding genes from several other bacterial species. The LpxA and LpxD proteins catalyze early steps in the lipid A biosynthetic pathway, adding the O- and N-linked 3-OH fatty acyl chains, respectively. In E. coli and N. meningitidis, LpxD has the same specificity, in both cases adding 3-OH myristoyl chains; in contrast to E. coli, the meningococcal LpxA protein is presumed to add 3-OH lauroyl chains instead. The established sequence points the way to further experiments to define the basis for this difference in specificity, and should allow modification of meningococcal lipid A biosynthesis through gene exchange.
Steeghs
L
L
Laboratory of Vaccine Development and Immune Mechanisms, National Institute of Public Health and the Environment, Antonie van Leeuwenhoeklaan, Bilthoven, The Netherlands.
Jennings
M P
MP
Poolman
J T
JT
van der Ley
P
P
D000217:Acyltransferases / Q000235:genetics*; D000595:Amino Acid Sequence; D001483:Base Sequence; D003001:Cloning, Molecular; D006090:Gram-Negative Bacteria / Q000235:genetics; D006836:Hydro-Lyases / Q000235:genetics*; D008050:Lipid A / Q000096:biosynthesis*; D008969:Molecular Sequence Data; D005810:Multigene Family; D009345:Neisseria meningitidis / Q000235:genetics*; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid
D008050:Lipid A; D000217:Acyltransferases; C050304:acyl-(acyl-carrier-protein)-UDP-N-acetylglucosamine acyltransferase; D006836:Hydro-Lyases; C036180:beta-hydroxyacyl-(acyl-carrier-protein)dehydrase