title: Evolution of the Kdo2-lipid A biosynthesis in bacteria.
abstract: BACKGROUND
  Lipid A is the highly immunoreactive endotoxic center of lipopolysaccharide (LPS). It anchors the LPS into the outer membrane of most Gram-negative bacteria. Lipid A can be recognized by animal cells, triggers defense-related responses, and causes Gram-negative sepsis. The biosynthesis of Kdo2-lipid A, the LPS substructure, involves with nine enzymatic steps.
  
  
  RESULTS
  In order to elucidate the evolutionary pathway of Kdo2-lipid A biosynthesis, we examined the distribution of genes encoding the nine enzymes across bacteria. We found that not all Gram-negative bacteria have all nine enzymes. Some Gram-negative bacteria have no genes encoding these enzymes and others have genes only for the first four enzymes (LpxA, LpxC, LpxD, and LpxB). Among the nine enzymes, five appeared to have arisen from three independent gene duplication events. Two of such events happened within the Proteobacteria lineage, followed by functional specialization of the duplicated genes and pathway optimization in these bacteria.
  
  
  CONCLUSIONS
  The nine-enzyme pathway, which was established based on the studies mainly in Escherichia coli K12, appears to be the most derived and optimized form. It is found only in E. coli and related Proteobacteria. Simpler and probably less efficient pathways are found in other bacterial groups, with Kdo2-lipid A variants as the likely end products. The Kdo2-lipid A biosynthetic pathway exemplifies extremely plastic evolution of bacterial genomes, especially those of Proteobacteria, and how these mainly pathogenic bacteria have adapted to their environment.
authors.affiliation: School of Biological Sciences and Center for Plant Science Innovation, University of Nebraska-Lincoln, Lincoln, NE 68588-0118, USA.
authors.forename: Stephen O
authors.initials: SO
authors.lastname: Opiyo
authors.forename: Rosevelt L
authors.initials: RL
authors.lastname: Pardy
authors.forename: Hideaki
authors.initials: H
authors.lastname: Moriyama
authors.forename: Etsuko N
authors.initials: EN
authors.lastname: Moriyama
mesh_terms: D005075:Biological Evolution; D020440:Gene Duplication; D016680:Genome, Bacterial; D006090:Gram-Negative Bacteria / Q000201:enzymology / Q000235:genetics*; D016013:Likelihood Functions; D008070:Lipopolysaccharides / Q000096:biosynthesis*; D008958:Models, Molecular; D005810:Multigene Family; D010802:Phylogeny; D016415:Sequence Alignment; D020539:Sequence Analysis, Protein
chemical_list: C506188:Kdo2-lipid A; D008070:Lipopolysaccharides