Biosynthesis of lipid A. Formation of acyl-deficient lipopolysaccharides in Salmonella typhimurium and Escherichia coli.
The effect of cerulenin on conversion of an acyl-deficient precursor of lipid A to lipopolysaccharide was investigated in a mutant of Salmonella typhimurium (PRX22H9) conditionally defective in synthesis of 3-deoxy-D-mannooctulosonate (KDO). The precursor lacks both KDO and the saturated O-fatty acyl chains of lipopolysaccharide and contains beta-hydroxymyristate as sole fatty acid. Concentrations of cerulenin which inhibited de novo synthesis of fatty acids and lipopolysaccharide more than 95% had no effect on the rate or extent of conversion of preformed lipid A precursor to a lipopolysaccharide product. The product was identified as a polymer containing the Rc type core polysaccharide of PRX22H9 linked to the acyl-deficient lipid A unit of the precursor. The acyl-deficient lipopolysaccharide was translocated to the outer membrane at a normal rate. Lipopolysaccharide deficient in saturated fatty acids was also produced by a fabD mutant of Escherichia coli under conditions of limited endogenous fatty acid synthesis. The results indicate that prior incorporation of the saturated O-acyl chains of lipid A is not necessary for extension of the core polysaccharide chain and that synthesis of underacylated lipopolysaccharides occurs under conditions of restricted fatty acid synthesis which permit formation of the beta-hydroxymyristate-containing lipid A precursor.
D004926:Escherichia coli / Q000378:metabolism*; D007700:Kinetics; D008050:Lipid A / Q000096:biosynthesis*; D008070:Lipopolysaccharides / Q000096:biosynthesis*; D008563:Membrane Lipids / Q000378:metabolism; D012486:Salmonella typhimurium / Q000378:metabolism*; D013045:Species Specificity; D013400:Sugar Acids / Q000378:metabolism; D013696:Temperature
D008050:Lipid A; D008070:Lipopolysaccharides; D008563:Membrane Lipids; D013400:Sugar Acids; C002532:2-keto-3-deoxyoctonate