Free flow electrophoresis as a tool for enrichment of mutants with temperature-dependent lethal mutations in lipid A synthesis

Eur J Biochem. 1985 Apr 1;148(1):21-7. doi: 10.1111/j.1432-1033.1985.tb08801.x.

Abstract

Free flow electrophoresis was shown to be a useful tool to enrich for mutants conditionally defective in lipid A synthesis. The method was based on the observation that electrophoretic mobility of bacterial cells is dependent on the structure of lipopolysaccharides and is influenced by lesions in the synthesis of the O-specific chains as well as by lesion in the synthesis of the complete 3-deoxy-D-manno-octulosonic acid (dOclA) lipid A region. Using this procedure a new mutant conditionally defective in dOclA-8-P synthesis was isolated (mutant Ts5). Following a shift to nonpermissive conditions it accumulates a mixture of at least two equally represented lipid A precursor structures. One is made up of glucosamine, phosphate and 3-hydroxymyristic acid in a molar ratio 1.0:1.0:2.0 and lacks dOclA and the nonhydroxylated fatty acids lauric, myristic and palmitic acid. The precursor preparation derived from mutant Ts5 thus differs from previously described lipid A intermediates by the relatively high substitution by palmitic acid. The implications of the above findings to the biosynthesis of lipid A are discussed.

MeSH terms

  • Aldehyde-Lyases / metabolism
  • Chromatography, Affinity
  • Chromatography, DEAE-Cellulose
  • Electrophoresis / methods
  • Lipid A / biosynthesis*
  • Lipid A / genetics
  • Mutation
  • Salmonella typhimurium / genetics*
  • Salmonella typhimurium / metabolism
  • Structure-Activity Relationship
  • Temperature

Substances

  • Lipid A
  • 2-dehydro-3-deoxyphosphooctonate aldolase
  • Aldehyde-Lyases