The Sulfonylurea Herbicide Sulfometuron Methyl Is an Extremely Potent and Selective Inhibitor of Acetolactate Synthase in Salmonella Typhimurium

J Biol Chem. 1984 Jul 25;259(14):8753-7.

Abstract

The sulfonylurea herbicide sulfometuron methyl inhibits the growth of several bacterial species. In the presence of L-valine, sulfometuron methyl inhibits Salmonella typhimurium, this inhibition can be reversed by L-isoleucine. Reversal of growth retardation by L-isoleucine, accumulation of guanosine 5'-diphosphate 3'-diphosphate (magic spot), and relA mutant hypersensitivity suggest sulfometuron methyl interference with branched-chain amino acid biosynthesis. Growth inhibition of S. typhimurium is mediated by sulfometuron methyl's inhibition of acetolactate synthase, the first common enzyme in the branched-chain amino acid biosynthetic pathway. Sulfometuron methyl exhibits slow-binding inhibition of acetolactate synthase isozyme II from S. typhimurium with an initial Ki of 660 +/- 60 nM and a final, steady-state Ki of 65 +/- 25 nM. Inhibition of acetolactate synthase by sulfometuron methyl is substantially more rapid (10 times) in the presence of pyruvate with a maximal first-order rate constant for conversion from initial to final steady-state inhibition of 0.25 +/- 0.07 min-1 (minimal half-time of 2.8 min). Mutants of S. typhimurium able to grow in the presence of sulfometuron methyl were obtained. They have acetolactate synthase activity that is insensitive to sulfometuron methyl because of mutations in or near ilvG, the structural gene for acetolactate synthase isozyme II.

MeSH terms

  • Acetolactate Synthase / antagonists & inhibitors*
  • Amino Acids / pharmacology
  • Crosses, Genetic
  • Herbicides / toxicity*
  • Kinetics
  • Mutation
  • Oxo-Acid-Lyases / antagonists & inhibitors*
  • Salmonella typhimurium / drug effects
  • Salmonella typhimurium / enzymology*
  • Salmonella typhimurium / growth & development
  • Species Specificity
  • Sulfonylurea Compounds / toxicity*

Substances

  • Amino Acids
  • Herbicides
  • Sulfonylurea Compounds
  • Acetolactate Synthase
  • Oxo-Acid-Lyases
  • sulfometuron methyl