The sulfonylurea herbicide sulfometuron methyl is an extremely potent and selective inhibitor of acetolactate synthase in Salmonella typhimurium.

R A Larossa,J V Schloss

doi:10.1016/s0021-9258(17)47217-6

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.

Highlights

The Sulfonylurea Herbicide Sulfometuron MethyIl s an Extremely Potent and Selective Inhibitor of AcetolactateSynthase in Salmonella typhimurium”
Inhibition in the presence of valine is reversed by isoleucine, suggesting sulfometuron methyl inhibitsa step in the biosynthesis of branched-chain amino acids (Table I)
Thiamine partiallyandthiaminetogether with a-ketobutyrate protectagainstsulfometuron methyl inhibition(datanot shown). ppGpp and pppGpp accumulatedupon treatment of

Summary

Introduction

The Sulfonylurea Herbicide Sulfometuron MethyIl s an Extremely Potent and Selective Inhibitor of AcetolactateSynthase in Salmonella typhimurium”. Rateconstantforconversionfrom initial tofinal steady-state inhibition of 0.25 f 0.07 min” (minimal half-timeof 2.8 min).Mutants ofS.typhimurium able to grow in the presence of sulfometuron methyl were obtained. On minimal medium.Only inthe presence of valine, is growth inhibition of wild-type S. typhimurium by sulfometuron methyl observed.

Results

Conclusion