Abstract
Biochemical and genetic analyses of the bacterium Salmonella typhimurium suggest that accumulation of alpha-ketobutyrate partially mediates the herbicidal activity of acetolactate synthase inhibitors. Growth inhibition of wild-type bacteria by the herbicide sulfometuron methyl was prevented by supplementing the medium with isoleucine, an allosteric inhibitor of threonine deaminase-catalyzed synthesis of alpha-ketobutyrate. In contrast, isoleucine did not rescue the growth of a mutant containing a threonine deaminase unresponsive to isoleucine. Moreover, the hypersensitivity of seven Tn10 insertion mutants to growth inhibition by sulfometuron methyl and alpha-ketobutyrate correlated with their inability to convert alpha-ketobutyrate to less noxious metabolites. We propose that alpha-ketobutyrate accumulation is an important component of sulfonylurea and imidazolinone herbicide action.
MeSH Terms
Acetolactate Synthase/antagonists & inhibitors
Butyrates/metabolism
DNA Transposable Elements
Isoleucine/pharmacology
Kinetics
Mutation
Oxo-Acid-Lyases/antagonists & inhibitors
Salmonella typhimurium/drug effects,enzymology,genetics,metabolism
Sulfonylurea Compounds/pharmacology
Valine/pharmacology
Chemicals
Butyrates
DNA Transposable Elements
Sulfonylurea Compounds
Isoleucine
alpha-ketobutyric acid
Acetolactate Synthase
Oxo-Acid-Lyases
Valine
sulfometuron methyl
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
LaRossa R A
Van Dyk T K
Smulski D R
References (24)
24 references, click to expand
-
2-Ketobutyrate: a putative alarmone of Escherichia coli.
Mol Gen Genet. 1983;190(3):452-8
PMID: 6348482
-
Organization and regulation of the ilvGEDA operon in Salmonella typhimurium LT2.
J Bacteriol. 1981 Feb;145(2):984-9
PMID: 7007356
-
Mechanisms of suppression.
Adv Genet. 1973;17:1-105
PMID: 4585532
-
Threonine deaminase from Salmonella typhimurium. Substrate-specific patterns of inhibition in an activator site-deficient form of the enzyme.
J Biol Chem. 1979 Feb 25;254(4):1074-9
PMID: 368068
-
Genetic analysis of mutants of Saccharomyces cerevisiae resistant to the herbicide sulfometuron methyl.
Genetics. 1985 Jan;109(1):21-35
PMID: 3881312
-
Metabolic basis for the isoleucine, pantothenate or methionine requirement of ilvG strains of Salmonella typhimurium.
J Bacteriol. 1982 Jun;150(3):1202-11
PMID: 7042686
-
Site of action of chlorsulfuron: inhibition of valine and isoleucine biosynthesis in plants.
Plant Physiol. 1984 Jul;75(3):827-31
PMID: 16663712
-
Correlation between the serine sensitivity and the derepressibility of the ilv genes in Escherichia coli relA- mutants.
Mol Gen Genet. 1978 Sep 20;165(1):21-30
PMID: 362163
-
ZTP (5-amino 4-imidazole carboxamide riboside 5'-triphosphate): a proposed alarmone for 10-formyl-tetrahydrofolate deficiency.
Cell. 1982 Jul;29(3):929-37
PMID: 6185232
-
Metabolic alterations mediated by 2-ketobutyrate in Escherichia coli K12.
Mol Gen Genet. 1984;193(3):473-8
PMID: 6369074
-
Acetolactate synthase is the site of action of two sulfonylurea herbicides in higher plants.
Science. 1984 Jun 29;224(4656):1443-5
PMID: 17793381
-
Sensitivity of a Salmonella typhimurium aspC mutant to sulfometuron methyl, a potent inhibitor of acetolactate synthase II.
J Bacteriol. 1986 Feb;165(2):386-92
PMID: 3003025
-
A survey of inborn errors of amino acid metabolism and transport in man.
Annu Rev Biochem. 1981;50:911-68
PMID: 6791581
-
Toxicity of the pyrimidine biosynthetic pathway intermediate carbamyl aspartate in Salmonella typhimurium.
J Bacteriol. 1985 Aug;163(2):500-5
PMID: 3894327
-
Acetohydroxy acid synthase isoenzymes of Escherichia coli K12 and Salmonella typhimurium.
Ann Microbiol (Paris). 1982 Mar-Apr;133(2):251-6
PMID: 6805381
-
Defect in alpha-ketobutyrate metabolism: a new inborn error.
Clin Chim Acta. 1985 Jan 30;145(2):173-82
PMID: 3918815
-
Role of L-threonine dehydrogenase in the catabolism of threonine and synthesis of glycine by Escherichia coli.
J Bacteriol. 1976 Jun;126(3):1245-9
PMID: 7548
-
Amino acid biosynthesis and its regulation.
Annu Rev Biochem. 1978;47:532-606
PMID: 354503
-
ilvB-encoded acetolactate synthase is resistant to the herbicide sulfometuron methyl.
J Bacteriol. 1984 Oct;160(1):391-4
PMID: 6090425
-
A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding.
Anal Biochem. 1976 May 7;72:248-54
PMID: 942051
-
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
PMID: 6378902
-
Substrate channeling: alpha-ketobutyrate inhibition of acetohydroxy acid synthase in Salmonella typhimurium.
J Bacteriol. 1980 Sep;143(3):1509-12
PMID: 6997277
-
Synthesis of the isoleucyl- and valyl-tRNA synthetases and the isoleucine-valine biosynthetic enzymes in a threonine deaminase regulatory mutant of Escherichia coli K-12.
J Mol Biol. 1984 May 5;175(1):39-55
PMID: 6374157
-
Imidazolinones: potent inhibitors of acetohydroxyacid synthase.
Plant Physiol. 1984 Oct;76(2):545-6
PMID: 16663878