Inhibition of Escherichia coli isoleucine biosynthesis by isoleucine tetrazole

J Bacteriol. 1975 Sep;123(3):862-70. doi: 10.1128/jb.123.3.862-870.1975.

Abstract

Growth of a derivative of Escherichia coli K-10 was strongly inhibited by 2 times 10(-4) M L-5(1-amino-2-methylbutyl)-tetrazole (isoleucine tetrazole). Growth inhibition was reversed by isoleucine, threonine, glycyl-L-isoleucine, or glycyl-L-threonine, and, in a valine-resistant mutant, by L-valine. Partial reversal of growth inhibiton was effected by L-leucine, L-methionine, or L-homoserine. The tetrazole inhibited the activity of the biosynthetic threonine deaminase (EC 4.2.1.16 L-threonine hydrolyase [deaminating]), the inhibition being relieved by L-valine. The tetrazole also inhibited isoleucyl-transfer ribonucleic acid (tRNA) synthetase (EC 6.1.1.5 L-isoleucine: tRNA ligase [adenosine monophosphate]), but was without effect on the activities of alpha-isopropylmalate synthetase or acetohydroxy acid synthetase. One class of isoleucine tetrazole-resistant mutants produced biosynthetic threonine deaminases which were no longer subject to feedback inhibition by either isoleucine or the tetrazole.

MeSH terms

  • 2-Isopropylmalate Synthase / metabolism
  • Acetolactate Synthase / metabolism
  • Azoles / pharmacology*
  • Depression, Chemical
  • Drug Resistance, Microbial
  • Escherichia coli / growth & development
  • Escherichia coli / metabolism*
  • Homoserine / pharmacology
  • Isoleucine / analogs & derivatives
  • Isoleucine / biosynthesis*
  • Isoleucine / pharmacology
  • Isoleucine-tRNA Ligase / metabolism
  • Membrane Transport Proteins / metabolism
  • Methionine / pharmacology
  • Mutation
  • Peptides / pharmacology
  • Tetrazoles / antagonists & inhibitors
  • Tetrazoles / pharmacology*
  • Threonine / pharmacology
  • Threonine Dehydratase / metabolism
  • Valine / pharmacology

Substances

  • Azoles
  • Membrane Transport Proteins
  • Peptides
  • Tetrazoles
  • Isoleucine
  • Threonine
  • isoleucine tetrazole
  • Homoserine
  • Methionine
  • Acetolactate Synthase
  • 2-Isopropylmalate Synthase
  • Threonine Dehydratase
  • Isoleucine-tRNA Ligase
  • Valine