Regulation of branched-chain amino acid biosynthesis in Salmonella typhimurium: isolation of regulatory mutants.
5',5',5'-Trifluoro-dl-leucine inhibited the activity of alpha-isopropylmalate synthetase (the initial enzyme unique to leucine biosynthesis) as well as the growth of Salmonella typhimurium. Mutants of S. typhimurium resistant to the analogue were isolated and characterized. In most cases, they overproduced and excreted leucine or leucine, valine, and isoleucine as a result of an alteration in the regulation of branched-chain amino acid biosynthesis. Biochemical and genetic tests allowed the mutants to be grouped into three classes: I, a moderately large group (13%) which had high, constitutive leucine biosynthetic enzyme levels and mutant sites linked to the leucine operon (operator constitutive); II, a single mutant in which the mutant site was linked to the leucine operon and in which alpha-isopropylmalate synthetase was not inhibited by leucine (feedback negative); III, a majority type which had constitutive levels of leucine, valine, and isoleucine biosynthetic enzymes and mutant sites unlinked to the leucine operon. Mutants of class I provide important evidence for the concept of an operon organization of genes involved in leucine biosynthesis. The properties of class III mutants indicate that there is some element involved in regulation which is common to the three pathways.
D005246:Feedback; D005809:Genes, Regulator; D005827:Genetics, Microbial; D006836:Hydro-Lyases / Q000378:metabolism; D007532:Isoleucine / Q000096:biosynthesis*; D007930:Leucine / Q000096:biosynthesis* / Q000494:pharmacology; D008025:Ligases / Q000378:metabolism; D008962:Models, Theoretical; D008967:Molecular Biology; D009154:Mutation; D009876:Operon; D010088:Oxidoreductases / Q000378:metabolism; D012486:Salmonella typhimurium / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D014633:Valine / Q000096:biosynthesis*
D007532:Isoleucine; D010088:Oxidoreductases; D006836:Hydro-Lyases; D008025:Ligases; D007930:Leucine; D014633:Valine