Mechanism of 3-methylanthranilic acid derepression of the tryptophan operon in Escherichia coli.
3-Methylanthranilic acid (3MA) inhibits growth and causes derepression of the tryptophan biosynthetic enzymes in wild-type strains of Escherichia coli. Previous reports attributed this effect to an inhibition of the conversion of 1-(o-carboxyphenylamino)-1-deoxyribulose 5-phosphate to indole-3-glycerol phosphate and a consequent reduction in the concentration of endogenous tryptophan. Our studies have shown that 3MA-resistant mutants linked to the tryptophan operon have a feedback-resistant anthranilate synthetase; mutants with an altered indole-3-glycerol phosphate synthetase were not found. 3MA or 7-methylindole can be metabolized to 7-methyltryptophan, and 3MA, 7-methylindole, and 7-methyltryptophan lead to derepression of the tryptophan operon. Furthermore, 3MA-resistant mutants are also resistant to 7-methylindole derepression. These results strongly suggest that the primary cause of derepression by 3MA is through its conversion to 7-methyltryptophan, which can inhibit anthranilate synthetase, thereby decreasing the concentration of endogenous tryptophan. Unlike 5- or 6-methyltryptophan, 7-methyltryptophan does not appear to function as an active corepressor.
D003470:Culture Media; D004794:Enzyme Repression / Q000187:drug effects; D004926:Escherichia coli / Q000201:enzymology* / Q000254:growth & development; D005990:Glycerol / Q000378:metabolism; D007211:Indoles / Q000378:metabolism; D007700:Kinetics; D008025:Ligases; D008967:Molecular Biology; D009154:Mutation; D009876:Operon; D010429:Pentoses / Q000378:metabolism; D010710:Phosphates / Q000378:metabolism; D014316:Tritium; D014364:Tryptophan / Q000096:biosynthesis / Q000378:metabolism*; D062367:ortho-Aminobenzoates / Q000032:analysis / Q000378:metabolism*
D003470:Culture Media; D007211:Indoles; D010429:Pentoses; D010710:Phosphates; D062367:ortho-Aminobenzoates; D014316:Tritium; D014364:Tryptophan; D008025:Ligases; D005990:Glycerol