Suppression of a deletion mutation in the glutamine amidotransferase region of the Salmonella typhimurium trpD gene by mutations in pheA and tyrA.
Prototrophic revertants of a trpD deletion mutant that lacks the glutamine amidotransferase domain of the bifunctional component II subunit of the anthranilate synthetase-phosphoribosyltransferase complex have been found to arise by the occurrence of sublethal missense mutations in either the pheA or tyrA loci. Such suppressor mutations were obtained directly by mutation of the wild-type pheA gene as well as indirectly by partial reversion of a variety of nonleaky pheA and tyrA mutations. The suppressor strains have only a portion of the normal level of the pheA or tyrA enzyme activity and thus experience a partial limitation in the synthesis of phenylalanine or tyrosine. This limitation leads to a relaxation of end-product regulation of the phenylalanine- or tyrosine-specific enzymes of the common aromatic pathway and to the overproduction of the branch point intermediate, chorismic acid, which is one of the substrates of the anthranilate synthetase reaction. It is proposed that the high intracellular level of chorismic acid acts to elevate the non-physiological NH3-dependent anthranilate synthetase activity of the component I subunit, thereby eliminating the need for the glutamine amidotransferase activity of the component II subunit. Consistent with this is the finding that phenylalanine and tyrosine are specific inhibitors of growth of the pheA and tyrA suppressor strains, respectively, causing a shutdown of the overproduction of chorismic acid by reestablishing normal end-product control of the common pathway.
D000877:Anthranilate Phosphoribosyltransferase / Q000235:genetics*; D000878:Anthranilate Synthase / Q000235:genetics*; D002827:Chorismic Acid / Q000378:metabolism; D002874:Chromosome Mapping; D002876:Chromosomes, Bacterial; D005796:Genes; D005973:Glutamine; D009154:Mutation; D010430:Pentosyltransferases / Q000235:genetics*; D010649:Phenylalanine / Q000494:pharmacology; D012486:Salmonella typhimurium / Q000235:genetics*; D013489:Suppression, Genetic; D014166:Transferases / Q000235:genetics*
D005973:Glutamine; D010649:Phenylalanine; D014166:Transferases; D010430:Pentosyltransferases; D000877:Anthranilate Phosphoribosyltransferase; D000878:Anthranilate Synthase; D002827:Chorismic Acid