Regulatory mutants of the tryptophan operon of Salmonella typhimurium.

HE tryptophan ( t rp) operon of Salmonella typhimurium consists of five Tstructural genes regulated as a unit by tryptophan (BLUME and BALBINDER 1966; BAUERLE and MARGOLIN 1966a, 196613; BLUME, WEBER and BALBINDER 1968). The biosynthetic reactions involved and the order of the genes (see Figure 1 ), as well as the regulation of the trp operon have been shown to be identical in Escherichia coli (ITO and CRAWFORD 1965; MATSUSHIRO et al. 1965; YANOFSKY and LENNOX 1959). Regulatory mutants which permit constitutive synthesis of the tryptophan enzymes have been isolated in E. coli by selecting for strains which are resistant to 5-methyltryptophan, a structural analogue of tryptophan (COHEN and JACOB 1959; HIRAGA 1969). In this paper we deal with the isolation and characterization of regulatory mutants for the trp operon of S. typhimurium. Constitutive mutants for the trp operon of Salmonella were obtained by selecting for resistance to either of two tryptophan analogues: 5-methyltryptophan or 6-fluorotryptophan, both of which inhibit bacterial growth. It has been known for some time that 5-methyltryptophan acts by inhibiting the activity of anthranilate synthetase (MOYED 1960). As we shall see, and as other workers have reported (ITo, HIRAGA and YURA 1969) this analogue as well as 6-fluorotryptophan is also capable of mimicking the role of tryptophan as a co-repressor. The regulatory mutants we have found have been classified into at least four different genetic groups, of which two correspond to regulatory mutations already described in E. coli and two belong to previously unreported classes.