Abstract.-Recent studies on repression of the enzymes for histidine biosynthesis in Salmonella typhimurium demonstrated that the kinetic pattern in which the enzymes become repressed is influenced by the state of the feedbacksensitive site of the first enzyme of the pathway (Kovach et al., J. Bacteriol., 97, 1283). In the present study we demonstrate that under certain conditions alteration of the feedback-sensitive site of the first enzyme prevents repression of the histidine operon. We conclude that the first enzyme plays a previously unrecognized role ill regulation of the histidine system.The pathway for histidine biosynthesis in Salmonella typhimurium consists of a series of ten reactions, each catalyzed by a specific enzyme.2-6 The genes which specify the structures of these enzymes, together with an operator gene, are localized in a small segment of the Salmonella chromosome known as the histidine operon.7-9 Extensive studies on regulation of the histidine system in Salmonella have shown that there are two different mechanisms by which histidine biosynthesis is regulated. One mechanism, feedback inhibition, involves inhibition of the enzyme (G enzyme) which catalyzes the first step of the pathway by the end product of the pathway, histidine.4 10-12 The other mechanism, repression and derepression, involves changes in the intracellular concentration of the enzymes for histidine biosynthesis.2' 7, 13-15 Repression and derepression are mediated by the intracellular level of His-tRNA.9 16-19 Whether His-tRNA acts alone or together with some other molecule(s), and whether it acts at the level of transcription or translation are not yet known.Recently, we proposed that in the histidine system the G enzyme has some influence on the repression process.1 The basis for this proposal was the finding that the kinetic pattern in which the enzymes for histidine biosynthesis become repressed is modified by the state of the feedback-sensitive site of the G enzyme.We now report studies in which alterations in the function of the feedbacksensitive site of the G enzyme completely prevent repression of the histidine operon. Materials and Mlethods.-The organisms employed in this study were the LT-2 (wildtype) strain of S. typhimurium and the following histidine auxotrophs derived from it: the nonpolar, "complete" mutants, hisG1102 hisIF135, hisGl109 hisIF135, hisIF135, and hisG52; and the "leaky" mutant, hisG1306. In addition we used the nonpolar, "complete" mutants, hisA3O and hisG70, which are derived from the LT-7 strain of S. typhimurium. All organisms were obtained from the collection of Dr. P. E. Hartman.Cells were routinely grown in minimal medium20 with glucose at 0.5% in 1 liter of culture medium in a 2-liter flask. The cultures were aerated vigorously in a New Brunswick 481

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