Possible regulation of the Salmonella typhimurium histidine operon by adenosine triphosphate phosphoribosyltransferase: large metabolic effects.

An effort to find growth conditions leading to conditional regulation of the histidine operon of Salmonella typhimurium by the allosteric first enzyme of the pathway, adenosine triphosphate phosphoribosyltransferase (EC 2.4.2.17), is reported. A strain deleting the enzyme, TR3343, behaved simply and predictably under all growth conditions, whereas histidine auxotrophs containing active enzyme behaved in complicated ways dependent upon the location of the histidine pathway lesion. hisE strains derepressed the operon only one-half as much as TR3343 when grown on limiting histidine and a poor carbon source, but they also grew more slowly, probably as a result of high N1-(5-phospho-beta-D-ribosyl)-adenosine triphosphate levels in the cell. hisC strains exhibited oscillatory growth behavior and oscillatory histidine operon expression when grown on intermediate concentrations of the histidine precursor histidinol. This behavior probably was caused by synergistic in-phase variations in the histidine, purine nucleotide, and ppGpp pools of the cell. All of the growth and histidine operon expression effects associated with the presence of adenosine triphosphate phosphoribosyltransferase could be assigned to metabolic perturbation of the cell caused by unregulated enzymatic activity.