Role of 4-aminoimidazole-5-carboxamide in purine synthesis by Escherichia coli.

In a previous communication (1) it has been shown that the accumulation of 4-aminoimidazole-5-carboxamide (“amine”) in sulfadiazine-inhibited Escherichia coli is suppressed by the addition of methionine and catalytic quantities of p-aminobenzoic acid (PABA), and it was assumed that the “labile methyl” group of the sulfur-containing amino acid is used, with the help of PABA as carrier, for the completion of the “amine” structure to the purine skeleton. The implication that the “amine” is a precursor of the purines still required experimental proof. In the present investigation, an attempt was made to solve the question by the use of purine-requiring mutants of E. coli. If it could be shown that these mutants respond to the “amine” in a similar manner as to purines, it could be concluded that the “amine” is converted into purines. This is, indeed, the case. The utility of 4-formamidoimidazole-5carboxamide, 4 acetamidoimidazoled-carboxamide, formamidomalonamidamidine hydrochloride, and aminomalonamidamidine dihydrochloride as precursors of the purine bases also was tested, and the effect of PABA, folic acid, and vitamin Blz on the biosynthesis of the purines was studied. Some of the results have been briefly reported elsewhere (2).