Aromatic biosynthesis. IV. Preferential conversion, in incompletely blocked mutants, of a common precursor of several metabolites.

Mutants of Escherichia coli have been isolated with blocks in a variety of reactions in aromatic biosynthesis. In addition to strains with single requirements for tyrosine, phenylalanine, tryptophan, and p-aminobenzoic acid, respectively, strains have been obtained with requirements for the first two, the first three, and all four of these compounds (Davis, 1950a). Moreover, most of the mutants with this quadruple requirement were found later to have an additional, relative requirement for a fifth compound, p-hydroxybenzoic acid (Davis, 1950b). Certain intermediates in the biosynthesis of these five aromatic metabolites have been recognized. Some of these multiple aromatic auxotrophs can respond to shikimic acid (a 3,4,5-trihydroxycyclohexene-1-carboxylic acid; cf. figure 1) as a substitute for their requirement for two or more aromatic metabolites (Davis, 1950a); others accumulate this compound in the culture medium (Davis, 1951a); and still others accumulate a precursor of shikimic acid, provisionally designated as compound X (Davis, 1951a), which has been isolated and identified as 5-dehydroshikimic acid (Salamon and Davis, 1951a, b). In the present paper the accumulations and nutritional responses of the 62 available multiple aromatic auxotrophs of several bacterial species will be summarized; and the double, triple, and quadruple auxotrophs of this series will be shown to be blocked in the same group of reactions as the quintuple auxotrophs. The differences in nutritional requirement will be shown to depend on (a) differences in the completeness of the genetic block, resulting in different limited rates of synthesis of a precursor, and (b) the preferential order in which this common precursor, when present in limited amounts, is converted to its various products. On the basis of these observations a general scheme of aromatic biosynthesis, accounting for the behavior of all these strains, will be proposed. This scheme will include, in addition to the compounds mentionied, a previously unrecognized intermediate, compound WV, and a previously unrecognized sixth metabolite derived from this series of intermediates. Finally, the nutritional requirements of the multiple aromatic auxotrophs will be shown to be at odds with the conclusion, based on inhibition analysis, that certain aromatic amino acids serve as precursors of others in E. coli.