The tryptophan operon of Salmonella typhimurium. Fine structure analysis by deletion mapping and abortive transduction.

HE general model proposed by JACOB and MONOD (1961) to explain the control of inducible and repressible enzymes in bacteria has received considerable support to date (AMES and MARTIN 1964). According to this hypothesis, the genetic elements controlling sequential biochemical reactions are clustered on a genetic map into units of regulation called operons. An operon consists of a group of structural genes under the control of a single L‘operator”, located at one end of the cluster. For a specific biochemical pathway the functional state of the operator is determined by its interaction with a repressor substance composed of the product of a topographically independent regulator gene and a substrate or product of the pathway. From their extensive studies of the histidine operon of Salmonella typhimurium, AMES and HARTMAN (1962, 1963) expanded the original model to account for the order of the structural genes in an operon and the phenomenon of polarity. The clustering of genetic elements controlling the biosynthesis of the amino acid tryptophan in S. typhimurium was first demonstrated by DEMEREC and HARTMAN (1956). Mutants blocked at different steps in the pathway were classified by growth responses and cross feeding tests for accumulation of intermediates into four closely linked groups: tryA-tryB-tryC-tryD. Their map order, with respect to a co-transducible cysB marker, was determined by three-point tests to be cysB, tryA-tryB-tryD-tryC (DEMEREC and HARTMAN 1956; BALBINDER 1962). Similar studies with Escherichia coli (YANOFSKY and LENNOX 1959) showed that both the biosynthetic pathway and the map order of the genes involved are identical in both organisms. Recent investigations with both E. coli (MATSUSHIRO et al. 1965) and S. typhimurium (BAUERLE and MARGOLIN 1965) have shown that the tryptophan structural genes constitute an operon with the “operator” located near o r within the structural gene for anthranilate synthetase, the first enzyme in the sequence. A detailed genetic and biochemical correlated study of the structure of the tryptophan operon along the lines followed by AMES and HARTMAN in their work with the histidine system seemed desirable as a first step in investigating the regulation of the tryptophan enzymes. Such a study has been made possible by