The Mechanism of Activation of the Lac Operon

Abstract

The lac operon consists of a cluster of genes found on the single chromosome of the bacterium Escherichia coli. Starting from one side the cluster contains a promoter, an operator, the structural genes for β-galactosiäase, permease and thiogalactoside transacetylase.¹ Such a grouping of regulating and structural genes is termed an operon. In 1961 Jacob and Monod proposed a mechanism for the regulation of the activity of this operon. At this time no promoter region had been defined although no reasonable person would have denied that there must be preferred regions for the initiation of RNA synthesis. The Jacob-Monod mechanism proposed that a repressor molecule produced from a nearby ι gene forms a strong complex with the operator which prevents gene expression, i.e. RNA and protein synthesis. The complex can be broken by the low spontaneous rate of dissociation of the complex or more effectively by interceding of a small molecule inducer which is a derivative of lactose. It so happens that lactose is the natural substrate of the enzymes encoded by the operon indicating the immediate value of such a system of regulation. Thus if substrate is available for a certain class of enzymes, one produces the enzymes necessary for action on this substrate but not otherwise. Since the Jacob-Monod model was proposed, this negative control mechanism functioning between repressor and operator has been verified by direct isolation of the repressor and demonstration of its conditional affinity for operator both on purified DNA² and in in vitro systems for transcription and translation of lac messenger RNA.³