Integrated response to inducers by communication between a catabolic pathway and its regulatory system

Department of Biología Molecular e Ingeniería Bioquímica and Centro Andaluz de Biología del Desarrollo, Universidad Pablo de Olavide-CSIC, Ctra. Utrera, Km. 1. 41013-Sevilla, SPAIN

^* To whom correspondence should be addressed. Email: esansan{at}upo.es.

	Abstract

Efficient gene regulation of metabolic pathways implies that the profile of molecules inducing the pathway matches that of the molecules that are metabolized. Gratuitous induction, a well-known phenomenon in catabolic pathways, is the consequence of having differences in the substrate and inducer profiles. This phenomenon is particularly evident in biodegradation pathways of organic contaminants that can be induced by a variety of molecules similar to the real substrates. Analysis of the regulation of tetralin biodegradation genes in mutant strains affected in each component of the initial dioxygenase enzymatic complex indicated that the response of the regulatory system to potential inducers is differently altered, depending on the mutated component. Based on the expression phenotype of a number of single or double mutants, we propose a model that represents an unprecedented way of communication between a catabolic pathway and its regulatory system to prevent efficient induction by a molecule that is not a real substrate. This communication allows a better fit of the substrate and inducer profiles, thus minimizing gratuitous induction, without need of optimal co-evolution to match the specificity of catabolic enzymes and their regulatory systems. Modulation of the regulatory system in this way not only provides a more appropriate response to potential inducers recognized by the regulatory system but, in turn, it may also properly adjust the gene expression levels to the substrate availability.