The overall aim of this research project is to define the molecular mechanisms involved in iron-mediated regulation of gene expression in Escherichia coli, using the complex genetic system encoding components responsible for the biosynthesis (ent), transport (fep) and iron removal (fes) this 22 kb gene cluster is now characterized; the six ent biosynthesis genes, fes five fep transport genes, and three genes of unknown function are arranged as four polycistronic and two monocistronic operons, the expression of which are controlled by three bidirectional promoter operation regions that interact with the repressor molecule, Fe(II)-Fur. The objectives of the current study are: (i) to continue the molecular analysis of nucleotide sequences required for iron-controlled expression of ent-fep region genes and the interaction of these sequences with Fur and other regulatory factors; (ii) to continue examination of the role of untranslated leader regions of some of the mRNAs in the ultimate expression of these genes; and (iii) to investigate the regulation, localization and potential function of the fepE gene product, a membrane protein of as yet unknown function. In this last aim, we will pursue whether this protein, along with the products of the two other uncharacterized ent region genes (P43 and P15), function to control ent-fep gene expression in response to environmental fluctuations. %%% These studies will provide a molecular model for iron-mediated control of enterobactin gene expression as complex metabolic pathway requiring coordination between biosynthetic and transport components. In addition, they will provide a foundation for initiating a molecular investigation of the complex metabolic and regulatory interrelationships between the iron (Fur) region and other global stress response systems
