Even though several different theories have been suggested, the origin and evolution of metabolic pathways is still an open question. The histidine metabolic pathway represents an optimal model system for the study of these events. The aim of this project is to study the histidine operon of E. coli, trying to demonstrate the existence of the compartmentalization of proteins involved in the same metabolic pathway and the formation of multi-enzymatic complexes in bacterial cells, and to deeply investigate the events that led to the evolution of this pathway such as gene duplication, gene elongation and gene fusion.