HISTIDINE BIOSYNTHETIC-PATHWAY AND GENES - STRUCTURE, REGULATION, ANDEVOLUTION

The essential amino acid histidine is synthesized by organisms belongi ng to the three cell domains Archaea, Bacteria, and Eukarya. The biosy nthetic pathway appears to be the same in all the organisms irrespecti ve of complexity, and is a good example of the unity of biochemistry. Details of this process have only recently been elucidated. Because of the high metabolic cost for its synthesis, the histidine pathway is s ubject to multiple and tight control mechanisms which have been studie d in detail in only a few species: Salmonella typhimurium, Escherichia coli, and Saccharomyces cerevisiae. In S. typhimurium and E. coli, th e biosynthetic pathway is specifically controlled in response to the a vailability of histidine by two distinct mechanisms: (i) enzymatic fee dback inhibition and (ii) transcription attenuation. In addition, the system is responsive to metabolic control. Moreover, a nonspecific mec hanism operating during the elongation step of transcription has been proposed to modulate tire levels of transcription in response to the r ate of protein synthesis. Finally, it has been recently discovered tha t his operon expression is regulated posttranscriptionally by a comple x mechanism of segmental stabilization of regions of the native messag e. The cloning and sequencing of more than 60 his genes in more than 2 0 species has now made possible a detailed analysis of their structure , organization and evolution, revealing that major gene rearrangements (gene fusion, gene elongation, and gene duplication) have played an i mportant role in shaping the pathway in the early stages of molecular evolution and also in its evolution in different microorganisms. Aside from the intrinsic importance of this metabolic pathway, this system fins been and is widely used to investigate fundamental aspects of mol ecular and cellular biology.