Histidine biosynthetic pathway and genes: structure, regulation, and evolution

Abstract

The essential amino acid histidine is synthesized by organisms belonging to the three cell domains Archaea, Bacteria, and Eukarya. The biosynthetic pathway appears to be the same in all the organisms irrespective 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 subject to multiple and tight control mechanisms which have been studied in detail in only a few species: Salmonella typhimurium, Escherichia coli, and Saccharomyces cerevisiae. In S. typhimurium and E. coli, the biosynthetic pathway is specifically controlled in response to the availability of histidine by two distinct mechanisms: (i) enzymatic feedback inhibition and (ii) transcription attenuation. In addition, the system is responsive to metabolic control. Moreover, a nonspecific mechanism operating during the elongation step of transcription has been proposed to modulate tire levels of transcription in response to the rate of protein synthesis. Finally, it has been recently discovered that his operon expression is regulated posttranscriptionally by a complex mechanism of segmental stabilization of regions of the native message. The cloning and sequencing of more than 60 his genes in more than 20 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 important role in shaping the pathway in the early stages of molecular evolution and also in its evolution in different microorganisms. Aside freom the intrinsic importance of this metabolic pathway, this system fins been and is widely used to investigate fundamental aspects of molecular and cellular biology.