Barona-Gómez Francisco, Hodgson David A
Department of Biological Sciences, University of Warwick, Gibbet Hill Road, Coventry CV4 7AL, UK.
EMBO Rep. 2003 Mar;4(3):296-300. doi: 10.1038/sj.embor.embor771.
We report the occurrence of an isomerase with a putative (betaalpha)(8)-barrel structure involved in both histidine and trypto-phan biosynthesis in Streptomyces coelicolor A3(2) and Mycobacterium tuberculosis HR37Rv. Deletion of a hisA homologue (SCO2050) putatively encoding N'-[(5'-phosphoribosyl)-formimino]-5 amino-imidazole-4-carboxamide ribonucleotide isomerase from the chromosome of S. coelicolor A3(2) generated a double auxotrophic mutant for histidine and tryptophan. The bifunctional gene SCO2050 and its orthologue Rv1603 from M. tuberculosis complemented both hisA and trpF mutants of Escherichia coli. Expression of the E. coli trpF gene in the S. coelicolor mutant only complemented the tryptophan auxo-trophy, and the hisA gene only complemented the histidine auxotrophy. The discovery of this enzyme, which has a broad-substrate specificity, has implications for the evolution of metabolic pathways and may prove to be important for understanding the evolution of the (betaalpha)(8)-barrels.
我们报道了在天蓝色链霉菌A3(2)和结核分枝杆菌HR37Rv中存在一种具有假定的(betaalpha)(8)-桶状结构的异构酶,该异构酶参与组氨酸和色氨酸的生物合成。从天蓝色链霉菌A3(2)染色体上缺失一个假定编码N'-[(5'-磷酸核糖基)-甲脒基]-5-氨基咪唑-4-甲酰胺核糖核苷酸异构酶的hisA同源物(SCO2050),产生了一个组氨酸和色氨酸双营养缺陷型突变体。来自结核分枝杆菌的双功能基因SCO2050及其直向同源物Rv1603补充了大肠杆菌的hisA和trpF突变体。在天蓝色链霉菌突变体中表达大肠杆菌trpF基因仅补充了色氨酸营养缺陷,而hisA基因仅补充了组氨酸营养缺陷。这种具有广泛底物特异性的酶的发现,对代谢途径的进化具有启示意义,并且可能被证明对理解(betaalpha)(8)-桶状结构的进化很重要。