Function of hisF and hisH gene products in histidine biosynthesis.

A mutant of the enterobacterium Klebsiella pneumoniae with a defect in the hisF gene (in the histidine biosynthesis pathway) was isolated, which can only grow with high but not low ammonia concentrations. The mutated hisF product can use ammonia for the formation of the imidazole ring of histidine but not glutamine provided by the hisH product. Site-directed insertional mutagenesis of hisH led to the same dependence of prototrophic growth on high ammonia levels. The nucleotide sequence of K. pneumoniae hisF is almost identical to that of hisF from other enterobacteria. Similarities of the hisF product with the hisA product and of HisH sequences with the glutamine binding domains of TrpG-type amidotransferases provide additional evidence for the functions of the hisF and hisH products in histidine biosynthesis, namely that HisF catalyzes the ammonolytic cleavage of N'-(5'-phosphoribulosyl)-formimino-5- aminoimidazole-4-carboxamide ribonucleotide either utilizing free ammonia or deriving the ammonia moiety from glutamine bound to HisH.