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, w hich can only grow with high but not low ammonia concentrations. The m utated hisF product can use ammonia for the formation of the imidazole ring of histidine but not glutamine provided by the hisH product. Sit e-directed insertional mutagenesis of hisH led to the same dependence of prototrophic growth on high ammonia levels. The nucleotide sequence of g pneumoniae hisF is almost identical to that of hisF from other e nterobacteria. 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 ca talyzes the ammonolytic cleavage of ibulosyl)-formimino-5-aminoimidazo le-4-carboxamide ribonucleotide either utilizing free ammonia or deriv ing the ammonia moiety from glutamine bound to HisH.