In bacteria the biosynthetic pathway for histidine involves the series of reactions depicted below. The first intermediate of the pathway (phosphoribosyl pyrophosphate) is also the starting point for purine and pyrimidine biosynthesis.

Recently, Ohta et al (2000) have cloned and characterized ATP-phosphoribosytransferase [EC 2.4.2.17] (the first key enzyme in the histidine biosynthetic pathway) from Arabidopsis. The enzyme exists in two isoforms encoded by separate genes (AtATP-PRT1 and AtATP-PRT2); these share 74.6% overall amino acid identity and both contain N-terminal chloroplast transit peptide sequences (Ohta et al, 2000). The recombinant AtATP-PRTs are inhibited by L-His (50% inhibition of initial activity = 40-320 micromolar), suggesting that His biosynthesis is regulated through feedback inhibition (Ohta et al, 2000).

Fujimori and Ohta (1998b) reported isolation of a histidine biosynthetic gene (At-IE) in Arabidopsis encoding a polypeptide with two separate domains for phosphoribosyl-ATP pyrophosphohydrolase (also known as phosphoribosyl-ATP pyrophosphatase [EC 3.6.1.31]) and phosphoribosyl-AMP cyclohydrolase [EC 3.5.4.19]; the 2nd and 3rd enzymatic steps in the histidine pathway. This was achieved by complementation of the hisI mutation of E. coli, defective in the cyclohydrolase activity. The bifunctional At-IE gene has a N-terminal extension with the properties of a chloroplast transit peptide.

The gene encoding N-(5'-phospho-D-ribosylformimino)-5-amino-1-(5''-phosphoribosyl)-4-imidazole carboxamide isomerase [EC 5.3.1.16] (also known as N'-[(5'-phosphoribosyl)-formimino]-5-aminoimidazole-4-carboxamide ribonucleotide (BBM II) isomerase) [the 4th enzyme of the histidine pathway] has been cloned and characterized from Arabidopsis thaliana by functional complementation of the E. coli hisA (Fujimori et al, 1998). The isolated cDNA encodes a polypeptide of 304 amino acids with a calculated molecular weight of 33,363 and contains an N-terminal chloroplast transit sequence.

In Arabidopsis the 5th and 6th enzymes of the histidine pathway (glutamine amidotransferase and cyclase) are encoded by a single cDNA (Fujimori and Ohta, 1998a). In the above scheme, the combined enzyme activity of glutamine amidotransferase/cyclase is referred to as "glutamine amidotransferase". These combined activities are also referred to as "imidazoleglycerol-phosphate synthase"; EC numbers do not appear to have been assigned to these enzymes.

cDNAs encoding imidazoleglycerol-phosphate dehydratase (IGPD) [EC 4.2.1.19] have been isolated from wheat and Arabidopsis (Tada et al, 1994; 1995; Mori et al, 1995). The Arabidopsis genome appears to contain two genes encoding IGPD (Tada et al, 1994). In both wheat and Arabidopsis, IGPD is produced with an N-terminal chloroplast transit peptide which is cleaved to produce the mature form of the enzyme.

A cDNA sequence encoding histidinol-phosphate aminotransferase [EC 2.6.1.9] (HPA) has been isolated from Nicotiana tabacum by complementation of an Escherichia coli histidine auxotroph defective in this activity (El Malki et al, 1998). The predicted protein contains a chloroplast transit peptide sequence at the N-terminal end (El Malki et al, 1998). The mature HPA protein has an apparent molecular mass of about 40 kDa. Southern analysis indicates the presence of at least two genes per haploid genome coding for HPA in Nicotiana sp. (El Malki et al, 1998).

In contrast to Salmonella, where (IGPD) [EC 4.2.1.19] and histidinol phosphatase [EC 3.1.3.15] are embodied in a single protein (encoded by the hisB gene), the plant IGPD is devoid of histidinol phosphatase activity. This resembles the situation in Saccharomyces where IGPD does not harbor histidinol phosphatase activity. These activities are encoded by 2 separate genes his2 and his3, respectively, in Saccharomyces. The plant IGPD has a mol. wt. of about 600,000 - 670,000 daltons (Mato et al, 1993).

Histidinol dehydrogenase [EC 1.1.1.23] was purified and its cDNA cloned from cabbage (Nagai and Scheidegger, 1991; Nagai et al, 1991).

A novel lysine- and histidine-specific amino acid transporter has recently been described in Arabidopsis (Chen and Bush, 1997). This transporter is distinct from other amino acid transporters characterized thus far, including the high affinity cationic amino acid transporter (Frommer et al, 1995).

El Malki F, Frankard V, Jacobs M 1998 Molecular cloning and expression of a cDNA sequence encoding histidinol phosphate aminotransferase from Nicotiana tabacum. Plant Mol. Biol. 37: 1013-1022.

Frommer WB, Hummel S, Unseld M, Ninneman O 1995 Seed and vascular expression of a high affinity transporter for cationic amino acids in Arabidopsis. Proc. Natl. Acad. Sci. U.S.A. 92: 12036-12040.

Fujimori K, Ohta D 1998a An Arabidopsis cDNA encoding a bifunctional glutamine amidotransferase/cyclase suppresses the histidine auxotrophy of a Saccharomyces cerevisiae his7 mutant. FEBS Lett. 428: 229-234.

Fujimori K, Ohta D 1998b Isolation and characterization of a histidine biosynthetic gene in Arabidopsis encoding a polypeptide with two separate domains for phosphoribosyl-ATP pyrophosphohydrolase and phosphoribosyl-AMP cyclohydrolase. Plant Physiol. 118: 275-283.

Fujimori K, Tada S, Kanai S, Ohta D 1998 Molecular cloning and characterization of the gene encoding N'-[(5'-phosphoribosyl)-formimino]-5-aminoimidazole-4-carboxamide ribonucleotide (BBM II) isomerase from Arabidopsis thaliana. Mol. Gen. Genet. 259: 216-223.

Mato J, Hatano M, Koizumi S, Tada S, Hashimoto M, Scheidegger A 1993 Purification and properties of a monofunctional IGPD from wheat. Plant Physiol. 103: 733-739.

Mori I, Fonne-Pfister R, Matsunaga S-I, Tada S, Kimura Y, Iwasaki G, Mano J-I, Hatano M, Nakano T, Koizumi S-I, Scheidegger A, Hayakawa K, Ohya D 1995 A novel class of herbicides: specific inhibitors of imidazoleglycerol phosphate dehydratase. Plant Physiol. 107: 719-723.

Nagai A, Scheidegger A 1991 Purification and characterization of histidinol dehydrogenase from cabbage. Arch. Biochem. Biophys. 284: 127-132.

Nagai A, Ward E, Beck J, Tada S, Chang J-Y, Scheidegger A, Ryals J 1991 Structural and functional conservation of histidinol dehydrogenase between plants and microbes. Proc. Natl. Acad. Sci. U.S.A. 88: 4133-4137.

Ohta D, Fujimori K, Mizutani M, Nakayama Y, Kunpaisal-Hashimoto R, Munzer S, Kozaki A 2000 Molecular cloning and characterization of ATP-phosphoribosyl transferase from Arabidopsis, a key enzyme in the histidine biosynthetic pathway. Plant Physiol. 122: 907-914.

Tada S, Hatano M, Nakayama Y, Volrath S, Guyer D, Ward E, Ohta D 1995 Insect cell expression of recombinant imidazoleglycerolphosphate dehydratase of Arabidopsis and wheat and inhibition by triazole herbicides. Plant Physiol. 109: 153-159.

Tada S, Volrath S, Guyer D, Scheidegger A, Ryals J, Ohta D, Ward E 1994 Isolation and characterization of cDNAs encoding imidazoleglycerolphosphate dehydratase from Arabidopsis thaliana. Plant Physiol. 105: 579-583.