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Escherichia coli K-12 substr. MG1655 Pathway: L-histidine biosynthesis
Inferred from experiment

Pathway diagram: L-histidine biosynthesis

If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.

Locations of Mapped Genes:

Schematic showing all replicons, marked with selected genes

Genetic Regulation Schematic

Genetic regulation schematic for L-histidine biosynthesis

Superclasses: BiosynthesisAmino Acids BiosynthesisProteinogenic Amino Acids BiosynthesisL-histidine Biosynthesis

The pathway of histidine biosynthesis comprises ten reactions carried out by nine enzymes coded for by eight genes. There are nine free and one enzyme-bound intermediate. This complexity derives from the existence of three bifunctional proteins in the pathway as well as one holoenzyme composed of two separate gene products.

The overall regulation of the pathway stems from feedback inhibition of the first pathway step by the final product of the pathway, L-histidine.

The histidine biosynthesis pathway shares metabolites with the purine and nucleotide biosynthesis pathways. This affords the opportunity to connect synthesis of amino acids with the synthesis of nucleotides. The common metabolites are PRPP (which is also fundamental to intermediate metabolism), and 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR).

Superpathways: superpathway of histidine, purine, and pyrimidine biosynthesis

Revised 10-Oct-2008 by Caspi R, SRI International
Last-Curated 22-Aug-2007 by Shearer A, SRI International

References Related to Enzymes, Genes, Subpathways, and Substrates of this Pathway

Adams54: Adams E (1954). "The enzymatic synthesis of histidine from histidinol." J Biol Chem 209(2);829-46. PMID: 13192138

Adams55: Adams E (1955). "L-Histidinal, a biosynthetic precursor of histidine." J Biol Chem 217(1);325-44. PMID: 13271397

Andorn82: Andorn N, Aronovitch J (1982). "Purification and properties of histidinol dehydrogenase from Escherichia coli B." J Gen Microbiol 128(3);579-84. PMID: 7042909

Barbosa02: Barbosa JA, Sivaraman J, Li Y, Larocque R, Matte A, Schrag JD, Cygler M (2002). "Mechanism of action and NAD+-binding mode revealed by the crystal structure of L-histidinol dehydrogenase." Proc Natl Acad Sci U S A 99(4);1859-64. PMID: 11842181

Beckler86: Beckler GS, Reeve JN (1986). "Conservation of primary structure in the hisI gene of the archaebacterium, Methanococcus vannielii, the eubacterium Escherichia coli, and the eucaryote Saccharomyces cerevisiae." Mol Gen Genet 204(1);133-40. PMID: 3018439

Bitar77: Bitar KG, Firca JR, Loper JC (1977). "Histidinol dehydrogenase from salmonella typhimurium and Escherichia coli. Purification, some characteristics and the amino acid sequence around a reactive thiol group." Biochim Biophys Acta 493(2);429-40. PMID: 329890

Brady73: Brady DR, Houston LL (1973). "Some properties of the catalytic sites of imidazoleglycerol phosphate dehydratase-histidinol phosphate phosphatase, a bifunctional enzyme from Salmonella typhimurium." J Biol Chem 1973;248(7);2588-92. PMID: 4349042

Brilli04: Brilli M, Fani R (2004). "Molecular evolution of hisB genes." J Mol Evol 58(2);225-37. PMID: 15042344

Bruni86: Bruni CB, Carlomagno MS, Formisano S, Paolella G (1986). "Primary and secondary structural homologies between the HIS4 gene product of Saccharomyces cerevisiae and the hisIE and hisD gene products of Escherichia coli and Salmonella typhimurium." Mol Gen Genet 1986;203(3);389-96. PMID: 3528746

Carlomagno88: Carlomagno MS, Chiariotti L, Alifano P, Nappo AG, Bruni CB (1988). "Structure and function of the Salmonella typhimurium and Escherichia coli K-12 histidine operons." J Mol Biol 1988;203(3);585-606. PMID: 3062174

Chiariotti86: Chiariotti L, Alifano P, Carlomagno MS, Bruni CB (1986). "Nucleotide sequence of the Escherichia coli hisD gene and of the Escherichia coli and Salmonella typhimurium hisIE region." Mol Gen Genet 1986;203(3);382-8. PMID: 3018428

Chumley81: Chumley FG, Roth JR (1981). "Genetic fusions that place the lactose genes under histidine operon control." J Mol Biol 145(4);697-712. PMID: 6267294

DallLarsen75: Dall-Larsen T, Fasold H, Klungsoyr L, Kryvi H, Meyer C, Ortanderl F (1975). "Affinity labelling to - SH groups in adenosine - triphosphate - phosphoribosyl transferase with the dinitrophenyl group from S-dinitrophenyl-6-mercaptopurine-riboside 5'-phosphate." Eur J Biochem 60(1);103-7. PMID: 1204631

DallLarsen76: Dall-Larsen T, Klungsoyr L (1976). "The binding of specific ligands to adenosine-triphosphate phosphoribosyltransferase." Eur J Biochem 69(1);195-201. PMID: 991855

Demin04: Demin OV, Goryanin II, Dronov S, Lebedeva GV (2004). "Kinetic model of imidazologlycerol-phosphate synthetase from Escherichia coli." Biochemistry (Mosc) 69(12);1324-35. PMID: 15627387

DiazMejia09: Diaz-Mejia JJ, Babu M, Emili A (2009). "Computational and experimental approaches to chart the Escherichia coli cell-envelope-associated proteome and interactome." FEMS Microbiol Rev 33(1);66-97. PMID: 19054114

Fujimori98: Fujimori K, Ohta D (1998). "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(1);275-83. PMID: 9733547

Gaudet10: Gaudet P, Livstone M, Thomas P (2010). "Annotation inferences using phylogenetic trees." PMID: 19578431

GOA01: GOA, MGI (2001). "Gene Ontology annotation based on Enzyme Commission mapping." Genomics 74;121-128.

GOA01a: GOA, DDB, FB, MGI, ZFIN (2001). "Gene Ontology annotation through association of InterPro records with GO terms."

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Please cite the following article in publications resulting from the use of EcoCyc: Nucleic Acids Research 41:D605-12 2013
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