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MetaCyc Pathway: chorismate biosynthesis I

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

Synonyms: aromatic amino acid biosynthesis, shikimate pathway

Superclasses: Biosynthesis Aromatic Compounds Biosynthesis Chorismate Biosynthesis
Superpathways

Some taxa known to possess this pathway include ? : Arabidopsis thaliana col Inferred from experiment [Tzin12], Bacillus subtilis , Escherichia coli K-12 substr. MG1655 , Haemophilus influenzae Rd KW20 , Petunia x hybrida , Saccharomyces cerevisiae , Salmonella enterica enterica serovar Typhimurium , Toxoplasma gondii

Expected Taxonomic Range: Apicomplexa , Ascomycota , Bacillariophyta , Bacteria , Basidiomycota , Chlorophyta , Euglenozoa , Nephridiophagidae , Oomycetes , Rhodophyta , Viridiplantae

Summary:
Chorismate is an important intermediate that leads to the biosyntrhesis of several essential metabolites, including the aromatic amino acids L-phenylalanine, L-tyrosine and L-tryptophan, vitamins E and K, ubiquinone and certain siderophores [Hoch73, Editors93, Bentley90].

In this pathway, which is often referred to as the shikimate pathway, chorismate is synthesized from the central metabolite D-erythrose 4-phosphate. The pathway is found in prokaryotes (mostly bacteria) and several eukaryotes, including ascomycete fungi, apicomplexans, plants and algae [Richards06]. The presence of the pathway in many parasites and pathogens, but not in metazoa, makes it a prime drug target [Dias07]. The broad-spectrum systemic herbicide glyphosate, which is used to kill weeds (known best under the tradename Roundup) is an inhibitor of the enzyme 5-enolpyruvylshikimate-3-phosphate synthase (EC 2.5.1.19), which catalyzes a reaction in the pathway (the condensation of shikimate 3-phosphate and phosphoenolpyruvate to form 5-enolpyruvyl-shikimate 3-phosphate).

The organization and structure of the shikimate pathway enzymes varies between taxonomic groups [Coggins87], with a differential distribution of fused genes. In most prokaryotes the seven shikimate pathway enzymes are encoded as separate polypeptides. The plant enzymes (which are nucleus encoded, but assumed to function within the plastid) are also encoded as separate polypeptides, with the exception of AroD and AroE that have fused to a single bifunctional polypeptide. In contrast, all fungi, as well as the apicomplexan Toxoplasma gondii, possess a pentafunctional supergene which includes conserved domains homologous to the genes (in fusion order) AroB, AroA, AroL/K, AroD, and AroE [Duncan87, Campbell04].

In Escherichia coli, the first reaction in the pathway is catalyzed by three separate enzymes, each of which is subject to feedback inhibition by one of the three amino acids that are synthesized from chorismate - L-phenylalanine, L-tyrosine and L-tryptophan. The enzyme subject to regulation by tryptophan (encoded by aroH) cannot be inhibited more than 60 percent, ensuring that sufficient enzymatic activity is present to permit synthesis of the other four metabolites synthesized from chorismate even in the presence of all three amino acids [Pittard04].

Superpathways: superpathway of tryptophan biosynthesis , superpathway of tyrosine biosynthesis , superpathway of phenylalanine biosynthesis , superpathway of phenylalanine, tyrosine, and tryptophan biosynthesis , superpathway of chorismate metabolism

Subpathways: chorismate biosynthesis from 3-dehydroquinate , 3-dehydroquinate biosynthesis I

Variants: chorismate biosynthesis II (archaea)

Unification Links: EcoCyc:ARO-PWY

Credits:
Revised 09-May-2006 by Ingraham JL , UC Davis
Revised 04-Aug-2009 by Caspi R , SRI International


References

Bentley90: Bentley R (1990). "The shikimate pathway--a metabolic tree with many branches." Crit Rev Biochem Mol Biol 25(5);307-84. PMID: 2279393

Campbell04: Campbell SA, Richards TA, Mui EJ, Samuel BU, Coggins JR, McLeod R, Roberts CW (2004). "A complete shikimate pathway in Toxoplasma gondii: an ancient eukaryotic innovation." Int J Parasitol 34(1);5-13. PMID: 14711585

Coggins87: Coggins JR, Duncan K, Anton IA, Boocock MR, Chaudhuri S, Lambert JM, Lewendon A, Millar G, Mousdale DM, Smith DD (1987). "The anatomy of a multifunctional enzyme." Biochem Soc Trans 15(4);754-9. PMID: 2824247

Dias07: Dias MV, Ely F, Palma MS, de Azevedo WF, Basso LA, Santos DS (2007). "Chorismate synthase: an attractive target for drug development against orphan diseases." Curr Drug Targets 8(3);437-44. PMID: 17348836

Duncan87: Duncan K, Edwards RM, Coggins JR (1987). "The pentafunctional arom enzyme of Saccharomyces cerevisiae is a mosaic of monofunctional domains." Biochem J 246(2);375-86. PMID: 2825635

Editors93: Editors: Abraham L. Sonenshein, James A. Hoch, Richard Losick (1993). "Bacillus subtilis and Other Gram-Positive Bacteria: Biochemistry, Physiology, and Molecular Genetics." American Society For Microbiology, Washington, DC 20005.

Hoch73: Hoch JA, Nester EW (1973). "Gene-enzyme relationships of aromatic acid biosynthesis in Bacillus subtilis." J Bacteriol 116(1);59-66. PMID: 4200844

Pittard04: Pittard, J., Yang, J. (2004). "Biosynthesis of Phenylalanine and Tyrosine." Escherichia Coli and Salmonella Typhimurium: Cellular and Molecular Biology 3.6.1.8.

Richards06: Richards TA, Dacks JB, Campbell SA, Blanchard JL, Foster PG, McLeod R, Roberts CW (2006). "Evolutionary origins of the eukaryotic shikimate pathway: gene fusions, horizontal gene transfer, and endosymbiotic replacements." Eukaryot Cell 5(9);1517-31. PMID: 16963634

Tzin12: Tzin V, Malitsky S, Zvi MM, Bedair M, Sumner L, Aharoni A, Galili G (2012). "Expression of a bacterial feedback-insensitive 3-deoxy-d-arabino-heptulosonate 7-phosphate synthase of the shikimate pathway in Arabidopsis elucidates potential metabolic bottlenecks between primary and secondary metabolism." New Phytol. PMID: 22296303

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

AbdelMeguid85: Abdel-Meguid SS, Smith WW, Bild GS (1985). "Crystallization of 5-enolpyruvylshikimate 3-phosphate synthase from Escherichia coli." J Mol Biol 186(3);673. PMID: 3912512

Adachi08: Adachi O, Ano Y, Toyama H, Matsushita K (2008). "A novel 3-dehydroquinate dehydratase catalyzing extracellular formation of 3-dehydroshikimate by oxidative fermentation of Gluconobacter oxydans IFO 3244." Biosci Biotechnol Biochem 72(6);1475-82. PMID: 18540103

Akowski97: Akowski JP, Bauerle R (1997). "Steady-state kinetics and inhibitor binding of 3-deoxy-D-arabino-heptulosonate-7-phosphate synthase (tryptophan sensitive) from Escherichia coli." Biochemistry 1997;36(50);15817-22. PMID: 9398312

Anderson88: Anderson KS, Sikorski JA, Johnson KA (1988). "Evaluation of 5-enolpyruvoylshikimate-3-phosphate synthase substrate and inhibitor binding by stopped-flow and equilibrium fluorescence measurements." Biochemistry 1988;27(5);1604-10. PMID: 3284585

Anton88: Anton IA, Coggins JR (1988). "Sequencing and overexpression of the Escherichia coli aroE gene encoding shikimate dehydrogenase." Biochem J 1988;249(2);319-26. PMID: 3277621

Arifuzzaman06: Arifuzzaman M, Maeda M, Itoh A, Nishikata K, Takita C, Saito R, Ara T, Nakahigashi K, Huang HC, Hirai A, Tsuzuki K, Nakamura S, Altaf-Ul-Amin M, Oshima T, Baba T, Yamamoto N, Kawamura T, Ioka-Nakamichi T, Kitagawa M, Tomita M, Kanaya S, Wada C, Mori H (2006). "Large-scale identification of protein-protein interaction of Escherichia coli K-12." Genome Res 16(5);686-91. PMID: 16606699

Baasov89: Baasov T, Knowles JR (1989). "Is the first enzyme of the shikimate pathway, 3-deoxy-D-arabino-heptulosonate-7-phosphate synthase (tyrosine sensitive), a copper metalloenzyme?." J Bacteriol 171(11);6155-60. PMID: 2572582

Bairoch93a: Bairoch A, Boeckmann B (1993). "The SWISS-PROT protein sequence data bank, recent developments." Nucleic Acids Res. 21:3093-3096. PMID: 8332529

Benach03: Benach J, Lee I, Edstrom W, Kuzin AP, Chiang Y, Acton TB, Montelione GT, Hunt JF (2003). "The 2.3-A crystal structure of the shikimate 5-dehydrogenase orthologue YdiB from Escherichia coli suggests a novel catalytic environment for an NAD-dependent dehydrogenase." J Biol Chem 278(21);19176-82. PMID: 12624088

Bender89: Bender SL, Mehdi S, Knowles JR (1989). "Dehydroquinate synthase: the role of divalent metal cations and of nicotinamide adenine dinucleotide in catalysis." Biochemistry 28(19);7555-60. PMID: 2514789

Berlyn69: Berlyn MB, Giles NH (1969). "Organization of enzymes in the polyaromatic synthetic pathway: separability in bacteria." J Bacteriol 99(1);222-30. PMID: 4979440

Berti09: Berti PJ, Chindemi P (2009). "Catalytic residues and an electrostatic sandwich that promote enolpyruvyl shikimate 3-phosphate synthase (AroA) catalysis." Biochemistry 48(17);3699-707. PMID: 19271774

Bondinell71: Bondinell WE, Vnek J, Knowles PF, Sprecher M, Sprinson DB (1971). "On the mechanism of 5-enolpyruvylshikimate 3-phosphate synthetase." J Biol Chem 1971;246(20);6191-6. PMID: 4942558

Bornemann00: Bornemann S, Theoclitou ME, Brune M, Webb MR, Thorneley RN, Abell C (2000). "A Secondary beta Deuterium Kinetic Isotope Effect in the Chorismate Synthase Reaction." BIO-ORGANIC CHEMISTRY 28(4);191-204. PMID: 11034781

Bornemann02: Bornemann S (2002). "Flavoenzymes that catalyse reactions with no net redox change." Nat Prod Rep 19(6);761-72. PMID: 12521268

Bornemann95: Bornemann S, Balasubramanian S, Coggins JR, Abell C, Lowe DJ, Thorneley RN (1995). "Escherichia coli chorismate synthase: a deuterium kinetic-isotope effect under single-turnover and steady-state conditions shows that a flavin intermediate forms before the C-(6proR)-H bond is cleaved." Biochem J 305 ( Pt 3);707-10. PMID: 7848266

Bornemann95a: Bornemann S, Ramjee MK, Balasubramanian S, Abell C, Coggins JR, Lowe DJ, Thorneley RN (1995). "Escherichia coli chorismate synthase catalyzes the conversion of (6S)-6-fluoro-5-enolpyruvylshikimate-3-phosphate to 6-fluorochorismate. Implications for the enzyme mechanism and the antimicrobial action of (6S)-6-fluoroshikimate." J Biol Chem 270(39);22811-5. PMID: 7559411

Bornemann96: Bornemann S, Lowe DJ, Thorneley RN (1996). "The transient kinetics of Escherichia coli chorismate synthase: substrate consumption, product formation, phosphate dissociation, and characterization of a flavin intermediate." Biochemistry 35(30);9907-16. PMID: 8703965

Bornemann96a: Bornemann S, Lowe DJ, Thorneley RN (1996). "Escherichia coli chorismate synthase." Biochem Soc Trans 24(1);84-8. PMID: 8674765

BRENDA14: BRENDA team (2014). "Imported from BRENDA version existing on Aug 2014." http://www.brenda-enzymes.org.

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Report Errors or Provide Feedback
Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
Page generated by SRI International Pathway Tools version 18.5 on Sat Nov 22, 2014, biocyc14.