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MetaCyc Pathway: chorismate biosynthesis from 3-dehydroquinate

Enzyme View:

This view shows enzymes only for those organisms listed below, in the list of taxa known to possess the pathway. If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.

Superclasses: Biosynthesis Aromatic Compounds Biosynthesis Chorismate Biosynthesis

Some taxa known to possess this pathway include ? : Bacillus subtilis , Escherichia coli K-12 substr. MG1655 , Haemophilus influenzae Rd KW20 , Methanocaldococcus jannaschii , Petunia x hybrida , Saccharomyces cerevisiae , Salmonella enterica enterica serovar Typhimurium , Sulfolobus solfataricus

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

Summary:
Background

In this pathway chorismate is synthesized from 3-dehydroquinate. The pathway is found in prokaryotes (both bacteria and archaea) and several eukaryotes, including ascomycete fungi, apicomplexans, plants and algae [Richards06]. However, it's starting point, 3-dehydroquinate, can be synthesized in different routes. In most microorganisms it is synthesized from D-erythrose 4-phosphate (see 3-dehydroquinate biosynthesis I), but the methanogens of the Euryarchaeota phylum utilize an alternative route [White04] (see 3-dehydroquinate biosynthesis II (archaea)).

Chorismate is an intermediate in the synthesis of the three aromatic amino acids: L-phenylalanine, L-tyrosine and L-tryptophan. These amino acids serve as substrates in other pathways for secondary metabolites such as alkaloids, flavonoids, lignin, coumarin, indole derivatives and other phenolic compounds [Tzin12].

Shikimate is an important intermediate in the chorismate biosynthetic pathway. It was first isolated from Japanese star anise. Shikimate is used for the production of some antiviral drugs used to halt the spread of the flu virus, but as a biosynthetic intermediate, it is usually not found in high concentrations in organisms. Shikimate can be easily harvested from the needles of several species of pine trees, and biosynthetic pathways in Escherichia coli have been enhanced to obtain sufficient amounts of the metabolite for commercial use.

About this Pathway

3-deoxy-d-arabino-heptulosonate 7-phosphate synthase (DAHP synthase) catalyzes the condensation of phosphoenolpyruvate and D-erythrose 4-phosphate to form 3-deoxy-D-arabino-heptulosonate-7-phosphate (DAHP). It is a crucial enzyme that controls flux through the chorismate pathway in plants [Tzin12]. Three different isoforms of the enzyme encoded by aroF, aroG and aroH are expressed in Escherichia coli and these enzymes are subject to feedback inhibition by the aromatic amino acids produced [Brown68].

3-dehydroquinate synthase catalyzes the transformation of DAHP to 3-dehydroquinate (DHQ). While this reaction requires NAD as a cofactor, there is no net use of NAD as the reaction regenerates it. 3-dehydroquinate dehydratase hydrolyzes DHQ to 3-dehydroshikimate which is subsequently reduced to shikimate by shikimate dehydrogenase. Shikimate kinase catalyzes the fifth reaction in chorismate biosynthesis. The kinase forms a complex with the bifunctional DAHP synthase-chorismate mutase enzyme. The complex may serve as a regulatory unit [Huang75, Editors93].

5-enolpyruvoylshikimate-3-phosphate synthase catalyzes the penultimate step in chorismate biosynthesis. The synthase is activated by ammonium ions and exhibits allosteric behavior. Glyphosate (N-phosphonomethyl glycine) acts as a competitive inhibitor with respect to PEP and as a partial uncompetitive inhibitor with respect to shikimate 3-P [Fischer87, Majumder95, Selvapandiyan95].

Chorismate synthase acts in the shikimate pathway. It catalyses the conversion of 5-enolpyruvylshikimate 3-phosphate into chorismate, the key branch-point intermediate in aromatic biosynthesis.

Superpathways: chorismate biosynthesis II (archaea) , chorismate biosynthesis I , superpathway of tryptophan biosynthesis , superpathway of tyrosine biosynthesis , superpathway of phenylalanine biosynthesis , superpathway of phenylalanine, tyrosine, and tryptophan biosynthesis , superpathway of chorismate metabolism

Unification Links: EcoCyc:PWY-6163

Credits:
Created 17-Mar-2009 by Caspi R , SRI International
Revised 05-Mar-2012 by Weerasinghe D , SRI International


References

Brown68: Brown KD (1968). "Regulation of aromatic amino acid biosynthesis Escherichia coli K12." Genetics 60(1);31-48. PMID: 4884590

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.

Fischer87: Fischer RS, Rubin JL, Gaines CG, Jensen RA (1987). "Glyphosate sensitivity of 5-enol-pyruvylshikimate-3-phosphate synthase from Bacillus subtilis depends upon state of activation induced by monovalent cations." Arch Biochem Biophys 1987;256(1);325-34. PMID: 3111378

Huang75: Huang L, Montoya AL, Nester EW (1975). "Purification and characterization of shikimate kinase enzyme activity in Bacillus subtilis." J Biol Chem 1975;250(19);7675-81. PMID: 170268

Majumder95: Majumder K, Selvapandiyan A, Fattah FA, Arora N, Ahmad S, Bhatnagar RK (1995). "5-Enolpyruvylshikimate-3-phosphate synthase of Bacillus subtilis is an allosteric enzyme. Analysis of Arg24-->Asp, Pro105-->Ser and His385-->Lys mutations suggests a hidden phosphoenolpyruvate-binding site." Eur J Biochem 1995;229(1);99-106. PMID: 7744055

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

Selvapandiyan95: Selvapandiyan A, Majumder K, Fattah FA, Ahmad S, Arora N, Bhatnagar RK (1995). "Point mutation of a conserved arginine (104) to lysine introduces hypersensitivity to inhibition by glyphosate in the 5-enolpyruvylshikimate-3-phosphate synthase of Bacillus subtilis." FEBS Lett 1995;374(2);253-6. PMID: 7589547

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

White04: White RH (2004). "L-Aspartate semialdehyde and a 6-deoxy-5-ketohexose 1-phosphate are the precursors to the aromatic amino acids in Methanocaldococcus jannaschii." Biochemistry 43(23);7618-27. PMID: 15182204

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

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

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

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.

Charles90: Charles IG, Lamb HK, Pickard D, Dougan G, Hawkins AR (1990). "Isolation, characterization and nucleotide sequences of the aroC genes encoding chorismate synthase from Salmonella typhi and Escherichia coli." J Gen Microbiol 1990;136 ( Pt 2);353-8. PMID: 2182772

Chatfield92: Chatfield SN, Fairweather N, Charles I, Pickard D, Levine M, Hone D, Posada M, Strugnell RA, Dougan G (1992). "Construction of a genetically defined Salmonella typhi Ty2 aroA, aroC mutant for the engineering of a candidate oral typhoid-tetanus vaccine." Vaccine 10(1);53-60. PMID: 1311488

Chaudhuri85: Chaudhuri S, Coggins JR (1985). "The purification of shikimate dehydrogenase from Escherichia coli." Biochem J 1985;226(1);217-23. PMID: 3883995

Chaudhuri86: Chaudhuri S, Lambert JM, McColl LA, Coggins JR (1986). "Purification and characterization of 3-dehydroquinase from Escherichia coli." Biochem J 1986;239(3);699-704. PMID: 2950851

Chaudhuri91: Chaudhuri S, Duncan K, Graham LD, Coggins JR (1991). "Identification of the active-site lysine residues of two biosynthetic 3-dehydroquinases." Biochem J 275 ( Pt 1);1-6. PMID: 1826831

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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 Sun Nov 23, 2014, biocyc14.