2.02012-05-31 13:57:48 -06002015-09-13 12:56:12 -0600ECMDB03070M2MDB000477Shikimic acidShikimic acid, more commonly known as its anionic form shikimate, is an important biochemical intermediate in plants and microorganisms. Its name comes from the Japanese flower shikimi ((-)-Shikimate(-)-Shikimic acidL-ShikimateL-Shikimic acidShikimateShikimic acidSkikimateSkikimic acidC7H10O5174.1513174.05282343(3R,4S,5R)-3,4,5-trihydroxycyclohex-1-ene-1-carboxylic acid(-)-shikimate138-59-0O[C@@H]1CC(=C[C@@H](O)[C@H]1O)C(O)=OInChI=1S/C7H10O5/c8-4-1-3(7(11)12)2-5(9)6(4)10/h1,4-6,8-10H,2H2,(H,11,12)/t4-,5-,6-/m1/s1JXOHGGNKMLTUBP-HSUXUTPPSA-NSolidCytosolExtra-organismPeriplasmlogp-1.70logs0.07solubility2.06e+02 g/lmelting_point186 oClogp-1.6pka_strongest_acidic4.1pka_strongest_basic-3.2iupac(3R,4S,5R)-3,4,5-trihydroxycyclohex-1-ene-1-carboxylic acidaverage_mass174.1513mono_mass174.05282343smilesO[C@@H]1CC(=C[C@@H](O)[C@H]1O)C(O)=OformulaC7H10O5inchiInChI=1S/C7H10O5/c8-4-1-3(7(11)12)2-5(9)6(4)10/h1,4-6,8-10H,2H2,(H,11,12)/t4-,5-,6-/m1/s1inchikeyJXOHGGNKMLTUBP-HSUXUTPPSA-Npolar_surface_area97.99refractivity38.96polarizability15.75rotatable_bond_count1acceptor_count5donor_count4physiological_charge-1formal_charge0Phenylalanine, tyrosine and tryptophan biosynthesisec00400Metabolic pathwayseco01100Chorismate biosynthesisChorismate is an intermediate in the synthesis of three amino acids: tyrosine, phenylalanine and tryptophan. In addition it is a precursor of folic acid, ubiquinone, menaquinone, and enterochelin. The first reaction in the chorismate pathway is catalyzed by three separate enzymes, all involved in the biosynthesis of Shikimic acid, each of which is subject to feedback inhibition by one of the three amino acids. However, even in the presence of all three amino acids, sufficient enzymatic activity is present to permit synthesis of the other four metabolites synthesized from chorismate because the enzyme subject to regulation by tryptophan cannot be inhibited more than 60 percent.
The biosynthesis of chorismate starts with D-Erythrose-4-phosphate getting transformed into 3-deoxy-D-arabino-heptulosonate-7-phosphate through a phospho-2-dehydro-3-deoxyheptonate aldolase. This is followed by a 3-dehydroquinate synthase converting the 3-deoxy-D-arabino-heptulosonate-7-phosphate into a 3-dehydroquinate which in turn is conveted to 3-dehydroshikimate through a 3-dehydroquinate dehydratase. A this point 3-dehydroshikimate can be turned into Shikimic acid through 2 different reactions involving Quinate/shikimate dehydrogenase and shikimate dehydrogenase 2. Shikimic acid is phosphorylated by Shikimate kinase 2 into shikimate 3-phosphate. Shikimate 3- phophate and a phosphoenolpyruvic acid are then joined through a 3-phosphoshikimate 1-carboxyvinyltransferase to produce a 5-enoylpyruvyl-shikimate 3-phosphate while releasing a phosphate. This in turns produces our final product Chorismate through a chorismate synthase. PW000816MetabolicSecondary Metabolites: Shikimate PathwayThe biosynthesis of shikimate starts with D-Erythrose-4-phosphate getting transformed into 3-deoxy-D-arabino-heptulosonate-7-phosphate through a phospho-2-dehydro-3-deoxyheptonate aldolase. This is followed by a 3-dehydroquinate synthase converting the 3-deoxy-D-arabino-heptulosonate-7-phosphate into a 3-dehydroquinate which in turn is conveted to 3-dehydroshikimate through a 3-dehydroquinate dehydratase. A this point 3-dehydroshikimate can be turned into Shikimic acid through 2 different reactions involving an NADPH driven Quinate/shikimate dehydrogenase or a NADPH driven shikimate dehydrogenase 2.
Shikimate can also be transported through a shikimate:H+ symporter.PW000985Metabolicchorismate biosynthesis from 3-dehydroquinatePWY-6163Specdb::CMs831Specdb::CMs832Specdb::CMs833Specdb::CMs1474Specdb::CMs2461Specdb::CMs30093Specdb::CMs30230Specdb::CMs30691Specdb::CMs30746Specdb::CMs31439Specdb::CMs38517Specdb::CMs146527Specdb::NmrOneD1924Specdb::NmrOneD4795Specdb::NmrOneD4796Specdb::NmrOneD129238Specdb::NmrOneD129239Specdb::NmrOneD129240Specdb::NmrOneD129241Specdb::NmrOneD129242Specdb::NmrOneD129243Specdb::NmrOneD129244Specdb::NmrOneD129245Specdb::NmrOneD129246Specdb::NmrOneD129247Specdb::NmrOneD129248Specdb::NmrOneD129249Specdb::NmrOneD129250Specdb::NmrOneD129251Specdb::NmrOneD129252Specdb::NmrOneD129253Specdb::NmrOneD129254Specdb::NmrOneD129255Specdb::NmrOneD129256Specdb::NmrOneD129257Specdb::MsMs5834Specdb::MsMs5835Specdb::MsMs5836Specdb::MsMs5837Specdb::MsMs5838Specdb::MsMs5842Specdb::MsMs438418Specdb::MsMs438419Specdb::MsMs438420Specdb::MsMs438421Specdb::MsMs438422Specdb::MsMs439011Specdb::MsMs2237941Specdb::MsMs2239967Specdb::MsMs2241764Specdb::MsMs2242051Specdb::MsMs2243795Specdb::MsMs2244129Specdb::MsMs2245946Specdb::MsMs2248783Specdb::MsMs2249618Specdb::MsMs2250755Specdb::MsMs2251633Specdb::MsMs2188Specdb::MsMs2189Specdb::NmrTwoD1096Specdb::NmrTwoD1859HMDB0307087428412C0049316119SHIKIMATESKMShikimic acidKeseler, I. 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Br J Urol. 1976 Feb;48(1):61-71.5168http://hmdb.ca/system/metabolites/msds/000/002/653/original/HMDB03070.pdf?1358462763Quinate/shikimate dehydrogenaseP0A6D5YDIB_ECOLIydiBhttp://ecmdb.ca/proteins/P0A6D5.xmlShikimate kinase 1P0A6D7AROK_ECOLIaroKhttp://ecmdb.ca/proteins/P0A6D7.xmlShikimate kinase 2P0A6E1AROL_ECOLIaroLhttp://ecmdb.ca/proteins/P0A6E1.xmlShikimate dehydrogenaseP15770AROE_ECOLIaroEhttp://ecmdb.ca/proteins/P15770.xmlShikimate transporterP76350SHIA_ECOLIshiAhttp://ecmdb.ca/proteins/P76350.xmlOuter membrane protein NP77747OMPN_ECOLIompNhttp://ecmdb.ca/proteins/P77747.xmlOuter membrane pore protein EP02932PHOE_ECOLIphoEhttp://ecmdb.ca/proteins/P02932.xmlOuter membrane protein FP02931OMPF_ECOLIompFhttp://ecmdb.ca/proteins/P02931.xmlOuter membrane protein CP06996OMPC_ECOLIompChttp://ecmdb.ca/proteins/P06996.xml3-Dehydro-shikimate + Hydrogen ion + NADPH <> NADP + Shikimic acidR02413SHIKIMATE-5-DEHYDROGENASE-RXNAdenosine triphosphate + Shikimic acid <> ADP + Hydrogen ion + Shikimate 3-phosphateR02412SHIKIMATE-KINASE-RXNAdenosine triphosphate + Shikimic acid <> ADP + Shikimate 3-phosphateR02412Shikimic acid + NADP <> 3-Dehydro-shikimate + NADPH + Hydrogen ionR02413Shikimic acid + NAD <> 3-Dehydro-shikimate + NADH + Hydrogen ionR06847NAD(P)<sup>+</sup> + Shikimic acid < NAD(P)H + 3-Dehydro-shikimate + Hydrogen ionRXN-7968NADP + Shikimic acid < Hydrogen ion + NADPH + 3-Dehydro-shikimateSHIKIMATE-5-DEHYDROGENASE-RXNShikimic acid + Adenosine triphosphate > Hydrogen ion + Shikimate 3-phosphate + ADPSHIKIMATE-KINASE-RXNShikimic acid + NADP > 3-dehydroshikimate + NADPHAdenosine triphosphate + Shikimic acid > ADP + Shikimate 3-phosphateShikimic acid + NAD(P)(+) > 3-dehydroshikimate + NAD(P)HQuinate + NAD + NADP + Shikimic acid <> 3-Dehydroquinate + NADH + NADPH + Hydrogen ion + 3-Dehydro-shikimateR01872 R06846 3-dehydroshikimate + Hydrogen ion + NADPH + 3-Dehydro-shikimate + NADPH > NADP + Shikimic acidPW_R002913Shikimic acid + Adenosine triphosphate > Adenosine diphosphate + Hydrogen ion + shikimate 3-phosphate + ADP + Shikimate 3-phosphatePW_R0029153 3-Dehydro-shikimate + Hydrogen ion + NADPH <> NADP + Shikimic acidAdenosine triphosphate + Shikimic acid <> ADP + Hydrogen ion + Shikimate 3-phosphate3 3-Dehydro-shikimate + Hydrogen ion + NADPH <> NADP + Shikimic acidGutnick minimal complete medium (4.7 g/L KH2PO4; 13.5 g/L K2HPO4; 1 g/L K2SO4; 0.1 g/L MgSO4-7H2O; 10 mM NH4Cl) with 4 g/L glucoseShake flask and filter culture14.1uM0.037 oCK12 NCM3722Mid-Log Phase564000Bennett, B. D., Kimball, E. H., Gao, M., Osterhout, R., Van Dien, S. J., Rabinowitz, J. D. (2009). "Absolute metabolite concentrations and implied enzyme active site occupancy in Escherichia coli." Nat Chem Biol 5:593-599.19561621