2.0 2012-05-31 13:57:48 -0600 2015-09-13 12:56:12 -0600 ECMDB03070 M2MDB000477 Shikimic acid Shikimic 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 acid L-Shikimate L-Shikimic acid Shikimate Shikimic acid Skikimate Skikimic acid C7H10O5 174.1513 174.05282343 (3R,4S,5R)-3,4,5-trihydroxycyclohex-1-ene-1-carboxylic acid (-)-shikimate 138-59-0 O[C@@H]1CC(=C[C@@H](O)[C@H]1O)C(O)=O InChI=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/s1 JXOHGGNKMLTUBP-HSUXUTPPSA-N Solid Cytosol Extra-organism Periplasm logp -1.70 ALOGPS logs 0.07 ALOGPS solubility 2.06e+02 g/l ALOGPS melting_point 186 oC logp -1.6 ChemAxon pka_strongest_acidic 4.1 ChemAxon pka_strongest_basic -3.2 ChemAxon iupac (3R,4S,5R)-3,4,5-trihydroxycyclohex-1-ene-1-carboxylic acid ChemAxon average_mass 174.1513 ChemAxon mono_mass 174.05282343 ChemAxon smiles O[C@@H]1CC(=C[C@@H](O)[C@H]1O)C(O)=O ChemAxon formula C7H10O5 ChemAxon inchi InChI=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/s1 ChemAxon inchikey JXOHGGNKMLTUBP-HSUXUTPPSA-N ChemAxon polar_surface_area 97.99 ChemAxon refractivity 38.96 ChemAxon polarizability 15.75 ChemAxon rotatable_bond_count 1 ChemAxon acceptor_count 5 ChemAxon donor_count 4 ChemAxon physiological_charge -1 ChemAxon formal_charge 0 ChemAxon Phenylalanine, tyrosine and tryptophan biosynthesis ec00400 Metabolic pathways eco01100 Chorismate biosynthesis Chorismate 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. PW000816 Metabolic Secondary Metabolites: Shikimate Pathway The 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. PW000985 Metabolic chorismate biosynthesis from 3-dehydroquinate PWY-6163 Specdb::CMs 831 Specdb::CMs 832 Specdb::CMs 833 Specdb::CMs 1474 Specdb::CMs 2461 Specdb::CMs 30093 Specdb::CMs 30230 Specdb::CMs 30691 Specdb::CMs 30746 Specdb::CMs 31439 Specdb::CMs 38517 Specdb::CMs 146527 Specdb::NmrOneD 1924 Specdb::NmrOneD 4795 Specdb::NmrOneD 4796 Specdb::NmrOneD 129238 Specdb::NmrOneD 129239 Specdb::NmrOneD 129240 Specdb::NmrOneD 129241 Specdb::NmrOneD 129242 Specdb::NmrOneD 129243 Specdb::NmrOneD 129244 Specdb::NmrOneD 129245 Specdb::NmrOneD 129246 Specdb::NmrOneD 129247 Specdb::NmrOneD 129248 Specdb::NmrOneD 129249 Specdb::NmrOneD 129250 Specdb::NmrOneD 129251 Specdb::NmrOneD 129252 Specdb::NmrOneD 129253 Specdb::NmrOneD 129254 Specdb::NmrOneD 129255 Specdb::NmrOneD 129256 Specdb::NmrOneD 129257 Specdb::MsMs 2188 Specdb::MsMs 2189 Specdb::MsMs 2190 Specdb::MsMs 5834 Specdb::MsMs 5835 Specdb::MsMs 5836 Specdb::MsMs 5837 Specdb::MsMs 5838 Specdb::MsMs 5842 Specdb::MsMs 178185 Specdb::MsMs 178186 Specdb::MsMs 178187 Specdb::MsMs 180501 Specdb::MsMs 180502 Specdb::MsMs 180503 Specdb::MsMs 438418 Specdb::MsMs 438419 Specdb::MsMs 438420 Specdb::MsMs 438421 Specdb::MsMs 438422 Specdb::MsMs 439011 Specdb::MsMs 2235887 Specdb::MsMs 2237512 Specdb::MsMs 2237941 Specdb::MsMs 2239615 Specdb::NmrTwoD 1096 Specdb::NmrTwoD 1859 HMDB03070 8742 8412 C00493 16119 SHIKIMATE SKM Shikimic acid Keseler, I. 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Br J Urol. 1976 Feb;48(1):61-71. 5168 http://hmdb.ca/system/metabolites/msds/000/002/653/original/HMDB03070.pdf?1358462763 Quinate/shikimate dehydrogenase P0A6D5 YDIB_ECOLI ydiB http://ecmdb.ca/proteins/P0A6D5.xml Shikimate kinase 1 P0A6D7 AROK_ECOLI aroK http://ecmdb.ca/proteins/P0A6D7.xml Shikimate kinase 2 P0A6E1 AROL_ECOLI aroL http://ecmdb.ca/proteins/P0A6E1.xml Shikimate dehydrogenase P15770 AROE_ECOLI aroE http://ecmdb.ca/proteins/P15770.xml Shikimate transporter P76350 SHIA_ECOLI shiA http://ecmdb.ca/proteins/P76350.xml Outer membrane protein N P77747 OMPN_ECOLI ompN http://ecmdb.ca/proteins/P77747.xml Outer membrane pore protein E P02932 PHOE_ECOLI phoE http://ecmdb.ca/proteins/P02932.xml Outer membrane protein F P02931 OMPF_ECOLI ompF http://ecmdb.ca/proteins/P02931.xml Outer membrane protein C P06996 OMPC_ECOLI ompC http://ecmdb.ca/proteins/P06996.xml 3-Dehydro-shikimate + Hydrogen ion + NADPH <> NADP + Shikimic acid R02413 SHIKIMATE-5-DEHYDROGENASE-RXN Adenosine triphosphate + Shikimic acid <> ADP + Hydrogen ion + Shikimate 3-phosphate R02412 SHIKIMATE-KINASE-RXN Adenosine triphosphate + Shikimic acid <> ADP + Shikimate 3-phosphate R02412 Shikimic acid + NADP <> 3-Dehydro-shikimate + NADPH + Hydrogen ion R02413 Shikimic acid + NAD <> 3-Dehydro-shikimate + NADH + Hydrogen ion R06847 NAD(P)⁺ + Shikimic acid < NAD(P)H + 3-Dehydro-shikimate + Hydrogen ion RXN-7968 NADP + Shikimic acid < Hydrogen ion + NADPH + 3-Dehydro-shikimate SHIKIMATE-5-DEHYDROGENASE-RXN Shikimic acid + Adenosine triphosphate > Hydrogen ion + Shikimate 3-phosphate + ADP SHIKIMATE-KINASE-RXN Shikimic acid + NADP > 3-dehydroshikimate + NADPH Adenosine triphosphate + Shikimic acid > ADP + Shikimate 3-phosphate Shikimic acid + NAD(P)(+) > 3-dehydroshikimate + NAD(P)H Quinate + NAD + NADP + Shikimic acid <> 3-Dehydroquinate + NADH + NADPH + Hydrogen ion + 3-Dehydro-shikimate R01872 R06846 3-dehydroshikimate + Hydrogen ion + NADPH + 3-Dehydro-shikimate + NADPH > NADP + Shikimic acid PW_R002913 Shikimic acid + Adenosine triphosphate > Adenosine diphosphate + Hydrogen ion + shikimate 3-phosphate + ADP + Shikimate 3-phosphate PW_R002915 3 3-Dehydro-shikimate + Hydrogen ion + NADPH <> NADP + Shikimic acid Adenosine triphosphate + Shikimic acid <> ADP + Hydrogen ion + Shikimate 3-phosphate 3 3-Dehydro-shikimate + Hydrogen ion + NADPH <> NADP + Shikimic acid Gutnick 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 glucose Shake flask and filter culture 14.1 uM 0.0 37 oC K12 NCM3722 Mid-Log Phase 56400 0 Bennett, 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