2.0 2012-05-31 14:22:16 -0600 2015-09-17 15:41:51 -0600 ECMDB20002 M2MDB000851 (1R,6R)-6-Hydroxy-2-succinylcyclohexa-2,4-diene-1-carboxylate 2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylic acid (SHCHC) is the first identified intermediate in the menaquinone biosynthetic pathway. This pathway requires two reactions. They are the decarboxylation of alpha-ketoglutarate by an alpha-ketoglutarate decarboxylase, which results in the formation of succinic semialdehyde-thiamine PPi (TPP) anion, and the addition of the succinic semialdehyde-TPP anion to isochorismate carried out by the enzyme SHCHC synthase. In E. coli, addition of succinic semialdehyde-TPP anion (from 2-oxoglutarate) to isochorismate results in the formation of 2-succinyl-5-enolpyruvyl-6-hydroxy-3-cyclohexene-1-carboxylate (SEPHCHC). In the subsequent reaction, the pyruvoyl group is eliminated, resulting in the prearomatic compound (1R,6R)-6-hydroxy-2-succinylcyclohexa-2,4-diene-1-carboxylate (SHCHC). This is then aromatized to the benzenoid aromatic compound o-succinylbenzoate (OSB) and used as the framework for the construction of the rest of the menaquinone molecule. In this pathway, prenylation in the last step leads to the formation of 1,4-dihydroxy-2-naphtoic acid (DHNA). Subsequently OSB and DHNA formed in this pathway are incorporated into the naphthoquinone ring of menaquinone. SEPHCHC is an unstable compound and in mildly basic solutions, spontaneously undergoes a 2,5-elimination reaction resulting in the formation SHCHC and pyruvate. But the in vivo conversion of SEPHCHC to SHCHC is carried out by SHCHC synthase MenH. Dehydration from SHCHC by the enzyme OSB synthase (MenC) leads to the formation of the benzenoid aromatic compound OSB. The conversion of the benzenoid aromatic compound OSB to the naphthalenoid aromatic compound DHNA is catalyzed by the enzyme OSB-CoA synthetase (MenE). The process has been shown to have an absolute requirement for ATP and CoA. OSB-CoA is suggested as an intermediate. During the formation of OSB-CoA, ATP is hydrolyzed to AMP and PPi. (1<i>R</i>,6<i>R</i>)-2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylate (1R,6R)-2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylate (1R,6R)-2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylic acid (1R,6R)-6-Hydroxy-2-succinylcyclohexa-2,4-diene-1-carboxylic acid 2-(3-CARBOXYPROPIONYL)-6-hydroxy-cyclohexa-2,4-diene carboxylate 2-(3-CARBOXYPROPIONYL)-6-HYDROXY-CYCLOHEXA-2,4-DIENE CARBOXYLIC ACID 2-Succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylate 2-Succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylic acid NChemBio.2007.11-comp3 Shchc SucCycHexCA C11H10O6 238.196 238.048835202 (1R,6R)-2-(3-carboxypropanoyl)-6-hydroxycyclohexa-2,4-diene-1-carboxylic acid shchc [H][C@@]1(O)C=CC=C(C(=O)CCC([O-])=O)[C@@]1([H])C([O-])=O InChI=1S/C11H12O6/c12-7(4-5-9(14)15)6-2-1-3-8(13)10(6)11(16)17/h1-3,8,10,13H,4-5H2,(H,14,15)(H,16,17)/p-2/t8-,10-/m1/s1 QJYRAJSESKVEAE-PSASIEDQSA-L Cytosol logp -0.41 ALOGPS logs -1.94 ALOGPS solubility 2.73e+00 g/l ALOGPS logp -0.32 ChemAxon pka_strongest_acidic 3.63 ChemAxon pka_strongest_basic -3.1 ChemAxon iupac (1R,6R)-2-(3-carboxypropanoyl)-6-hydroxycyclohexa-2,4-diene-1-carboxylic acid ChemAxon average_mass 238.196 ChemAxon mono_mass 238.048835202 ChemAxon smiles [H][C@@]1(O)C=CC=C(C(=O)CCC([O-])=O)[C@@]1([H])C([O-])=O ChemAxon formula C11H10O6 ChemAxon inchi InChI=1S/C11H12O6/c12-7(4-5-9(14)15)6-2-1-3-8(13)10(6)11(16)17/h1-3,8,10,13H,4-5H2,(H,14,15)(H,16,17)/p-2/t8-,10-/m1/s1 ChemAxon inchikey QJYRAJSESKVEAE-PSASIEDQSA-L ChemAxon polar_surface_area 111.9 ChemAxon refractivity 57.88 ChemAxon polarizability 22.36 ChemAxon rotatable_bond_count 5 ChemAxon acceptor_count 6 ChemAxon donor_count 3 ChemAxon physiological_charge -2 ChemAxon formal_charge 0 ChemAxon Ubiquinone and other terpenoid-quinone biosynthesis ec00130 Metabolic pathways eco01100 Menaquinol biosythesis Menaquinol biosynthesis starts with chorismate being metabolized into isochorismate through a isochorismate synthase. Isochorismate then interacts with 2-oxoglutare and a hydrogen ion through a 2-succinyl-5-enolpyruvyl-6-hydroxy-3-cyclohexene-1-carboxylate synthase resulting in the release of a carbon dioxide and a 2-succinyl-5-enolpyruvyl-6-hydroxy-3-cyclohexene-1-carboxylate. The latter compound then interacts with (1R,6R)-2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylate synthase resulting in the release of a pyruvate and a (1R,6R)-6-hydroxy-2-succinylcyclohexa-2,4-diene-1-carboxylate. This compound is the dehydrated through a o-succinylbenzoate synthase resulting in the release of a water molecule and a 2-succinylbenzoate. This compound then interacts with a coenzyme A and an ATP through a o-succinylbenzoate CoA ligase resulting in the release of a diphosphate, a AMP and a succinylbenzoyl-CoA. The latter compound interacts with a hydrogen ion through a 1,4-dihydroxy-2-naphthoyl-CoA synthase resulting in the release of a water molecule or a 1,4-dihydroxy-2-naphthoyl-CoA. This compound then interacts with water through a 1,4-dihydroxy-2-naphthoyl-CoA thioesterase resulting in the release of a coenzyme A, a hydrogen ion and a 1,4-dihydroxy-2-naphthoate. The 1,4-dihydroxy-2-naphthoate can interact with either farnesylfarnesylgeranyl-PP or octaprenyl diphosphate and a hydrogen ion through a 1,4-dihydroxy-2-naphthoate octaprenyltransferase resulting in a release of a carbon dioxide, a pyrophosphate and a demethylmenaquinol-8. This compound then interacts with SAM through a bifunctional 2-octaprenyl-6-methoxy-1,4-benzoquinone methylase and S-adenosylmethionine:2-DMK methyltransferase resulting in a hydrogen ion, a s-adenosyl-L-homocysteine and a menaquinol. PW001897 Metabolic 1,4-dihydroxy-2-naphthoate biosynthesis I PWY-5837 Specdb::MsMs 23378 Specdb::MsMs 23379 Specdb::MsMs 23380 Specdb::MsMs 30176 Specdb::MsMs 30177 Specdb::MsMs 30178 Specdb::MsMs 3607615 Specdb::MsMs 3607616 Specdb::MsMs 3607617 Specdb::MsMs 3607618 Specdb::MsMs 3607619 Specdb::MsMs 3607620 5287432 4449817 C05817 39564 CPD-9923 164 Keseler, I. M., Collado-Vides, J., Santos-Zavaleta, A., Peralta-Gil, M., Gama-Castro, S., Muniz-Rascado, L., Bonavides-Martinez, C., Paley, S., Krummenacker, M., Altman, T., Kaipa, P., Spaulding, A., Pacheco, J., Latendresse, M., Fulcher, C., Sarker, M., Shearer, A. G., Mackie, A., Paulsen, I., Gunsalus, R. P., Karp, P. D. (2011). "EcoCyc: a comprehensive database of Escherichia coli biology." Nucleic Acids Res 39:D583-D590. 21097882 Kanehisa, M., Goto, S., Sato, Y., Furumichi, M., Tanabe, M. (2012). "KEGG for integration and interpretation of large-scale molecular data sets." Nucleic Acids Res 40:D109-D114. 22080510 o-succinylbenzoate synthase P29208 MENC_ECOLI menC http://ecmdb.ca/proteins/P29208.xml 2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylate synthase P37355 MENH_ECOLI menH http://ecmdb.ca/proteins/P37355.xml (1R,6R)-6-Hydroxy-2-succinylcyclohexa-2,4-diene-1-carboxylate <> Water + 2-Succinylbenzoate R04031 O-SUCCINYLBENZOATE-COA-SYN-RXN 2-Succinyl-5-enolpyruvyl-6-hydroxy-3-cyclohexene-1-carboxylate <> (1R,6R)-6-Hydroxy-2-succinylcyclohexa-2,4-diene-1-carboxylate + Pyruvic acid R08166 RXN-9310 2-Succinylbenzoate + Water <> (1R,6R)-6-Hydroxy-2-succinylcyclohexa-2,4-diene-1-carboxylate R04031 (1R,6R)-6-Hydroxy-2-succinylcyclohexa-2,4-diene-1-carboxylate > 2-Succinylbenzoate + Water R04031 O-SUCCINYLBENZOATE-COA-SYN-RXN 2-Succinyl-5-enolpyruvyl-6-hydroxy-3-cyclohexene-1-carboxylate > (1R,6R)-6-Hydroxy-2-succinylcyclohexa-2,4-diene-1-carboxylate + Pyruvic acid R08166 RXN-9310 2-Succinyl-5-enolpyruvyl-6-hydroxy-3-cyclohexene-1-carboxylate > (1R,6R)-6-hydroxy-2-succinylcyclohexa-2,4-diene-1-carboxylate + Pyruvic acid + (1R,6R)-6-Hydroxy-2-succinylcyclohexa-2,4-diene-1-carboxylate PW_R005216 (1R,6R)-6-hydroxy-2-succinylcyclohexa-2,4-diene-1-carboxylate + (1R,6R)-6-Hydroxy-2-succinylcyclohexa-2,4-diene-1-carboxylate > 2-succinylbenzoate + Water + 2-Succinylbenzoate PW_R005217