2.0 2012-05-31 14:25:12 -0600 2015-06-03 17:19:13 -0600 ECMDB20057 M2MDB000906 2,3,2'3'-Tetrakis(3-hydroxytetradecanoyl)-D-glucosaminyl-1,6-beta-D-glucosamine 1,4'-bisphosphate 2,3,2'3'-tetrakis(3-hydroxytetradecanoyl)-D-glucosaminyl-1,6-beta-D-glucosamine 1,4'-bisphosphate is a member of the chemical class known as Dihexoses. These are disaccharides containing two hexose carbohydrates. E. coli KdtA (EcKdtA) is a bifunctional enzyme that transfers two KDO units from two CMP-KDO molecules to lipid IV(A). (PMID 20394418) 2,3,2'3'-Tetrakis(3-hydroxytetradecanoyl)-D-glucosaminyl-1,6-b-D-glucosamine 1,4'-bisphosphate 2,3,2'3'-Tetrakis(3-hydroxytetradecanoyl)-D-glucosaminyl-1,6-b-D-glucosamine 1,4'-bisphosphoric acid 2,3,2'3'-Tetrakis(3-hydroxytetradecanoyl)-D-glucosaminyl-1,6-beta-D-glucosamine 1,4'-bisphosphoric acid 2,3,2'3'-Tetrakis(3-hydroxytetradecanoyl)-D-glucosaminyl-1,6-β-D-glucosamine 1,4'-bisphosphate 2,3,2'3'-Tetrakis(3-hydroxytetradecanoyl)-D-glucosaminyl-1,6-β-D-glucosamine 1,4'-bisphosphoric acid Lipid a disaccharide bisphosphate Lipid a disaccharide bisphosphoric acid Lipid IV(a) C68H130N2O23P2 1405.7069 1404.8539615 N-[(2S,3R,4R,5S,6R)-6-({[(2R,3R,4R,5S,6R)-3-[(1,3-dihydroxytetradecylidene)amino]-6-(hydroxymethyl)-4-[(3-hydroxytetradecanoyl)oxy]-5-(phosphonooxy)oxan-2-yl]oxy}methyl)-5-hydroxy-4-[(3-hydroxytetradecanoyl)oxy]-2-(phosphonooxy)oxan-3-yl]-3-hydroxytetradecanimidic acid N-[(2S,3R,4R,5S,6R)-6-({[(2R,3R,4R,5S,6R)-3-[(1,3-dihydroxytetradecylidene)amino]-6-(hydroxymethyl)-4-[(3-hydroxytetradecanoyl)oxy]-5-(phosphonooxy)oxan-2-yl]oxy}methyl)-5-hydroxy-4-[(3-hydroxytetradecanoyl)oxy]-2-(phosphonooxy)oxan-3-yl]-3-hydroxytetradecanimidic acid [H]C(O)(CCCCCCCCCCC)CC(=O)O[C@@]1([H])[C@]([H])(O)[C@@]([H])(CO[C@]2([H])O[C@]([H])(CO)[C@@]([H])(OP(O)(O)=O)[C@]([H])(OC(=O)CC([H])(O)CCCCCCCCCCC)[C@@]2([H])N=C(O)CC([H])(O)CCCCCCCCCCC)O[C@@]([H])(OP(O)(O)=O)[C@]1([H])N=C(O)CC([H])(O)CCCCCCCCCCC InChI=1S/C68H130N2O23P2/c1-5-9-13-17-21-25-29-33-37-41-51(72)45-57(76)69-61-65(90-59(78)47-53(74)43-39-35-31-27-23-19-15-11-7-3)63(80)56(89-68(61)93-95(84,85)86)50-87-67-62(70-58(77)46-52(73)42-38-34-30-26-22-18-14-10-6-2)66(64(55(49-71)88-67)92-94(81,82)83)91-60(79)48-54(75)44-40-36-32-28-24-20-16-12-8-4/h51-56,61-68,71-75,80H,5-50H2,1-4H3,(H,69,76)(H,70,77)(H2,81,82,83)(H2,84,85,86)/t51?,52?,53?,54?,55-,56-,61-,62-,63-,64-,65-,66-,67-,68+/m1/s1 KVJWZTLXIROHIL-XFXUPMIZSA-N Inner membrane Membrane Outer membrane logp 5.26 ALOGPS logs -5.06 ALOGPS solubility 1.21e-02 g/l ALOGPS logp 14.43 ChemAxon pka_strongest_acidic 0.55 ChemAxon pka_strongest_basic -3.7 ChemAxon iupac N-[(2S,3R,4R,5S,6R)-6-({[(2R,3R,4R,5S,6R)-3-[(1,3-dihydroxytetradecylidene)amino]-6-(hydroxymethyl)-4-[(3-hydroxytetradecanoyl)oxy]-5-(phosphonooxy)oxan-2-yl]oxy}methyl)-5-hydroxy-4-[(3-hydroxytetradecanoyl)oxy]-2-(phosphonooxy)oxan-3-yl]-3-hydroxytetradecanimidic acid ChemAxon average_mass 1405.7069 ChemAxon mono_mass 1404.8539615 ChemAxon smiles [H]C(O)(CCCCCCCCCCC)CC(=O)O[C@@]1([H])[C@]([H])(O)[C@@]([H])(CO[C@]2([H])O[C@]([H])(CO)[C@@]([H])(OP(O)(O)=O)[C@]([H])(OC(=O)CC([H])(O)CCCCCCCCCCC)[C@@]2([H])N=C(O)CC([H])(O)CCCCCCCCCCC)O[C@@]([H])(OP(O)(O)=O)[C@]1([H])N=C(O)CC([H])(O)CCCCCCCCCCC ChemAxon formula C68H130N2O23P2 ChemAxon inchi InChI=1S/C68H130N2O23P2/c1-5-9-13-17-21-25-29-33-37-41-51(72)45-57(76)69-61-65(90-59(78)47-53(74)43-39-35-31-27-23-19-15-11-7-3)63(80)56(89-68(61)93-95(84,85)86)50-87-67-62(70-58(77)46-52(73)42-38-34-30-26-22-18-14-10-6-2)66(64(55(49-71)88-67)92-94(81,82)83)91-60(79)48-54(75)44-40-36-32-28-24-20-16-12-8-4/h51-56,61-68,71-75,80H,5-50H2,1-4H3,(H,69,76)(H,70,77)(H2,81,82,83)(H2,84,85,86)/t51?,52?,53?,54?,55-,56-,61-,62-,63-,64-,65-,66-,67-,68+/m1/s1 ChemAxon inchikey KVJWZTLXIROHIL-XFXUPMIZSA-N ChemAxon polar_surface_area 400.37 ChemAxon refractivity 358.65 ChemAxon polarizability 158.55 ChemAxon rotatable_bond_count 62 ChemAxon acceptor_count 21 ChemAxon donor_count 12 ChemAxon physiological_charge -4 ChemAxon formal_charge 0 ChemAxon Lipopolysaccharide biosynthesis E. coli lipid A is synthesized on the cytoplasmic surface of the inner membrane. The pathway can start from the fructose 6-phosphate that is either produced in the glycolysis and pyruvate dehydrogenase or be obtained from the interaction with D-fructose interacting with a mannose PTS permease. Fructose 6-phosphate interacts with L-glutamine through a D-fructose-6-phosphate aminotransferase resulting into a L-glutamic acid and a glucosamine 6-phosphate. The latter compound is isomerized through a phosphoglucosamine mutase resulting a glucosamine 1-phosphate. This compound is acetylated, interacting with acetyl-CoA through a bifunctional protein glmU resulting in a Coenzyme A, hydrogen ion and N-acetyl-glucosamine 1-phosphate. This compound interact with UTP and hydrogen ion through the bifunctional protein glmU resulting in a pyrophosphate and a UDP-N-acetylglucosamine. This compound interacts with (3R)-3-hydroxymyristoyl-[acp] through an UDP-N-acetylglucosamine acyltransferase resulting in a holo-[acp] and a UDP-3-O[(3R)-3-hydroxymyristoyl]-N-acetyl-alpha-D-glucosamine. This compound interacts with water through UDP-3-O-acyl-N-acetylglucosamine deacetylase resulting in an acetic acid and UDP-3-O-(3-hydroxymyristoyl)-α-D-glucosamine. The latter compound interacts with (3R)-3-hydroxymyristoyl-[acp] through UDP-3-O-(R-3-hydroxymyristoyl)-glucosamine N-acyltransferase releasing a hydrogen ion, a holo-acp and UDP-2-N,3-O-bis[(3R)-3-hydroxytetradecanoyl]-α-D-glucosamine. The latter compound is hydrolase by interacting with water and a UDP-2,3-diacylglucosamine hydrolase resulting in UMP, hydrogen ion and 2,3-bis[(3R)-3-hydroxymyristoyl]-α-D-glucosaminyl 1-phosphate. This last compound then interacts with a UDP-2-N,3-O-bis[(3R)-3-hydroxytetradecanoyl]-α-D-glucosamine through a lipid A disaccharide synthase resulting in a release of UDP, hydrogen ion and a lipid A disaccharide. The lipid A disaccharide is phosphorylated by an ATP mediated tetraacyldisaccharide 4'-kinase resulting in the release of hydrogen ion and lipid IVA. A D-ribulose 5-phosphate is isomerized with D-arabinose 5-phosphate isomerase 2 to result in a D-arabinose 5-phosphate. This compounds interacts with water and phosphoenolpyruvic acid through a 3-deoxy-D-manno-octulosonate 8-phosphate synthase resulting in the release of phosphate and 3-deoxy-D-manno-octulosonate 8-phosphate. This compound interacts with water through a 3-deoxy-D-manno-octulosonate 8-phosphate phosphatase thus releasing a phosphate and a 3-deoxy-D-manno-octulosonate. The latter compound interacts with CTP through a 3-deoxy-D-manno-octulosonate cytidylyltransferase resulting in a pyrophosphate and CMP-3-deoxy-α-D-manno-octulosonate. CMP-3-deoxy-α-D-manno-octulosonate and lipid IVA interact with each other through a KDO transferase resulting in CMP, hydrogen ion and alpha-Kdo-(2-->6)-lipid IVA. The latter compound reacts with CMP-3-deoxy-α-D-manno-octulosonate through a KDO transferase resulting in a CMP, hydrogen ion, and a a-Kdo-(2->4)-a-Kdo-(2->6)-lipid IVA. The latter compound interacts with a dodecanoyl-[acp] lauroyl acyltransferase resulting in a holo-[acp] and a (KDO)2-(lauroyl)-lipid IVA. The latter compound reacts with a myristoyl-[acp] through a myristoyl-acyl carrier protein (ACP)-dependent acyltransferase resulting in a holo-[acp], (KDO)2-lipid A. The latter compound reacts with ADP-L-glycero-beta-D-manno-heptose through ADP-heptose:LPS heptosyltransferase I resulting hydrogen ion, ADP, heptosyl-KDO2-lipid A. The latter compound interacts with ADP-L-glycero-beta-D-manno-heptose through ADP-heptose:LPS heptosyltransferase II resulting in ADP, hydrogen ion and (heptosyl)2-Kdo2-lipid A. The latter compound UDP-glucose interacts with (heptosyl)2-Kdo2-lipid A resulting in UDP, hydrogen ion and glucosyl-(heptosyl)2-Kdo2-lipid A. Glucosyl-(heptosyl)2-Kdo2-lipid A (Escherichia coli) is phosphorylated through an ATP-mediated lipopolysaccharide core heptose (I) kinase resulting in ADP, hydrogen ion and glucosyl-(heptosyl)2-Kdo2-lipid A-phosphate. The latter compound interacts with ADP-L-glycero-beta-D-manno-heptose through a lipopolysaccharide core heptosyl transferase III resulting in ADP, hydrogen ion, and glucosyl-(heptosyl)3-Kdo2-lipid A-phosphate. The latter compound is phosphorylated through an ATP-driven lipopolysaccharide core heptose (II) kinase resulting in ADP, hydrogen ion and glucosyl-(heptosyl)3-Kdo2-lipid A-bisphosphate. The latter compound interacts with UDP-alpha-D-galactose through a UDP-D-galactose:(glucosyl)lipopolysaccharide-1,6-D-galactosyltransferase resulting in a UDP, a hydrogen ion and a galactosyl-glucosyl-(heptosyl)3-Kdo2-lipid A-bisphosphate. The latter compound interacts with UDP-glucose through a (glucosyl)LPS α-1,3-glucosyltransferase resulting in a hydrogen ion, a UDP and galactosyl-(glucosyl)2-(heptosyl)3-Kdo2-lipid A-bisphosphate. This compound then interacts with UDP-glucose through a UDP-glucose:(glucosyl)LPS α-1,2-glucosyltransferase resulting in UDP, a hydrogen ion and galactosyl-(glucosyl)3-(heptosyl)3-Kdo2-lipid A-bisphosphate. This compound then interacts with ADP-L-glycero-beta-D-manno-heptose through a lipopolysaccharide core biosynthesis; heptosyl transferase IV; probably hexose transferase resulting in a Lipid A-core. A lipid A-core is then exported into the periplasmic space by a lipopolysaccharide ABC transporter. The lipid A-core is then flipped to the outer surface of the inner membrane by the ATP-binding cassette (ABC) transporter, MsbA. An additional integral membrane protein, YhjD, has recently been implicated in LPS export across the IM. The smallest LPS derivative that supports viability in E. coli is lipid IVA. However, it requires mutations in either MsbA or YhjD, to suppress the normally lethal consequence of an incomplete lipid A . Recent studies with deletion mutants implicate the periplasmic protein LptA, the cytosolic protein LptB, and the IM proteins LptC, LptF, and LptG in the subsequent transport of nascent LPS to the outer membrane (OM), where the LptD/LptE complex flips LPS to the outer surface. PW000831 ec00540 Metabolic 2,3-dihydroxybenzoate biosynthesis PWY-5901 Specdb::MsMs 28646 Specdb::MsMs 28647 Specdb::MsMs 28648 Specdb::MsMs 35204 Specdb::MsMs 35205 Specdb::MsMs 35206 24892757 C04919 29056 DIHYDRO-DIOH-BENZOATE 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 van der Werf, M. J., Overkamp, K. M., Muilwijk, B., Coulier, L., Hankemeier, T. (2007). "Microbial metabolomics: toward a platform with full metabolome coverage." Anal Biochem 370:17-25. 17765195 Winder, C. L., Dunn, W. B., Schuler, S., Broadhurst, D., Jarvis, R., Stephens, G. M., Goodacre, R. (2008). "Global metabolic profiling of Escherichia coli cultures: an evaluation of methods for quenching and extraction of intracellular metabolites." Anal Chem 80:2939-2948. 18331064 Chung, H. S., Raetz, C. R. (2010). "Interchangeable domains in the Kdo transferases of Escherichia coli and Haemophilus influenzae." Biochemistry 49:4126-4137. 20394418 3-deoxy-D-manno-octulosonic-acid transferase P0AC75 KDTA_ECOLI waaA http://ecmdb.ca/proteins/P0AC75.xml Tetraacyldisaccharide 4'-kinase P27300 LPXK_ECOLI lpxK http://ecmdb.ca/proteins/P27300.xml Undecaprenyl phosphate-alpha-4-amino-4-deoxy-L-arabinose arabinosyl transferase P76473 ARNT_ECOLI arnT http://ecmdb.ca/proteins/P76473.xml Adenosine triphosphate + 2,3,2',3'-Tetrakis(3-hydroxytetradecanoyl)-D-glucosaminyl-1,6-beta-D-glucosamine 1-phosphate <> ADP + 2,3,2'3'-Tetrakis(3-hydroxytetradecanoyl)-D-glucosaminyl-1,6-beta-D-glucosamine 1,4'-bisphosphate R04657 2,3,2'3'-Tetrakis(3-hydroxytetradecanoyl)-D-glucosaminyl-1,6-beta-D-glucosamine 1,4'-bisphosphate + CMP-3-Deoxy-D-manno-octulosonate + 2,3,2'3'-Tetrakis(beta-hydroxymyristoyl)-D-glucosaminyl-1,6-beta-D-glucosamine 1,4'-bisphosphate <> KDO-lipid IV(A) + Cytidine monophosphate R04658 Undecaprenyl phosphate alpha-L-Ara4N + 2,3,2'3'-Tetrakis(3-hydroxytetradecanoyl)-D-glucosaminyl-1,6-beta-D-glucosamine 1,4'-bisphosphate <> Lipid IIA + Di-trans,poly-cis-undecaprenyl phosphate R09773 Adenosine triphosphate + 2 2,3,2',3'-Tetrakis(3-hydroxytetradecanoyl)-D-glucosaminyl-1,6-beta-D-glucosamine 1-phosphate <> ADP +2 2,3,2'3'-Tetrakis(3-hydroxytetradecanoyl)-D-glucosaminyl-1,6-beta-D-glucosamine 1,4'-bisphosphate Adenosine triphosphate + 2 2,3,2',3'-Tetrakis(3-hydroxytetradecanoyl)-D-glucosaminyl-1,6-beta-D-glucosamine 1-phosphate <> ADP +2 2,3,2'3'-Tetrakis(3-hydroxytetradecanoyl)-D-glucosaminyl-1,6-beta-D-glucosamine 1,4'-bisphosphate