2.0 2012-05-31 14:55:18 -0600 2015-06-03 17:20:27 -0600 ECMDB21031 M2MDB001447 KDO2-Lipid A KDO2-Lipid A is an intermediate in the synthesis of LPS. It has two 3-deoxy-D-manno-octulosonic acid (KDO) sugar residues in place of the core, and has no O-antigen. α-Kdo-(2→4)-α-Kdo-(2→6)-lipid A a-kdo-(2->4)-a-kdo-(2->6)-lipid a Alpha-KDO-(2->4)-alpha-KDO-(2->6)-lipid A Re endotoxin α-kdo-(2->4)-α-kdo-(2->6)-lipid a C110H202N2O39P2 2238.7184 2237.335997756 (2R,4R,5R,6R)-4-{[(2R,4R,5R,6R)-2-carboxy-6-[(1R)-1,2-dihydroxyethyl]-4,5-dihydroxyoxan-2-yl]oxy}-6-[(1R)-1,2-dihydroxyethyl]-2-{[(2R,3S,4R,5R,6R)-6-{[(2R,3S,4R,5R,6R)-5-[(1,3-dihydroxytetradecylidene)amino]-3-hydroxy-4-[(3-hydroxytetradecanoyl)oxy]-6-(phosphonooxy)oxan-2-yl]methoxy}-5-{[3-(dodecanoyloxy)-1-hydroxytetradecylidene]amino}-3-(phosphonooxy)-4-{[3-(tetradecanoyloxy)tetradecanoyl]oxy}oxan-2-yl]methoxy}-5-hydroxyoxane-2-carboxylic acid (2R,4R,5R,6R)-4-{[(2R,4R,5R,6R)-2-carboxy-6-[(1R)-1,2-dihydroxyethyl]-4,5-dihydroxyoxan-2-yl]oxy}-6-[(1R)-1,2-dihydroxyethyl]-2-{[(2R,3S,4R,5R,6R)-6-{[(2R,3S,4R,5R,6R)-5-[(1,3-dihydroxytetradecylidene)amino]-3-hydroxy-4-[(3-hydroxytetradecanoyl)oxy]-6-(phosphonooxy)oxan-2-yl]methoxy}-5-{[3-(dodecanoyloxy)-1-hydroxytetradecylidene]amino}-3-(phosphonooxy)-4-{[3-(tetradecanoyloxy)tetradecanoyl]oxy}oxan-2-yl]methoxy}-5-hydroxyoxane-2-carboxylic 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@@]3(C[C@@]([H])(O[C@@]4(C[C@@]([H])(O)[C@@]([H])(O)[C@]([H])(O4)[C@]([H])(O)CO)C(O)=O)[C@@]([H])(O)[C@]([H])(O3)[C@]([H])(O)CO)C(O)=O)[C@@]([H])(OP(O)(O)=O)[C@]([H])(OC(=O)CC([H])(CCCCCCCCCCC)OC(=O)CCCCCCCCCCCCC)[C@@]2([H])N=C(O)CC([H])(CCCCCCCCCCC)OC(=O)CCCCCCCCCCC)O[C@]([H])(OP(O)(O)=O)[C@]1([H])N=C(O)CC([H])(O)CCCCCCCCCCC InChI=1S/C110H202N2O39P2/c1-7-13-19-25-31-37-38-44-50-56-62-68-92(123)142-82(66-60-54-48-42-35-29-23-17-11-5)72-94(125)146-104-96(112-90(121)71-81(65-59-53-47-41-34-28-22-16-10-4)141-91(122)67-61-55-49-43-36-30-24-18-12-6)105(144-88(102(104)150-152(133,134)135)78-140-109(107(129)130)74-86(98(127)101(148-109)85(119)76-114)147-110(108(131)132)73-83(117)97(126)100(149-110)84(118)75-113)139-77-87-99(128)103(145-93(124)70-80(116)64-58-52-46-40-33-27-21-15-9-3)95(106(143-87)151-153(136,137)138)111-89(120)69-79(115)63-57-51-45-39-32-26-20-14-8-2/h79-88,95-106,113-119,126-128H,7-78H2,1-6H3,(H,111,120)(H,112,121)(H,129,130)(H,131,132)(H2,133,134,135)(H2,136,137,138)/t79?,80?,81?,82?,83-,84-,85-,86-,87-,88-,95-,96-,97-,98-,99-,100-,101-,102-,103-,104-,105-,106-,109-,110-/m1/s1 DIXUKJUHGLIZGU-ZKUMOPDFSA-N Cytosol Extra-organism Membrane Periplasm logp 4.35 ALOGPS logs -5.08 ALOGPS solubility 1.86e-02 g/l ALOGPS logp 22.64 ChemAxon pka_strongest_acidic 0.55 ChemAxon iupac (2R,4R,5R,6R)-4-{[(2R,4R,5R,6R)-2-carboxy-6-[(1R)-1,2-dihydroxyethyl]-4,5-dihydroxyoxan-2-yl]oxy}-6-[(1R)-1,2-dihydroxyethyl]-2-{[(2R,3S,4R,5R,6R)-6-{[(2R,3S,4R,5R,6R)-5-[(1,3-dihydroxytetradecylidene)amino]-3-hydroxy-4-[(3-hydroxytetradecanoyl)oxy]-6-(phosphonooxy)oxan-2-yl]methoxy}-5-{[3-(dodecanoyloxy)-1-hydroxytetradecylidene]amino}-3-(phosphonooxy)-4-{[3-(tetradecanoyloxy)tetradecanoyl]oxy}oxan-2-yl]methoxy}-5-hydroxyoxane-2-carboxylic acid ChemAxon average_mass 2238.7184 ChemAxon mono_mass 2237.335997756 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@@]3(C[C@@]([H])(O[C@@]4(C[C@@]([H])(O)[C@@]([H])(O)[C@]([H])(O4)[C@]([H])(O)CO)C(O)=O)[C@@]([H])(O)[C@]([H])(O3)[C@]([H])(O)CO)C(O)=O)[C@@]([H])(OP(O)(O)=O)[C@]([H])(OC(=O)CC([H])(CCCCCCCCCCC)OC(=O)CCCCCCCCCCCCC)[C@@]2([H])N=C(O)CC([H])(CCCCCCCCCCC)OC(=O)CCCCCCCCCCC)O[C@]([H])(OP(O)(O)=O)[C@]1([H])N=C(O)CC([H])(O)CCCCCCCCCCC ChemAxon formula C110H202N2O39P2 ChemAxon inchi InChI=1S/C110H202N2O39P2/c1-7-13-19-25-31-37-38-44-50-56-62-68-92(123)142-82(66-60-54-48-42-35-29-23-17-11-5)72-94(125)146-104-96(112-90(121)71-81(65-59-53-47-41-34-28-22-16-10-4)141-91(122)67-61-55-49-43-36-30-24-18-12-6)105(144-88(102(104)150-152(133,134)135)78-140-109(107(129)130)74-86(98(127)101(148-109)85(119)76-114)147-110(108(131)132)73-83(117)97(126)100(149-110)84(118)75-113)139-77-87-99(128)103(145-93(124)70-80(116)64-58-52-46-40-33-27-21-15-9-3)95(106(143-87)151-153(136,137)138)111-89(120)69-79(115)63-57-51-45-39-32-26-20-14-8-2/h79-88,95-106,113-119,126-128H,7-78H2,1-6H3,(H,111,120)(H,112,121)(H,129,130)(H,131,132)(H2,133,134,135)(H2,136,137,138)/t79?,80?,81?,82?,83-,84-,85-,86-,87-,88-,95-,96-,97-,98-,99-,100-,101-,102-,103-,104-,105-,106-,109-,110-/m1/s1 ChemAxon inchikey DIXUKJUHGLIZGU-ZKUMOPDFSA-N ChemAxon polar_surface_area 645.41 ChemAxon refractivity 564.64 ChemAxon polarizability 249.16 ChemAxon rotatable_bond_count 98 ChemAxon acceptor_count 35 ChemAxon donor_count 18 ChemAxon physiological_charge -5 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 Cationic antimicrobial peptide (CAMP) resistance eco01503 polymyxin resistance PWY0-1338 Lipid A-core biosynthesis LIPA-CORESYN-PWY superpathway of (KDO)2-lipid A biosynthesis KDO-NAGLIPASYN-PWY (KDO)2-lipid A biosynthesis I KDO-LIPASYN-PWY superpathway of lipopolysaccharide biosynthesis LPSSYN-PWY Specdb::MsMs 3640587 Specdb::MsMs 3640588 Specdb::MsMs 3640589 Specdb::MsMs 3640590 Specdb::MsMs 3640591 Specdb::MsMs 3640592 440886 389718 C06026 27963 KDO2-LIPID-A 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 Lipid A biosynthesis (KDO)2-(lauroyl)-lipid IVA acyltransferase P24205 MSBB_ECOLI msbB http://ecmdb.ca/proteins/P24205.xml Phosphoethanolamine transferase eptB P37661 EPTB_ECOLI eptB http://ecmdb.ca/proteins/P37661.xml Undecaprenyl phosphate-alpha-4-amino-4-deoxy-L-arabinose arabinosyl transferase P76473 ARNT_ECOLI arnT http://ecmdb.ca/proteins/P76473.xml Lipopolysaccharide heptosyltransferase 1 P24173 RFAC_ECOLI rfaC http://ecmdb.ca/proteins/P24173.xml Lipopolysaccharide export system permease protein lptG P0ADC6 LPTG_ECOLI lptG http://ecmdb.ca/proteins/P0ADC6.xml Lipopolysaccharide export system permease protein lptF P0AF98 LPTF_ECOLI lptF http://ecmdb.ca/proteins/P0AF98.xml Lipid A export ATP-binding/permease protein msbA P60752 MSBA_ECOLI msbA http://ecmdb.ca/proteins/P60752.xml Lipopolysaccharide export system ATP-binding protein lptB P0A9V1 LPTB_ECOLI lptB http://ecmdb.ca/proteins/P0A9V1.xml Protein crcA P37001 CRCA_ECOLI crcA http://ecmdb.ca/proteins/P37001.xml Lipopolysaccharide export system protein lptC P0ADV9 LPTC_ECOLI lptC http://ecmdb.ca/proteins/P0ADV9.xml Lipopolysaccharide export system protein lptA P0ADV1 LPTA_ECOLI lptA http://ecmdb.ca/proteins/P0ADV1.xml Lipopolysaccharide export system permease protein lptG P0ADC6 LPTG_ECOLI lptG http://ecmdb.ca/proteins/P0ADC6.xml Lipopolysaccharide export system permease protein lptF P0AF98 LPTF_ECOLI lptF http://ecmdb.ca/proteins/P0AF98.xml Lipid A export ATP-binding/permease protein msbA P60752 MSBA_ECOLI msbA http://ecmdb.ca/proteins/P60752.xml Adenosine triphosphate + Water + KDO2-Lipid A > ADP + Hydrogen ion + Phosphate + KDO2-Lipid A Adenosine triphosphate + Water + KDO2-Lipid A > ADP + Hydrogen ion + Phosphate + KDO2-Lipid A Hydrogen ion + Palmitic acid + KDO2-Lipid A > Water + Hepta-acylated KDO2-lipid A Adenosine triphosphate + Water + KDO2-Lipid A > ADP + Hydrogen ion + Phosphate + KDO2-Lipid A Adenosine triphosphate + Water + KDO2-Lipid A > ADP + Hydrogen ion + Phosphate + KDO2-Lipid A KDO(2)-lipid IV(A) with laurate + Myristoyl-ACP (n-C14:0ACP) > acyl carrier protein + KDO2-Lipid A KDO2-Lipid A + PE(14:0/14:0) > 1,2-Diacyl-sn-glycerol (dihexadec-9-enoyl, n-C16:1) + Phosphoethanolamine KDO(2)-lipid (A) KDO2-Lipid A + PE(14:0/14:0) > 1,2-Diacyl-sn-glycerol (dioctadec-11-enoyl, n-C18:1) + Phosphoethanolamine KDO(2)-lipid (A) ADP-L-Glycero-D-manno-heptose + KDO2-Lipid A > ADP + Hydrogen ion + heptosyl-kdo2-lipidA KDO2-Lipid A + Acyl-carrier protein + Tetradecanoyl-[acp] + Lauroyl-KDO2-lipid IV(A) <> Tetradecanoyl-[acp] + Lauroyl-KDO2-lipid IV(A) + Acyl-carrier protein R05075 a phospholipid + KDO2-Lipid A > a glycerol ester + Hepta-acylated KDO2-lipid A RXN0-1842 KDO2-Lipid A + 4-amino-4-deoxy-α-L-arabinopyranosyl ditrans,octacis-undecaprenyl phosphate > L-Ara4N-modified KDO2-Lipid A + Di-trans,poly-cis-undecaprenyl phosphate RXN0-2001 Hydrogen ion + KDO2-Lipid A + ADP-L-Glycero-D-manno-heptose > Heptosyl-KDO2-lipid A + ADP RXN0-5118 undecaprenyl phosphate-4-amino-4-deoxy-L-arabinose + KDO2-Lipid A + 2,3,2'3'-Tetrakis(beta-hydroxymyristoyl)-D-glucosaminyl-1,6-beta-D-glucosamine 1,4'-bisphosphate <> alpha-Kdo-(2->4)-alpha-Kdo-(2->6)-[4-P-L-Ara4N]-lipid A + Di-trans,poly-cis-undecaprenyl phosphate + Lipid IIA R09781 undecaprenyl phosphate-4-amino-4-deoxy-L-arabinose + KDO2-Lipid A + 2 2,3,2'3'-Tetrakis(beta-hydroxymyristoyl)-D-glucosaminyl-1,6-beta-D-glucosamine 1,4'-bisphosphate <> alpha-Kdo-(2->4)-alpha-Kdo-(2->6)-[4-P-L-Ara4N]-lipid A + Di-trans,poly-cis-undecaprenyl phosphate + Lipid IIA