2.02012-05-31 13:59:58 -06002015-09-13 12:56:13 -0600ECMDB03581M2MDB000517DethiobiotinDethiobiotin is a synthetic metabolite that mimic the effects of biotin on gene expression and thus have biotin-like activities. It is an intermediate in biotin metabolism, and converted to biotin via biotin synthase (EC:2.8.1.6). (KEGG) Biotin serves as a coenzyme for carboxylases such as propionyl-CoA carboxylase. (PMID 12730407)DesthiobiotinDTBC10H18N2O3214.2615214.1317424526-[(4R,5S)-5-methyl-2-oxoimidazolidin-4-yl]hexanoic acid(4R,5S)-dethiobiotin533-48-2[H][C@@]1(C)NC(=O)N[C@]1([H])CCCCCC(O)=OInChI=1S/C10H18N2O3/c1-7-8(12-10(15)11-7)5-3-2-4-6-9(13)14/h7-8H,2-6H2,1H3,(H,13,14)(H2,11,12,15)/t7-,8+/m0/s1AUTOLBMXDDTRRT-JGVFFNPUSA-NSolidCytosollogp0.72logs-2.23solubility1.27e+00 g/lmelting_point157 oClogp0.73pka_strongest_acidic4.63pka_strongest_basic-1.8iupac6-[(4R,5S)-5-methyl-2-oxoimidazolidin-4-yl]hexanoic acidaverage_mass214.2615mono_mass214.131742452smiles[H][C@@]1(C)NC(=O)N[C@]1([H])CCCCCC(O)=OformulaC10H18N2O3inchiInChI=1S/C10H18N2O3/c1-7-8(12-10(15)11-7)5-3-2-4-6-9(13)14/h7-8H,2-6H2,1H3,(H,13,14)(H2,11,12,15)/t7-,8+/m0/s1inchikeyAUTOLBMXDDTRRT-JGVFFNPUSA-Npolar_surface_area78.43refractivity54.4polarizability23.15rotatable_bond_count6acceptor_count3donor_count3physiological_charge-1formal_charge0Biotin metabolismBiotin (vitamin H or vitamin B7) is the essential cofactor of biotin-dependent carboxylases, such as pyruvate carboxylase and acetyl-CoA carboxylase.In E. coli and many organisms, pimelate thioester is derived from malonyl-ACP. The pathway starts with a malonyl-[acp] interacting with S-adenosylmethionine through a biotin synthesis protein BioC resulting in a S-adenosylhomocysteine and a malonyl-[acp] methyl ester. The latter compound is then involved in the synthesis of a 3-ketoglutaryl-[acp] methyl ester through a 3-oxoacyl-[acyl-carrier-protein] synthase. The compound 3-ketoglutaryl-[acp] methyl ester is reduced by a NADPH mediated 3-oxoacyl-[acyl-carrier-protein] reductase resulting in a 3R-hydroxyglutaryl-[acp] methyl ester. This compound is then dehydrated through ad (3R)-hydroxymyristoyl-[acp] dehydratase producing a enoylglutaryl-[acp] methyl ester. This compound is then reduced through a NADPH mediated enoyl-acp-reductase [NADH] resulting in a glutaryl-[acp] methyl ester. This compound interacts with a malonyl-[acp] through a 3-oxoacyl-[acp] synthase 2 resulting in a 3-ketopimeloyl [acp] methyl ester. This compound is then reduced through a NADPH 3-oxoacyl [acp] reductase producing a 3-hydroxypimeloyl-[acp] methyl ester and then dehydrated by (3R)-hydroxymyristoyl-[acp] dehydratase to produce a enoylpimeloyl-[acp] methyl ester. This compound is then reduced by a NADPH dependent enoyl-[acp]reductase resulting in a pimeloyl-[acp] methyl ester. This compound then reacts with water through a carboxylesterase resulting in a pimeloyl-[acp] and a methanol. The pimeloyl-acp reacts with L-alanine through a 8-amino-7-oxononanoate synthase resulting in 8-amino-7-oxononanoate which in turn reacts with S-adenosylmethionine through a 7,8 diaminonanoate transaminase resulting in a S-adenosyl-4-methylthio-2-oxobutanoate and 7,8 diaminononanoate. The latter compound is then dephosphorylated through a dethiobiotin synthetase resulting in a dethiobiotin. This compound interacts with a sulfurated[sulfur carrier), a hydrogen ion and a S-adenosylmethionine through a biotin synthase to produce Biotin and releasing l-methionine and a 5-deoxyadenosine.
Biotin is then metabolized by a bifunctional protein resulting in pyrophosphate and Biotinyl-5-AMP which in turn reacts with the same protein (bifunctional protein birA resulting ina biotin caroxyl carrying protein.This product then enters the fatty acid biosynthesis.
PW000762ec00780MetabolicMetabolic pathwayseco01100biotin biosynthesis from 7-keto-8-aminopelargonatePWY0-1507Specdb::CMs1886Specdb::CMs2351Specdb::CMs30510Specdb::CMs31470Specdb::CMs38635Specdb::CMs137197Specdb::CMs144931Specdb::NmrOneD4757Specdb::NmrOneD4758Specdb::NmrOneD315341Specdb::NmrOneD315342Specdb::NmrOneD315343Specdb::NmrOneD315344Specdb::NmrOneD315345Specdb::NmrOneD315346Specdb::NmrOneD315347Specdb::NmrOneD315348Specdb::NmrOneD315349Specdb::NmrOneD315350Specdb::NmrOneD315351Specdb::NmrOneD315352Specdb::NmrOneD315353Specdb::NmrOneD315354Specdb::NmrOneD315355Specdb::NmrOneD315356Specdb::NmrOneD315357Specdb::NmrOneD315358Specdb::NmrOneD315359Specdb::NmrOneD315360Specdb::MsMs25019Specdb::MsMs25020Specdb::MsMs25021Specdb::MsMs31577Specdb::MsMs31578Specdb::MsMs31579Specdb::MsMs374815Specdb::MsMs446034Specdb::MsMs446035Specdb::MsMs446036Specdb::MsMs446037Specdb::MsMs447254Specdb::MsMs451501Specdb::MsMs2236383Specdb::MsMs2236981Specdb::MsMs2238550Specdb::MsMs2239047Specdb::MsMs2240511Specdb::MsMs2241176Specdb::MsMs2242576Specdb::MsMs2243285Specdb::MsMs2355789Specdb::MsMs2355790Specdb::MsMs2355791Specdb::MsMs2607264HMDB03581643392787C0190916691DETHIOBIOTINDTBKeseler, 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-D590.21097882Kanehisa, 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-D114.22080510van 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 370:17-25.17765195Winder, 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 80:2939-2948.18331064Rodriguez-Melendez, R., Lewis, B., McMahon, R. J., Zempleni, J. (2003). "Diaminobiotin and desthiobiotin have biotin-like activities in Jurkat cells." J Nutr 133:1259-1264.12730407Kuzuhara, Hiroyoshi; Ohrui, Hiroshi; Emoto, Sakae. Syntheses with azido sugars. II. Conversion of D-glucose to (+)-dethiobiotin. Agricultural and Biological Chemistry (1971), 35(1), 8-17.http://hmdb.ca/system/metabolites/msds/000/003/162/original/HMDB03581.pdf?1358462377Putative dethiobiotin synthetaseP0A6E9BIOD2_ECOLIynfKhttp://ecmdb.ca/proteins/P0A6E9.xmlBiotin synthaseP12996BIOB_ECOLIbioBhttp://ecmdb.ca/proteins/P12996.xmlDethiobiotin synthetaseP13000BIOD_ECOLIbioDhttp://ecmdb.ca/proteins/P13000.xml[2Fe-2S] iron-sulfur cluster + S-Adenosylmethionine + Dethiobiotin > [2Fe-1S] desulfurated iron-sulfur cluster + Biotin + 5'-Deoxyadenosine + Hydrogen ion + L-MethionineAdenosine triphosphate + Carbon dioxide + 7,8-Diaminononanoate <> ADP + Dethiobiotin +3 Hydrogen ion + PhosphateR03182DETHIOBIOTIN-SYN-RXNDethiobiotin + Sulfur donor + 2 S-Adenosylmethionine + 2 e- + 2 Hydrogen ion <> Biotin +2 L-Methionine +2 5'-DeoxyadenosineR01078Adenosine triphosphate + 7,8-Diaminononanoate + Carbon dioxide <> ADP + Phosphate + DethiobiotinR03182<i>S</i>-sulfanyl-[acceptor] + Dethiobiotin + S-Adenosylmethionine > an unsulfurated sulfur acceptor + Biotin + 5'-Deoxyadenosine + L-Methionine + Hydrogen ion2.8.1.6-RXNCarbon dioxide + 7,8-Diaminononanoate + Adenosine triphosphate > Hydrogen ion + Dethiobiotin + Phosphate + ADPDETHIOBIOTIN-SYN-RXNDethiobiotin + Hydrogen sulfide + 2 S-adenosyl-L-methionine > Biotin +2 L-Methionine +2 5'-DeoxyadenosineAdenosine triphosphate + 7,8-Diaminononanoate + Carbon dioxide > ADP + Inorganic phosphate + Dethiobiotin7,8-Diaminononanoate + Adenosine triphosphate + Carbon dioxide + 7,8-Diaminononanoate > Dethiobiotin + Adenosine diphosphate + Phosphate + ADPPW_R002498Dethiobiotin + 2 S-adenosyl-L-methionine + 2 Hydrogen ion + a sulfurated [sulfur carrier] > Biotin +2 L-Methionine +2 5'-DeoxyadenosinePW_R002499Dethiobiotin + Sulfur donor + 2 S-Adenosylmethionine + 2 e- + 2 Hydrogen ion <> Biotin +2 L-Methionine +2 5'-DeoxyadenosineAdenosine triphosphate + Carbon dioxide + 7 7,8-Diaminononanoate <> ADP + Dethiobiotin +3 Hydrogen ion + PhosphateDethiobiotin + Sulfur donor + 2 S-Adenosylmethionine + 2 e- + 2 Hydrogen ion <> Biotin +2 L-Methionine +2 5'-DeoxyadenosineAdenosine triphosphate + Carbon dioxide + 7 7,8-Diaminononanoate <> ADP + Dethiobiotin +3 Hydrogen ion + Phosphate