2.02012-05-31 14:27:57 -06002015-09-17 15:41:56 -0600ECMDB20109M2MDB0009577,8-Diaminononanoate7,8-diaminononanoate (or DAPA) is an intermediate in biotin biosynthesis. It is a substrate for Adenosylmethionine-8-amino-7-oxononanoate aminotransferase (or bioA). This enzyme catalyzes the transfer of the alpha-amino group from S-adenosyl-L-methionine (SAM) to 7-keto-8-aminopelargonic acid (KAPA) to form 7,8-diaminopelargonic acid (DAPA). The reaction is S-adenosyl-L-methionine + 8-amino-7-oxononanoate = S-adenosyl-4-methylthio-2-oxobutanoate + 7,8-diaminononanoate. DAPA is a simple intercalator, much like the widely studied 9-aminoacridine. (PMID 16180206; 16984394)(7R,8S)-7,8-diaminononanoate(7R,8S)-7,8-diaminononanoic acid7,8-Diamino-Nonanoate7,8-Diamino-Nonanoic Acid7,8-Diaminononanoate7,8-Diaminononanoic acid7,8-Diaminopelargonate7,8-Diaminopelargonic acid7,8DANADAPADiaminononanoateDiaminononanoic acidDNNC9H19N2O2187.264187.145201447,8-diaminononanoic acid7,8-diaminopelargonic acid21738-21-6CC(N)C(N)CCCCCC([O-])=OInChI=1S/C9H20N2O2/c1-7(10)8(11)5-3-2-4-6-9(12)13/h7-8H,2-6,10-11H2,1H3,(H,12,13)/p-1KCEGBPIYGIWCDH-UHFFFAOYSA-MCytosollogp-2.11logs-1.58solubility4.94e+00 g/llogp-1.9pka_strongest_acidic4.73pka_strongest_basic9.97iupac7,8-diaminononanoic acidaverage_mass187.264mono_mass187.14520144smilesCC(N)C(N)CCCCCC([O-])=OformulaC9H19N2O2inchiInChI=1S/C9H20N2O2/c1-7(10)8(11)5-3-2-4-6-9(12)13/h7-8H,2-6,10-11H2,1H3,(H,12,13)/p-1inchikeyKCEGBPIYGIWCDH-UHFFFAOYSA-Mpolar_surface_area89.34refractivity51.3polarizability21.87rotatable_bond_count7acceptor_count4donor_count3physiological_charge1formal_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::CMs3470Specdb::NmrOneD305171Specdb::NmrOneD305172Specdb::NmrOneD305173Specdb::NmrOneD305174Specdb::NmrOneD305175Specdb::NmrOneD305176Specdb::NmrOneD305177Specdb::NmrOneD305178Specdb::NmrOneD305179Specdb::NmrOneD305180Specdb::NmrOneD305181Specdb::NmrOneD305182Specdb::NmrOneD305183Specdb::NmrOneD305184Specdb::NmrOneD305185Specdb::NmrOneD305186Specdb::NmrOneD305187Specdb::NmrOneD305188Specdb::NmrOneD305189Specdb::NmrOneD305190Specdb::MsMs28199Specdb::MsMs28200Specdb::MsMs28201Specdb::MsMs34757Specdb::MsMs34758Specdb::MsMs34759Specdb::MsMs3608344Specdb::MsMs3608345Specdb::MsMs3608346Specdb::MsMs3608347Specdb::MsMs3608348Specdb::MsMs3608349652632C010372247DIAMINONONANOATEKeseler, 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 80:2939-2948.18331064Hoffmann, G. R., Yin, C. C., Terry, C. E., Ferguson, L. R., Denny, W. A. (2006). "Frameshift mutations induced by four isomeric nitroacridines and their des-nitro counterpart in the lacZ reversion assay in Escherichia coli." Environ Mol Mutagen 47:82-94.16180206Mann, S., Ploux, O. (2006). "7,8-Diaminoperlargonic acid aminotransferase from Mycobacterium tuberculosis, a potential therapeutic target. Characterization and inhibition studies." FEBS J 273:4778-4789.16984394Yurtsever D. (2007). Fatty acid methyl ester profiling of Enterococcus and Esherichia coli for microbial source tracking. M.sc. Thesis. Villanova University: U.S.APutative dethiobiotin synthetaseP0A6E9BIOD2_ECOLIynfKhttp://ecmdb.ca/proteins/P0A6E9.xmlAdenosylmethionine-8-amino-7-oxononanoate aminotransferaseP12995BIOA_ECOLIbioAhttp://ecmdb.ca/proteins/P12995.xmlDethiobiotin synthetaseP13000BIOD_ECOLIbioDhttp://ecmdb.ca/proteins/P13000.xml8-Amino-7-oxononanoate + S-Adenosylmethionine <> S-Adenosyl-4-methylthio-2-oxobutanoate + 7,8-DiaminononanoateR03231DAPASYN-RXNAdenosine triphosphate + Carbon dioxide + 7,8-Diaminononanoate <> ADP + Dethiobiotin +3 Hydrogen ion + PhosphateR03182DETHIOBIOTIN-SYN-RXNAdenosine triphosphate + 7,8-Diaminononanoate + Carbon dioxide <> ADP + Phosphate + DethiobiotinR03182S-Adenosylmethionine + 8-Amino-7-oxononanoate > S-Adenosyl-4-methylthio-2-oxobutanoate + 7,8-DiaminononanoateDAPASYN-RXNCarbon dioxide + 7,8-Diaminononanoate + Adenosine triphosphate > Hydrogen ion + Dethiobiotin + Phosphate + ADPDETHIOBIOTIN-SYN-RXNS-adenosyl-L-methionine + 8-Amino-7-oxononanoate > S-Adenosyl-4-methylthio-2-oxobutanoate + 7,8-DiaminononanoateAdenosine triphosphate + 7,8-Diaminononanoate + Carbon dioxide > ADP + Inorganic phosphate + Dethiobiotin8-Amino-7-oxononanoate + S-adenosyl-L-methionine > a sulfurated [sulfur carrier] + 7,8-Diaminononanoate + 7,8-DiaminononanoatePW_R0024977,8-Diaminononanoate + Adenosine triphosphate + Carbon dioxide + 7,8-Diaminononanoate > Dethiobiotin + Adenosine diphosphate + Phosphate + ADPPW_R0024988 8-Amino-7-oxononanoate + S-Adenosylmethionine <> S-Adenosyl-4-methylthio-2-oxobutanoate +7 7,8-DiaminononanoateAdenosine triphosphate + Carbon dioxide + 7 7,8-Diaminononanoate <> ADP + Dethiobiotin +3 Hydrogen ion + Phosphate8 8-Amino-7-oxononanoate + S-Adenosylmethionine <> S-Adenosyl-4-methylthio-2-oxobutanoate +7 7,8-DiaminononanoateAdenosine triphosphate + Carbon dioxide + 7 7,8-Diaminononanoate <> ADP + Dethiobiotin +3 Hydrogen ion + Phosphate