2.02012-07-30 14:55:19 -06002015-06-03 17:21:10 -0600ECMDB21328M2MDB001730DehydroglycineDehydroglycine is a member of the chemical class known as Alpha Amino Acids and Derivatives. These are amino acids in which the amino group is attached to the carbon atom immediately adjacent to the carboxylate group (alpha carbon).Dehydroglycine is catalyzed by ThiH. ThiH is a tyrosine lyase that cleaves the C alpha-C beta bond of tyrosine, generating p-cresol as a by-product, to form dehydroglycine. (PMID 19923213)2-Iminoacetate2-Iminoacetic acidDehydroglycineIminoacetateIminoacetic acidC2H2NO272.042872.0085533132-iminoacetate2-iminoacetate[O-]C(=O)C=NInChI=1S/C2H3NO2/c3-1-2(4)5/h1,3H,(H,4,5)/p-1TVMUHOAONWHJBV-UHFFFAOYSA-MCytosollogp-0.94logs-0.98solubility9.41e+00 g/llogp-0.77pka_strongest_acidic3.93pka_strongest_basic3.27iupac2-iminoacetateaverage_mass72.0428mono_mass72.008553313smiles[O-]C(=O)C=NformulaC2H2NO2inchiInChI=1S/C2H3NO2/c3-1-2(4)5/h1,3H,(H,4,5)/p-1inchikeyTVMUHOAONWHJBV-UHFFFAOYSA-Mpolar_surface_area63.98refractivity36.81polarizability5.49rotatable_bond_count1acceptor_count3donor_count1physiological_charge-1formal_charge-1Thiazole Biosynthesis IThis pathway describes only the synthesis of the thiazole moiety of thiamin. Different variations of this pathway exist, this particular pathway describes the pathway that occurs in Escherichia coli K-12 and Salmonella enterica enterica serovar Typhimurium.
The biosynthesis of the thiazole moiety is complex. In Escherichia coli it involves six proteins, the products of the thiS, thiF, thiG, thiH, thiI, and iscS genes.
The process begins when IscS, a protein that is also involved in the biosynthesis of iron-sulfur clusters, catalyzes the transfer of a sulfur atom from cysteine to a ThiI sulfur-carrier protein, generating a an S-sulfanyl-[ThiI sulfur-carrier protein].
In a parallel route, the ThiF protein activates a ThiS sulfur-carrier protein by adenylation of its carboxy terminus, generating a carboxy-adenylated-[ThiS sulfur-carrier protein]. In a second reaction, which may also be catalyzed by ThiF, the sulfur from an S-sulfanyl-[ThiI sulfur-carrier protein] is transferred to ThiS, generating a thiocarboxy-[ThiS-Protein].
The final reaction of this pathway, which is catalyzed by the ThiG protein, requires three inputs: a thiocarboxy-[ThiS-Protein], 1-deoxy-D-xylulose 5-phosphate and 2-iminoacetate.
2-iminoacetate is formed in Escherichia coli from L-tyrosine by tyrosine lyase (ThiH), which forms a complex with ThiG.
For many years the products of this reaction was assumed to be 4-methyl-5-(β-hydroxyethyl)thiazole (thiazole). However, recent work performed with the thiazole synthase from Bacillus subtilis has shown that the actual product is the thiazole tautomer 2-[(2R,5Z)-(2-carboxy-4-methylthiazol-5(2H)-ylidene]ethyl phosphate. While in Bacillus a dedicated thiazole tautomerase converts this product into a different tautomer (2-(2-carboxy-4-methylthiazol-5-yl)ethyl phosphate), most of the proteobacteria lack the tautomerase. (EcoCyc)PW002041Metabolicthiazole biosynthesis I (E. coli)PWY-6892Specdb::MsMs28904Specdb::MsMs28905Specdb::MsMs28906Specdb::MsMs35462Specdb::MsMs35463Specdb::MsMs35464233478141527227253664CPD-12279Keseler, 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-D590.21097882Challand, M. R., Martins, F. T., Roach, P. L. (2010). "Catalytic activity of the anaerobic tyrosine lyase required for thiamine biosynthesis in Escherichia coli." J Biol Chem 285:5240-5248.19923213Cysteine desulfuraseP0A6B7ISCS_ECOLIiscShttp://ecmdb.ca/proteins/P0A6B7.xmlSulfur carrier protein ThiS adenylyltransferaseP30138THIF_ECOLIthiFhttp://ecmdb.ca/proteins/P30138.xmltRNA sulfurtransferaseP77718THII_ECOLIthiIhttp://ecmdb.ca/proteins/P77718.xmlThiazole synthaseP30139THIG_ECOLIthiGhttp://ecmdb.ca/proteins/P30139.xmlSulfur carrier protein ThiSO32583THIS_ECOLIthiShttp://ecmdb.ca/proteins/O32583.xmlDehydroglycine synthaseP30140THIH_ECOLIthiHhttp://ecmdb.ca/proteins/P30140.xmlAdenosine triphosphate + Dehydroglycine + 1-Deoxy-D-xylulose 5-phosphate + Hydrogen ion + IscS with bound sulfur + NADPH > 4-Methyl-5-(2-phosphoethyl)-thiazole + Adenosine monophosphate + Carbon dioxide +2 Water + IscS sulfur acceptor protein + NADP + PyrophosphateS-Adenosylmethionine + NADPH + L-Tyrosine > p-Cresol + 5'-Deoxyadenosine + Dehydroglycine + Hydrogen ion + L-Methionine + NADPDehydroglycine + Water > Glyoxylic acid + AmmoniaRXN-13329L-Tyrosine + S-Adenosylmethionine + a reduced electron acceptor > Dehydroglycine + p-Cresol + 5'-Deoxyadenosine + L-Methionine + an oxidized electron acceptor + Hydrogen ionRXN-113191-Deoxy-D-xylulose 5-phosphate + Dehydroglycine + a thiocarboxy-[ThiS-Protein] > 2-((2R,5Z)-2-Carboxy-4-methylthiazol-5(2H)-ylidene)ethyl phosphate + a ThiS sulfur-carrier protein +2 WaterPW_R005964L-Tyrosine + S-adenosyl-L-methionine + NADPH > Dehydroglycine + 4-Methylcatechol + 5'-Deoxyadenosine + L-Methionine + NADP + Hydrogen ionPW_R005962