Reaction: (1) 4-amino-2-methyl-5-(diphosphooxymethyl)pyrimidine + 2-[(2R,5Z)-2-carboxy-4-methylthiazol-5(2H)-ylidene]ethyl phosphate = diphosphate + thiamine phosphate + CO2
(2) 4-amino-2-methyl-5-(diphosphooxymethyl)pyrimidine + 2-(2-carboxy-4-methylthiazol-5-yl)ethyl phosphate = diphosphate + thiamine phosphate + CO2
(3) 4-amino-2-methyl-5-(diphosphooxymethyl)pyrimidine + 4-methyl-5-(2-phosphooxyethyl)thiazole = diphosphate + thiamine phosphate
For diagram of reaction click here.
Other name(s): thiamine phosphate pyrophosphorylase; thiamine monophosphate pyrophosphorylase; TMP-PPase; thiamine-phosphate diphosphorylase; thiE (gene name); TH1 (gene name); THI6 (gene name); 2-methyl-4-amino-5-hydroxymethylpyrimidine-diphosphate:4-methyl-5-(2-phosphoethyl)thiazole 2-methyl-4-aminopyrimidine-5-methenyltransferase; 4-amino-2-methyl-5-diphosphomethylpyrimidine:2-[(2R,5Z)-2-carboxy-4-methylthiazol-5(2H)-ylidene]ethyl phosphate 4-amino-2-methylpyrimidine-5-methenyltransferase (decarboxylating)
Systematic name: 4-amino-2-methyl-5-diphosphomethylpyrimidine:2-[(2R,5Z)-2-carboxy-4-methylthiazol-5(2H)-ylidene]ethyl-phosphate (4-amino-2-methylpyrimidin-5-yl)methyltransferase (decarboxylating)
Comments: The enzyme catalyses the penultimate reaction in thiamine de novo biosynthesis, condensing the pyrimidine and thiazole components. The enzyme is thought to accept the product of EC 126.96.36.199, thiazole synthase, as its substrate. However, it has been shown that in some bacteria, such as Bacillus subtilis, an additional enzyme, thiazole tautomerase (EC 188.8.131.52) converts that compound into its tautomer 2-(2-carboxy-4-methylthiazol-5-yl)ethyl phosphate, and that it is the latter that serves as the substrate for the synthase. In addition to this activity, the enzyme participates in a salvage pathway, acting on 4-methyl-5-(2-phosphono-oxyethyl)thiazole, which is produced from thiamine degradation products. In yeast this activity is found in a bifunctional enzyme (THI6) and in the plant Arabidopsis thaliana the activity is part of a trifunctional enzyme (TH1).
Links to other databases: BRENDA, EXPASY, GTD, KEGG, MetaCyc, PDB, CAS registry number: 9030-30-2
1. Camiener, G.W. and Brown, G.M. The biosynthesis of thiamine. 2. Fractionation of enzyme system and identification of thiazole monophosphate and thiamine monophosphate as intermediates. J. Biol. Chem. 235 (1960) 2411-2417. [PMID: 13807175]
2. Leder, I.G. The enzymatic synthesis of thiamine monophosphate. J. Biol. Chem. 236 (1961) 3066-3071. [PMID: 14463407]
3. Kawasaki, Y. Copurification of hydroxyethylthiazole kinase and thiamine-phosphate pyrophosphorylase of Saccharomyces cerevisiae: characterization of hydroxyethylthiazole kinase as a bifunctional enzyme in the thiamine biosynthetic pathway. J. Bacteriol. 175 (1993) 5153-5158. [PMID: 8394314]
4. Backstrom, A.D., McMordie, R.A.S. and Begley, T.P. Biosynthesis of thiamin I: the function of the thiE gene product. J. Am. Chem. Soc. 117 (1995) 2351-2352.
5. Chiu, H.J., Reddick, J.J., Begley, T.P. and Ealick, S.E. Crystal structure of thiamin phosphate synthase from Bacillus subtilis at 1.25 Å resolution. Biochemistry 38 (1999) 6460-6470. [PMID: 10350464]
6. Ajjawi, I., Tsegaye, Y. and Shintani, D. Determination of the genetic, molecular, and biochemical basis of the Arabidopsis thaliana thiamin auxotroph th1. Arch. Biochem. Biophys. 459 (2007) 107-114. [PMID: 17174261]