Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
BioCyc websites down
12/28 - 12/31
for maintenance.
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
BioCyc websites down
12/28 - 12/31
for maintenance.
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
BioCyc websites down
12/28 - 12/31
for maintenance.
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
BioCyc websites down
12/28 - 12/31
for maintenance.
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
BioCyc websites down
12/28 - 12/31
for maintenance.
twitter

MetaCyc Pathway: thiazole biosynthesis III (eukaryotes)

Enzyme View:

This view shows enzymes only for those organisms listed below, in the list of taxa known to possess the pathway. If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.

Superclasses: Biosynthesis Cofactors, Prosthetic Groups, Electron Carriers Biosynthesis Vitamins Biosynthesis Thiamin Biosynthesis

Some taxa known to possess this pathway include ? : Arabidopsis thaliana col , Saccharomyces cerevisiae

Expected Taxonomic Range: Alveolata , Fungi , Viridiplantae

Summary:
General Background

Thiamin diphosphate, also known as vitamin B1, is known to play a fundamental role in energy metabolism. It is an essential cofactor for a variety of enzymes such as transketolase, pyruvate dehydrogenase, pyruvate decarboxylase, and α-ketoglutarate dehydrogenase [Lawhorn04]. Its discovery followed from the original early research on the anti-beriberi factor found in rice bran. Beriberi, a neurological disease, was particularly prevalent in Asia, where the refining of rice resulted in the removal of the thiamin-containing husk [Begley96]. Thiamin is synthesized de novo by microorganisms, plants and some lower eukaryotes (e.g. Plasmodium ), but not by higher eukaryotes, which must obtain it through their diet.

About This Pathway

Thiamin phosphate is formed by the coupling of two moieties, the pyrimidine 4-amino-2-methyl-5-diphosphomethylpyrimidine and the thiazole 4-methyl-5-(2-phosphonooxyethyl)thiazole, which are produced by two different pathways. This pathway describes the formation of the thiazole moiety in eukaryotes.

Genetic studies in Saccharomyces cerevisiae have demonstrated that THI4 is the only gene required for thiamin thiazole formation [Praekelt94]. The donor of the sulphur incorporated in adenylated thiazole was elusive for a long time. It has been shown that THI4 promotes a very unusual chemical reaction in which it acts as a co-substrate and supplies the sulphur through an iron-dependent transfer from an internal cysteine amino acid residue (Cys-205) to the reaction product. The reaction converts Cys-205 to 2-aminoprop-2-enoate and renders THI4 inactive. Hence, THI4 represents a single-turnover (suicide) enzyme [Chatterjee11]. Insofar THI4 resembles another single-turnover enzyme, i.e. 4-amino-2-methyl-5-phosphomethylpyrimidine synthase (THI5) which is involved in the pyrimidine moiety formation in Saccharomyces cerevisiae (see 4-amino-2-methyl-5-phosphomethylpyrimidine biosynthesis (yeast)).

The protein, overexpressed in Escherichia coli, copurified with its product (adenylated thiazole) and two additional adenylated intermediates that shed light on its complex mechanism [Chatterjee08]. Similarly, in the plant Arabidopsis thaliana the multifunctional protein THI1 is sufficient for thiazole production. While it has been shown that NAD and glycine are substrates for the enzyme, the exact source of sulfur is still not known.

The THI1 protein localizes to the chloroplasts, suggesting that this part of the pathway occurs in this organelle [Raschke07, Kong08, Ajjawi07, Chabregas01]. However, THI1 can also localize to the mitochondria [Chabregas01], and the downstream TPK1 and TPK2 enzymes are both cytosolic in Arabidopsis [Ajjawi07a], suggesting that intermediates in the vitamin B1 biosynthesis pathway may need to be transported out of organelles for thiamin diphosphate synthesis to be completed.

Superpathways: superpathway of thiamin diphosphate biosynthesis III (eukaryotes)

Variants: 4-amino-2-methyl-5-diphosphomethylpyrimidine biosynthesis , 4-amino-2-methyl-5-phosphomethylpyrimidine biosynthesis (yeast) , superpathway of thiamin diphosphate biosynthesis I , superpathway of thiamin diphosphate biosynthesis II , thiamin diphosphate biosynthesis I (E. coli) , thiamin diphosphate biosynthesis II (Bacillus) , thiamin diphosphate biosynthesis III (Staphylococcus) , thiamin diphosphate biosynthesis IV (eukaryotes) , thiamin formation from pyrithiamine and oxythiamine (yeast) , thiamin triphosphate metabolism , thiazole biosynthesis I (E. coli) , thiazole biosynthesis II (Bacillus)

Credits:
Created 23-Sep-2011 by Caspi R , SRI International
Revised 05-Jun-2013 by Foerster H , Boyce Thompson Institute


References

Ajjawi07: Ajjawi I, Tsegaye Y, Shintani D (2007). "Determination of the genetic, molecular, and biochemical basis of the Arabidopsis thaliana thiamin auxotroph th1." Arch Biochem Biophys 459(1);107-14. PMID: 17174261

Ajjawi07a: Ajjawi I, Rodriguez Milla MA, Cushman J, Shintani DK (2007). "Thiamin pyrophosphokinase is required for thiamin cofactor activation in Arabidopsis." Plant Mol Biol 65(1-2);151-62. PMID: 17611796

Begley96: Begley, T.P. (1996). "The biosynthesis and degradation of thiamin (vitamin B1)." Natural products report.

Chabregas01: Chabregas SM, Luche DD, Farias LP, Ribeiro AF, van Sluys MA, Menck CF, Silva-Filho MC (2001). "Dual targeting properties of the N-terminal signal sequence of Arabidopsis thaliana THI1 protein to mitochondria and chloroplasts." Plant Mol Biol 46(6);639-50. PMID: 11575719

Chatterjee08: Chatterjee A, Schroeder FC, Jurgenson CT, Ealick SE, Begley TP (2008). "Biosynthesis of the thiamin-thiazole in eukaryotes: identification of a thiazole tautomer intermediate." J Am Chem Soc 130(34);11394-8. PMID: 18652458

Chatterjee11: Chatterjee A, Abeydeera ND, Bale S, Pai PJ, Dorrestein PC, Russell DH, Ealick SE, Begley TP (2011). "Saccharomyces cerevisiae THI4p is a suicide thiamine thiazole synthase." Nature 478(7370);542-6. PMID: 22031445

Kong08: Kong D, Zhu Y, Wu H, Cheng X, Liang H, Ling HQ (2008). "AtTHIC, a gene involved in thiamine biosynthesis in Arabidopsis thaliana." Cell Res 18(5);566-76. PMID: 18332905

Lawhorn04: Lawhorn BG, Mehl RA, Begley TP (2004). "Biosynthesis of the thiamin pyrimidine: the reconstitution of a remarkable rearrangement reaction." Org Biomol Chem 2(17);2538-46. PMID: 15326535

Machado96: Machado CR, de Oliveira RL, Boiteux S, Praekelt UM, Meacock PA, Menck CF (1996). "Thi1, a thiamine biosynthetic gene in Arabidopsis thaliana, complements bacterial defects in DNA repair." Plant Mol Biol 31(3);585-93. PMID: 8790291

Praekelt94: Praekelt UM, Byrne KL, Meacock PA (1994). "Regulation of THI4 (MOL1), a thiamine-biosynthetic gene of Saccharomyces cerevisiae." Yeast 10(4);481-90. PMID: 7941734

Raschke07: Raschke M, Burkle L, Muller N, Nunes-Nesi A, Fernie AR, Arigoni D, Amrhein N, Fitzpatrick TB (2007). "Vitamin B1 biosynthesis in plants requires the essential iron sulfur cluster protein, THIC." Proc Natl Acad Sci U S A 104(49);19637-42. PMID: 18048325

Other References Related to Enzymes, Genes, Subpathways, and Substrates of this Pathway

Chatterjee06: Chatterjee A, Jurgenson CT, Schroeder FC, Ealick SE, Begley TP (2006). "Thiamin biosynthesis in eukaryotes: characterization of the enzyme-bound product of thiazole synthase from Saccharomyces cerevisiae and its implications in thiazole biosynthesis." J Am Chem Soc 128(22);7158-9. PMID: 16734458

Chatterjee07: Chatterjee A, Jurgenson CT, Schroeder FC, Ealick SE, Begley TP (2007). "Biosynthesis of thiamin thiazole in eukaryotes: conversion of NAD to an advanced intermediate." J Am Chem Soc 129(10);2914-22. PMID: 17309261

Godoi06: Godoi PH, Galhardo RS, Luche DD, Van Sluys MA, Menck CF, Oliva G (2006). "Structure of the thiazole biosynthetic enzyme THI1 from Arabidopsis thaliana." J Biol Chem 281(41);30957-66. PMID: 16912043

Jurgenson06: Jurgenson CT, Chatterjee A, Begley TP, Ealick SE (2006). "Structural insights into the function of the thiamin biosynthetic enzyme Thi4 from Saccharomyces cerevisiae." Biochemistry 45(37);11061-70. PMID: 16964967

Jurgenson09: Jurgenson CT, Begley TP, Ealick SE (2009). "The structural and biochemical foundations of thiamin biosynthesis." Annu Rev Biochem 78;569-603. PMID: 19348578

Koornneef81: Koornneef, M., Hanhart, C. J. (1981). "A New Thiamin Locus in Arabidopsis." Arabidopsis Information Resource. 18:52.

Kowalska08: Kowalska E, Kozik A (2008). "The genes and enzymes involved in the biosynthesis of thiamin and thiamin diphosphate in yeasts." Cell Mol Biol Lett 13(2);271-82. PMID: 18161008

Latendresse13: Latendresse M. (2013). "Computing Gibbs Free Energy of Compounds and Reactions in MetaCyc."

Machado97: Machado CR, Praekelt UM, de Oliveira RC, Barbosa AC, Byrne KL, Meacock PA, Menck CF (1997). "Dual role for the yeast THI4 gene in thiamine biosynthesis and DNA damage tolerance." J Mol Biol 273(1);114-21. PMID: 9367751

Roach11: Roach P (2011). "Biochemistry: Suicide of a protein." Nature 478(7370);463-4. PMID: 22031434


Report Errors or Provide Feedback
Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
Page generated by SRI International Pathway Tools version 18.5 on Fri Dec 19, 2014, biocyc14.