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MetaCyc Pathway: thiazole biosynthesis II (Bacillus)

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.

Synonyms: 2-(2-carboxy-4-methylthiazol-5-yl)ethyl phosphate biosynthesis

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

Some taxa known to possess this pathway include ? : Bacillus subtilis subtilis 168

Expected Taxonomic Range: Bacteria

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.

Thiamin biosynthesis is composed of the separate formation of the pyrimidine and thiazole moieties, which are subsequently coupled to form thiamin phosphate (see thiamin diphosphate biosynthesis II (Bacillus)).

About This Pathway

This 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 Bacillus subtilis.

The biosynthesis of the thiazole moiety is complex. In Bacillus subtilis it involves six proteins, the products of the iscS, thiF, thiS, thiO, thiG and tenI genes.

The process begins when the ThiF protein activates a ThiS sulfur-carrier protein by adenylation of its carboxy terminus, generating a carboxy-adenylated-[ThiS sulfur-carrier protein]. IscS, a protein that is also involved in the biosynthesis of iron-sulfur clusters, catalyzes the transfer of a sulfur atom from cysteine to the adenylated ThiS, generating a thiocarboxy-adenylated-[ThiS-Protein].

In a parallel reaction, glycine oxidase (ThiO) forms 2-iminoacetate from glycine.

The main reaction of this pathway is a very complex reaction catalyzed by thiazole synthase (ThiG), that requires three inputs: a thiocarboxy-adenylated-[ThiS-Protein], 1-deoxy-D-xylulose 5-phosphate (DXP) and 2-iminoacetate. For many years the product 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 [Hazra09]. A dedicated thiazole tautomerase converts this product into a different tautomer, 2-(2-carboxy-4-methylthiazol-5-yl)ethyl phosphate, which is the actual substrate for the thiamine-phosphate diphosphorylase enzyme [Hazra11].

There are a few differences between the pathways in Bacillus subtilis (see thiazole biosynthesis I (E. coli)) and Escherichia coli K-12. 2-iminoacetate is formed from glycine rather than from L-tyrosine [Settembre03]. The ThiI protein of Bacillus does not seem to be essential or even participate in this pathway [Park03], and thiazole tautomerase does not exist in Escherichia coli [Hazra11].

Superpathways: superpathway of thiamin diphosphate biosynthesis II

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 III (eukaryotes) , 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 III (eukaryotes)

Credits:
Created 14-Sep-2011 by Caspi R , SRI International


References

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

Hazra09: Hazra A, Chatterjee A, Begley TP (2009). "Biosynthesis of the thiamin thiazole in Bacillus subtilis: identification of the product of the thiazole synthase-catalyzed reaction." J Am Chem Soc 131(9);3225-9. PMID: 19216519

Hazra11: Hazra AB, Han Y, Chatterjee A, Zhang Y, Lai RY, Ealick SE, Begley TP (2011). "A missing enzyme in thiamin thiazole biosynthesis: identification of TenI as a thiazole tautomerase." J Am Chem Soc 133(24);9311-9. PMID: 21534620

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

Park03: Park JH, Dorrestein PC, Zhai H, Kinsland C, McLafferty FW, Begley TP (2003). "Biosynthesis of the thiazole moiety of thiamin pyrophosphate (vitamin B1)." Biochemistry 42(42);12430-8. PMID: 14567704

Settembre03: Settembre EC, Dorrestein PC, Park JH, Augustine AM, Begley TP, Ealick SE (2003). "Structural and mechanistic studies on ThiO, a glycine oxidase essential for thiamin biosynthesis in Bacillus subtilis." Biochemistry 42(10);2971-81. PMID: 12627963

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

Begley99: Begley TP, Downs DM, Ealick SE, McLafferty FW, Van Loon AP, Taylor S, Campobasso N, Chiu HJ, Kinsland C, Reddick JJ, Xi J (1999). "Thiamin biosynthesis in prokaryotes." Arch Microbiol 1999;171(5);293-300. PMID: 10382260

Brammer09: Brammer LA, Meyers CF (2009). "Revealing substrate promiscuity of 1-deoxy-D-xylulose 5-phosphate synthase." Org Lett 11(20);4748-51. PMID: 19778006

Brammer11: Brammer LA, Smith JM, Wade H, Meyers CF (2011). "1-Deoxy-D-xylulose 5-phosphate synthase catalyzes a novel random sequential mechanism." J Biol Chem 286(42);36522-31. PMID: 21878632

BRENDA14: BRENDA team (2014). "Imported from BRENDA version existing on Aug 2014." http://www.brenda-enzymes.org.

Dorrestein04: Dorrestein PC, Zhai H, Taylor SV, McLafferty FW, Begley TP (2004). "The biosynthesis of the thiazole phosphate moiety of thiamin (vitamin B1): the early steps catalyzed by thiazole synthase." J Am Chem Soc 126(10);3091-6. PMID: 15012138

Dorrestein04a: Dorrestein PC, Zhai H, McLafferty FW, Begley TP (2004). "The biosynthesis of the thiazole phosphate moiety of thiamin: the sulfur transfer mediated by the sulfur carrier protein ThiS." Chem Biol 11(10);1373-81. PMID: 15489164

Estevez00: Estevez JM, Cantero A, Romero C, Kawaide H, Jimenez LF, Kuzuyama T, Seto H, Kamiya Y, Leon P (2000). "Analysis of the expression of CLA1, a gene that encodes the 1-deoxyxylulose 5-phosphate synthase of the 2-C-methyl-D-erythritol-4-phosphate pathway in Arabidopsis." Plant Physiol 124(1);95-104. PMID: 10982425

Flint96: Flint DH (1996). "Escherichia coli contains a protein that is homologous in function and N-terminal sequence to the protein encoded by the nifS gene of Azotobacter vinelandii and that can participate in the synthesis of the Fe-S cluster of dihydroxy-acid dehydratase." J Biol Chem 1996;271(27);16068-74. PMID: 8663056

GOA00: GOA (2000). "Gene Ontology annotation based on Swiss-Prot keyword mapping."

GOA01: GOA, MGI (2001). "Gene Ontology annotation based on Enzyme Commission mapping." Genomics 74;121-128.

GOA01a: GOA, DDB, FB, MGI, ZFIN (2001). "Gene Ontology annotation through association of InterPro records with GO terms."

GOA07: GOA, UniProt (2007). "Gene Ontology annotation based on Swiss-Prot Subcellular Location vocabulary mapping."

Herz00: Herz S, Wungsintaweekul J, Schuhr CA, Hecht S, Luttgen H, Sagner S, Fellermeier M, Eisenreich W, Zenk MH, Bacher A, Rohdich F (2000). "Biosynthesis of terpenoids: YgbB protein converts 4-diphosphocytidyl-2C-methyl-D-erythritol 2-phosphate to 2C-methyl-D-erythritol 2,4-cyclodiphosphate." Proc Natl Acad Sci U S A 2000;97(6);2486-90. PMID: 10694574

Job02: Job V, Marcone GL, Pilone MS, Pollegioni L (2002). "Glycine oxidase from Bacillus subtilis. Characterization of a new flavoprotein." J Biol Chem 277(9);6985-93. PMID: 11744710

Julsing07: Julsing MK, Rijpkema M, Woerdenbag HJ, Quax WJ, Kayser O (2007). "Functional analysis of genes involved in the biosynthesis of isoprene in Bacillus subtilis." Appl Microbiol Biotechnol 75(6);1377-84. PMID: 17458547

Kambampati99: Kambampati R, Lauhon CT (1999). "IscS is a sulfurtransferase for the in vitro biosynthesis of 4-thiouridine in Escherichia coli tRNA." Biochemistry 1999;38(50);16561-8. PMID: 10600118

Kriek07: Kriek M, Martins F, Leonardi R, Fairhurst SA, Lowe DJ, Roach PL (2007). "Thiazole synthase from Escherichia coli: an investigation of the substrates and purified proteins required for activity in vitro." J Biol Chem 282(24);17413-23. PMID: 17403671

Kuzuyama00: Kuzuyama T, Takagi M, Takahashi S, Seto H (2000). "Cloning and characterization of 1-deoxy-D-xylulose 5-phosphate synthase from Streptomyces sp. Strain CL190, which uses both the mevalonate and nonmevalonate pathways for isopentenyl diphosphate biosynthesis." J Bacteriol 182(4);891-7. PMID: 10648511

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

Lawhorn04a: Lawhorn BG, Gerdes SY, Begley TP (2004). "A genetic screen for the identification of thiamin metabolic genes." J Biol Chem 279(42);43555-9. PMID: 15292217

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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 Wed Nov 26, 2014, BIOCYC14B.