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Pathway Description
Thiamine Pyrophosphate Biosynthesis
Escherichia coli (strain K12)
Category:
Metabolite Pathway
Sub-Category:
Metabolic
Created: 2025-02-11
Last Updated: 2025-06-17
The biosynthesis of thiamin begins with a PRPP being degraded by reacting with a water molecule and an L-glutamine through a amidophosphoribosyl transferase resulting in the release of an L-glutamate, a diphosphate and a 5-phospho-beta-d-ribosylamine(PRA). The latter compound, PRA, is further degrade through a phosphoribosylamine glycine ligase by reacting with a glycine and an ATP. This reaction results in the release of a hydrogen ion, an ADP, a phosphate and a N1-(5-phospho-beta-d-ribosyl)glycinamide(GAR). GAR can be metabolized by two different phosphoribosylglycinamide formyltransferase. GAR reacts with a N10-formyl tetrahydrofolate, in this case 10-formyl-tetrahydrofolate mono-L-glutamate, through a phosphoribosylglycinamide formyltransferase 1 resulting in the release of a hydroge ion, a tetrahydrofolate and a N2-formyl-N1-(5-phospho-Beta-D-ribosyl)glycinamide(FGAR). On the other hand, GAR can react with a formate and an ATP molecule through a phosphoribosylglycinamide formyltransferase 2 resulting in a release of a ADP, a phosphate, a hydrogen ion and a FGAR. The FGAR compound gets degraded by interacting with a water molecule, an L-glutamine and an ATP molecule thorugh a phosphoribosylformylglycinamide synthase resulting in the release of a L-glutamate, a phosphate, an ADP molecule, a hydrogen ion and a 2-(formamido)-N1-(5-phopho-Beta-D-ribosyl)acetamidine (FGAM). This compound is further degraded by reacting with an ATP molecule through a phosphoribosylformylglycinamide cyclo-ligase resulting in the release of a phosphate, an ADP, a hydrogen ion and a 5-amino-1-(5-phospho-beta-d-ribosyl)imidazole (AIR). The AIR molecule is degraded by reacting with a S-adenosyl-L-methionine through a HMP-P synthase resulting in the release of 3 hydrogen ions, a carbon monoxide, a formate molecule, L-methionine, 5'-deoxyadenosine and 4- amino-2-methyl-5-phophomethylpyrimidine (HMP-P). This resulting compound is phosphorylated thorugh a ATP driven phosphohydroxymethylpyrimidine kinase resulting in the release of an ADP and 4-amino-2-methyl-5-diphosphomethylpyrimidine (HMP-PP). The resulting compound interacts with a thiazole tautomer and 2 hydrogen ion through a Thiamine phosphate synthase resulting in the release of a pyrophosphate, a carbon dioxide molecule and Thiamin phosphate. This compound is phosphorylated through an ATP driven thiamin monophosphate kinase resulting in a release of an ADP and a thiamin diphosphate.
References
Thiamine Pyrophosphate Biosynthesis References
Tso JY, Zalkin H, van Cleemput M, Yanofsky C, Smith JM: Nucleotide sequence of Escherichia coli purF and deduced amino acid sequence of glutamine phosphoribosylpyrophosphate amidotransferase. J Biol Chem. 1982 Apr 10;257(7):3525-31.
Pubmed: 6277938
Nonet ML, Marvel CC, Tolan DR: The hisT-purF region of the Escherichia coli K-12 chromosome. Identification of additional genes of the hisT and purF operons. J Biol Chem. 1987 Sep 5;262(25):12209-17.
Pubmed: 3040734
Tso JY, Hermodson MA, Zalkin H: Glutamine phosphoribosylpyrophosphate amidotransferase from cloned Escherichia coli purF. NH2-terminal amino acid sequence, identification of the glutamine site, and trace metal analysis. J Biol Chem. 1982 Apr 10;257(7):3532-6.
Pubmed: 7037784
Aiba A, Mizobuchi K: Nucleotide sequence analysis of genes purH and purD involved in the de novo purine nucleotide biosynthesis of Escherichia coli. J Biol Chem. 1989 Dec 15;264(35):21239-46.
Pubmed: 2687276
Cheng YS, Shen Y, Rudolph J, Stern M, Stubbe J, Flannigan KA, Smith JM: Glycinamide ribonucleotide synthetase from Escherichia coli: cloning, overproduction, sequencing, isolation, and characterization. Biochemistry. 1990 Jan 9;29(1):218-27. doi: 10.1021/bi00453a030.
Pubmed: 2182115
Blattner FR, Burland V, Plunkett G 3rd, Sofia HJ, Daniels DL: Analysis of the Escherichia coli genome. IV. DNA sequence of the region from 89.2 to 92.8 minutes. Nucleic Acids Res. 1993 Nov 25;21(23):5408-17. doi: 10.1093/nar/21.23.5408.
Pubmed: 8265357
Smith JM, Daum HA 3rd: Identification and nucleotide sequence of a gene encoding 5'-phosphoribosylglycinamide transformylase in Escherichia coli K12. J Biol Chem. 1987 Aug 5;262(22):10565-9.
Pubmed: 3301838
Yamamoto Y, Aiba H, Baba T, Hayashi K, Inada T, Isono K, Itoh T, Kimura S, Kitagawa M, Makino K, Miki T, Mitsuhashi N, Mizobuchi K, Mori H, Nakade S, Nakamura Y, Nashimoto H, Oshima T, Oyama S, Saito N, Sampei G, Satoh Y, Sivasundaram S, Tagami H, Horiuchi T, et al.: Construction of a contiguous 874-kb sequence of the Escherichia coli -K12 genome corresponding to 50.0-68.8 min on the linkage map and analysis of its sequence features. DNA Res. 1997 Apr 28;4(2):91-113. doi: 10.1093/dnares/4.2.91.
Pubmed: 9205837
Blattner FR, Plunkett G 3rd, Bloch CA, Perna NT, Burland V, Riley M, Collado-Vides J, Glasner JD, Rode CK, Mayhew GF, Gregor J, Davis NW, Kirkpatrick HA, Goeden MA, Rose DJ, Mau B, Shao Y: The complete genome sequence of Escherichia coli K-12. Science. 1997 Sep 5;277(5331):1453-62. doi: 10.1126/science.277.5331.1453.
Pubmed: 9278503
Sampei G, Mizobuchi K: The organization of the purL gene encoding 5'-phosphoribosylformylglycinamide amidotransferase of Escherichia coli. J Biol Chem. 1989 Dec 15;264(35):21230-8.
Pubmed: 2531746
Schendel FJ, Mueller E, Stubbe J, Shiau A, Smith JM: Formylglycinamide ribonucleotide synthetase from Escherichia coli: cloning, sequencing, overproduction, isolation, and characterization. Biochemistry. 1989 Mar 21;28(6):2459-71. doi: 10.1021/bi00432a017.
Pubmed: 2659070
Smith JM, Daum HA 3rd: Nucleotide sequence of the purM gene encoding 5'-phosphoribosyl-5-aminoimidazole synthetase of Escherichia coli K12. J Biol Chem. 1986 Aug 15;261(23):10632-6.
Pubmed: 3015935
Vander Horn PB, Backstrom AD, Stewart V, Begley TP: Structural genes for thiamine biosynthetic enzymes (thiCEFGH) in Escherichia coli K-12. J Bacteriol. 1993 Feb;175(4):982-92. doi: 10.1128/jb.175.4.982-992.1993.
Pubmed: 8432721
Mizote T, Tsuda M, Smith DD, Nakayama H, Nakazawa T: Cloning and characterization of the thiD/J gene of Escherichia coli encoding a thiamin-synthesizing bifunctional enzyme, hydroxymethylpyrimidine kinase/phosphomethylpyrimidine kinase. Microbiology. 1999 Feb;145 ( Pt 2):495-501. doi: 10.1099/13500872-145-2-495.
Pubmed: 10075431
Itoh T, Aiba H, Baba T, Hayashi K, Inada T, Isono K, Kasai H, Kimura S, Kitakawa M, Kitagawa M, Makino K, Miki T, Mizobuchi K, Mori H, Mori T, Motomura K, Nakade S, Nakamura Y, Nashimoto H, Nishio Y, Oshima T, Saito N, Sampei G, Seki Y, Horiuchi T, et al.: A 460-kb DNA sequence of the Escherichia coli K-12 genome corresponding to the 40.1-50.0 min region on the linkage map. DNA Res. 1996 Dec 31;3(6):379-92. doi: 10.1093/dnares/3.6.379.
Pubmed: 9097040
Hayashi K, Morooka N, Yamamoto Y, Fujita K, Isono K, Choi S, Ohtsubo E, Baba T, Wanner BL, Mori H, Horiuchi T: Highly accurate genome sequences of Escherichia coli K-12 strains MG1655 and W3110. Mol Syst Biol. 2006;2:2006.0007. doi: 10.1038/msb4100049. Epub 2006 Feb 21.
Pubmed: 16738553
Nishino H: Biogenesis of cocarboxylase in Escherichia coli. Partial purification and some properties of thiamine monophosphate kinase. J Biochem. 1972 Nov;72(5):1093-100. doi: 10.1093/oxfordjournals.jbchem.a129996.
Pubmed: 4567662
This pathway was propagated using PathWhiz -
Pon, A. et al. Pathways with PathWhiz (2015) Nucleic Acids Res. 43(Web Server issue): W552–W559.
Propagated from SMP0002042
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