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 → Folate Biosynthesis → 6-Hydroxymethyl-Dihydropterin Diphosphate Biosynthesis|
Some taxa known to possess this pathway include : Arabidopsis thaliana col, Escherichia coli K-12 substr. MG1655, Lactococcus lactis, Oryza sativa, Pisum sativum, Saccharomyces cerevisiae, Solanum lycopersicum, Spinacia oleracea
6-hydroxymethyl-7,8-dihydropterin diphosphate (6-hydroxymethyl-dihydropterin diphosphate) is the pterin precursor for the biosynthesis of several important cofactors, including tetrahydropteroyl mono-L-glutamate, methanopterin and sarcinapterin. The compound is always synthesized from GTP, but the enzymes involve may differ among organisms.
This pathway, which is found in bacteria, fungi and plants, starts with GTP cyclohydrolase I, an enzyme that converts GTP into 7,8-dihydroneopterin 3'-triphosphate. The triphosphate motif is removed in a process that is still not completely understood, and the resulting 7,8-dihydroneopterin is converted to 6-hydroxymethyl-7,8-dihydropterin by dihydroneopterin aldolase (FolB).
In plants the pterin moiety is formed from GTP in the cytosol.
Unification Links: EcoCyc:PWY-6147
Basset02: Basset G, Quinlivan EP, Ziemak MJ, Diaz De La Garza R, Fischer M, Schiffmann S, Bacher A, Gregory JF, Hanson AD (2002). "Folate synthesis in plants: the first step of the pterin branch is mediated by a unique bimodular GTP cyclohydrolase I." Proc Natl Acad Sci U S A 99(19);12489-94. PMID: 12221287
Adams14: Adams NE, Thiaville JJ, Proestos J, Juarez-Vazquez AL, McCoy AJ, Barona-Gomez F, Iwata-Reuyl D, de Crecy-Lagard V, Maurelli AT (2014). "Promiscuous and adaptable enzymes fill "holes" in the tetrahydrofolate pathway in Chlamydia species." MBio 5(4). PMID: 25006229
Auerbach00: Auerbach G, Herrmann A, Bracher A, Bader G, Gutlich M, Fischer M, Neukamm M, Garrido-Franco M, Richardson J, Nar H, Huber R, Bacher A (2000). "Zinc plays a key role in human and bacterial GTP cyclohydrolase I." Proc Natl Acad Sci U S A 97(25);13567-72. PMID: 11087827
Babitzke92: Babitzke P, Gollnick P, Yanofsky C (1992). "The mtrAB operon of Bacillus subtilis encodes GTP cyclohydrolase I (MtrA), an enzyme involved in folic acid biosynthesis, and MtrB, a regulator of tryptophan biosynthesis." J Bacteriol 174(7);2059-64. PMID: 1551827
Ballantine94: Ballantine SP, Volpe F, Delves CJ (1994). "The hydroxymethyldihydropterin pyrophosphokinase domain of the multifunctional folic acid synthesis Fas protein of Pneumocystis carinii expressed as an independent enzyme in Escherichia coli: refolding and characterization of the recombinant enzyme." Protein Expr Purif 5(4);371-8. PMID: 7950384
Bauer04: Bauer S, Schott AK, Illarionova V, Bacher A, Huber R, Fischer M (2004). "Biosynthesis of tetrahydrofolate in plants: crystal structure of 7,8-dihydroneopterin aldolase from Arabidopsis thaliana reveals a novel aldolase class." J Mol Biol 339(4);967-79. PMID: 15165863
Bermingham00: Bermingham A, Bottomley JR, Primrose WU, Derrick JP (2000). "Equilibrium and kinetic studies of substrate binding to 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase from Escherichia coli." J Biol Chem 275(24);17962-7. PMID: 10751386
Blaszczyk00: Blaszczyk J, Shi G, Yan H, Ji X (2000). "Catalytic center assembly of HPPK as revealed by the crystal structure of a ternary complex at 1.25 A resolution." Structure 8(10);1049-58. PMID: 11080626
Blaszczyk03: Blaszczyk J, Li Y, Shi G, Yan H, Ji X (2003). "Dynamic roles of arginine residues 82 and 92 of Escherichia coli 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase: crystallographic studies." Biochemistry 42(6);1573-80. PMID: 12578370
Blaszczyk04: Blaszczyk J, Li Y, Wu Y, Shi G, Ji X, Yan H (2004). "Essential roles of a dynamic loop in the catalysis of 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase." Biochemistry 43(6);1469-77. PMID: 14769023
Blaszczyk04a: Blaszczyk J, Shi G, Li Y, Yan H, Ji X (2004). "Reaction trajectory of pyrophosphoryl transfer catalyzed by 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase." Structure (Camb) 12(3);467-75. PMID: 15016362
Blaszczyk14: Blaszczyk J, Lu Z, Li Y, Yan H, Ji X (2014). "Crystallographic and molecular dynamics simulation analysis of Escherichia coli dihydroneopterin aldolase." Cell Biosci 4(1);52. PMID: 25264482
Bolotin01: Bolotin A, Wincker P, Mauger S, Jaillon O, Malarme K, Weissenbach J, Ehrlich SD, Sorokin A (2001). "The complete genome sequence of the lactic acid bacterium Lactococcus lactis ssp. lactis IL1403." Genome Res 11(5);731-53. PMID: 11337471
Burg68: Burg AW, Brown GM (1968). "The biosynthesis of folic acid. 8. Purification and properties of the enzyme that catalyzes the production of formate from carbon atom 8 of guanosine triphosphate." J Biol Chem 1968;243(9);2349-58. PMID: 4296838
deCrecyLagard12: de Crecy-Lagard V, Phillips G, Grochowski LL, El Yacoubi B, Jenney F, Adams MW, Murzin AG, White RH (2012). "Comparative genomics guided discovery of two missing archaeal enzyme families involved in the biosynthesis of the pterin moiety of tetrahydromethanopterin and tetrahydrofolate." ACS Chem Biol 7(11);1807-16. PMID: 22931285
DiazMejia09: Diaz-Mejia JJ, Babu M, Emili A (2009). "Computational and experimental approaches to chart the Escherichia coli cell-envelope-associated proteome and interactome." FEMS Microbiol Rev 33(1);66-97. PMID: 19054114
Dobrzanska02: Dobrzanska M, Szurmak B, Wyslouch-Cieszynska A, Kraszewska E (2002). "Cloning and characterization of the first member of the Nudix family from Arabidopsis thaliana." J Biol Chem 277(52);50482-6. PMID: 12399474
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