MetaCyc Pathway: 6-hydroxymethyl-dihydropterin diphosphate biosynthesis II (archaea)
Inferred from experiment

Enzyme View:

Pathway diagram: 6-hydroxymethyl-dihydropterin diphosphate biosynthesis II (archaea)

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: BiosynthesisCofactors, Prosthetic Groups, Electron Carriers BiosynthesisVitamins BiosynthesisFolate Biosynthesis6-Hydroxymethyl-Dihydropterin Diphosphate Biosynthesis

Some taxa known to possess this pathway include : Methanocaldococcus jannaschii, Methanosarcina thermophila

Expected Taxonomic Range: Archaea

(7,8-dihydropterin-6-yl)methyl 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.

The archaeal pathway differs somewhat from the pathway found in bacteria and eukarya (see 6-hydroxymethyl-dihydropterin diphosphate biosynthesis I). The first step of the pathway is catalyzed by the archaeal EC, GTP cyclohydrolase IV. Unlike the analogous GTP cyclohydrolase I enzymes found in bacteria, where the product is 7,8-dihydroneopterin 3'-triphosphate, the product of the archaeal enzyme, characterized from Methanocaldococcus jannaschii, is 7,8-dihydroneopterin 2',3'-cyclic phosphate [Grochowski07]. This cyclic phosphate compound is hydrolyzed by EC, 7,8-dihydroneopterin 2′,3′-cyclic phosphate phosphodiesterase, which forms a mixture of 7,8-dihydroneopterin 2'-phosphate and 7,8-dihydroneopterin 3'-phosphate [Mashhadi09].

The phosphate group of these two compounds is then removed by an as-yet unidentified enzyme. The resulting 7,8-dihydroneopterin is converted to (7,8-dihydropterin-6-yl)methyl diphosphate in two steps, catalyzed by enzymes encoded by the mptD and mptE genes. Even though these enzymes catalyze the same functions as the bacterial enzymes encoded by folB and folK, respectively, the archaeal genes have no sequence similarity to their bacterial counterparts [deCrecyLagard12].

Variants: 6-hydroxymethyl-dihydropterin diphosphate biosynthesis I, 6-hydroxymethyl-dihydropterin diphosphate biosynthesis III (Chlamydia)

Created 26-Apr-2011 by Caspi R, SRI International


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

Grochowski07: Grochowski LL, Xu H, Leung K, White RH (2007). "Characterization of an Fe(2+)-dependent archaeal-specific GTP cyclohydrolase, MptA, from Methanocaldococcus jannaschii." Biochemistry 46(22);6658-67. PMID: 17497938

Mashhadi09: Mashhadi Z, Xu H, White RH (2009). "An Fe2+-dependent cyclic phosphodiesterase catalyzes the hydrolysis of 7,8-dihydro-D-neopterin 2',3'-cyclic phosphate in methanopterin biosynthesis." Biochemistry 48(40);9384-92. PMID: 19746965

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

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

Allen14: Allen KD, Xu H, White RH (2014). "Identification of a unique radical SAM methylase likely involved in methanopterin biosynthesis in Methanocaldococcus jannaschii." J Bacteriol. PMID: 25002541

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

BRENDA14: BRENDA team (2014). Imported from BRENDA version existing on Aug 2014.

Brown71: Brown GM (1971). "The biosynthesis of pteridines." Adv Enzymol Relat Areas Mol Biol 1971;35;35-77. PMID: 4361155

Goyer04: Goyer A, Illarionova V, Roje S, Fischer M, Bacher A, Hanson AD (2004). "Folate biosynthesis in higher plants. cDNA cloning, heterologous expression, and characterization of dihydroneopterin aldolases." Plant Physiol 135(1);103-11. PMID: 15107504

Haussmann98: Haussmann C, Rohdich F, Schmidt E, Bacher A, Richter G (1998). "Biosynthesis of pteridines in Escherichia coli. Structural and mechanistic similarity of dihydroneopterin-triphosphate epimerase and dihydroneopterin aldolase." J Biol Chem 273(28);17418-24. PMID: 9651328

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

Li03b: Li Y, Wu Y, Blaszczyk J, Ji X, Yan H (2003). "Catalytic roles of arginine residues 82 and 92 of Escherichia coli 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase: site-directed mutagenesis and biochemical studies." Biochemistry 42(6);1581-8. PMID: 12578371

Mathis70: Mathis JB, Brown GM (1970). "The biosynthesis of folic acid. XI. Purification and properties of dihydroneopterin aldolase." J Biol Chem 1970;245(11);3015-25. PMID: 4912541

Rebeille97: Rebeille F, Macherel D, Mouillon JM, Garin J, Douce R (1997). "Folate biosynthesis in higher plants: purification and molecular cloning of a bifunctional 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase/7,8-dihydropteroate synthase localized in mitochondria." EMBO J 16(5);947-57. PMID: 9118956

Richey69: Richey DP, Brown GM (1969). "The biosynthesis of folic acid. IX. Purification and properties of the enzymes required for the formation of dihydropteroic acid." J Biol Chem 1969;244(6);1582-92. PMID: 4304228

Shi00: Shi G, Gong Y, Savchenko A, Zeikus JG, Xiao B, Ji X, Yan H (2000). "Dissecting the nucleotide binding properties of Escherichia coli 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase with fluorescent 3'(2)'-o-anthraniloyladenosine 5'-triphosphate." Biochim Biophys Acta 1478(2);289-99. PMID: 10825540

Talarico91: Talarico TL, Dev IK, Dallas WS, Ferone R, Ray PH (1991). "Purification and partial characterization of 7,8-dihydro-6-hydroxymethylpterin-pyrophosphokinase and 7,8-dihydropteroate synthase from Escherichia coli MC4100." J Bacteriol 173(21);7029-32. PMID: 1657875

Wang06a: Wang Y, Li Y, Yan H (2006). "Mechanism of dihydroneopterin aldolase: functional roles of the conserved active site glutamate and lysine residues." Biochemistry 45(51);15232-9. PMID: 17176045

Wang06b: Wang Y, Scherperel G, Roberts KD, Jones AD, Reid GE, Yan H (2006). "A point mutation converts dihydroneopterin aldolase to a cofactor-independent oxygenase." J Am Chem Soc 128(40);13216-23. PMID: 17017801

Wang07: Wang Y, Li Y, Wu Y, Yan H (2007). "Mechanism of dihydroneopterin aldolase. NMR, equilibrium and transient kinetic studies of the Staphylococcus aureus and Escherichia coli enzymes." FEBS J 274(9):2240-52. PMID: 17388809

Wang14a: Wang Y, Xu H, Grochowski LL, White RH (2014). "Biochemical characterization of a dihydroneopterin aldolase used for methanopterin biosynthesis in methanogens." J Bacteriol 196(17);3191-8. PMID: 24982305

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Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
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