Escherichia coli K-12 substr. MG1655 Pathway: 6-hydroxymethyl-dihydropterin diphosphate biosynthesis I
Inferred from experiment

Pathway diagram: 6-hydroxymethyl-dihydropterin diphosphate biosynthesis I

If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.

Locations of Mapped Genes:

Schematic showing all replicons, marked with selected genes

Genetic Regulation Schematic

Genetic regulation schematic for 6-hydroxymethyl-dihydropterin diphosphate biosynthesis I

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

Reduced folate cofactors are required for the syntheses of various essential cell nutrients. E. coli and other microorganisms must synthesize folates de novo as they lack the transport pathway to take up folate cofactors.

6-hydroxymethyl-7,8-dihydropterin diphosphate is the pterin precursor for the biosynthesis of tetrahydropteroyl mono-L-glutamate. This pterin is synthesized from GTP in a pathway that starts with GTP cyclohydrolase I, which converts GTP into 7,8-dihydroneopterin 3'-triphosphate. The NudB pyrophosphohydrolase then generates 7,8-dihydroneopterin 3'-phosphate. The remaining phosphate group may be removed by one or more non-specific phosphatases. The resulting 7,8-dihydroneopterin is fist converted to 6-hydroxymethyl-7,8-dihydropterin by dihydroneopterin aldolase and subsequently phosphorylated to 6-hydroxymethyl-7,8-dihydropterin diphosphate by FolK.

Review: [Bermingham02]

Superpathways: superpathway of tetrahydrofolate biosynthesis, superpathway of chorismate metabolism

Created 05-Mar-2009 by Caspi R, SRI International
Last-Curated 12-Jul-2011 by Keseler I, SRI International


Bermingham02: Bermingham A, Derrick JP (2002). "The folic acid biosynthesis pathway in bacteria: evaluation of potential for antibacterial drug discovery." Bioessays 24(7);637-48. PMID: 12111724

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

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

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

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

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

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

Derrick08: Derrick JP (2008). "The structure and mechanism of 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase." Vitam Horm 79;411-33. PMID: 18804704

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

Eydallin07: Eydallin G, Viale AM, Moran-Zorzano MT, Munoz FJ, Montero M, Baroja-Fernandez E, Pozueta-Romero J (2007). "Genome-wide screening of genes affecting glycogen metabolism in Escherichia coli K-12." FEBS Lett 581(16);2947-53. PMID: 17543954

Gabelli07: Gabelli SB, Bianchet MA, Xu W, Dunn CA, Niu ZD, Amzel LM, Bessman MJ (2007). "Structure and function of the E. coli dihydroneopterin triphosphate pyrophosphatase: a Nudix enzyme involved in folate biosynthesis." Structure 15(8);1014-22. PMID: 17698004

Garcon04: Garcon A, Bermingham A, Lian LY, Derrick JP (2004). "Kinetic and structural characterization of a product complex of 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase from Escherichia coli." Biochem J 380(Pt 3);867-73. PMID: 15018613

Gaudet10: Gaudet P, Livstone M, Thomas P (2010). "Annotation inferences using phylogenetic trees." PMID: 19578431

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."

GOA06: GOA, SIB (2006). "Electronic Gene Ontology annotations created by transferring manual GO annotations between orthologous microbial proteins."

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Please cite the following article in publications resulting from the use of EcoCyc: Nucleic Acids Research 41:D605-12 2013
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