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Pathway Description
Folate Biosynthesis
Escherichia coli (strain MS 21-1)
Category:
Metabolite Pathway
Sub-Category:
Metabolic
Created: 2025-01-20
Last Updated: 2025-01-20
The biosynthesis of folic acid begins as a product of purine nucleotides de novo biosynthesis pathway. Purine nucleotides are involved in a reaction with water through a GTP cyclohydrolase 1 protein complex, resulting in a hydrogen ion, formic acid and 7,8-dihydroneopterin 3-triphosphate. The latter compound is dephosphorylated through a dihydroneopterin triphosphate pyrophosphohydrolase resulting in the release of a pyrophosphate, hydrogen ion and 7,8-dihydroneopterin 3-phosphate. The latter product reacts with water spontaneously resulting in the release of a phosphate and a 7,8 -dihydroneopterin. 7,8 -dihydroneopterin reacts with a dihydroneopterin aldolase, releasing a glycoaldehyde and 6-hydroxymethyl-7,9-dihydropterin. Continuing, 6-hydroxymethyl-7,9-dihydropterin is phosphorylated with a ATP-driven 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase resulting in a (2-amino-4-hydroxy-7,8-dihydropteridin-6-yl)methyl diphosphate.
Chorismate is metabolized by reacting with L-glutamine through a 4-amino-4-deoxychorismate synthase resulting in L-glutamic acid and 4-amino-4-deoxychorismate. The latter product is then catalyzed via an aminodeoxychorismate lyase resulting in pyruvic acid, hydrogen ion and p-aminobenzoic acid.
(2-amino-4-hydroxy-7,8-dihydropteridin-6-yl)methyl diphosphate and p-aminobenzoic acid react with the help of a dihydropteroate synthase resulting in pyrophosphate and 7,8-dihydropteroic acid. This compound then reacts with L-glutamic acid through an ATP driven bifunctional folylpolyglutamate synthease / dihydrofolate synthease resulting in a 7,8-dihydrofolate monoglutamate. 7,8-dihydrofolate monoglutamate is then reduced via a NADPH mediated dihydrofolate reductase resulting in a tetrahydrofate which will continue and become a metabolite of the folate pathway
References
Folate Biosynthesis References
Katzenmeier G, Schmid C, Kellermann J, Lottspeich F, Bacher A: Biosynthesis of tetrahydrofolate. Sequence of GTP cyclohydrolase I from Escherichia coli. Biol Chem Hoppe Seyler. 1991 Nov;372(11):991-7.
Pubmed: 1665332
Schmid C, Meining W, Weinkauf S, Bachmann L, Ritz H, Eberhardt S, Gimbel W, Werner T, Lahm HW, Nar H, et al.: Studies on GTP cyclohydrolase I of Escherichia coli. Adv Exp Med Biol. 1993;338:157-62. doi: 10.1007/978-1-4615-2960-6_30.
Pubmed: 8304099
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
Sharples GJ, Lloyd RG: Resolution of Holliday junctions in Escherichia coli: identification of the ruvC gene product as a 19-kilodalton protein. J Bacteriol. 1991 Dec;173(23):7711-5. doi: 10.1128/jb.173.23.7711-7715.1991.
Pubmed: 1657895
Takahagi M, Iwasaki H, Nakata A, Shinagawa H: Molecular analysis of the Escherichia coli ruvC gene, which encodes a Holliday junction-specific endonuclease. J Bacteriol. 1991 Sep;173(18):5747-53. doi: 10.1128/jb.173.18.5747-5753.1991.
Pubmed: 1885548
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
Cain BD, Norton PJ, Eubanks W, Nick HS, Allen CM: Amplification of the bacA gene confers bacitracin resistance to Escherichia coli. J Bacteriol. 1993 Jun;175(12):3784-9. doi: 10.1128/jb.175.12.3784-3789.1993.
Pubmed: 8389741
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
Talarico TL, Ray PH, Dev IK, Merrill BM, Dallas WS: Cloning, sequence analysis, and overexpression of Escherichia coli folK, the gene coding for 7,8-dihydro-6-hydroxymethylpterin-pyrophosphokinase. J Bacteriol. 1992 Sep;174(18):5971-7. doi: 10.1128/jb.174.18.5971-5977.1992.
Pubmed: 1325970
Fujita N, Mori H, Yura T, Ishihama A: Systematic sequencing of the Escherichia coli genome: analysis of the 2.4-4.1 min (110,917-193,643 bp) region. Nucleic Acids Res. 1994 May 11;22(9):1637-9. doi: 10.1093/nar/22.9.1637.
Pubmed: 8202364
Swedberg G, Fermer C, Skold O: Point mutations in the dihydropteroate synthase gene causing sulfonamide resistance. Adv Exp Med Biol. 1993;338:555-8. doi: 10.1007/978-1-4615-2960-6_113.
Pubmed: 8304179
Dallas WS, Gowen JE, Ray PH, Cox MJ, Dev IK: Cloning, sequencing, and enhanced expression of the dihydropteroate synthase gene of Escherichia coli MC4100. J Bacteriol. 1992 Sep;174(18):5961-70. doi: 10.1128/jb.174.18.5961-5970.1992.
Pubmed: 1522070
Green JM, Nichols BP: p-Aminobenzoate biosynthesis in Escherichia coli. Purification of aminodeoxychorismate lyase and cloning of pabC. J Biol Chem. 1991 Jul 15;266(20):12971-5.
Pubmed: 2071583
Green JM, Merkel WK, Nichols BP: Characterization and sequence of Escherichia coli pabC, the gene encoding aminodeoxychorismate lyase, a pyridoxal phosphate-containing enzyme. J Bacteriol. 1992 Aug;174(16):5317-23. doi: 10.1128/jb.174.16.5317-5323.1992.
Pubmed: 1644759
Oshima T, Aiba H, Baba T, Fujita K, Hayashi K, Honjo A, Ikemoto K, Inada T, Itoh T, Kajihara M, Kanai K, Kashimoto K, Kimura S, Kitagawa M, Makino K, Masuda S, Miki T, Mizobuchi K, Mori H, Motomura K, Nakamura Y, Nashimoto H, Nishio Y, Saito N, Horiuchi T, et al.: A 718-kb DNA sequence of the Escherichia coli K-12 genome corresponding to the 12.7-28.0 min region on the linkage map. DNA Res. 1996 Jun 30;3(3):137-55. doi: 10.1093/dnares/3.3.137.
Pubmed: 8905232
Goncharoff P, Nichols BP: Nucleotide sequence of Escherichia coli pabB indicates a common evolutionary origin of p-aminobenzoate synthetase and anthranilate synthetase. J Bacteriol. 1984 Jul;159(1):57-62.
Pubmed: 6330050
Rayl EA, Green JM, Nichols BP: Escherichia coli aminodeoxychorismate synthase: analysis of pabB mutations affecting catalysis and subunit association. Biochim Biophys Acta. 1996 Jun 7;1295(1):81-8. doi: 10.1016/0167-4838(96)00029-5.
Pubmed: 8679677
Kaplan JB, Nichols BP: Nucleotide sequence of Escherichia coli pabA and its evolutionary relationship to trp(G)D. J Mol Biol. 1983 Aug 15;168(3):451-68. doi: 10.1016/s0022-2836(83)80295-2.
Pubmed: 6350604
Tran PV, Bannor TA, Doktor SZ, Nichols BP: Chromosomal organization and expression of Escherichia coli pabA. J Bacteriol. 1990 Jan;172(1):397-410. doi: 10.1128/jb.172.1.397-410.1990.
Pubmed: 2403545
Bognar AL, Osborne C, Shane B: Primary structure of the Escherichia coli folC gene and its folylpolyglutamate synthetase-dihydrofolate synthetase product and regulation of expression by an upstream gene. J Biol Chem. 1987 Sep 5;262(25):12337-43.
Pubmed: 3040739
Kimlova LJ, Pyne C, Keshavjee K, Huy J, Beebakhee G, Bognar AL: Mutagenesis of the folC gene encoding folylpolyglutamate synthetase-dihydrofolate synthetase in Escherichia coli. Arch Biochem Biophys. 1991 Jan;284(1):9-16. doi: 10.1016/0003-9861(91)90254-g.
Pubmed: 1989505
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
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 SMP0000925
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