If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.
Synonyms: vitamin B6 biosynthesis
|Superclasses:||Biosynthesis → Cofactors, Prosthetic Groups, Electron Carriers Biosynthesis → Vitamins Biosynthesis → Vitamin B6 Biosynthesis|
Some taxa known to possess this pathway include : Escherichia coli K-12 substr. MG1655
Expected Taxonomic Range:
Vitamin B6 is a group term for pyridoxal (PL), pyridoxine (PN), pyridoxamine (PM) and their 5'-phosphorylated derivatives pyridoxal 5'-phosphate (PLP), pyridoxine 5'-phosphate (PNP) and pyridoxamine 5'-phosphate (PMP), which are also referred to as vitamers. Pyridoxal 5'-phosphate (PLP) is the biochemically active form, and is an essential cofactor in all living systems [John95]. It plays an important role in amino acid and carbohydrate metabolism and has recently been implicated in singlet oxygen resistance [Daub00]. Most bacteria, archaebacteria, fungi, and plants synthesize PLP in a single reaction, as described in pyridoxal 5'-phosphate biosynthesis II, although some bacteria, such as Escherichia coli, use a longer, more complex pathway (pyridoxal 5'-phosphate biosynthesis I) [Yang98a, Sivaraman03a]. Animals do not synthesize this compound, making it an essential nutrient in their diet.
PLP is an essential cofactor of numerous metabolic enzymes, predominantly in amino acid metabolism. It is one of the most versatile cofactors and participates in transamination, decarboxylation, racemization, Cα-Cβ cleavage and α-β elimination reactions. In humans this vitamin has a role in numerous functions ranging from modulation of hormone function to potent antioxidant activity.
About This Pathway
The biosynthesis of this vitamin was thoroughly studied in Escherichia coli and involves two branches with seven enzymatic steps. In one branch, the sequential action of the enzymes Epd, PdxB and SerC results in the convesrion of erythrose 4-phosphate into 4-phosphohydroxy-L-threonine. The latter then undergoes oxidation and decarboxylation by PdxA to form 3-hydroxy-1-aminoacetone phosphate. In the other branch, deoxyxylulose 5-phosphate (DXP) is derived from glyceraldehyde 3-phosphate (GAP) and pyruvate by the action of Dxs. The products of the two branches, i.e. 3-hydroxy-1-aminoacetone phosphate and DXP, are then condensed by PdxJ to form PNP, which enters the salvage pathway to undergo oxidation by PdxH to form the PLP cofactor.
From the six pdx genes, two of them, epd and serC, are involved in other metabolic processes, but pdxA, pdxB, pdxJ and pdxH are unique for PLP biosynthesis [Lam92a]. PdxJ, the PNP synthase is the key ezyme that catalyzes a multistep ring closure yielding PNP and inorganic phosphate (Pi). This is the last step in the de novo synthetic pathway.
An alternative DXP-independent pathway for PNP biosynthesis is described at pyridoxal 5'-phosphate biosynthesis II.
Unification Links: EcoCyc:PYRIDOXSYN-PWY
Fitzpatrick07: Fitzpatrick TB, Amrhein N, Kappes B, Macheroux P, Tews I, Raschle T (2007). "Two independent routes of de novo vitamin B6 biosynthesis: not that different after all." Biochem J 407(1);1-13. PMID: 17822383
Lam92a: Lam HM, Tancula E, Dempsey WB, Winkler ME (1992). "Suppression of insertions in the complex pdxJ operon of Escherichia coli K-12 by lon and other mutations." J Bacteriol 1992;174(5);1554-67. PMID: 1537800
Sivaraman03a: Sivaraman J, Li Y, Banks J, Cane DE, Matte A, Cygler M (2003). "Crystal structure of Escherichia coli PdxA, an enzyme involved in the pyridoxal phosphate biosynthesis pathway." J Biol Chem 278(44);43682-90. PMID: 12896974
Yang98a: Yang Y, Zhao G, Man TK, Winkler ME (1998). "Involvement of the gapA- and epd (gapB)-encoded dehydrogenases in pyridoxal 5'-phosphate coenzyme biosynthesis in Escherichia coli K-12." J Bacteriol 1998;180(16);4294-9. PMID: 9696782
Alefounder89: Alefounder PR, Perham RN (1989). "Identification, molecular cloning and sequence analysis of a gene cluster encoding the class II fructose 1,6-bisphosphate aldolase, 3-phosphoglycerate kinase and a putative second glyceraldehyde 3-phosphate dehydrogenase of Escherichia coli." Mol Microbiol 3(6);723-32. PMID: 2546007
Baek03: Baek JY, Jun DY, Taub D, Kim YH (2003). "Characterization of human phosphoserine aminotransferase involved in the phosphorylated pathway of L-serine biosynthesis." Biochem J 373(Pt 1);191-200. PMID: 12633500
Banks04: Banks J, Cane DE (2004). "Biosynthesis of vitamin B6: direct identification of the product of the PdxA-catalyzed oxidation of 4-hydroxy-l-threonine-4-phosphate using electrospray ionization mass spectrometry." Bioorg Med Chem Lett 14(7);1633-6. PMID: 15026039
Begley99: Begley TP, Downs DM, Ealick SE, McLafferty FW, Van Loon AP, Taylor S, Campobasso N, Chiu HJ, Kinsland C, Reddick JJ, Xi J (1999). "Thiamin biosynthesis in prokaryotes." Arch Microbiol 1999;171(5);293-300. PMID: 10382260
BoschiMuller97: Boschi-Muller S, Azza S, Pollastro D, Corbier C, Branlant G (1997). "Comparative enzymatic properties of GapB-encoded erythrose-4-phosphate dehydrogenase of Escherichia coli and phosphorylating glyceraldehyde-3-phosphate dehydrogenase." J Biol Chem 272(24);15106-12. PMID: 9182530
Clarke73: Clarke SJ, Low B, Konigsberg WH (1973). "Close linkage of the genes serC (for phosphohydroxy pyruvate transaminase) and serS (for seryl-transfer ribonucleic acid synthetase) in Escherichia coli K-12." J Bacteriol 113(3);1091-5. PMID: 4570768
Di98: Di Salvo M, Yang E, Zhao G, Winkler ME, Schirch V (1998). "Expression, purification, and characterization of recombinant Escherichia coli pyridoxine 5'-phosphate oxidase." Protein Expr Purif 1998;13(3);349-56. PMID: 9693059
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
diSalvo03: di Salvo ML, Safo MK, Musayev FN, Bossa F, Schirch V (2003). "Structure and mechanism of Escherichia coli pyridoxine 5'-phosphate oxidase." Biochim Biophys Acta 1647(1-2);76-82. PMID: 12686112
Drewke96: Drewke C, Klein M, Clade D, Arenz A, Muller R, Leistner E (1996). "4-O-phosphoryl-L-threonine, a substrate of the pdxC(serC) gene product involved in vitamin B6 biosynthesis." FEBS Lett 1996;390(2);179-82. PMID: 8706854
Duncan86: Duncan K, Coggins JR (1986). "The serC-aro A operon of Escherichia coli. A mixed function operon encoding enzymes from two different amino acid biosynthetic pathways." Biochem J 1986;234(1);49-57. PMID: 3518706
Estevez00: Estevez JM, Cantero A, Romero C, Kawaide H, Jimenez LF, Kuzuyama T, Seto H, Kamiya Y, Leon P (2000). "Analysis of the expression of CLA1, a gene that encodes the 1-deoxyxylulose 5-phosphate synthase of the 2-C-methyl-D-erythritol-4-phosphate pathway in Arabidopsis." Plant Physiol 124(1);95-104. PMID: 10982425
Garrido00: Garrido Franco M, Huber R, Schmidt FS, Laber B, Clausen T (2000). "Crystallization and preliminary X-ray crystallographic analysis of PdxJ, the pyridoxine 5'-phosphate synthesizing enzyme." Acta Crystallogr D Biol Crystallogr 2000;56 ( Pt 8);1045-8. PMID: 10944349
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