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: Bacteria
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) [Yang98, 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 [Lam92]. 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
Lam92: 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
Yang98: 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
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Di98a: 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
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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
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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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