Vitamin B6 in its active form pyridoxal phosphate (PLP) is an essential coenzyme of many diverse enzymes. PLP has multiple roles as a versatile cofactor of enzymes that are mainly involved in the metabolism of amino acid compounds. Moreover, VB6 appears to play an important role against photosensitization in fungi. Most unicellular organisms and plants biosynthesize PLP by themselves.

Three metabolic pathways for pyridoxal 5'-phosphate are known (ref. 1, 2):
-the de novo pathway,
-the salvage pathway,
-and the Alternate (yeast/fungal type) pathway.

Most unicellular organisms and plants biosynthesize VB6 using one or two of these three biosynthetic pathways. However, animals such as insects and mammals do not possess any of the pathways and, thus, need to intake VB6 in their diet to survive.

======VARIANT CODES:================

1.0 - De novo pathway,
1.x - some genes are missed from the De novo pathway;
2.0 - de novo pathway and salvage pathway
2.x - de novo pathway with some genes missed and salvage pathway;
3.0 - Salvage pathway;
4.0 - the Alternate (yeast/fungal type) pathway;
5.0 - de novo pathway + salvage pathway + Alternate pathway;
5.x - de novo pathway with some genes missed, salvage pathway and Alternate pathway ( as in Deinococcus radiodurans R1);
6.0 - some genes of de novo pathway and Alternate pathway ( as in Listeria) ternate pathway ( as in Listeria)

Many studies of VB6 metabolism have been conducted in Escherichia coli and fungi such as Cercospora nicotianae, Neurospora crassa, Aspergillus nidulans, and Saccharomyces cerevisiae.
In the case of E. coli, both de novo and salvage pathways have been identified.
These two pathways include enzymes encoded by eight genes in total and share only one gene, pdxH. In the de novo pathway, the pyridine ring of VB6 is generated from D-erythrose-4-phosphate and glyceraldehyde-3-phosphate. On the other hand, in the salvage pathway, PLP is synthesized without pyridine ring generation. A corresponding de novo pathway has not been discovered in fungi or plants. Instead, fungi were found to have another biosynthetic pathway, the fungal type pathway. This pathway has two genes, SNZ and SNO, whose functions are currently unknown. Therefore, species that synthesize PLP have been reported to have at least one of the three PLP biosynthetic pathways.
Database searches revealed (ref. 1, 2) that the key enzymes involved in ring closure of the aromatic pyridoxin ring (PdxA; PdxJ) are present mainly in genomes of bacteria constituting the gamma subdivision of proteobacteria. The distribution of DXS, a transketolase-like enzyme involved in vitamin B6 biosynthesis as well as in thiamine and isoprenoid biosynthesis and the distribution of vitamin B6 modifying enzymes (PdxH: oxidase; PdxK: kinase) was also analyzed. These enzymes are also present in the genomes of animals.

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Oxidation of D-erythrose-4-phosphate to 4-phosphoerythronate is the first step of branch 1 of the de novo pathwayand is catalyzed by the E4P dehydrogenase activities of the GapA and Epd (GapB) enzymes(that proofed in the work of Yang Y.- see Ref.5)

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Recently, the alternate pathway of Pyridoxal 5'-phosphate (PLP) biosynthesis was discovered (ref.8, 9):

Two proteins, known as PdxS and PdxT, together form a PLP synthase in plants, fungi, archaea, and some eubacteria. PLP synthase is a heteromeric glutamine amidotransferase in which PdxT produces ammonia from glutamine and PdxS combines ammonia with five- and three-carbon phosphosugars to form PLP.
The pdxS- and pdxT-like genes are proximal or adjacent to one another in most organisms where the PdxS/PdxT pathway exists.
The overall catalytic conversion by PLP synthase is more complex than reactions catalyzed by other glutamine amidotransferases (Ref.9). In addition to ammonia transfer, the enzyme catalyzes condensation of two phosphosugars, closure of the pyridine ring, as well as isomerase reactions for its phosphosugar substrates. The complexity of the enzyme correlates well with the strong conservation of the PdxS sequence. Cross-talk between glutaminase and synthase active sites also appears more complex. Binding of one synthase substrate inhibits the glutaminase activity below basal levels, and full stimulation likely requires binding both phosphosugar substrates.

PdxT – Homologs are known as yaaE, pdx2, PDX2, SNO, and SNZB - Pyridoxine biosynthesis glutamine amidotransferase, glutaminase subunit (EC 2.4.2.-)

PdxS - Homologs are known as yaaD, pdx1, PDX1, SNZ, SOR1, PYROA, and HEVER - Pyridoxine biosynthesis glutamine amidotransferase, synthase subunit (EC 2.4.2.-)

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Missing gene PdxB alternative:

PdxB is missing in a large group of organisms ( Haemophilus, Xylella, Campylobacter).
Winkler suggests that SerA enzyme acts in a an alternate pathway of pyridoxine biosynthesis in pdxB mutants (Ref.6,7).

This pathway, which parallels the phosphorylated pathway of serine biosynthesis, is predicted on the homology between PdxB and SerA, the structural similarity between serine and 4-hydroxythreonine, and the possible involvement of SerC ( PdxF ) in pyridoxine biosynthesis.
serA-encoded 3-phosphoglycerate (3PG) dehydrogenase catalyzes the first step of the major phosphorylated pathway of L-serine (Ser) biosynthesis. The SerA enzyme is evolutionarily related to the pdxB gene product, 4-phosphoerythronate dehydrogenase, which catalyzes the second step in one branch of pyridoxal 5'-phosphate coenzyme biosynthesis. Both the Ser and pyridoxal 5'-phosphate biosynthetic pathways use the serC(pdxF)-encoded transaminase in their next steps.

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REFERENCES:

1.T. Tanaka, Y. Tateno, and T. Gojobori. Evolution of Vitamin B6 (Pyridoxine) Metabolism by Gain and Loss of Genes. Mol. Biol. Evol., February 1, 2005; 22(2): 243 - 250.

2. Mittenhuber, G. 2001. Phylogenetic analyses and comparative genomics of VB6 (pyridoxine) and pyridoxal phosphate biosynthesis pathways. J. Mol. Microbiol. Biotechnol. 3:1–20.

3. Hill RE, Himmeldirk K, Kennedy IA, Pauloski RM, Sayer BG, Wolf E, Spenser ID. The biogenetic anatomy of vitamin B6. A 13C NMR investigation of the biosynthesis of pyridoxol in Escherichia coli. J Biol Chem. 1996 Nov 29;271(48):30426-35.

4. Dong YX, Sueda S, Nikawa J, Kondo H. Characterization of the products of the genes SNO1 and SNZ1 involved in pyridoxine synthesis in Saccharomyces cerevisiae. Eur J Biochem. 2004 Feb;271(4):745-52.

5. 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

6. Schoenlein PV, Roa BB, Winkler ME. Divergent transcription of pdxB and homology between the pdxB and serA gene products in Escherichia coli K-12.J Bacteriol. 1989 Nov;171(11):6084-92.

7. Lam HM, Winkler ME. Metabolic relationships between pyridoxine (vitamin B6) and serine biosynthesis in Escherichia coli K-12.J Bacteriol. 1990 Nov;172(11):6518-28.

8. Raschle, T., Amrhein, N., Fitzpatrick, T. B. (2005). On the Two Components of Pyridoxal 5'-Phosphate Synthase from Bacillus subtilis. J. Biol. Chem. 280: 32291-32300

9. Zhu, J., Burgner, J. W., Harms, E., Belitsky, B. R., Smith, J. L. (2005). A New Arrangement of ({beta}/{alpha})8 Barrels in the Synthase Subunit of PLP Synthase. J. Biol. Chem. 280: 27914-27923

10. Sakai A, Kita M, Katsuragi T, Tani Y. serC is involved in vitamin B6 biosynthesis in Escherichia coli but not in Bacillus subtilis.J Biosci Bioeng. 2002;93(3):334-7.PMID: 16233211

11. Fitzpatrick TB, Amrhein N, Kappes B, Macheroux P, Tews I, Raschle T.
Two independent routes of de novo vitamin B6 biosynthesis: not that different after all.
Biochem J. 2007 Oct 1;407(1):1-13. Review.PMID: 17822383