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The genes and enzymes involved in the biosynthesis of thiamin and thiamin diphosphate in yeasts

Abstract

Thiamin (vitamin B1) is an essential molecule for all living organisms. Its major biologically active derivative is thiamin diphosphate, which serves as a cofactor for several enzymes involved in carbohydrate and amino acid metabolism. Important new functions for thiamin and its phosphate esters have recently been suggested, e.g. in gene expression regulation by influencing mRNA structure, in DNA repair after UV illumination, and in the protection of some organelles against reactive oxygen species. Unlike higher animals, which rely on nutritional thiamin intake, yeasts can synthesize thiamin de novo. The biosynthesis pathways include the separate synthesis of two precursors, 4-amino-5-hydroxymethyl-2-methylpyrimidine diphosphate and 5-(2-hydroxyethyl)-4-methylthiazole phosphate, which are then condensed into thiamin monophosphate. Additionally, yeasts evolved salvage mechanisms to utilize thiamin and its dephosphorylated late precursors, 4-amino-5-hydroxymethyl-2-methylpyrimidine and 5-(2-hydroxyethyl)-4-methylthiazole, from the environment. The current state of knowledge on the discrete steps of thiamin biosynthesis in yeasts is far from satisfactory; many intermediates are postulated only by analogy to the much better understood biosynthesis process in bacteria. On the other hand, the genetic mechanisms regulating thiamin biosynthesis in yeasts are currently under extensive exploration. Only recently, the structures of some of the yeast enzymes involved in thiamin biosynthesis, such as thiamin diphosphokinase and thiazole synthase, were determined at the atomic resolution, and mechanistic proposals for the catalysis of particular biosynthetic steps started to emerge.

Abbreviations

HET:

5-(2-hydroxyethyl)-4-methylthiazole

HMP:

4-amino-5-hydroxymethyl-2-methyl pyrimidine

TDP:

thiamin diphosphate

TMP:

thiamin monophosphate

TTP:

thiamin triphosphate

References

  1. Friedrich, W. Thiamin (Vitamin B1, aneurin). in: Hanbuch der Vitamine, Urban & Schwarzenberg, München, Vien, Baltimore, 1987, 240–258.

    Google Scholar 

  2. Hohmann, S. and Meacock, P.A. Thiamin metabolism and thiamin diphosphate-dependent enzymes in the yeast Saccharomyces cerevisiae: genetic regulation. Biochim. Biophys. Acta 1385 (1998) 201–219.

    PubMed  CAS  Google Scholar 

  3. Nosaka, K. Recent progress in understanding thiamin biosynthesis and its genetic regulation in Saccharomyces cerevisiae. Appl. Microbiol. Biotechnol. 72 (2006) 30–40.

    Article  PubMed  CAS  Google Scholar 

  4. Lai, E.C. RNA sensors and riboswitches: self-regulating messages. Curr. Biol. 13 (2003) 285–291.

    Article  CAS  Google Scholar 

  5. Bettendorff, L. A non-cofactor role of thiamine derivatives in excitable cells? Arch. Physiol. Biochem. 104 (1996) 745–751.

    Article  PubMed  CAS  Google Scholar 

  6. Lakaye, B., Wirtzfeld, B., Wins, P., Grisar, T. and Bettendorff, L. Thiamine triphosphate, a new signal required for optimal growth of Escherichia coli during amino acid starvation. J. Biol. Chem. 279 (2004) 17142–17147.

    Article  PubMed  CAS  Google Scholar 

  7. Machado, C.R., Praekelt, U.M., Costa de Oliveira, R.L., Barbosa, A.C.C., Byrne, K.L., Meacock, P.A. and Menck, C.F.M. Dual role for yeast THI4 gene in thiamine biosynthesis and DNA damage tolerance. J. Mol. Biol. 273 (1997) 114–121.

    Article  PubMed  CAS  Google Scholar 

  8. Medina-Silva, R., Barros, M.P., Galhardo, R.S., Netto, L.S., Colepicolo, P. and Menck, C.F. Heat stress promotes mitochondrial instability and oxidative responses in yeast deficient in thiazole biosynthesis. Res. Microbiol. 157 (2005) 275–281.

    Article  PubMed  Google Scholar 

  9. Ahn, I-P., Kim, S. and Lee, Y-H. Vitamin B1 functions as an activator of plant disease resistance. Plant Physiol. 138 (2005) 1505–1515.

    Article  PubMed  CAS  Google Scholar 

  10. Begley, T., Downs, D., Ealick S., McLafferty, F., Van Loon, D., Taylor, S., Campobasso, N., Chiu, J., Kinsland, C., Reddick, J. and Xi, J. Thiamin biosynthesis in prokaryotes. Arch. Microbiol. 171 (1999) 293–300.

    Article  PubMed  CAS  Google Scholar 

  11. Chatterjee, A., Jurgenson, C.T., Schroeder, F.C., Ealick, S.E. and Begley, T.P. Biosynthesis of thiamin thiazole in eukaryotes: conversion of NAD to an advanced intermediate. J. Am. Chem. Soc. 14 (2007) 2914–2922.

    Article  Google Scholar 

  12. Nosaka, K., Nishimura, H., Kawasaki, Y., Tsujihara, T. and Iwashima, A. Isolation and characterization of the THI6 gene encoding a bifunctional thiamin-phosphate pyrophosphorylase/hydroxyethylthiazole kinase from Saccharomyces cerevisiae. J. Biol. Chem. 269 (1994) 30510–3-516.

    PubMed  CAS  Google Scholar 

  13. Zeidler, J., Sayer, B.G. and Spenser, I.D. Biosynthesis of vitamin B1 in yeast. Derivation of the pyrimidine unit from pyridoxine and histidine. Intermediacy of urocanic acid. J. Am. Chem. Soc. 125 (2003) 13094–13105.

    Article  PubMed  CAS  Google Scholar 

  14. Kawasaki, Y., Onozuka, M., Mizote, T. and Nosaka, K. Biosynthesis of hydroxymethylpyrimidine pyrophosphate in Saccharomyces cerevisiae. Curr. Genet. 47 (2005) 156–162.

    Article  PubMed  CAS  Google Scholar 

  15. Nosaka, K., Kaneko, Y., Nishimura, H. and Iwashima, A. Isolation and characterization of a thiamin pyrophosphokinase gene, THI80, from Saccharomyces cerevisiae. J. Biol. Chem. 268 (1993) 17440–17447.

    PubMed  CAS  Google Scholar 

  16. Enjo, F., Nosaka, K., Ogata, M., Iwashima, A. and Nishimura, H. Isolation and characterization of a thiamin transport gene, THI10, from Saccharomyces cerevisiae. J. Biol. Chem. 272 (1997) 19165–19170.

    Article  PubMed  CAS  Google Scholar 

  17. Jurgenson, C.T., Chatterjee, A., Begley, T.P. and Ealick, S.E. Structural insights into the function of the thiamine biosynthetic enzyme Thi4 from Saccharomyces cerevisiae. Biochemistry 45 (2006) 11061–11070.

    Article  PubMed  CAS  Google Scholar 

  18. Faou, P. and Tropschug, M. Neurospora crassa CyPBP37: a cytosolic stress protein that is able to replace yeast Thi4p function in the synthesis of vitamin B1. J. Mol. Biol. 344 (2004) 1147–1157.

    Article  PubMed  CAS  Google Scholar 

  19. Wightman, R. and Meacock, P.A. The THI5 gene family of Saccharomyces cerevisiae: distribution of homologues among the hemiascomycetes and functional redundancy in the aerobic biosynthesis of thiamin from pyridoxine. Microbiology 149 (2003) 1447–1460.

    Article  PubMed  CAS  Google Scholar 

  20. Haas, A.L., Laun, N.P. and Begley, T.P. Thi20, a remarkable enzyme from Saccharomyces cerevisiae with dual thiamin biosynthetic and degradation activities. Bioorg. Chem. 33 (2005) 338–344.

    Article  PubMed  CAS  Google Scholar 

  21. Llorente, B., Fairhead, C. and Dujon, B. Genetic redundancy and gene fusion in the genome of the baker’s yeast Saccharomyces cerevisiae: functional characterization of a three-member gene family involved in the thiamine biosynthetic pathway. Mol. Microbiol. 32 (1999) 1140–1152.

    Article  PubMed  CAS  Google Scholar 

  22. Nosaka, K., Kaneko, Y., Nishimura, H. and Iwashima, A. A possible role for acid phosphatase with thiamin-binding activity encoded by PHO3 in yeast. FEMS Microbiol. Lett. 51 (1989) 55–59.

    Article  PubMed  CAS  Google Scholar 

  23. Marobbio, C.M., Vozza, A., Harding, M., Bissaccia, F., Palmieri, F. and Walker, J.E. Identification and reconstitution of the yeast mitochondrial transporter for thiamine pyrophosphate. EMBO J. 21 (2002) 5653–5661.

    Article  PubMed  CAS  Google Scholar 

  24. Nosaka, K., Onozuka, M., Konno, H., Kawasaki, Y., Nishimura H., Sano, M. and Akaji, K. Genetic regulation mediated by thiamin pyrophosphate-binding motif in Saccharomyces cerevisiae. Mol. Microbiol. 58 (2005) 467–479.

    Article  PubMed  CAS  Google Scholar 

  25. Mojzita D. and Hohmann, S. Pdc2 coordinates expression of the THI regulon in the yeast Saccharomyces cerevisiae. Mol. Gen. Genomics 276 (2006) 147–161.

    Article  CAS  Google Scholar 

  26. Baker, L.J., Dorocke, J.A., Harris, R.A. and Timm, D.E. The crystal structure of yeast thiamin pyrophosphokinase. Structure 9 (2001) 539–546.

    Article  PubMed  CAS  Google Scholar 

  27. Voskoboyev, A.I. and Ostrovsky, Y.M. Thiamin pyrophosphokinase: structure, properties, and role in thiamin metabolism. Ann. N. Y. Acad. Sci. 378 (1982) 161–176.

    Article  PubMed  CAS  Google Scholar 

  28. Kawasaki, Y. Copurification of hydroxyethylthiazole kinase and thiamine-phosphate pyrophosphorylase of Saccharomyces cerevisiae: characterization of hydroxyethylthiazole kinase as a bifunctional enzyme in the thiamine biosynthetic pathway. J. Bacteriol. 175 (1993) 5153–5158.

    PubMed  CAS  Google Scholar 

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Correspondence to Ewa Kowalska.

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Paper authored by participants of the international conference: XXXIV Winter School of the Faculty of Biochemistry, Biophysics and Biotechnology of Jagiellonian University, Zakopane, March 7–11, 2007, “The Cell and Its Environment”. Publication cost was partially covered by the organisers of this meeting.

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Kowalska, E., Kozik, A. The genes and enzymes involved in the biosynthesis of thiamin and thiamin diphosphate in yeasts. Cell Mol Biol Lett 13, 271–282 (2008). https://doi.org/10.2478/s11658-007-0055-5

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