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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

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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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  • DOI: https://doi.org/10.2478/s11658-007-0055-5

Key words

  • Thiamin biosynthesis
  • Thiamin diphosphate
  • Thiazole
  • Pyrimidine
  • THI genes
  • Saccharomyces cerevisiae