Thiamin biosynthesis in <i>Saccharomyces cerevisiae</i>. Origin of carbon-2 of the thiazole moiety

White, Robert L.; Spenser, Ian D.

doi:10.1042/bj1790315

Cited by 35 publications

(22 citation statements)

References 28 publications

(51 reference statements)

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“…Another interesting feature of AZH is the presence of a carboxylate group linked at the carbon-2 atom of the thiazole ring, in agreement with a previous work showing that a carboxylated thiazole moiety is an intermediate for the thiazole biosynthesis (11). Despite this, we do not have experimental evidence that the thiazole ring was entirely synthesized by THI1, although it was suggested that THI1 homologues are functionally equivalent to ThiH (or ThiO) and ThiG, the last two enzymes responsible for the incorporation of carbon-2, nitrogen-3, and for the thiazole ring closure (42 and Fig.…”

Section: Thi1 Structure In Complex With a Putative Thiazolesupporting

confidence: 71%

Structure of the Thiazole Biosynthetic Enzyme THI1 from Arabidopsis thaliana

Godoi

Galhardo

Luche

et al. 2006

Journal of Biological Chemistry

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Thiamin pyrophosphate is an essential coenzyme in all organisms that depend on fermentation, respiration or photosynthesis to produce ATP. It is synthesized through two independent biosynthetic routes: one for the synthesis of 2-methyl-4-amino-5-hydroxymethylpyrimidine pyrophosphate (pyrimidine moiety) and another for the synthesis of 4-methyl-5-(␤-hydroxyethyl) thiazole phosphate (thiazole moiety). Herein, we will describe the three-dimensional structure of THI1 protein from Arabidopsis thaliana determined by single wavelength anomalous diffraction to 1.6 Å resolution. The protein was produced using heterologous expression in bacteria, unexpectedly bound to 2-carboxylate-4-methyl-5-␤-(ethyl adenosine 5-diphosphate) thiazole, a potential intermediate of the thiazole biosynthesis in Eukaryotes. THI1 has a topology similar to dinucleotide binding domains and although details concerning its function are unknown, this work provides new clues about the thiazole biosynthesis in Eukaryotes.

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Section: Thi1 Structure In Complex With a Putative Thiazolesupporting

confidence: 71%

Structure of the Thiazole Biosynthetic Enzyme THI1 from Arabidopsis thaliana

Godoi

Galhardo

Luche

et al. 2006

Journal of Biological Chemistry

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“…As is the case for bacteria, the thiazole and pyrimidine moieties are generated through separate pathways, coupled by a single enzyme and phosphorylated by a variety of kinases ( Figure 20 ). The thiazole ring is made from glycine, cysteine, and a five-carbon sugar, using a single enzyme, Thi4 (108–111). …”

Section: Eukaryotic Thiamin Biosynthesismentioning

confidence: 99%

The Structural and Biochemical Foundations of Thiamin Biosynthesis

Jurgenson

Begley

Ealick

2009

Annu. Rev. Biochem.

283

323

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Thiamin is synthesized by most prokaryotes and by eukaryotes such as yeast and plants. In all cases, the thiazole and pyrimidine moieties are synthesized in separate branches of the pathway and coupled to form thiamin phosphate. A final phosphorylation gives thiamin pyrophosphate, the active form of the cofactor. Over the past decade or so, biochemical and structural studies have elucidated most of the details of the thiamin biosynthetic pathway in bacteria. Formation of the thiazole requires six gene products, and formation of the pyrimidine requires two. In contrast, details of the thiamin biosynthetic pathway in yeast are only just beginning to emerge. Only one gene product is required for the biosynthesis of the thiazole and one for the biosynthesis of the pyrimidine. Thiamin can also be transported into the cell and can be salvaged through several routes. In addition, two thiamin degrading enzymes have been characterized, one of which is linked to a novel salvage pathway.

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“…Two genes involved in the acquisition of exogenously Communicated by A. Aguilera available thiamine are THI7 (also known as THI10), which encodes a plasma membrane thiamine transporter (Enjo et al 1997;Singleton 1997) and PHO3, which encodes a periplasmic acid phosphatase that catalyses the release of thiamine from thiamine phosphates (Nosaka et al 1989). Biosynthesis of ThDP involves the independent formation of 2-methyl-4-amino-5-hydroxymethylpyrimidine (HMP) and 4-methyl-5--hydroxyethylthiazole (HET), their subsequent phosphorylation and condensation to form thiamine monophosphate, its hydrolysis to free thiamine, and Wnally its pyrophosphorylation to ThDP (White and Spenser 1979;Begley 1996). Several genes encoding enzymes in yeast ThDP synthesis have been identiWed.…”

Section: Introductionmentioning

confidence: 99%

Pdc2 coordinates expression of the THI regulon in the yeast Saccharomyces cerevisiae

Mojžita

Hohmann

2006

Mol Genet Genomics

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Coordination of gene expression in response to different metabolic signals is crucial for cellular homeostasis. In this work, we addressed the role of Pdc2 in the coordinated control of biosynthesis and demand of an essential metabolic cofactor, thiaminediphosphate (ThDP). The DNA binding protein Pdc2 was initially identified as a regulator of the genes PDC1 and PDC5, which encode isoforms of the glycolytic enzyme pyruvate decarboxylase (Pdc). The Pdc2 has also been implicated as a regulator of genes encoding enzymes in ThDP metabolism. The ThDP is the cofactor of Pdc. Using global and gene-specific expression analysis, we show that Pdc2 is required for the upregulation of all genes controlled by thiamine availability. The Pdc2 seems to act together with Thi2, a known transcriptional regulator of THI genes. The requirement for these two factors differs in a gene-specific manner. While the Thi2, in conjunction with Thi3, seems to control expression of THI genes with respect to thiamine availability, the Pdc2 may link the ThDP demand to carbon source availability. Interestingly, the enzymes Pdc1 and Pdc5 are enriched in the nucleus. Both are known to affect gene expression in an autoregulatory mechanism and expression of both is regulated by glucose and Pdc2, further pointing to a role of Pdc2 in coordinating different metabolic signals. Our analysis helps to further define the THI regulon and hence the spectrum of genes/proteins involved in the ThDP homeostasis. In particular, we identify novel proteins putatively involved in thiamine and/or ThDP transport across the plasma and the mitochondrial membrane. In conclusion, the THI regulon is the most interesting system to study principles of genes expression and metabolic coordination and deserves further attention.

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Thiamin biosynthesis in Saccharomyces cerevisiae. Origin of carbon-2 of the thiazole moiety

Abstract: Radioactivity from [2-14C]glycine enters C-2 of the thiazole moiety of thiamin and no other site, in Saccharomyces cerevisiae (strains A.T.C.C. 24903 and 39916, H.J. Bunker). Radioactivity from L-[Me-14C]methionine or from DL-[2-14C]tyrosine does not enter thiamin.

Cited by 35 publications

References 28 publications

Structure of the Thiazole Biosynthetic Enzyme THI1 from Arabidopsis thaliana

Structure of the Thiazole Biosynthetic Enzyme THI1 from Arabidopsis thaliana

The Structural and Biochemical Foundations of Thiamin Biosynthesis

Pdc2 coordinates expression of the THI regulon in the yeast Saccharomyces cerevisiae

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