Thiamine repression and pyruvate decarboxylase autoregulation independently control the expression of the <i>Saccharomyces cerevisiae PDC5</i> gene

Müller, E.; Richards, Emma J.; Norbeck, Joakim; Byrne, Kerry L.; Karlsson, Karl‐Anders; Pretorius, G. H. J.; Meacock, Peter A.; Blomberg, Anders; Hohmann, Stefan

doi:10.1016/s0014-5793(99)00449-4

Cited by 43 publications

(41 citation statements)

References 33 publications

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“…PDC5 becomes strongly expressed in pdc1⌬ mutants, and promoter activity of PDC1 is upregulated in mutants lacking the coding region of PDC1 (75). In addition, thiamine represses PDC5 and thus under thiamine limitation, both PDC1 and PDC5 are expressed (76).…”

Section: Synthesis Of Acetyl-coamentioning

confidence: 99%

Protein Acetylation and Acetyl Coenzyme A Metabolism in Budding Yeast

et al. 2014

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Section: Synthesis Of Acetyl-coamentioning

confidence: 99%

Protein Acetylation and Acetyl Coenzyme A Metabolism in Budding Yeast

et al. 2014

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“…Remarkably, in the absence of thiamine, several THI gene products belong to the most highly expressed proteins (Muller et al 1999). Several genes not listed above are known to be upregulated in the absence of external thiamine as well: PET18 (function unknown; weak homology to THI20 family), PDC5 (isoform of pyruvate decarboxylase) and YLR004C (function unknown) (Llorente et al 1999;Muller et al 1999;Llorente and Dujon 2000;Nosaka et al 2005).…”

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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“…Three PDC isoenzymes are encoded by the S. cerevisiae PDC1, PDC5, and PDC6 genes (25). Pdc1, the main isoenzyme, is highly expressed under most conditions, while PDC5 exhibits tight transcriptional control, with high expression levels in the absence of a functional PDC1 gene (48), under nitrogen-limited conditions (3)(4)(5)53), and under conditions of thiamine limitation (40). PDC1 and PDC5 expressions are subject to autoregulation (24) and require the transcription factor Pdc2 (23).…”

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Substrate Specificity of Thiamine Pyrophosphate-Dependent 2-Oxo-Acid Decarboxylases in Saccharomyces cerevisiae

Romagnoli

Luttik

Kötter

et al. 2012

Appl Environ Microbiol

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dFusel alcohols are precursors and contributors to flavor and aroma compounds in fermented beverages, and some are under investigation as biofuels. The decarboxylation of 2-oxo acids is a key step in the Ehrlich pathway for fusel alcohol production. In Saccharomyces cerevisiae, five genes share sequence similarity with genes encoding thiamine pyrophosphate-dependent 2-oxoacid decarboxylases (2ODCs). PDC1, PDC5, and PDC6 encode differentially regulated pyruvate decarboxylase isoenzymes; ARO10 encodes a 2-oxo-acid decarboxylase with broad substrate specificity, and THI3 has not yet been shown to encode an active decarboxylase. Despite the importance of fusel alcohol production in S. cerevisiae, the substrate specificities of these five 2ODCs have not been systematically compared. When the five 2ODCs were individually overexpressed in a pdc1⌬ pdc5⌬ pdc6⌬ aro10⌬ thi3⌬ strain, only Pdc1, Pdc5, and Pdc6 catalyzed the decarboxylation of the linear-chain 2-oxo acids pyruvate, 2-oxobutanoate, and 2-oxo-pentanoate in cell extracts. The presence of a Pdc isoenzyme was also required for the production of n-propanol and n-butanol in cultures grown on threonine and norvaline, respectively, as nitrogen sources. These results demonstrate the importance of pyruvate decarboxylases in the natural production of n-propanol and n-butanol by S. cerevisiae. No decarboxylation activity was found for Thi3 with any of the substrates tested. Only Aro10 and Pdc5 catalyzed the decarboxylation of the aromatic substrate phenylpyruvate, with Aro10 showing superior kinetic properties. Aro10, Pdc1, Pdc5, and Pdc6 exhibited activity with all branched-chain and sulfur-containing 2-oxo acids tested but with markedly different decarboxylation kinetics. The high affinity of Aro10 identified it as a key contributor to the production of branched-chain and sulfur-containing fusel alcohols. P yruvate decarboxylase (PDC) catalyzes the thiamine pyrophosphate (TPP)-dependent decarboxylation of pyruvate to acetaldehyde. In Saccharomyces cerevisiae, PDC is not only a key enzyme of alcoholic fermentation but is also required for the synthesis of cytosolic acetyl coenzyme A (acetyl-CoA) (15, 16), a key precursor for the synthesis of lipids and lysine. Three PDC isoenzymes are encoded by the S. cerevisiae PDC1, PDC5, and PDC6 genes (25). Pdc1, the main isoenzyme, is highly expressed under most conditions, while PDC5 exhibits tight transcriptional control, with high expression levels in the absence of a functional PDC1 gene (48), under nitrogen-limited conditions (3-5, 53), and under conditions of thiamine limitation (40). PDC1 and PDC5 expressions are subject to autoregulation (24) and require the transcription factor Pdc2 (23). The third PDC isoenzyme, Pdc6, has a very low content of sulfur-containing amino acids and is highly expressed in sulfur-limited cultures (4, 53). This transcriptional regulation of PDC6 has been interpreted as a "sulfur economy" response (4, 14, 53).The ARO10 and THI3 genes show sequence homology to the PDC genes but do not encode pyruva...

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Thiamine repression and pyruvate decarboxylase autoregulation independently control the expression of the Saccharomyces cerevisiae PDC5 gene

Cited by 43 publications

References 33 publications

Protein Acetylation and Acetyl Coenzyme A Metabolism in Budding Yeast

Protein Acetylation and Acetyl Coenzyme A Metabolism in Budding Yeast

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

Substrate Specificity of Thiamine Pyrophosphate-Dependent 2-Oxo-Acid Decarboxylases in Saccharomyces cerevisiae

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