Combinatorial effects of environmental parameters on transcriptional regulation in Saccharomyces cerevisiae: A quantitative analysis of a compendium of chemostat-based transcriptome data

Knijnenburg, Theo; Daran, Jean‐Marc; Broek, Marcel A. van den; Daran‐Lapujade, Pascale; Winde, Johannes H. de; Pronk, Jack T.; Reinders, Marcel J. T.; Wessels, Lodewyk

doi:10.1186/1471-2164-10-53

Cited by 57 publications

(73 citation statements)

References 42 publications

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“…K. lactis, a hemiascomycetous yeast that is more closely related to S. cerevisiae, also possesses these two pathways (16). Meanwhile, we observed an absence of regulation of the OAS pathway and a regulation of the transsulfuration pathway in K. lactis (17) that was identical to that observed in S. cerevisiae (25). This suggests that cysteine biosynthesis could be regulated differently in Y. lipolytica.…”

Section: Discussionsupporting

confidence: 51%

New Insights into Sulfur Metabolism in Yeasts as Revealed by Studies of Yarrowia lipolytica

Hébert

Forquin-Gomez

Roux

et al. 2013

Appl Environ Microbiol

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Yarrowia lipolytica, located at the frontier of hemiascomycetous yeasts and fungi, is an excellent candidate for studies of metabolism evolution. This yeast, widely recognized for its technological applications, in particular produces volatile sulfur compounds (VSCs) that fully contribute to the flavor of smear cheese. We report here a relevant global vision of sulfur metabolism in Y. lipolytica based on a comparison between high-and low-sulfur source supplies (sulfate, methionine, or cystine) by combined approaches (transcriptomics, metabolite profiling, and VSC analysis). The strongest repression of the sulfate assimilation pathway was observed in the case of high methionine supply, together with a large accumulation of sulfur intermediates. A high sulfate supply seems to provoke considerable cellular stress via sulfite production, resulting in a decrease of the availability of the glutathione pathway's sulfur intermediates. The most limited effect was observed for the cystine supply, suggesting that the intracellular cysteine level is more controlled than that of methionine and sulfate. Using a combination of metabolomic profiling and genetic experiments, we revealed taurine and hypotaurine metabolism in yeast for the first time. On the basis of a phylogenetic study, we then demonstrated that this pathway was lost by some of the hemiascomycetous yeasts during evolution.

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Section: Discussionsupporting

confidence: 51%

New Insights into Sulfur Metabolism in Yeasts as Revealed by Studies of Yarrowia lipolytica

Hébert

Forquin-Gomez

Roux

et al. 2013

Appl Environ Microbiol

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“…Spf1p, a P-type ATPase that may provide an electrochemical gradient across the plasma membrane needed for active amino acid transport, has physical interactions with amino acid permeases such as Bap2p and Gap1p, as well as Dip5p and Can1p that are dicarboxylic amino acid and arginine permeases, respectively [30]. Finally, Wsc4p interacts genetically with amino acid transporter, Tat1p, and is both co-expressed and co-localized with Gap1p [31].…”

Section: Resultsmentioning

confidence: 99%

The Antifungal Eugenol Perturbs Dual Aromatic and Branched-Chain Amino Acid Permeases in the Cytoplasmic Membrane of Yeast

et al. 2013

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Eugenol is an aromatic component of clove oil that has therapeutic potential as an antifungal drug, although its mode of action and precise cellular target(s) remain ambiguous. To address this knowledge gap, a chemical-genetic profile analysis of eugenol was done using ∼4700 haploid Saccharomyces cerevisiae gene deletion mutants to reveal 21 deletion mutants with the greatest degree of susceptibility. Cellular roles of deleted genes in the most susceptible mutants indicate that the main targets for eugenol include pathways involved in biosynthesis and transport of aromatic and branched-chain amino acids. Follow-up analyses showed inhibitory effects of eugenol on amino acid permeases in the yeast cytoplasmic membrane. Furthermore, phenotypic suppression analysis revealed that eugenol interferes with two permeases, Tat1p and Gap1p, which are both involved in dual transport of aromatic and branched-chain amino acids through the yeast cytoplasmic membrane. Perturbation of cytoplasmic permeases represents a novel antifungal target and may explain previous observations that exposure to eugenol results in leakage of cell contents. Eugenol exposure may also contribute to amino acid starvation and thus holds promise as an anticancer therapeutic drug. Finally, this study provides further evidence of the usefulness of the yeast Gene Deletion Array approach in uncovering the mode of action of natural health products.

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“…In the current metabolic engineering design, heterologous genes were placed under the control of highly active glycolytic promoters (Knijnenburg et al, 2009). While placing ure2, the catalytic enzyme behind such a promoter may be useful to enable high in vivo fluxes, the high expression of the accessory enzymes might not be necessary and, in contrast, may have led to an increased general protein burden (Sauer et al, 2014) and/or interference with metal metabolism and homoeostasis or protein folding.…”

Section: Expression Of a Ni-dependent Atp-independent Urease In S Cementioning

confidence: 99%

Functional expression of a heterologous nickel-dependent, ATP-independent urease in Saccharomyces cerevisiae

Milne

Luttik

Cueto-Rojas

et al. 2015

Metabolic Engineering

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a b s t r a c tIn microbial processes for production of proteins, biomass and nitrogen-containing commodity chemicals, ATP requirements for nitrogen assimilation affect product yields on the energy producing substrate. In Saccharomyces cerevisiae, a current host for heterologous protein production and potential platform for production of nitrogen-containing chemicals, uptake and assimilation of ammonium requires 1 ATP per incorporated NH 3 . Urea assimilation by this yeast is more energy efficient but still requires 0.5 ATP per NH 3 produced. To decrease ATP costs for nitrogen assimilation, the S. cerevisiae gene encoding ATP-dependent urease (DUR1,2) was replaced by a Schizosaccharomyces pombe gene encoding ATP-independent urease (ure2), along with its accessory genes ureD, ureF and ureG. Since S. pombe ure2 is a Ni 2 þ -dependent enzyme and Saccharomyces cerevisiae does not express native Ni 2 þ -dependent enzymes, the S. pombe high-affinity nickel-transporter gene (nic1) was also expressed. Expression of the S. pombe genes into dur1,2Δ S. cerevisiae yielded an in vitro ATPindependent urease activity of 0.4470.01 mmol min À 1 mg protein À 1 and restored growth on urea as sole nitrogen source. Functional expression of the Nic1 transporter was essential for growth on urea at low Ni 2 þ concentrations. The maximum specific growth rates of the engineered strain on urea and ammonium were lower than those of a DUR1,2 reference strain. In glucose-limited chemostat cultures with urea as nitrogen source, the engineered strain exhibited an increased release of ammonia and reduced nitrogen content of the biomass. Our results indicate a new strategy for improving yeast-based production of nitrogen-containing chemicals and demonstrate that Ni 2 þ -dependent enzymes can be functionally expressed in S. cerevisiae.

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Combinatorial effects of environmental parameters on transcriptional regulation in Saccharomyces cerevisiae: A quantitative analysis of a compendium of chemostat-based transcriptome data

Cited by 57 publications

References 42 publications

New Insights into Sulfur Metabolism in Yeasts as Revealed by Studies of Yarrowia lipolytica

New Insights into Sulfur Metabolism in Yeasts as Revealed by Studies of Yarrowia lipolytica

The Antifungal Eugenol Perturbs Dual Aromatic and Branched-Chain Amino Acid Permeases in the Cytoplasmic Membrane of Yeast

Functional expression of a heterologous nickel-dependent, ATP-independent urease in Saccharomyces cerevisiae

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