The yeast hypoxic responses, resources for new biotechnological opportunities

González-Siso, María-Isabel; Becerra, Manuel; Lamas-Maceiras, Mónica; Vizoso-Vázquez, Ángel; Cerdán, M. Esperanza

doi:10.1007/s10529-012-1039-8

Cited by 15 publications

(10 citation statements)

References 68 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The ability to adapt to oxygen limitation is essential for cell survival but also produces important metabolic, functional and structural changes in the cell [19]. Cells can adapt to growth under oxygen limitation, termed hypoxia or microaerobic conditions [20].…”

Section: Introductionmentioning

confidence: 99%

The effect of hypoxia on the lipidome of recombinant Pichia pastoris

et al. 2017

View full text Add to dashboard Cite

BackgroundCultivation of recombinant Pichia pastoris (Komagataella sp.) under hypoxic conditions has a strong positive effect on specific productivity when the glycolytic GAP promoter is used for recombinant protein expression, mainly due to upregulation of glycolytic conditions. In addition, transcriptomic analyses of hypoxic P. pastoris pointed out important regulation of lipid metabolism and unfolded protein response (UPR). Notably, UPR that plays a role in the regulation of lipid metabolism, amino acid metabolism and protein secretion, was found to be upregulated under hypoxia.ResultsTo improve our understanding of the interplay between lipid metabolism, UPR and protein secretion, the lipidome of a P. pastoris strain producing an antibody fragment was studied under hypoxic conditions. Furthermore, lipid composition analyses were combined with previously available transcriptomic datasets to further understand the impact of hypoxia on lipid metabolism. Chemostat cultures operated under glucose-limiting conditions under normoxic and hypoxic conditions were analyzed in terms of intra/extracellular product distribution and lipid composition. Integrated analysis of lipidome and transcriptome datasets allowed us to demonstrate an important remodeling of the lipid metabolism under limited oxygen availability. Additionally, cells with reduced amounts of ergosterol through fluconazole treatment were also included in the study to observe the impact on protein secretion and its lipid composition.ConclusionsOur results show that cells adjust their membrane composition in response to oxygen limitation mainly by changing their sterol and sphingolipid composition. Although fluconazole treatment results a different lipidome profile than hypoxia, both conditions result in higher recombinant protein secretion levels.Electronic supplementary materialThe online version of this article (doi:10.1186/s12934-017-0699-4) contains supplementary material, which is available to authorized users.

show abstract

Section: Introductionmentioning

confidence: 99%

The effect of hypoxia on the lipidome of recombinant Pichia pastoris

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Various mechanisms of oxygen sensing and responses to hypoxia in yeast and pathogenic fungi have been reviewed recently [1]–[4]. C. neoformans utilizes Sre1, the mammalian sterol regulatory element-binding protein (SREBP) homolog, to control sterol homeostasis, oxygen sensing, and virulence in mice [5], [6].…”

Section: Introductionmentioning

confidence: 99%

“…However, there are no obvious SREBP orthologs in Saccharomyces cerevisiae or in any of the species belonging to the Candida clade. These yeast cells respond to limited-oxygen conditions by inducing expression of a large number of hypoxic genes, which encode oxygen-related functions in respiration and biosynthesis of heme, lipids, cell-wall and membranes [2], [4]. Studies using the hypoxia mimetic compound CoCl 2 revealed that the ability of C. neoformans to grow in low oxygen conditions was linked to mitochondrial function, the ability of cells to respond to reactive oxygen species, and gene expression associated with ubiquitination as well as sterol and iron homeostasis [8].…”

Section: Introductionmentioning

confidence: 99%

Molecular Mechanisms of Hypoxic Responses via Unique Roles of Ras1, Cdc24 and Ptp3 in a Human Fungal Pathogen Cryptococcus neoformans

et al. 2014

View full text Add to dashboard Cite

Cryptococcus neoformans encounters a low oxygen environment when it enters the human host. Here, we show that the conserved Ras1 (a small GTPase) and Cdc24 (the guanine nucleotide exchange factor for Cdc42) play an essential role in cryptococcal growth in hypoxia. Suppressor studies indicate that PTP3 functions epistatically downstream of both RAS1 and CDC24 in regulating hypoxic growth. Ptp3 shares sequence similarity to the family of phosphotyrosine-specific protein phosphatases and the ptp3Δ strain failed to grow in 1% O2. We demonstrate that RAS1, CDC24 and PTP3 function in parallel to regulate thermal tolerance but RAS1 and CDC24 function linearly in regulating hypoxic growth while CDC24 and PTP3 reside in compensatory pathways. The ras1Δ and cdc24Δ strains ceased to grow at 1% O2 and became enlarged but viable single cells. Actin polarization in these cells, however, was normal for up to eight hours after transferring to hypoxic conditions. Double deletions of the genes encoding Rho GTPase Cdc42 and Cdc420, but not of the genes encoding Rac1 and Rac2, caused a slight growth retardation in hypoxia. Furthermore, growth in hypoxia was not affected by the deletion of several central genes functioning in the pathways of cAMP, Hog1, or the two-component like phosphorylation system that are critical in the cryptococcal response to osmotic and genotoxic stresses. Interestingly, although deletion of HOG1 rescued the hypoxic growth defect of ras1Δ, cdc24Δ, and ptp3Δ, Hog1 was not hyperphosphorylated in these three mutants in hypoxic conditions. RNA sequencing analysis indicated that RAS1, CDC24 and PTP3 acted upon the expression of genes involved in ergosterol biosynthesis, chromosome organization, RNA processing and protein translation. Moreover, growth of the wild-type strain under low oxygen conditions was affected by sub-inhibitory concentrations of the compounds that inhibit these biological processes, demonstrating the importance of these biological processes in the cryptococcal hypoxia response.

show abstract

“…pressed gene expression under high concentrations of fermentable sugars (Gascón and Lampen 1968) and in the absence of molecular oxygen (Plattner et al 1970). Since S. cerevisiae is Crabtree-effect positive, it produces ethanol even in the presence of oxygen and glucose rather than the tricarboxylic acid (TCA) cyclerelated constituents (González Siso et al 2012).…”

Section: Sake Brewing Processmentioning

confidence: 99%

Analysis of the Role of Mitochondria of Sake Yeast during Sake Brewing and Its Applications in Fermentation Technologies

Kitagaki¹,

Tan²,

Jayakody³

2013

AGri-Biosci. Monogr. (AGBM)

View full text Add to dashboard Cite

Mitochondrion is an organelle necessary for oxidative respiration. During industrial fermentation, brewery yeasts are exposed to long periods of hypoxia; however, the structure, role, and metabolism of mitochondria of brewery yeast during hypoxia have not been studied in detail. Our recent studies, for the first time, elucidated that the mitochondrial structure of brewery yeast can be observed throughout the brewing of sake, the Japanese traditional rice wine. As sake brewing proceeded, mitochondria of sake yeast change their morphology, which is coupled with an increase in malate production. On the basis of these insights, new fermentation technologies were developed. They include (1) breeding of low pyruvate-producing sake yeast by isolation of a mutant resistant to an inhibitor of mitochondrial pyruvate transport; and (2) modification of malate and succinate production by manipulating mitochondrial activity. These approaches provide new and practical methods to improve industrial fermentation technologies of sake brewing.

show abstract

The yeast hypoxic responses, resources for new biotechnological opportunities

Cited by 15 publications

References 68 publications

The effect of hypoxia on the lipidome of recombinant Pichia pastoris

The effect of hypoxia on the lipidome of recombinant Pichia pastoris

Molecular Mechanisms of Hypoxic Responses via Unique Roles of Ras1, Cdc24 and Ptp3 in a Human Fungal Pathogen Cryptococcus neoformans

Analysis of the Role of Mitochondria of Sake Yeast during Sake Brewing and Its Applications in Fermentation Technologies

Contact Info

Product

Resources

About