FEMS yeast research最新文献

Most laboratory strains of the yeast Saccharomyces cerevisiae are incapable of invading agar, to form large colonies (mats), and to develop filament-like structures (pseudohyphae). A prominent strain that manifests these morphologies is ∑1278b. While induced transcription of the FLO11 gene is critical for executing invasive growth, mat formation, and pseudohyphal growth, downregulation of the 'general stress response' also seems to be required. As this response is weak in ∑1278b cells, we assumed that they may be sensitives to stresses. We report, however, that they are resistant to various stressors, but severely sensitive specifically to NaCl. We found that this sensitivity is a result of mutations in the single ∑1278b's ENA gene, encoding P-type sodium ATPase. Other laboratory strains harbor three to five copies of ENA, suggesting that ∑1278b was selected against Ena activity. Obtaining ∑1278b cells that can grow on NaCl allows checking its effect on colony morphologies. In the presence of NaCl, ∑1278b/ENA1+ cells do not invade agar, and do not form pseudohyphae or mats. Thus, we have found the following: (i) The ∑1278b strain differs from other laboratory strains with respect to sensitivity to NaCl, because it has no active Na+ ATPase exporter. (ii) NaCl is a suppressor of invasiveness, filamentous growth, and mat formation.

The production of second-generation (2 G) bioethanol, a key sector in industrial biotechnology, addresses the demand for sustainable energy by utilizing lignocellulosic biomass. Efficient fermentation of all sugars from lignocellulose hydrolysis is essential to enhance ethanol titers, improve biomass-to-biofuel yields, and lower costs. This review compares the potential of recombinant yeast strains for 2 G bioethanol production, focusing on their ability to metabolize diverse sugars, particularly xylose. Saccharomyces cerevisiae, engineered for enhanced pentose and hexose utilization, is compared with the nonconventional yeasts Scheffersomyces stipitis, Kluyveromyces marxianus, and Ogataea polymorpha. Key factors include sugar assimilation pathways, cofermentation with glucose, oxygen requirements, tolerance to hydrolysate inhibitors, and process temperature. Saccharomyces cerevisiae shows high ethanol tolerance but requires genetic modification for xylose use. Scheffersomyces stipitis ferments xylose naturally but lacks robustness. Kluyveromyces marxianus offers thermotolerance and a broad substrate range with lower ethanol yields, while O. polymorpha enables high-temperature fermentation but yields modest ethanol from xylose. The comparative analysis clarifies each yeast's advantages and limitations, supporting the development of more efficient 2 G bioethanol production strategies. Strain selection must balance ethanol yield, stress tolerance, and temperature adaptability to meet industrial requirements for cost-effective lignocellulosic bioethanol production.

Although endo-lysosomal abnormalities have been recognized as a pathognomonic feature of Alzheimer's disease, the lack of druggable targets has hampered the translation from bench to bedside. This article provides an overview of the insights gained from yeast research with a focus on understudied luminal acidification mechanisms and their major impact on disease progression. The yeast-to-human discovery and validation strategy identified a "druggable" triad featuring luminal pH, sterol content, and trafficking that (dys)regulate reciprocally. Endosomal Na+/H+ exchangers (eNHE), discovered in yeast and later described in mammals, provide independent support for this pathogenic model. The brain is often the most severely affected organ in patients with eNHE mutations, and a subset is causally linked to progressive and severe neurodegeneration, demonstrating that neurons heavily rely on fine-tuning of endosomal pH. We present recent advances on the role of eNHE in ageing related neurodegenerative diseases, which has implications for pathogenesis and therapy. Future studies should unravel the broader landscape of endo-lysosomal pH in neurodegenerative diseases. Given that pharmacologic correction of luminal hyperacidification defect completely ameliorates endo-lysosomal deficits in eNHE deletion yeast, there is compelling reason to believe that efforts to target endo-lysosomal acid-base homeostasis will eventually lead to novel therapeutic approaches for neurodegenerative diseases.

The lag phase is a temporary, nonreplicative period observed when a microbial population is introduced to a new, nutrient-rich environment. Although the theoretical concept of growth phases is clear, the practical application of methods for estimating lag lengths is often challenging. In fact, there are two distinct assumptions: (i) that cells do not divide at all during the lag phase or (ii) that they divide but at a suboptimal rate. Therefore, the choice of method should consider not only technical limitations but also consistency with the biological context. Here, we investigate the performance of the most common lag estimation methods, using empirical and simulated datasets. We apply different biological scenarios and simulate curves with varying parameters (i.e. growth rate, noise level, and frequency of measurements) to test their impact on the estimated lag phase duration. Our validation shows that infrequent measurements, low growth rate, longer lag phases, or higher level of noise in the measurements result in higher bias and higher variance of lag estimation. Additionally, in case of noisy data, the methods relying on model fitting perform best.

Hanseniaspora species are among the most prevalent yeasts found on grapes and other fruits, with a growing role in wine fermentation due to their distinctive metabolic profiles. This review focuses on the functional divergence within the genus, particularly between the fast-evolving fruit clade and the slow-evolving fermentation clade. While species in the fruit clade often exhibit limited fermentation capacity with interesting enzymatic activity, members of the fermentation clade-especially Hanseniaspora vineae-demonstrate moderate fermentative potential and a unique ability to enhance acetylated aromatic alcohols with healthy properties. When used in mixed fermentations with Saccharomyces cerevisiae, some Hanseniaspora species contribute significantly to the production of bioactive and aromatic compounds, including tyrosol and tryptophol, and their acetate esters, benzenoids, melatonin, and other derived compounds with functional properties. The metabolic activity of Hanseniaspora is also marked by robust extracellular enzymatic functions and a rapid autolytic profile, facilitating the release of aroma precursors and phenolic compounds. This review emphasizes the role of aromatic amino acid-derived pathways-namely the phenylpyruvate, mandelate, and Ehrlich routes-in the biosynthesis of aroma-active metabolites. Overall, Hanseniaspora species represent promising non-Saccharomyces yeasts for modulating wine aroma and composition, with implications for both industrial fermentation strategies and fundamental yeast biology.

Owing to the potential for commercialization, the recombinant production of hemoproteins has been heavily investigated. Yeast is a superior host for the synthesis of eukaryotic hemoproteins with optimal pathway to facilitate heme delivery and utilization, as well as suitable environment for the post-translational folding and modification. The efficient binding of heme is the critical determinant for the various functions of hemeproteins. Thus, many metabolic engineering strategies have been employed to modify heme synthetic pathways and balance the intracellular metabolic burden. This paper provides a comprehensive review on the improvement of heme supply, the enhancement of hemoprotein expression, and the current efforts to harmonize the synthesis of heme and the expression of protein components in yeast. These insights offer a solid foundation for the development of yeast chassis for the efficient production of high-active hemoproteins in the future.

Yeast-based sensors have shown great applicability for deorphanization of G protein-coupled receptors (GPCRs) and screening of ligands targeting these. A GPCR of great interest is free fatty acid 2 receptor (FFA2R), for which short-chain fatty acids such as propionate and acetate are agonists. FFA2R regulates a wide array of downstream receptor signaling pathways in both adipose tissue and immune cells and has been recognized as a promising therapeutic target, having been implicated in several metabolic and inflammatory diseases. While research aiming to identify ligands recognized by FFA2R for translational applications is ongoing, screening is complicated by the complex regulatory and cell-specific responses mediated by the receptor. To simplify screening towards identification of novel ligands, heterologous platforms are valuable tools that offer efficient identification of ligand activity in the absence of regulatory mechanisms. Here, we present a yeast-based sensor designed to evaluate G protein α i1-mediated FFA2R signaling, with an assay time of 3 h. We verify this platform towards the natural agonists, propionate and acetate, and show applicability towards evaluation of synthetic agonists, antagonists, and allosteric agonists. As such, we believe that the developed yeast strain constitutes a promising screening platform for effective evaluation of ligands acting on FFA2R.

The oleaginous yeast Rhodotorula toruloides is a promising microbial cell factory for the sustainable production of biofuels and value-added chemicals from renewable carbon sources. Unlike the conventional yeast Saccharomyces cerevisiae, R. toruloides can naturally metabolize xylose, the second most abundant sugar in lignocellulosic hydrolysates. However, its native xylose metabolism is inefficient, characterized by slow xylose uptake and accumulation of D-arabitol. Moreover, despite its phenotype, research on the enzymes involved in xylose metabolism has yet to reach a consensus. Therefore, this review provides a comprehensive analysis of the non-canonical xylose metabolism in R. toruloides, focusing on the properties of key enzymes involved in xylose metabolism. Native xylose reductase and xylitol dehydrogenase exhibit broad substrate promiscuity compared to their counterparts in the xylose-fermenting Scheffersomyces stipitis. Additionally, the absence of xylulokinase expression under xylose-utilizing conditions redirects metabolism toward D-arabitol accumulation. Consequently, D-arabitol dehydrogenases and ribulokinase play essential roles in the xylose metabolism of R. toruloides. These findings highlight the fundamental differences between R. toruloides xylose metabolism and the oxidoreductase pathways observed in other xylose-fermenting yeast, providing insights for metabolic engineering strategies to improve xylose utilization and enhance bioconversion of cellulosic hydrolysates to different bioproducts by R. toruloides.

Candida glabrata is a prominent causative agent of mucosal and disseminated human infections. Part of the success of C. glabrata as a human pathogen relies on its adherence capacity and ability to tolerate/surpass the activity of immune cells. Herein we describe the involvement of the transcription factor CgHaa1 and of its regulated genes CgAWP12, CgAWP13, CAGL0H07469 g, and CAGL0K10164 g in adherence of C. glabrata to vaginal cells in the presence of acetic acid, an organic acid usually found in this niche due to the activity of commensal bacteria. CgHaa1 and its target genes CgAWP12, CAGL0K10164 g and CAGL0E03740 g were also found to significantly increase C. glabrata-induced killing of the model wax moth Galleria mellonela, in part by modulating the interaction of the yeasts with the larvae's immune cells. Finally, we show that CgHAA1 expression reduces ingestion and subsequent killing of C. glabrata cells by THP-1 human macrophages. This demonstrated role of CgHaa1 in C. glabrata virulence and interaction with immune cells expands the biological role of this regulator positioning it (and its target genes) as a potential interesting candidate target for new therapies focused on reducing the burden of candidiasis.