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Yeasts: Model Systems for Molecular Research
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Yeasts: Model Systems for Molecular Research

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Genetics and Genomics".

Deadline for manuscript submissions: 20 May 2025 | Viewed by 4248

Special Issue Editor

Prof. Dr. Martin Kupiec

E-Mail Website
Guest Editor
The Shmunis School of Biomedicine & Cancer Research, Tel Aviv University, Ramat Aviv, Tel Aviv 69978, Israel
Interests: Saccharomyces cerevisiae; Schizosaccharomyces pombe; yeast; genome stability; DNA repair; telomeres
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The baker’s yeast (Saccharomyces cerevisiae) and the fission yeast (Schizosaccharomyces pombe) are two widely used and popular organisms due to their facilitation in dissecting complex and basic biological processes. Indeed, state-of-the-art genetic, biochemical, molecular biological and genomic tools have been developed for these organisms. This allows researchers to rapidly carry out sophisticated genetic screening, genomic manipulations and biochemical dissections with ease. Since more than half of the yeast proteins have a human ortholog, it is also possible to learn, by using yeast systems, about the properties and regulations of mammalian systems.

Moreover, yeasts have been proven to be very convenient for genetic engineering, synthetic biology, biotechnology projects and heterologous gene expression. A plethora of techniques and plasmids, as well as mutant and fusion libraries, allow for easy manipulation and engineering of these organisms. Sometimes, additional yeast species such as members of the Komagataella (formerly known as Pichia), Candida, Kluyveromyces  and other clades are used for particular projects.

The genome of the yeast Saccharomyces cerevisiae was the first eukaryotic genome to be sequenced, and gene knockout collections exist for both organisms. Numerous yeast databases make it easy to find up-to-date information about them; the most popular database for S. cerevisiae can be found at https://www.yeastgenome.org/. Similarly, the S. pombe research community has collaborated to make all data related to fission yeast available at https://www.pombase.org/.

Yeasts are widely used to analyze the genes of any other eukaryotic organism and to study genes associated with human diseases. The yeast two-hybrid system is commonly used to probe potential physical interactions between proteins. Many plasmids and yeast strains are commercially available, including sets of different deletion strains.

The main aim of this Special Issue is to highlight the advantages of yeasts as model organisms in which to dissect molecular mechanisms. We encourage the submission of research articles or short communications presenting results that advance our understanding of genetic regulation, protein interactions, biochemical pathway dissection or new biotechnological relevant techniques. Reviews and mini-reviews on various aspects of yeast molecular biology are also welcome.

Prof. Dr. Martin Kupiec
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • yeasts as a model organism
  • yeast genomics
  • DNA replication and repair
  • cell cycle and its regulation
  • transcription
  • translation and posttranslational modification
  • signal transduction
  • chromosomal biology
  • nuclear import and export
  • mitochondria
  • synthetic biology
  • yeast biotechnology
  • biomedicine
  • in lab evolution

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Published Papers (5 papers)

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Research

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32 pages, 6635 KiB  
Article
The Yeast Gsk-3 Kinase Mck1 Is Necessary for Cell Wall Remodeling in Glucose-Starved and Cell Wall-Stressed Cells
by Fan Zhang, Yingzhi Tang, Houjiang Zhou, Kaiqiang Li, James A. West, Julian L. Griffin, Kathryn S. Lilley and Nianshu Zhang
Int. J. Mol. Sci. 2025, 26(8), 3534; https://doi.org/10.3390/ijms26083534 - 9 Apr 2025
Viewed by 211
Abstract
The cell wall integrity (CWI) pathway is responsible for transcriptional regulation of cell wall remodeling in response to cell wall stress. How cell wall remodeling mediated by the CWI pathway is effected by inputs from other signaling pathways is not well understood. Here, [...] Read more.
The cell wall integrity (CWI) pathway is responsible for transcriptional regulation of cell wall remodeling in response to cell wall stress. How cell wall remodeling mediated by the CWI pathway is effected by inputs from other signaling pathways is not well understood. Here, we demonstrate that the Mck1 kinase cooperates with Slt2, the MAP kinase of the CWI pathway, to promote cell wall thickening in glucose-starved cells. Integrative analyses of the transcriptome, proteome and metabolic profiling indicate that Mck1 is required for the accumulation of UDP-glucose (UDPG), the substrate for β-glucan synthesis, through the activation of two regulons: the Msn2/4-dependent stress response and the Cat8-/Adr1-mediated metabolic reprogram dependent on the SNF1 complex. Analysis of the phosphoproteome suggests that similar to mammalian Gsk-3 kinases, Mck1 is involved in the regulation of cytoskeleton-dependent cellular processes, metabolism, signaling and transcription. Specifically, Mck1 may be implicated in the Snf1-dependent metabolic reprogram through PKA inhibition and SAGA (Spt-Ada-Gcn5 acetyltransferase)-mediated transcription activation, a hypothesis further underscored by the significant overlap between the Mck1- and Gcn5-activated transcriptomes. Phenotypic analysis also supports the roles of Mck1 in actin cytoskeleton-mediated exocytosis to ensure plasma membrane homeostasis and cell wall remodeling in cell wall-stressed cells. Together, these findings not only reveal the novel functions of Mck1 in metabolic reprogramming and polarized growth but also provide valuable omics resources for future studies to uncover the underlying mechanisms of Mck1 and other Gsk-3 kinases in cell growth and stress response. Full article
(This article belongs to the Special Issue Yeasts: Model Systems for Molecular Research)
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20 pages, 3303 KiB  
Article
Systematic Characterization and Analysis of the Freeze–Thaw Tolerance Gene Set in the Budding Yeast, Saccharomyces cerevisiae
by Donovan Hartnett, Michael Dotto, Ashley Aguirre, Sophia Brandao, Melanie Chauca, Sandra Chiang, Madison Cronin, Niti Deokar, Autum Martin, Zuri McCune, Joseph Onwusogh, Arisbeth Paulino-Cruz, Angelina D. Gonzalez Soto, Aisha Swaray, Maxwell Verdiner, Majda Rayah and James T. Arnone
Int. J. Mol. Sci. 2025, 26(5), 2149; https://doi.org/10.3390/ijms26052149 - 27 Feb 2025
Viewed by 742
Abstract
The budding yeast Saccharomyces cerevisiae is a widely utilized model system with myriad applications in terms of industrial, biotechnology, and synthetic biology purposes. One such application is the biosynthesis of commercially and medically important bioactive compounds and their precursors, which oftentimes require culturing [...] Read more.
The budding yeast Saccharomyces cerevisiae is a widely utilized model system with myriad applications in terms of industrial, biotechnology, and synthetic biology purposes. One such application is the biosynthesis of commercially and medically important bioactive compounds and their precursors, which oftentimes require culturing conditions at low temperatures to optimize production yield rather than cellular fitness. To lend insight into genetic modifications that may assist this goal, this work focuses on a systematic analysis of the genes that result in an increase in survival following freezing. At present, these genes have been identified in a wide variety of S. cerevisiae wild-type backgrounds—that vary significantly in their properties and behaviors—and in the conditions that led to the annotation of the freeze–thaw survival phenotype. In this work, we report a complete characterization of the thermal tolerance and viability for the freeze–thaw gene family following a standardized protocol within a unified genetic background, the extensively used BY4741 laboratory strain. Our results reveal that five out of these six genes are linked to increased viability in response to both freeze–thaw stress as well as enhanced survival during a heat shock stressor. Follow-up analysis characterized the local spatial effects that gene modification at each locus causes when utilizing the common kanamycin resistance cassette (KanMX6) for the creation of mutant strains and engineering purposes. Full article
(This article belongs to the Special Issue Yeasts: Model Systems for Molecular Research)
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22 pages, 5625 KiB  
Article
Genetic and Physiological Characterization of the Pentose Phosphate Pathway in the Yeast Kluyveromyces lactis
by Laura-Katharina Bertels, Stefan Walter and Jürgen J. Heinisch
Int. J. Mol. Sci. 2025, 26(3), 938; https://doi.org/10.3390/ijms26030938 - 23 Jan 2025
Viewed by 882
Abstract
The pentose phosphate pathway (PPP) is essential for human health and provides, amongst others, the reduction power to cope with oxidative stress. In contrast to the model baker’s yeast, the PPP also contributes to a large extent to glucose metabolism in the milk [...] Read more.
The pentose phosphate pathway (PPP) is essential for human health and provides, amongst others, the reduction power to cope with oxidative stress. In contrast to the model baker’s yeast, the PPP also contributes to a large extent to glucose metabolism in the milk yeast Kluyveromyces lactis. Yet, the physiological consequences of mutations in genes encoding PPP enzymes in K. lactis have been addressed for only a few. We here embarked on a systematic study of such mutants, deleting ZWF1, SOL4, GND1, RKI1, RPE1, TKL1, TAL1, and SHB17. Interestingly, GND1, RKI1, and TKL1 were found to be essential under standard growth conditions. Epistasis analyses revealed that a lack of Zwf1 rescued the lethality of the gnd1 deletion, indicating that it is caused by the accumulation of 6-phosphogluconate. Moreover, the slow growth of a tal1 null mutant, which lacks fructose-1,6-bisphosphate aldolase, was aggravated by deleting the SHB17 gene encoding sedoheptulose-1,7-bisphosphatase. A mitotically stable tetOFF system was established for conditional expression of TAL1 and TKL1, encoding transaldolase and transketolase in the non-oxidative part of the PPP, and employed in a global proteome analysis upon depletion of the enzymes. Results indicate that fatty acid degradation is upregulated, providing an alternative energy source. In addition, tal1 and tkl1 null mutants were complemented by heterologous expression of the respective genes from baker’s yeast and humans. These data demonstrate the importance of the PPP for basic sugar metabolism and oxidative stress response in K. lactis and the potential of this yeast as a model for the study of PPP enzymes from heterologous sources, including human patients. Full article
(This article belongs to the Special Issue Yeasts: Model Systems for Molecular Research)
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12 pages, 2572 KiB  
Article
Effects of PCNA Stability on the Formation of Mutations
by Matan Arbel-Groissman, Batia Liefshitz and Martin Kupiec
Int. J. Mol. Sci. 2024, 25(16), 8646; https://doi.org/10.3390/ijms25168646 - 8 Aug 2024
Cited by 1 | Viewed by 1133
Abstract
The fidelity of replication, especially in the presence of DNA damage, is essential for the proper function of cells. Mutations that inactivate genes involved in DNA damage repair or bypass are enriched in several types of cancer cells. Thus, it is important to [...] Read more.
The fidelity of replication, especially in the presence of DNA damage, is essential for the proper function of cells. Mutations that inactivate genes involved in DNA damage repair or bypass are enriched in several types of cancer cells. Thus, it is important to further our understanding of the mechanisms governing replication fidelity. PCNA is a ring-shaped complex that encircles DNA at the front of the replication fork, at the double-stranded/single-stranded DNA junction. It serves as a processivity factor for the different DNA replication polymerases, allowing them to replicate longer stretches of DNA by physically tethering them to the DNA and preventing their detachment. In addition, PCNA also regulates and coordinates different DNA damage bypass pathways meant to allow DNA replication in the presence of DNA damage. Due to its essentiality and the numerous functions it has in the cell, much is still unclear about PCNA. Here, we utilize PCNA mutants that lower the stability of the PCNA complex on the chromatin, and thus tend to disassociate and fall from the DNA. Using these mutants, we show that PCNA’s physical presence on the DNA can prevent DNA misalignment at repetitive sequences, leading to increased mutation formation. We also show that PCNA-interacting proteins play an important role in strengthening the ring’s stability on the chromatin. Such repetitive sequence-induced mutations are common in several human diseases and it is important to study their formation and the mechanisms guarding against them. Full article
(This article belongs to the Special Issue Yeasts: Model Systems for Molecular Research)
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Review

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22 pages, 991 KiB  
Review
Native and Recombinant Yeast Producers of Lactic Acid: Characteristics and Perspectives
by Aksyniia Tsaruk, Kamila Filip, Andriy Sibirny and Justyna Ruchala
Int. J. Mol. Sci. 2025, 26(5), 2007; https://doi.org/10.3390/ijms26052007 - 25 Feb 2025
Viewed by 649
Abstract
Lactic acid (LA) is a key chemical used in various industries, including food, pharmaceuticals, and bioplastics. Although traditionally produced using lactic acid bacteria, yeasts offer significant advantages, such as higher tolerance to acidic environments, a broader substrate range, and the potential for genetic [...] Read more.
Lactic acid (LA) is a key chemical used in various industries, including food, pharmaceuticals, and bioplastics. Although traditionally produced using lactic acid bacteria, yeasts offer significant advantages, such as higher tolerance to acidic environments, a broader substrate range, and the potential for genetic and metabolic engineering. This review explores the potential use of Lachancea thermotolerans, Saccharomyces cerevisiae, Kluyveromyces marxianus, Kluyveromyces lactis, Candida utilis, and Pichia kudriavzevii as LA producers, highlighting their unique characteristics and industrial applications. S. cerevisiae stands out due to its robust genetic toolkit and acid tolerance, while K. marxianus offers thermotolerance and the efficient utilization of lactose and pentoses, making it ideal for high-temperature fermentations. K. lactis is particularly suited for valorizing dairy by-products like whey, P. kudriavzevii exhibits high tolerance to multiple stresses, while C. utilis demonstrates superior resilience to lignocellulosic inhibitors, enabling its use in biorefineries. Key challenges, including enhancing LA tolerance and optimizing metabolic pathways, are addressed through strategies like heterologous lactate dehydrogenase (LDH) expression, redox balance modification, and adaptive laboratory evolution. The review also discusses industrial applications, particularly in the context of circular economy approaches, where yeasts can convert waste streams into high-value LA. Future research should focus on integrating yeasts into scalable, sustainable bioprocesses to meet the growing demand for renewable and biodegradable materials. Full article
(This article belongs to the Special Issue Yeasts: Model Systems for Molecular Research)
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