Ewout Knibbe, Ilja Westerlaken, Philip A de Groot, Jasper Diderich, Susan Zwijns, Thomas Perli, Jean-Marc Daran
{"title":"Reduction of off-flavour formation and improved α-oligoglucoside utilization enable use of Saccharomyces eubayanus as a novel lager brewing yeast.","authors":"Ewout Knibbe, Ilja Westerlaken, Philip A de Groot, Jasper Diderich, Susan Zwijns, Thomas Perli, Jean-Marc Daran","doi":"10.1093/femsyr/foag055","DOIUrl":"https://doi.org/10.1093/femsyr/foag055","url":null,"abstract":"<p><p>Lager beer, made by fermentation of barley malt using the hybrid yeast Saccharomyces pastorianus, is extremely popular worldwide. The low genetic variation of S. pastorianus strains limits the scope of development for novel lager beer types. The wild ancestor Saccharomyces eubayanus has potential for lager brewing, but its application is constrained by formation of phenolic off-flavours (POF+ phenotype) and limited uptake of the wort α-oligoglucosides maltose and maltotriose. Here, we addressed both limitations, using screening and evolutionary engineering of the Himalayan S. eubayanus strain ABFM5L.1, one of the closest known relatives of S. eubayanus sub-genome of modern hybrid lager yeasts. Prior to improving α-oligoglucoside utilisation, 4-vinyl guaiacol formation was abolished by mutagenesis and screening for POF⁻ mutants. Subsequently, evolution for improved sugar utilisation and reverse engineering identified SeMALR1 (the S. eubayanus ortholog of S. cerevisiae MAL63) as a key regulatory control point. Single-nucleotide substitutions in this maltose regulon activator gene enabled rapid maltose uptake and partial maltotriose utilisation in a previously maltose-negative background. The evolved non-genetically modified POF⁻ strains showed near-complete maltose consumption (>90-95%) and partial maltotriose consumption (approximately 25-32%) in industrial wort. These results reveal substantial regulatory flexibility in Holarctic S. eubayanus and support its further development as a novel lager brewing yeast.</p>","PeriodicalId":12290,"journal":{"name":"FEMS yeast research","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149180341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Engineering a stable high-copy episomal plasmid in Yarrowia lipolytica.","authors":"Fengyi Li, Sirui Peng, Huangwei Xu, Yalin Guo, Qingsheng Qi, Jin Hou","doi":"10.1093/femsyr/foag054","DOIUrl":"https://doi.org/10.1093/femsyr/foag054","url":null,"abstract":"<p><p>Episomal plasmids are widely used in yeast metabolic engineering for their flexibility and high transformation efficiency. However, their application in Yarrowia lipolytica is often limited by low copy number and insufficient genetic stability. In this study, a robust episomal plasmid that balanced genetic stability and protein expression capacity was developed in Y. lipolytica. The autonomously replicating sequence (ARS) elements were selected, and ARS1 was identified as a favorable element that balanced genetic stability and gene expression capacity. To improve plasmid copy number, different ubiquitin degrons were used to tune selection marker abundance, and Ubi-R-Δk-mediated marker resulted in an approximately fourfold increase in plasmid copy number (from ∼1 to ∼5 copies per cell). The copy number of the engineered plasmid was one of the highest‑copy episomal systems in Y. lipolytica. To further evaluate the engineered plasmid, we applied it to β‑carotene biosynthesis. The results showed that the β‑carotene titer was 3.43‑fold higher than that of the non‑optimized plasmid. Collectively, this work expands the episomal plasmid toolbox for Y. lipolytica and establishes a generalizable framework for robust protein expression plasmid engineering in non-conventional yeasts.</p>","PeriodicalId":12290,"journal":{"name":"FEMS yeast research","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149180382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Robyn J Ooi, Hannah Robinson, Ruth Pay, Peter W Bircham, Robert A Keyzers, Paul H Atkinson, Andrew B Munkacsi
{"title":"Yeast chemical genetics to investigate mechanism of action of Pacific natural products.","authors":"Robyn J Ooi, Hannah Robinson, Ruth Pay, Peter W Bircham, Robert A Keyzers, Paul H Atkinson, Andrew B Munkacsi","doi":"10.1093/femsyr/foag044","DOIUrl":"https://doi.org/10.1093/femsyr/foag044","url":null,"abstract":"<p><p>Natural products are a major source of bioactive molecules with important applications in medicine, and investigation of species native to the Pacific region has been particularly fruitful, including species used in traditional and Indigenous medicinal practices. Yeast represents a powerful model system for investigating mechanisms of action and other cellular processes; however, their use in natural product research is often limited to growth inhibition or cytotoxicity assays, with underlying mechanisms remaining unclear. This review summarises studies on 17 natural products derived from Pacific organisms, including fungi, plants, and marine organisms, and highlights the application of yeast-based chemical genetic approaches, such as haploinsufficiency and homozygous profiling (HIP/HOP) and gene deletion screens, to investigate their mechanisms of action. These case studies demonstrate how such methods enable the identification of molecular targets and affected pathways, providing insight into the molecular basis of Pacific natural products and, in the context of traditional medicine, complementing Indigenous knowledge with mechanistic understanding. Greater integration of yeast-based methodologies into natural product research will enhance the biological characterisation of newly discovered compounds.</p>","PeriodicalId":12290,"journal":{"name":"FEMS yeast research","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149016176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cheng Cheng, Yu-Zhen Li, Zhenzhi Wang, Hui Chen, Bei Liao, Kai Li, Xin-Qing Zhao
{"title":"Harnessing yeast biodiversity for advanced industrial applications.","authors":"Cheng Cheng, Yu-Zhen Li, Zhenzhi Wang, Hui Chen, Bei Liao, Kai Li, Xin-Qing Zhao","doi":"10.1093/femsyr/foag031","DOIUrl":"10.1093/femsyr/foag031","url":null,"abstract":"<p><p>Budding yeast Saccharomyces cerevisiae and various non-conventional species are widely applied in the production of diverse industrial products, including pharmaceuticals, biofuels, biochemicals, and biomaterials, due to their rich natural and engineered biodiversity. This review summarizes recent advances in harnessing yeast biodiversity for industrial applications, including natural yeast diversity derived from ecological adaptation and genetic variation across diverse environments, and artificial diversity generated through adaptive laboratory evolution, metabolic or epigenetic engineering, and synthetic biology. We highlight the establishment of strain-level culture libraries and extremophilic yeasts as models for stress adaptation. In addition, we emphasize that the integration of multi-omics analysis, AI-assisted enzyme and strain engineering, and process optimization strategies are critical for the fully exploration and utilization of yeast biodiversity for efficient bioproduction.</p>","PeriodicalId":12290,"journal":{"name":"FEMS yeast research","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13501539/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148789934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"High-throughput yeast engineering in biofoundries: towards autonomous and scalable synthetic biology.","authors":"Juan P O Martinez, Robert E Speight","doi":"10.1093/femsyr/foag003","DOIUrl":"10.1093/femsyr/foag003","url":null,"abstract":"<p><p>High-throughput yeast engineering is being transformed by biofoundries that integrate automation, artificial intelligence (AI), and standardized workflows. This review examines how these facilities accelerate strain development through the Design-Build-Test-Learn (DBTL) cycle, with advances in genome editing, phenotypic screening, and predictive modelling. It highlights Australia's involvement through the Australian Genome Foundry, Idea-BIO, and the CSIRO Biofoundiry and explores global efforts to overcome reproducibility and standardization challenges. Despite progress, key barriers remain, including protocol variability and integration of AI tools. We also highlight the opportunity for a shift toward autonomous, self-optimizing 'self-driving labs' that transition from DBTL to Design-Build-Deploy cycles. The future of yeast engineering depends not only on technological innovation, but also on the harmonization of international standards, data governance, and ethical safeguards. If fully realized, the convergence of robotics, AI, and synthetic biology will redefine yeast engineering, leading to step changes in strain performance for a variety of important products, thus enabling economic and sustainable biomanufacturing at scale.</p>","PeriodicalId":12290,"journal":{"name":"FEMS yeast research","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12927428/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146051091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Isabel Sá-Correia, Mónica A Fernandes, Madalena Matos
{"title":"Yeasts associated with microalgal cultures in marine environments: ecological roles and biotechnological potential.","authors":"Isabel Sá-Correia, Mónica A Fernandes, Madalena Matos","doi":"10.1093/femsyr/foag002","DOIUrl":"10.1093/femsyr/foag002","url":null,"abstract":"<p><p>The large-scale cultivation of microalgae for aquaculture feed, biofuels, and high value bioproducts is often limited by microbial contamination. While bacteria have long been recognized as major algal symbionts, yeasts, though typically less abundant, are emerging as functionally significant members of the phycosphere. Yeast physiological versatility, stress tolerance, and production of bioactive metabolites enable them to exert disproportionate ecological and biotechnological influence relative to their abundance. Yeasts contribute to algal systems through metabolic complementarity, enhancing nutrient cycling, stress resilience, and culture stability. Several yeast species secrete auxins such as indole-3-acetic acid, stimulating algal cell division and photosynthetic efficiency. Biosurfactants that suppress microbial contaminants, prevent biofilm formation, and stabilize algal cultures are also produced by several yeast species. In co-cultivation systems, yeast-microalgae interactions enhance biomass, lipids, and pigment yields whilst enabling efficient use of waste substrates. Moreover, yeasts associated with microalgae are valuable producers of compounds of biotechnological relevance such as lipids, biosurfactants, pigments, enzymes, and other proteins. This review synthesizes current knowledge on yeast-microalgae associations, emphasizing their ecological relevance, functional versatility, and underexplored potential in sustainable bioprocesses and circular bioeconomy. Highlighting yeasts within algal microbiomes provides new insight into cross-kingdom cooperation and tools for developing resilient, high-performance cultivation systems.</p>","PeriodicalId":12290,"journal":{"name":"FEMS yeast research","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12878336/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146009544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Elisângela de Souza Miranda Muynarsk, Angela Alves Dos Santos, Cristina Link Rüntzel, Brigitte Sthepani Orozco Colonia, Rafaela de Oliveira Penha, Bárbara Braga Vieira Marques, Danilo Grunig Humberto da Silva, Sergio Luiz Alves
{"title":"From discovery to application: twenty years of Meyerozyma caribbica.","authors":"Elisângela de Souza Miranda Muynarsk, Angela Alves Dos Santos, Cristina Link Rüntzel, Brigitte Sthepani Orozco Colonia, Rafaela de Oliveira Penha, Bárbara Braga Vieira Marques, Danilo Grunig Humberto da Silva, Sergio Luiz Alves","doi":"10.1093/femsyr/foag010","DOIUrl":"10.1093/femsyr/foag010","url":null,"abstract":"<p><p>Over the past two decades, Meyerozyma caribbica has been identified as a metabolically versatile and ecologically adaptable yeast with significant relevance to biotechnology, agriculture, environmental remediation, and food applications. Since its formal description in 2005, this species has demonstrated the ability to grow on a wide range of substrates and under various stress conditions, facilitating the production of valuable bioproducts such as ethanol, xylitol, arabitol, and volatile aroma compounds. Multiple strains efficiently ferment lignocellulosic hydrolysates, tolerate inhibitory compounds, and remain active at elevated temperatures, which supports their application in integrated biorefineries. In addition to its fermentative capabilities, M. caribbica serves as an effective biocontrol agent through the production of antifungal metabolites, hydrolytic enzymes, mycoparasitism, nutrient competition, and the induction of plant defense responses. Environmental functions include the degradation of dyes, hydrocarbons, and organochlorine pesticides, as well as metal biosorption and the mitigation of oxidative stress in plants. There is also increasing interest in its potential as a probiotic and as a starter culture that can modulate sensory attributes in fermented foods. This review synthesizes 20 years of research on M. caribbica, focusing on its roles in bioproduct production, plant disease management, bioremediation, and probiotic or food-related applications.</p>","PeriodicalId":12290,"journal":{"name":"FEMS yeast research","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12923170/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146164516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sujin Hong, Ho Bum Kang, Min-Jun Seong, Eunha Jeon, Sumin Seo, Seung-Gyun Woo, Eun Joong Oh, Young-Kyoung Park, Youngjoon Lee, Dae-Hee Lee
{"title":"Biological parts in yeast synthetic biology: from regulatory elements to predictive design platforms.","authors":"Sujin Hong, Ho Bum Kang, Min-Jun Seong, Eunha Jeon, Sumin Seo, Seung-Gyun Woo, Eun Joong Oh, Young-Kyoung Park, Youngjoon Lee, Dae-Hee Lee","doi":"10.1093/femsyr/foag048","DOIUrl":"10.1093/femsyr/foag048","url":null,"abstract":"<p><p>Yeasts, particularly Saccharomyces cerevisiae, are important eukaryotic chassis for synthetic biology because of their tractable genetics, versatile toolkits, and broad utility in metabolic engineering and functional genomics. Progress in this field has been driven by biological parts that enable programmable control of gene expression and cellular behavior. Early efforts focused mainly on promoters, terminators, and other regulatory elements for tuning individual genes. However, as engineering expanded to multigene pathways, genetic circuits, and dynamic regulatory systems, the limits of part-centric design became clear. Part performance is often shaped by genomic context, chromatin state, host physiology, and interactions with other components, which restricts modularity and predictability. In response, yeast synthetic biology is shifting toward integrated design frameworks combining multilayer regulation, standardized assembly, automated experimentation, and computational modeling. This review provides an integrated perspective on the evolution of biological parts across DNA-, RNA-, and protein-level regulation, connecting these advances with assembly frameworks, biofoundries, and machine learning to trace the trajectory from part-centric engineering toward predictive, system-level design in yeast synthetic biology.</p>","PeriodicalId":12290,"journal":{"name":"FEMS yeast research","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13618442/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148976220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Local acetyl-CoA metabolism and acetate recycling as epigenetic regulators of chromatin dynamics.","authors":"Jueun Kim, Fei He, Shanshan Li, Jung-Shin Lee","doi":"10.1093/femsyr/foag049","DOIUrl":"10.1093/femsyr/foag049","url":null,"abstract":"<p><p>Histone acetylation depends on acetyl-CoA, a central metabolic intermediate linking nutrient availability to chromatin regulation. Beyond bulk acetyl-CoA abundance, accumulating evidence indicates that chromatin-proximal acetyl-CoA production and acetate recycling provide spatial control over histone acetylation. In budding yeast, acetyl-CoA synthetase Acs2 supports nucleocytosolic acetyl-CoA production and associates with chromatin during transcriptional transitions, enabling local acetyl-CoA generation for histone acetyltransferases. Its mammalian ortholog, ACSS2, can accumulate in the nucleus in response to metabolic or signaling cues, where it recaptures acetate released by histone deacetylation to sustain promoter-localized histone acetylation. Acs2/ACSS2 also function within multi-enzyme or chromatin-associated assemblies, such as the yeast SESAME complex, coupling acetate metabolism with other metabolic and epigenetic pathways. These mechanisms influence gene expression, heterochromatin maintenance, senescence, and tumor-associated transcriptional programs. Together, these findings support a spatial model in which local metabolite production shapes epigenetic output independently of bulk metabolite abundance. Defining how such nuclear metabolic microenvironments are established and regulated may refine our understanding of metabolic control of chromatin and inform more selective therapeutic strategies.</p>","PeriodicalId":12290,"journal":{"name":"FEMS yeast research","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13637594/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149080292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dariusz R Kutyna, Sylvie Dequin, Amparo Querol, Isak S Pretorius
{"title":"Uncorking wine yeast genomics from grape to glass.","authors":"Dariusz R Kutyna, Sylvie Dequin, Amparo Querol, Isak S Pretorius","doi":"10.1093/femsyr/foag025","DOIUrl":"10.1093/femsyr/foag025","url":null,"abstract":"<p><p>Unravelling the genomic blueprint of a reference laboratory strain of the yeast Saccharomyces cerevisiae 30 years ago opened a new era in understanding yeast biology. Since then, genomics has transformed our ability to study, adapt, improve, and tailor wine yeast strains in the laboratory and manage them in the cellar. This minireview highlights key advances in wine yeast genomics, from early whole-genome sequencing of industrial S. cerevisiae strains to the recent assembly of complex non-Saccharomyces genomes, including the wine spoilage yeast Brettanomyces bruxellensis. Comparative genomics has revealed the genetic foundations of strain specific traits critical to fermentation performance, aroma production, stress tolerance, and microbial interactions in the vineyard and winery. Beyond cataloguing gene content, integrative genomic approaches have elucidated evolutionary dynamics, domestication events, and adaptation to industrial environments. These insights underpin the rational development of novel starter cultures and biotechnological interventions, fostering consistent wine quality and diversity of sensory profiles for targeted consumer markets. Looking ahead, advances in pan-genomics and functional genomics promise to deepen our understanding of metabolic networks, gene-environment interactions, and the broader ecological context of wine fermentation. Collectively, the study of wine yeast genomics not only illuminates fundamental biological principles but also provides practical tools for innovation, including pathway engineering with synthetic enzyme fusions, and the creation of purpose-built synthetic neo-chromosomes. Excitingly, S. cerevisiae, the first eukaryote to have its genome sequenced, is now poised to become the first eukaryote with an entirely synthetic genome ̶ the Sc2.0 project ̶ heralding a bold future for yeast genomics.</p>","PeriodicalId":12290,"journal":{"name":"FEMS yeast research","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13281101/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148156121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}