{"title":"Lignocellulosic biomass fermentation: a roadmap for Candida famata and Ogataea polymorpha.","authors":"Dominik Wojdyła, Roksolana Vasylyshyn, Alicja Najdecka, Justyna Ruchala","doi":"10.1093/femsyr/foaf046","DOIUrl":"10.1093/femsyr/foaf046","url":null,"abstract":"<p><p>The global transition to renewable energy sources requires efficient microbial platforms capable of fermenting carbon sources present in lignocellulosic biomass. Conventional yeasts like Saccharomyces cerevisiae face critical limitations, particularly in pentose sugar utilization and inhibitor resistance. This review focuses on two emerging nonconventional yeasts, Candida famata and Ogataea polymorpha, which exhibit native or engineered capacities to overcome these bottlenecks. We present a comparative analysis of their stress tolerance, metabolic versatility, and recent advances in genetic engineering, adaptive laboratory evolution, and heterologous expression systems. Their ability to grow on a wide range of sugars, tolerate fermentation inhibitors, and operate under industrial conditions underscores their potential as microbial platforms for sustainable bioprocessing. Key challenges and future directions are discussed to guide further development.</p>","PeriodicalId":12290,"journal":{"name":"FEMS yeast research","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12416285/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144948362","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}
Alican Topaloğlu, Can Holyavkin, Ömer Esen, Ogün Morkoç, Karl Persson, Cecilia Geijer, Zeynep Petek Çakar
{"title":"Evolutionary engineering and molecular characterization of an antimycin A-resistant Saccharomyces cerevisiae strain: the key role of pleiotropic drug resistance (PDR1).","authors":"Alican Topaloğlu, Can Holyavkin, Ömer Esen, Ogün Morkoç, Karl Persson, Cecilia Geijer, Zeynep Petek Çakar","doi":"10.1093/femsyr/foaf062","DOIUrl":"10.1093/femsyr/foaf062","url":null,"abstract":"<p><p>Antimycin A, an antifungal agent that inhibits mitochondrial respiration, provides a useful model for studying resistance mechanisms. Antifungal resistance is an escalating clinical concern with limited treatment options available. To understand the molecular mechanisms of antimycin A resistance, a genetically stable, antimycin A-resistant Saccharomyces cerevisiae strain was successfully developed for the first time through an evolutionary engineering strategy, based on long-term systematic application of gradually increasing antimycin A stress in repetitive batch cultures without prior chemical mutagenesis. Comparative whole genome resequencing analysis of the evolved strain ant905-9 revealed two missense mutations in PDR1 and PRP8 genes involved in pleiotropic drug resistance and RNA splicing, respectively. Using CRISPR/Cas9 genome editing tools, the identified mutations were introduced individually and together into the reference strain, and it was confirmed that the Pdr1p.M732R mutation alone confers antimycin A-resistance in S. cerevisiae. Comparative transcriptomic analysis of the reverse-engineered Pdr1p.M732R strain showed alterations in PDR (pleiotropic drug resistance), transmembrane transport, vesicular trafficking, and autophagy pathways. Our results highlight the potential key role of PDR1 in antifungal drug resistance. This study provides new insights into mitochondrial drug resistance and the adaptive potential of yeast under respiratory stress.</p>","PeriodicalId":12290,"journal":{"name":"FEMS yeast research","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12570882/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145307391","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":"Engineering recombination machinery facilitates the construction of yeast cell factories.","authors":"Nan Jia, Yongjin J Zhou, Jiaoqi Gao","doi":"10.1093/femsyr/foaf066","DOIUrl":"10.1093/femsyr/foaf066","url":null,"abstract":"<p><p>Advances in genome editing have been promoted by programmable nucleases like CRISPR-Cas9, which triggers endogenous DNA repair mechanisms by inducing double-strand break (DSB). Cellular responses to DSBs are governed by competing repair pathways: error-prone non-homologous end joining (NHEJ) and high-fidelity homologous recombination (HR). This review systematically compares the molecular mechanisms and key regulators of NHEJ and HR, with a focus on recent breakthroughs in recombination engineering in non-conventional yeasts. These advances address challenges in precise genome editing, enabling robust metabolic engineering of yeast cell factories for sustainable bioproduction.</p>","PeriodicalId":12290,"journal":{"name":"FEMS yeast research","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12684180/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145512377","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":"Advancing yeast metabolism for a sustainable single carbon bioeconomy.","authors":"Miriam Kuzman, Özge Ata, Diethard Mattanovich","doi":"10.1093/femsyr/foaf020","DOIUrl":"10.1093/femsyr/foaf020","url":null,"abstract":"<p><p>Single carbon (C1) molecules are considered as valuable substrates for biotechnology, as they serve as intermediates of carbon dioxide recycling, and enable bio-based production of a plethora of substances of our daily use without relying on agricultural plant production. Yeasts are valuable chassis organisms for biotech production, and they are able to use C1 substrates either natively or as synthetic engineered strains. This minireview highlights native yeast pathways for methanol and formate assimilation, their engineering, and the realization of heterologous C1 pathways including CO2, in different yeast species. Key features determining the choice among C1 substrates are discussed, including their chemical nature and specifics of their assimilation, their availability, purity, and concentration as raw materials, as well as features of the products to be made from them.</p>","PeriodicalId":12290,"journal":{"name":"FEMS yeast research","volume":"25 ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12020471/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143981676","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}
Minsung Kim, Yuri Tanaka, Hiroyuki Kajiura, Ryo Misaki, Kazuhito Fujiyama
{"title":"Optimization of the culture medium for an iron-sensitive oleaginous yeast, Rhodotorula toruloides NBRC 0559, through functional iron deficiency.","authors":"Minsung Kim, Yuri Tanaka, Hiroyuki Kajiura, Ryo Misaki, Kazuhito Fujiyama","doi":"10.1093/femsyr/foaf002","DOIUrl":"10.1093/femsyr/foaf002","url":null,"abstract":"<p><p>A complete iron deficiency in iron-sensitive oleaginous yeast showed insufficient biomass, resulting in a lower lipid amount, although lipid accumulation was greater compared to deficiency in other ions. In this study, the effect of functional iron deficiency on lipid production on Rhodotorula toruloides NBRC 0559 was examined. Two supplements, an iron-added (growth) supplement and an iron-free (lipid-producing) supplement were tested for detecting functional iron deficiency. The addition of iron-added supplement increased the biomass by 1.5-fold. Furthermore, the addition of iron-free supplement stimulated the growth of R. toruloides NBRC 0559 without loss of biomass (indeed, the biomass increased 1.2-fold) while also resulting in a deficiency of the iron needed for improved growth. Through iron-free supplement, the functional iron starvation effect resulted in improved lipid yield (1.7-fold) and an improved ratio of oleic acid (1.2-fold), which is considered an appropriate material for biodiesel, compared to the non-supplement-treated medium. Moreover, functional iron deficiency led to a 3.4-fold increase in the oleic acid rate compared to when all iron was completely removed from the medium. This study presents the effects and importance of iron in improving biomass and lipid production through the functional iron deficiency.</p>","PeriodicalId":12290,"journal":{"name":"FEMS yeast research","volume":"25 ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12042748/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144005293","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}
Guangchun Lu, Li Liu, Mitchell Opoku, Ruifan Zhu, Haiyang Wang, Gang Feng
{"title":"Characterization of oncohistone H2B variants in Schizosaccharomyces pombe reveals a key role of H2B monoubiquitination deficiency in genomic instability by altering gene expression.","authors":"Guangchun Lu, Li Liu, Mitchell Opoku, Ruifan Zhu, Haiyang Wang, Gang Feng","doi":"10.1093/femsyr/foaf027","DOIUrl":"10.1093/femsyr/foaf027","url":null,"abstract":"<p><p>Various amino acid substitutions commonly occur at one residue of a histone in human cancers, but it remains unclear whether these histone variants have distinct oncogenic effects and mechanisms. Our previous modeling study in the fission yeast Schizosaccharomyces pombe demonstrated that the oncohistone mutants H2BG52D, H2BD67N, and H2BP102L cause the homologous recombination defects and genomic instability by compromising H2B monoubiquitination (H2Bub). However, it is unknown whether other amino acid changes at the H2B-Gly52/Asp67/Pro102 residues influence H2Bub levels and whether they cause genomic instability by altering H2Bub-regulated gene expression. Here, we construct diverse oncomutants at the sole H2B gene htb1-Gly52/Asp67/Pro102 sites in S. pombe and study their impacts on genotoxic response, H2Bub levels, and gene expression. Interestingly, the oncomutants htb1-G52D, htb1-D67N, and htb1-P102L exclusively exhibit significant genotoxic sensitivity, reduced H2Bub levels, and altered gene expression. These defects can be rescued by restoring H2Bub levels with the deletion of the H2B deubiquitinase ubp8+. These strong genetic correlations suggest that H2Bub deficiency plays a determinant role in the genomic instability of htb1-Gly52/Asp67/Pro102 oncomutants and that the alteration of gene expression due to reduced H2Bub levels is a novel mechanism underlying the genomic instability caused by htb1-G52D, htb1-D67N, and htb1-P102L oncomutations.</p>","PeriodicalId":12290,"journal":{"name":"FEMS yeast research","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12128920/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144127063","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}
Emna Ben Saad, Anne Friedrich, Frédérique Fischer, Olivier Courot, Joseph Schacherer, Claudine Bleykasten
{"title":"Comprehensive survey of kombucha microbial communities of diverse origins and fermentation practices.","authors":"Emna Ben Saad, Anne Friedrich, Frédérique Fischer, Olivier Courot, Joseph Schacherer, Claudine Bleykasten","doi":"10.1093/femsyr/foaf005","DOIUrl":"10.1093/femsyr/foaf005","url":null,"abstract":"<p><p>Kombucha is a unique, naturally fermented sweetened tea produced for thousands of years, relying on a symbiotic microbiota in a floating biofilm, used for successive fermentations. The microbial communities consist of yeast and bacteria species, distributed across two phases: the liquid and the biofilm fractions. In the fermentation of kombucha, various starters of different shapes and origins are used, and there are multiple brewing practices. By metabarcoding, we explored here the consortia and their evolution from a collection of 23 starters coming from various origins summarizing the diversity of kombucha fermentation processes. A core microbiota of yeast and bacteria has been identified in these diverse kombucha symbiotic consortia, revealing consistent core taxa across symbiotic consortium of bacteria and yeasts from different starters. The common core consists of five taxa: two yeast species from the Brettanomyces genus (B. bruxellensis and B. anomalus) and bacterial taxa Komagataeibacter, Lactobacillus, and Acetobacteraceae, including the Acetobacter genus. The distribution of yeast and bacteria core taxa differs between the liquid and biofilm fractions, as well as between the \"mother\" and \"daughter\" biofilms used in successive fermentations. In terms of microbial composition, the diversity is relatively low, with only a few accessory taxa identified. Overall, our study provides a deeper understanding of the core and accessory taxa involved in kombucha fermentation.</p>","PeriodicalId":12290,"journal":{"name":"FEMS yeast research","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11851468/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143188642","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":"Cdr1 in focus: a personal reflection on multidrug transporter research.","authors":"Rajendra Prasad","doi":"10.1093/femsyr/foaf003","DOIUrl":"10.1093/femsyr/foaf003","url":null,"abstract":"<p><p>Drug resistance mechanisms in human pathogenic Candida species are constantly evolving. Over time, these species have developed diverse strategies to counter the effects of various drug classes, making them a significant threat to human health. In addition to well-known mechanisms such as drug target modification, overexpression, and chromosome duplication, Candida species have also developed permeability barriers to antifungal drugs through reduced drug import or increased efflux. The genomes of Candida species contain a multitude of drug resistance genes, many of which encode membrane efflux transporters that actively expel drugs, preventing their toxic accumulation inside the cells and contributing to multidrug resistance. This brief personal retrospective piece for the \"Thematic Issue on Celebrating 30 Years of Cdr1 Research: new trends in antifungal therapy and drug resistance\" looks back as to how antifungal research has shifted focus since the identification of the first multidrug transporter gene, CDR1 (Candida Drug Resistance 1), leading to new insights into how reduced azole permeability across Candida cell membranes influences antifungal susceptibility.</p>","PeriodicalId":12290,"journal":{"name":"FEMS yeast research","volume":"25 ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11781190/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064866","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}
Janny Liebregts, Lars van der Velden, Angie Lorena Fonseca-Fernández, Adriana Marcela Celis Ramírez, Hans de Cock
{"title":"Lipid-dependent growth of Malassezia spp. in defined medium with single fatty acids.","authors":"Janny Liebregts, Lars van der Velden, Angie Lorena Fonseca-Fernández, Adriana Marcela Celis Ramírez, Hans de Cock","doi":"10.1093/femsyr/foaf043","DOIUrl":"10.1093/femsyr/foaf043","url":null,"abstract":"<p><p>Details on fatty acid and lipid metabolism in Malassezia spp. are limited, amongst others, because efficient growth of Malassezia spp. in defined media with free fatty acids has not yet been described. Here, we describe a culturing method in a defined medium in which lipid-dependent growth of Malassezia spp. can be studied. We observed efficient growth of Malassezia furfur and Malassezia pachydermatis in liquid minimal medium supplemented with palmitic acid in the presence of NP-40 Tergitol™. We introduced a 3-day fatty acid-starvation phase to reduce residual growth due to the carry-over of lipids from rich media. The Malassezia spp. studied remained viable longer in liquid media lacking fatty acids and detergents, as described previously for a Saccharomyces cerevisiae fas1 mutant. This suggests that Malassezia spp. might have developed mechanisms to survive periods of fatty acid starvation. We compared the lipidome of both Malassezia species grown in mDixon or a defined medium with NP-40 Tergitol™ supplemented with either palmitate and/or oleic acid, or ox bile. Remarkably, the lipidome of mDixon grown cells is enriched in lipid species associated with lipid droplets. Malassezia spp. adapt their lipid composition after growth in a defined medium, and a subset of novel lipid species was identified.</p>","PeriodicalId":12290,"journal":{"name":"FEMS yeast research","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12416284/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144948292","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}
Laura Natalia Balarezo-Cisneros, Alistair Hanak, Leo Zeef, Aleksandr Mironov, Fernando Valle, Daniela Delneri
{"title":"Unveiling the genetic basis of the low pH response in the acidophilic yeast Maudiozyma bulderi as a potential host for biorefinery.","authors":"Laura Natalia Balarezo-Cisneros, Alistair Hanak, Leo Zeef, Aleksandr Mironov, Fernando Valle, Daniela Delneri","doi":"10.1093/femsyr/foaf053","DOIUrl":"10.1093/femsyr/foaf053","url":null,"abstract":"<p><p>Nonconventional yeasts represent a great genetic and phenotypic diversity with potential for industrial strain development in the bio-production of green chemicals. In recent years, mass genome sequencing of nonconventional yeasts has opened avenues to improved understanding of transcriptional networks and phenotypic plasticity and gene function, including the discovery of novel genes. Here, we investigated the expressional and morphological changes at low-pH in three strains of the acidophilic yeast Maudiozyma bulderi (previously Kazachstania bulderi and Saccharomyces bulderi): CBS 8638, CBS 8639, and NRRL Y-27205. The comparison of the transcriptome of cells growing in a bioreactor at pH = 5.5 vs pH = 2.5, primarily showed dysregulation of genes involved in cell wall integrity, with NRRL Y-27205 the least acidophilic strain, showing the largest transcriptional response when compared to the other strains. We identified four uncharacterized genes, unique to M. bulderi, and predicted function as transporters, upregulated at low pH. Microscopy studies showed that M. bulderi cell wall is not damaged in acidic environment, and the membrane lipid composition remains stable at low pH, unlike Saccharomyces cerevisiae. Overall, our data on transcriptional variability in M. bulderi highlights genes and cellular pathways involved in the acidophilic adaptation of this species and can aid further strain development.</p>","PeriodicalId":12290,"journal":{"name":"FEMS yeast research","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12509841/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091616","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}