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Exploring Saccharomycotina Yeast Ecology Through an Ecological Ontology Framework. 通过生态本体框架探索酵母生态学
IF 2.6 4区 生物学
Yeast Pub Date : 2024-09-18 DOI: 10.1002/yea.3981
Marie-Claire Harrison,Dana A Opulente,John F Wolters,Xing-Xing Shen,Xiaofan Zhou,Marizeth Groenewald,Chris Todd Hittinger,Antonis Rokas,Abigail Leavitt LaBella
{"title":"Exploring Saccharomycotina Yeast Ecology Through an Ecological Ontology Framework.","authors":"Marie-Claire Harrison,Dana A Opulente,John F Wolters,Xing-Xing Shen,Xiaofan Zhou,Marizeth Groenewald,Chris Todd Hittinger,Antonis Rokas,Abigail Leavitt LaBella","doi":"10.1002/yea.3981","DOIUrl":"https://doi.org/10.1002/yea.3981","url":null,"abstract":"Yeasts in the subphylum Saccharomycotina are found across the globe in disparate ecosystems. A major aim of yeast research is to understand the diversity and evolution of ecological traits, such as carbon metabolic breadth, insect association, and cactophily. This includes studying aspects of ecological traits like genetic architecture or association with other phenotypic traits. Genomic resources in the Saccharomycotina have grown rapidly. Ecological data, however, are still limited for many species, especially those only known from species descriptions where usually only a limited number of strains are studied. Moreover, ecological information is recorded in natural language format limiting high throughput computational analysis. To address these limitations, we developed an ontological framework for the analysis of yeast ecology. A total of 1,088 yeast strains were added to the Ontology of Yeast Environments (OYE) and analyzed in a machine-learning framework to connect genotype to ecology. This framework is flexible and can be extended to additional isolates, species, or environmental sequencing data. Widespread adoption of OYE would greatly aid the study of macroecology in the Saccharomycotina subphylum.","PeriodicalId":23870,"journal":{"name":"Yeast","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142257518","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}
引用次数: 0
Improving an Alternative Glycerol Catabolism Pathway in Yarrowia lipolytica to Enhance Erythritol Production 改进脂肪分解酵母中的另一种甘油分解途径以提高赤藓糖醇产量
IF 2.6 4区 生物学
Yeast Pub Date : 2024-09-12 DOI: 10.1002/yea.3980
Feng Liu, Jing‐Tao Tian, Ya‐Ting Wang, Lingxuan Zhao, Zhijie Liu, Jun Chen, Liu‐Jing Wei, Patrick Fickers, Qiang Hua
{"title":"Improving an Alternative Glycerol Catabolism Pathway in Yarrowia lipolytica to Enhance Erythritol Production","authors":"Feng Liu, Jing‐Tao Tian, Ya‐Ting Wang, Lingxuan Zhao, Zhijie Liu, Jun Chen, Liu‐Jing Wei, Patrick Fickers, Qiang Hua","doi":"10.1002/yea.3980","DOIUrl":"https://doi.org/10.1002/yea.3980","url":null,"abstract":"Engineering the glycerol‐3‐phosphate pathway could enhance erythritol production by accelerating glycerol uptake. However, little work has been conducted on the alternative dihydroxyacetone (DHA) pathway in <jats:italic>Yarrowia lipolytica</jats:italic>. Herein, this route was identified and characterized in <jats:italic>Y. lipolytica</jats:italic> by metabolomic and transcriptomic analysis. Moreover, the reaction catalyzed by dihydroxyacetone kinase encoded by <jats:italic>dak2</jats:italic> was identified as the rate‐limiting step. By combining NHEJ‐mediated insertion mutagenesis with a push‐and‐pull strategy, <jats:italic>Y. lipolytica</jats:italic> strains with high‐yield erythritol synthesis from glycerol were obtained. Screening of a library of insertion mutants allows the identification of a mutant with fourfold increased erythritol production. Overexpression of DAK2 and glycerol dehydrogenase GCY3 together with gene encoding transketolase and transaldolase from the nonoxidative part of the pentose phosphate pathway led to a strain with further increased productivity with a titer of 53.1 g/L and a yield 0.56 g/g glycerol, which were 8.1‐ and 4.2‐fold of starting strain.","PeriodicalId":23870,"journal":{"name":"Yeast","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142226656","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}
引用次数: 0
Rapid Fluorescence Assay for Polyphosphate in Yeast Extracts Using JC‐D7 利用 JC-D7 对酵母提取物中的多聚磷酸盐进行快速荧光测定
IF 2.6 4区 生物学
Yeast Pub Date : 2024-09-12 DOI: 10.1002/yea.3979
Alexander Deitert, Jana Fees, Anna Mertens, Duc Nguyen Van, Maria Maares, Hajo Haase, Lars Mathias Blank, Claudia Keil
{"title":"Rapid Fluorescence Assay for Polyphosphate in Yeast Extracts Using JC‐D7","authors":"Alexander Deitert, Jana Fees, Anna Mertens, Duc Nguyen Van, Maria Maares, Hajo Haase, Lars Mathias Blank, Claudia Keil","doi":"10.1002/yea.3979","DOIUrl":"https://doi.org/10.1002/yea.3979","url":null,"abstract":"Polyphosphate (polyP) is an intriguing molecule that is found in almost any organism, covering a multitude of cellular functions. In industry, polyP is used due to its unique physiochemical properties, including pH buffering, water binding, and bacteriostatic activities. Despite the importance of polyP, its analytics is still challenging, with the gold standard being <jats:sup>31</jats:sup>P NMR. Here, we present a simple staining method using the fluorescent dye JC‐D7 for the semi‐quantitative polyP evaluation in yeast extracts. Notably, fluorescence response was affected by polyP concentration and polymer chain length in the 0.5–500 µg/mL polyP concentration range. Hence, for polyP samples of unknown chain compositions, JC‐D7 cannot be used for absolute quantification. Fluorescence of JC‐D7 was unaffected by inorganic phosphate up to 50 mM. Trace elements (FeSO<jats:sub>4</jats:sub> &gt; CuSO<jats:sub>4</jats:sub> &gt; CoCl<jats:sub>2</jats:sub> &gt; ZnSO<jats:sub>4</jats:sub>) and toxic mineral salts (PbNO<jats:sub>3</jats:sub> and HgCl<jats:sub>2</jats:sub>) diminished polyP–induced JC‐D7 fluorescence, affecting its applicability to samples containing polyP–metal complexes. The fluorescence was only marginally affected by other parameters, such as pH and temperature. After validation, this simple assay was used to elucidate the degree of polyP production by yeast strains carrying gene deletions in (poly)phosphate homeostasis. The results suggest that staining with JC‐D7 provides a robust and sensitive method for detecting polyP in yeast extracts and likely in extracts of other microbes. The simplicity of the assay enables high‐throughput screening of microbes to fully elucidate and potentially enhance biotechnological polyP production, ultimately contributing to a sustainable phosphorus utilization.","PeriodicalId":23870,"journal":{"name":"Yeast","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142209970","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}
引用次数: 0
pSPObooster: A Plasmid System to Improve Sporulation Efficiency of Saccharomyces cerevisiae Lab Strains. pSPObooster:提高酿酒酵母实验室菌株繁殖效率的质粒系统
IF 2.2 4区 生物学
Yeast Pub Date : 2024-09-09 DOI: 10.1002/yea.3978
Raphael Loll-Krippleber, Yangyang Kate Jiang, Grant W Brown
{"title":"pSPObooster: A Plasmid System to Improve Sporulation Efficiency of Saccharomyces cerevisiae Lab Strains.","authors":"Raphael Loll-Krippleber, Yangyang Kate Jiang, Grant W Brown","doi":"10.1002/yea.3978","DOIUrl":"https://doi.org/10.1002/yea.3978","url":null,"abstract":"<p><p>Common Saccharomyces cerevisiae lab yeast strains derived from S288C have meiotic defects and therefore are poor sporulators. Here, we developed a plasmid system containing corrected alleles of the MKT1 and RME1 genes to rescue the meiotic defects and show that standard BY4741 and BY4742 strains containing the plasmid display faster and more efficient sporulation. The plasmid, pSPObooster, can be maintained as an episome and easily cured or stably integrated into the genome at a single locus. We demonstrate the use of pSPObooster in low- and high-throughput yeast genetic manipulations and show that it can expedite both procedures without impacting strain behavior.</p>","PeriodicalId":23870,"journal":{"name":"Yeast","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142156120","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}
引用次数: 0
Marker-free genomic editing in Saccharomyces cerevisiae using universal donor templates and multiplexing CRISPR-CAS9. 利用通用供体模板和复用 CRISPR-CAS9 在酿酒酵母中进行无标记基因组编辑。
IF 2.2 4区 生物学
Yeast Pub Date : 2024-08-23 DOI: 10.1002/yea.3977
J H Grissom, S E Moody, R J Chi
{"title":"Marker-free genomic editing in Saccharomyces cerevisiae using universal donor templates and multiplexing CRISPR-CAS9.","authors":"J H Grissom, S E Moody, R J Chi","doi":"10.1002/yea.3977","DOIUrl":"https://doi.org/10.1002/yea.3977","url":null,"abstract":"<p><p>The budding yeast Saccharomyces cerevisiae is an excellent model organism for studying a variety of critical cellular processes. Traditional methods to knock in or -out at specific yeast loci utilize polymerase chain reaction-based techniques, in which marker cassettes with gene-specific homologies are integrated into the genome via homologous recombination. While simple and cost-effective, these methods are limited by marker availability when multiple edits are desired. More recently, CRISPR-Cas9 technology has introduced methods to edit the yeast genome without the need for selectable markers. Although efficient, this method is hindered by additional reagents and lengthy protocols to design and test unique guide RNAs and donor templates for each desired edit. In this study, we have combined these two approaches and have developed a highly efficient economical method to edit the yeast genome marker-free. We have designed two universal donor templates that efficiently repair commonly used selectable markers when targeted by a novel guideRNA-Cas9 designed to promoter regions in Ashbya gossypii found in most integration modules. Furthermore, we find our newly designed guideRNA-Cas9 successfully multiplexes when multiple markers are present. Using these new tools, we have significantly improved the cost and efficiency to generate single or multiple marker-free genetic modifications. In this study, we demonstrate the effectiveness of these new tools by marker-free ablating PRC1, PEP4, and PRB1 vacuolar proteases typically inactivated before many biochemical and membrane-trafficking studies using budding yeast.</p>","PeriodicalId":23870,"journal":{"name":"Yeast","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142047281","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}
引用次数: 0
In vivo CRISPR-Cas9 expression in Candida glabrata, Candida bracarensis, and Candida nivariensis: A versatile tool to study chromosomal break repair. CRISPR-Cas9在格拉布氏念珠菌、布拉卡氏念珠菌和尼瓦瑞氏念珠菌中的体内表达:研究染色体断裂修复的多功能工具。
IF 2.2 4区 生物学
Yeast Pub Date : 2024-08-09 DOI: 10.1002/yea.3976
Killian Métivier, Youfang Zhou-Li, Cécile Fairhead
{"title":"In vivo CRISPR-Cas9 expression in Candida glabrata, Candida bracarensis, and Candida nivariensis: A versatile tool to study chromosomal break repair.","authors":"Killian Métivier, Youfang Zhou-Li, Cécile Fairhead","doi":"10.1002/yea.3976","DOIUrl":"https://doi.org/10.1002/yea.3976","url":null,"abstract":"<p><p>The CRISPR-Cas9 system is extremely useful for genome editing in many species, including the model yeast Saccharomyces cerevisiae, and other yeast species. We have previously reported the use of an inducible CRISPR-Cas9 system in Candida glabrata, which allows genome editing but also the study of double-strand break (DSB) repair. We report, in this study, a comparable system for C. glabrata, relying on a new plasmid, which is more stable than the previous one. We also report the use of this plasmid to induce DSBs in two additional human pathogens, Candida bracarensis and Candida nivariensis. We examine lethality induced by an in vivo DSB in the three species and describe the different types of nonhomologous end-joining (NHEJ) events detected in these three pathogens.</p>","PeriodicalId":23870,"journal":{"name":"Yeast","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141914143","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}
引用次数: 0
Discovery of novel cellobiose lipid gene clusters from Basidiomycetes: How chemical variation is reflected in gene cluster architecture. 从担子菌中发现新型纤维生物糖脂基因簇:基因簇结构如何反映化学变异。
IF 2.2 4区 生物学
Yeast Pub Date : 2024-08-01 Epub Date: 2024-06-14 DOI: 10.1002/yea.3969
Lobke Maria Sips, Laurens Lambrecht, Inge Noëlle Adrienne Van Bogaert
{"title":"Discovery of novel cellobiose lipid gene clusters from Basidiomycetes: How chemical variation is reflected in gene cluster architecture.","authors":"Lobke Maria Sips, Laurens Lambrecht, Inge Noëlle Adrienne Van Bogaert","doi":"10.1002/yea.3969","DOIUrl":"10.1002/yea.3969","url":null,"abstract":"<p><p>Cellobiose lipids are surface-active compounds or biological detergents produced by distinct Basidiomycetes yeasts, of which the most and best-described ones belong to the Ustilaginomycetes class. The molecules display slight variation in congener type, which is linked to the hydroxylation position of the long fatty acid, acetylation profile of the cellobiose unit, and presence or absence of the short fatty acid. In general, this variation is strain specific. Although cellobiose lipid biosynthesis has been described for about 11 yeast species, hitherto only two types of biosynthetic gene clusters are identified, and this for only three species. This work adds six more biosynthetic gene clusters and describes for the first time a novel type of cellobiose lipid biosynthetic cluster with a simplified architecture related to specific cellobiose lipids synthesized by Trichosporonaceae family members.</p>","PeriodicalId":23870,"journal":{"name":"Yeast","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141321657","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}
引用次数: 0
Altered S-AdenosylMethionine availability impacts dNTP pools in Saccharomyces cerevisiae. S-AdenosylMethionine 的可用性变化会影响酿酒酵母中的 dNTP 池。
IF 2.2 4区 生物学
Yeast Pub Date : 2024-08-01 Epub Date: 2024-07-03 DOI: 10.1002/yea.3973
Warunya Panmanee, Men T H Tran, Serigne N Seye, Erin D Strome
{"title":"Altered S-AdenosylMethionine availability impacts dNTP pools in Saccharomyces cerevisiae.","authors":"Warunya Panmanee, Men T H Tran, Serigne N Seye, Erin D Strome","doi":"10.1002/yea.3973","DOIUrl":"10.1002/yea.3973","url":null,"abstract":"<p><p>Saccharomyces cerevisiae has long been used as a model organism to study genome instability. The SAM1 and SAM2 genes encode AdoMet synthetases, which generate S-AdenosylMethionine (AdoMet) from Methionine (Met) and ATP. Previous work from our group has shown that deletions of the SAM1 and SAM2 genes cause changes to AdoMet levels and impact genome instability in opposite manners. AdoMet is a key product of methionine metabolism and the major methyl donor for methylation events of proteins, RNAs, small molecules, and lipids. The methyl cycle is interrelated to the folate cycle which is involved in de novo synthesis of purine and pyrimidine deoxyribonucleotides (dATP, dTTP, dCTP, and dGTP). AdoMet also plays a role in polyamine production, essential for cell growth and used in detoxification of reactive oxygen species (ROS) and maintenance of the redox status in cells. This is also impacted by the methyl cycle's role in production of glutathione, another ROS scavenger and cellular protectant. We show here that sam2∆/sam2∆ cells, previously characterized with lower levels of AdoMet and higher genome instability, have a higher level of each dNTP (except dTTP), contributing to a higher overall dNTP pool level when compared to wildtype. Unchecked, these increased levels can lead to multiple types of DNA damage which could account for the genome instability increases in these cells.</p>","PeriodicalId":23870,"journal":{"name":"Yeast","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141499154","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}
引用次数: 0
Pros and cons of auxin-inducible degron as a tool for regulated depletion of telomeric proteins from Saccharomyces cerevisiae. 将辅助素诱导的降解酵母作为一种工具,用于有序消耗酿酒酵母中的端粒蛋白的利弊。
IF 2.2 4区 生物学
Yeast Pub Date : 2024-08-01 Epub Date: 2024-06-24 DOI: 10.1002/yea.3971
Tomáš Petrík, Zuzana Brzáčová, Regina Sepšiová, Katarína Veljačiková, Ľubomír Tomáška
{"title":"Pros and cons of auxin-inducible degron as a tool for regulated depletion of telomeric proteins from Saccharomyces cerevisiae.","authors":"Tomáš Petrík, Zuzana Brzáčová, Regina Sepšiová, Katarína Veljačiková, Ľubomír Tomáška","doi":"10.1002/yea.3971","DOIUrl":"10.1002/yea.3971","url":null,"abstract":"<p><p>To assess the immediate responses of the yeast cells to telomere defects, we employed the auxin-inducible degron (AID) enabling rapid depletion of essential (Rap1, Tbf1, Cdc13, Stn1) and non-essential (Est1, Est2, Est3) telomeric proteins. Using two variants of AID systems, we show that most of the studied proteins are depleted within 10-30 min after the addition of auxin. As expected, depletion of essential proteins yields nondividing cells, provided that the strains are cultivated in an appropriate carbon source and at temperatures lower than 28°C. Cells with depleted Cdc13 and Stn1 exhibit extension of the single-stranded overhang as early as 3 h after addition of auxin. Notably, prolonged incubation of strains carrying AID-tagged essential proteins in the presence of auxin resulted in the appearance of auxin-resistant clones, caused at least in part by mutations within the OsTIR1 gene. Upon assessing the length of telomeres in strains carrying AID-tagged non-essential telomeric proteins, we found that the depletion of Est1 and Est3 leads to auxin-dependent telomere shortening. However, the EST3-AID strain had slightly shorter telomeres even in the absence of auxin. Furthermore, a strain with the AID-tagged version of Est2 (catalytic subunit of telomerase) not only had shorter telomeres in the absence of auxin but also did not exhibit auxin-dependent telomere shortening. Our results demonstrate that while AID can be useful in assessing immediate cellular responses to telomere deprotection, each strain must be carefully evaluated for the effect of AID-tag on the properties of the protein of interest.</p>","PeriodicalId":23870,"journal":{"name":"Yeast","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141459664","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}
引用次数: 0
Synthetic lethality between toxic amino acids, RTG-target genes and chaperones in Saccharomyces cerevisiae. 有毒氨基酸、RTG 目标基因和伴侣蛋白在酿酒酵母中的合成致死率。
IF 2.2 4区 生物学
Yeast Pub Date : 2024-07-30 DOI: 10.1002/yea.3975
Marina E Druseikis, Shay Covo
{"title":"Synthetic lethality between toxic amino acids, RTG-target genes and chaperones in Saccharomyces cerevisiae.","authors":"Marina E Druseikis, Shay Covo","doi":"10.1002/yea.3975","DOIUrl":"https://doi.org/10.1002/yea.3975","url":null,"abstract":"<p><p>The toxicity of non-proteinogenic amino acids has been known for decades. Numerous reports describe their antimicrobial/anticancer potential. However, these molecules are often toxic to the host as well; thus, a synthetic lethality approach that reduces the dose of these toxins while maintaining toxicity can be beneficial. Here we investigate synthetic lethality between toxic amino acids, the retrograde pathway, and molecular chaperones. In Saccharomyces cerevisiae, mitochondrial retrograde (RTG) pathway activation induces transcription of RTG-target genes to replenish alpha-ketoglutarate and its downstream product glutamate; both metabolites are required for arginine and lysine biosynthesis. We previously reported that tolerance of canavanine, a toxic arginine derivative, requires an intact RTG pathway, and low-dose canavanine exposure reduces the expression of RTG-target genes. Here we show that only a few of the examined chaperone mutants are sensitive to sublethal doses of canavanine. To predict synthetic lethality potential between RTG-target genes and chaperones, we measured the expression of RTG-target genes in canavanine-sensitive and canavanine-tolerant chaperone mutants. Most RTG-target genes were induced in all chaperone mutants starved for arginine; the same trend was not observed under lysine starvation. Canavanine exposure under arginine starvation attenuated and even reversed RTG-target-gene expression in the tested chaperone mutants. Importantly, under nearly all tested genetic and pharmacological conditions, the expression of IDH1 and/or IDH2 was induced. In agreement, idh1 and idh2 mutants are sensitive to canavanine and thialysine and show synthetic growth inhibition with chaperone mutants. Overall, we show that inhibiting molecular chaperones, RTG-target genes, or both can sensitize cells to low doses of toxic amino acids.</p>","PeriodicalId":23870,"journal":{"name":"Yeast","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141793596","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}
引用次数: 0
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