Dataset Information

Integrative Analysis of the Ethanol Tolerance of Saccharomyces cerevisiae.

ABSTRACT: Ethanol (EtOH) alters many cellular processes in yeast. An integrated view of different EtOH-tolerant phenotypes and their long noncoding RNAs (lncRNAs) is not yet available. Here, large-scale data integration showed the core EtOH-responsive pathways, lncRNAs, and triggers of higher (HT) and lower (LT) EtOH-tolerant phenotypes. LncRNAs act in a strain-specific manner in the EtOH stress response. Network and omics analyses revealed that cells prepare for stress relief by favoring activation of life-essential systems. Therefore, longevity, peroxisomal, energy, lipid, and RNA/protein metabolisms are the core processes that drive EtOH tolerance. By integrating omics, network analysis, and several other experiments, we showed how the HT and LT phenotypes may arise: (1) the divergence occurs after cell signaling reaches the longevity and peroxisomal pathways, with CTA1 and ROS playing key roles; (2) signals reaching essential ribosomal and RNA pathways via SUI2 enhance the divergence; (3) specific lipid metabolism pathways also act on phenotype-specific profiles; (4) HTs take greater advantage of degradation and membraneless structures to cope with EtOH stress; and (5) our EtOH stress-buffering model suggests that diauxic shift drives EtOH buffering through an energy burst, mainly in HTs. Finally, critical genes, pathways, and the first models including lncRNAs to describe nuances of EtOH tolerance are reported here.

SUBMITTER: Wolf IR

PROVIDER: S-EPMC10051466 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature

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Integrative Analysis of the Ethanol Tolerance of <i>Saccharomyces cerevisiae</i>.

Wolf Ivan Rodrigo IR Marques Lucas Farinazzo LF de Almeida Lauana Fogaça LF Lázari Lucas Cardoso LC de Moraes Leonardo Nazário LN Cardoso Luiz Henrique LH Alves Camila Cristina de Oliveira CCO Nakajima Rafael Takahiro RT Schnepper Amanda Piveta AP Golim Marjorie de Assis MA Cataldi Thais Regiani TR Nijland Jeroen G JG Pinto Camila Moreira CM Fioretto Matheus Naia MN Almeida Rodrigo Oliveira RO Driessen Arnold J M AJM Simōes Rafael Plana RP Labate Mônica Veneziano MV Grotto Rejane Maria Tommasini RMT Labate Carlos Alberto CA Fernandes Junior Ary A Justulin Luis Antonio LA Coan Rafael Luiz Buogo RLB Ramos Érica É Furtado Fabiana Barcelos FB Martins Cesar C Valente Guilherme Targino GT

International journal of molecular sciences 20230315 6

Ethanol (EtOH) alters many cellular processes in yeast. An integrated view of different EtOH-tolerant phenotypes and their long noncoding RNAs (lncRNAs) is not yet available. Here, large-scale data integration showed the core EtOH-responsive pathways, lncRNAs, and triggers of higher (HT) and lower (LT) EtOH-tolerant phenotypes. LncRNAs act in a strain-specific manner in the EtOH stress response. Network and omics analyses revealed that cells prepare for stress relief by favoring activation of li ...[more]

PMID: 36982719

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Project description:BackgroundSaccharomyces cerevisiae has been widely used for bio-ethanol production and development of rational genetic engineering strategies leading both to the improvement of productivity and ethanol tolerance is very important for cost-effective bio-ethanol production. Studies on the identification of the genes that are up- or down-regulated in the presence of ethanol indicated that the genes may be involved to protect the cells against ethanol stress, but not necessarily required for ethanol tolerance.ResultsIn the present study, a novel network based approach was developed to identify candidate genes involved in ethanol tolerance. Protein-protein interaction (PPI) network associated with ethanol tolerance (tETN) was reconstructed by integrating PPI data with Gene Ontology (GO) terms. Modular analysis of the constructed networks revealed genes with no previously reported experimental evidence related to ethanol tolerance and resulted in the identification of 17 genes with previously unknown biological functions. We have randomly selected four of these genes and deletion strains of two genes (YDR307W and YHL042W) were found to exhibit improved tolerance to ethanol when compared to wild type strain. The genome-wide transcriptomic response of yeast cells to the deletions of YDR307W and YHL042W in the absence of ethanol revealed that the deletion of YDR307W and YHL042W genes resulted in the transcriptional re-programming of the metabolism resulting from a mis-perception of the nutritional environment. Yeast cells perceived an excess amount of glucose and a deficiency of methionine or sulfur in the absence of YDR307W and YHL042W, respectively, possibly resulting from a defect in the nutritional sensing and signaling or transport mechanisms. Mutations leading to an increase in ribosome biogenesis were found to be important for the improvement of ethanol tolerance. Modulations of chronological life span were also identified to contribute to ethanol tolerance in yeast.ConclusionsThe system based network approach developed allows the identification of novel gene targets for improved ethanol tolerance and supports the highly complex nature of ethanol tolerance in yeast.

Project description:Saccharomyces cerevisiae is an important unicellular yeast species within the biotechnological and the food and beverage industries. A significant application of this species is the production of ethanol, where concentrations are limited by cellular toxicity, often at the level of the cell membrane. Here, we characterize 61 S. cerevisiae strains for ethanol tolerance and further analyze five representatives with various ethanol tolerances. The most tolerant strain, AJ4, was dominant in coculture at 0 and 10% ethanol. Unexpectedly, although it does not have the highest noninhibitory concentration or MIC, MY29 was the dominant strain in coculture at 6% ethanol, which may be linked to differences in its basal lipidome. Although relatively few lipidomic differences were observed between strains, a significantly higher phosphatidylethanolamine concentration was observed in the least tolerant strain, MY26, at 0 and 6% ethanol compared to the other strains that became more similar at 10%, indicating potential involvement of this lipid with ethanol sensitivity. Our findings reveal that AJ4 is best able to adapt its membrane to become more fluid in the presence of ethanol and that lipid extracts from AJ4 also form the most permeable membranes. Furthermore, MY26 is least able to modulate fluidity in response to ethanol, and membranes formed from extracted lipids are least leaky at physiological ethanol concentrations. Overall, these results reveal a potential mechanism of ethanol tolerance and suggest a limited set of membrane compositions that diverse yeast species use to achieve this. IMPORTANCE Many microbial processes are not implemented at the industrial level because the product yield is poorer and more expensive than can be achieved by chemical synthesis. It is well established that microbes show stress responses during bioprocessing, and one reason for poor product output from cell factories is production conditions that are ultimately toxic to the cells. During fermentative processes, yeast cells encounter culture media with a high sugar content, which is later transformed into high ethanol concentrations. Thus, ethanol toxicity is one of the major stresses in traditional and more recent biotechnological processes. We have performed a multilayer phenotypic and lipidomic characterization of a large number of industrial and environmental strains of Saccharomyces to identify key resistant and nonresistant isolates for future applications.

Project description:BackgroundDerived from our lignocellulosic conversion inhibitor-tolerant yeast, we generated an ethanol-tolerant strain Saccharomyces cerevisiae NRRL Y-50316 by enforced evolutionary adaptation. Using a newly developed robust mRNA reference and a master equation unifying gene expression data analyses, we investigated comparative quantitative transcription dynamics of 175 genes selected from previous studies for an ethanol-tolerant yeast and its closely related parental strain.ResultsA highly fitted master equation was established and applied for quantitative gene expression analyses using pathway-based qRT-PCR array assays. The ethanol-tolerant Y-50316 displayed significantly enriched background of mRNA abundance for at least 35 genes without ethanol challenge compared with its parental strain Y-50049. Under the ethanol challenge, the tolerant Y-50316 responded in consistent expressions over time for numerous genes belonging to groups of heat shock proteins, trehalose metabolism, glycolysis, pentose phosphate pathway, fatty acid metabolism, amino acid biosynthesis, pleiotropic drug resistance gene family and transcription factors. The parental strain showed repressed expressions for many genes and was unable to withstand the ethanol stress and establish a viable culture and fermentation. The distinct expression dynamics between the two strains and their close association with cell growth, viability and ethanol fermentation profiles distinguished the tolerance-response from the stress-response in yeast under the ethanol challenge. At least 82 genes were identified as candidate and key genes for ethanol-tolerance and subsequent fermentation under the stress. Among which, 36 genes were newly recognized by the present study. Most of the ethanol-tolerance candidate genes were found to share protein binding motifs of transcription factors Msn4p/Msn2p, Yap1p, Hsf1p and Pdr1p/Pdr3p.ConclusionEnriched background of transcription abundance and enhanced expressions of ethanol-tolerance genes associated with heat shock proteins, trehalose-glycolysis-pentose phosphate pathways and PDR gene family are accountable for the tolerant yeast to withstand the ethanol stress, maintain active metabolisms, and complete ethanol fermentation under the ethanol stress. Transcription factor Msn4p appeared to be a key regulator of gene interactions for ethanol-tolerance in the tolerant yeast Y-50316.

Dataset Information

Integrative Analysis of the Ethanol Tolerance of Saccharomyces cerevisiae.

Publications

Integrative Analysis of the Ethanol Tolerance of <i>Saccharomyces cerevisiae</i>.

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