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Genome-scale analyses of butanol tolerance in Saccharomyces cerevisiae reveal an essential role of protein degradation

BACKGROUND: n-Butanol and isobutanol produced from biomass-derived sugars are promising renewable transport fuels and solvents. Saccharomyces cerevisiae has been engineered for butanol production, but its high butanol sensitivity poses an upper limit to product titers that can be reached by further...

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Autores principales: González-Ramos, Daniel, van den Broek, Marcel, van Maris, Antonius JA, Pronk, Jack T, Daran, Jean-Marc G
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3621596/
https://www.ncbi.nlm.nih.gov/pubmed/23552365
http://dx.doi.org/10.1186/1754-6834-6-48
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author González-Ramos, Daniel
van den Broek, Marcel
van Maris, Antonius JA
Pronk, Jack T
Daran, Jean-Marc G
author_facet González-Ramos, Daniel
van den Broek, Marcel
van Maris, Antonius JA
Pronk, Jack T
Daran, Jean-Marc G
author_sort González-Ramos, Daniel
collection PubMed
description BACKGROUND: n-Butanol and isobutanol produced from biomass-derived sugars are promising renewable transport fuels and solvents. Saccharomyces cerevisiae has been engineered for butanol production, but its high butanol sensitivity poses an upper limit to product titers that can be reached by further pathway engineering. A better understanding of the molecular basis of butanol stress and tolerance of S. cerevisiae is important for achieving improved tolerance. RESULTS: By combining a screening of the haploid S. cerevisiae knock-out library, gene overexpression, and genome analysis of evolutionary engineered n-butanol-tolerant strains, we established that protein degradation plays an essential role in tolerance. Strains deleted in genes involved in the ubiquitin-proteasome system and in vacuolar degradation of damaged proteins showed hypersensitivity to n-butanol. Overexpression of YLR224W, encoding the subunit responsible for the recognition of damaged proteins of an ubiquitin ligase complex, resulted in a strain with a higher n-butanol tolerance. Two independently evolved n-butanol-tolerant strains carried different mutations in both RPN4 and RTG1, which encode transcription factors involved in the expression of proteasome and peroxisomal genes, respectively. Introduction of these mutated alleles in the reference strain increased butanol tolerance, confirming their relevance in the higher tolerance phenotype. The evolved strains, in addition to n-butanol, were also more tolerant to 2-butanol, isobutanol and 1-propanol, indicating a common molecular basis for sensitivity and tolerance to C3 and C4 alcohols. CONCLUSIONS: This study shows that maintenance of protein integrity plays an essential role in butanol tolerance and demonstrates new promising targets to engineer S. cerevisiae for improved tolerance.
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spelling pubmed-36215962013-04-12 Genome-scale analyses of butanol tolerance in Saccharomyces cerevisiae reveal an essential role of protein degradation González-Ramos, Daniel van den Broek, Marcel van Maris, Antonius JA Pronk, Jack T Daran, Jean-Marc G Biotechnol Biofuels Research BACKGROUND: n-Butanol and isobutanol produced from biomass-derived sugars are promising renewable transport fuels and solvents. Saccharomyces cerevisiae has been engineered for butanol production, but its high butanol sensitivity poses an upper limit to product titers that can be reached by further pathway engineering. A better understanding of the molecular basis of butanol stress and tolerance of S. cerevisiae is important for achieving improved tolerance. RESULTS: By combining a screening of the haploid S. cerevisiae knock-out library, gene overexpression, and genome analysis of evolutionary engineered n-butanol-tolerant strains, we established that protein degradation plays an essential role in tolerance. Strains deleted in genes involved in the ubiquitin-proteasome system and in vacuolar degradation of damaged proteins showed hypersensitivity to n-butanol. Overexpression of YLR224W, encoding the subunit responsible for the recognition of damaged proteins of an ubiquitin ligase complex, resulted in a strain with a higher n-butanol tolerance. Two independently evolved n-butanol-tolerant strains carried different mutations in both RPN4 and RTG1, which encode transcription factors involved in the expression of proteasome and peroxisomal genes, respectively. Introduction of these mutated alleles in the reference strain increased butanol tolerance, confirming their relevance in the higher tolerance phenotype. The evolved strains, in addition to n-butanol, were also more tolerant to 2-butanol, isobutanol and 1-propanol, indicating a common molecular basis for sensitivity and tolerance to C3 and C4 alcohols. CONCLUSIONS: This study shows that maintenance of protein integrity plays an essential role in butanol tolerance and demonstrates new promising targets to engineer S. cerevisiae for improved tolerance. BioMed Central 2013-04-03 /pmc/articles/PMC3621596/ /pubmed/23552365 http://dx.doi.org/10.1186/1754-6834-6-48 Text en Copyright © 2013 González-Ramos et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
González-Ramos, Daniel
van den Broek, Marcel
van Maris, Antonius JA
Pronk, Jack T
Daran, Jean-Marc G
Genome-scale analyses of butanol tolerance in Saccharomyces cerevisiae reveal an essential role of protein degradation
title Genome-scale analyses of butanol tolerance in Saccharomyces cerevisiae reveal an essential role of protein degradation
title_full Genome-scale analyses of butanol tolerance in Saccharomyces cerevisiae reveal an essential role of protein degradation
title_fullStr Genome-scale analyses of butanol tolerance in Saccharomyces cerevisiae reveal an essential role of protein degradation
title_full_unstemmed Genome-scale analyses of butanol tolerance in Saccharomyces cerevisiae reveal an essential role of protein degradation
title_short Genome-scale analyses of butanol tolerance in Saccharomyces cerevisiae reveal an essential role of protein degradation
title_sort genome-scale analyses of butanol tolerance in saccharomyces cerevisiae reveal an essential role of protein degradation
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3621596/
https://www.ncbi.nlm.nih.gov/pubmed/23552365
http://dx.doi.org/10.1186/1754-6834-6-48
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