Improving the flux distributions simulated with genome-scale metabolic models of Saccharomyces cerevisiae
Autor(a) principal: | |
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Data de Publicação: | 2016 |
Outros Autores: | , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/1822/41877 |
Resumo: | Abstract Genome-scale metabolic models (GEMs) can be used to evaluate genotype-phenotype relationships and their application to microbial strain engineering is increasing in popularity. Some of the algorithms used to simulate the phenotypes of mutant strains require the determination of a wild-type flux distribution. However, the accuracy of this reference, when calculated with flux balance analysis, has not been studied in detail before. Here, the wild-type simulations of selected GEMs for Saccharomyces cerevisiae have been analysed and most of the models tested predicted erroneous fluxes in central pathways, especially in the pentose phosphate pathway. Since the problematic fluxes were mostly related to areas of the metabolism consuming or producing NADPH/NADH, we have manually curated all reactions including these cofactors by forcing the use of NADPH/NADP+ in anabolic reactions and NADH/NAD+ for catabolic reactions. The curated models predicted more accurate flux distributions and performed better in the simulation of mutant phenotypes. |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Improving the flux distributions simulated with genome-scale metabolic models of Saccharomyces cerevisiaegenome-scale metabolic modelSaccharomyces cerevisiaeflux distributionNADH: NADPHmetabolic engineeringAbstract Genome-scale metabolic models (GEMs) can be used to evaluate genotype-phenotype relationships and their application to microbial strain engineering is increasing in popularity. Some of the algorithms used to simulate the phenotypes of mutant strains require the determination of a wild-type flux distribution. However, the accuracy of this reference, when calculated with flux balance analysis, has not been studied in detail before. Here, the wild-type simulations of selected GEMs for Saccharomyces cerevisiae have been analysed and most of the models tested predicted erroneous fluxes in central pathways, especially in the pentose phosphate pathway. Since the problematic fluxes were mostly related to areas of the metabolism consuming or producing NADPH/NADH, we have manually curated all reactions including these cofactors by forcing the use of NADPH/NADP+ in anabolic reactions and NADH/NAD+ for catabolic reactions. The curated models predicted more accurate flux distributions and performed better in the simulation of mutant phenotypes.FCT -Fuel Cell Technologies Program(SFRH/BD/51111/2010)Elsevier B.V.Universidade do MinhoPereira, R.Nielsen, JensRocha, Isabel2016-122016-12-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/41877engPereira, R.; Nielsen, Jens; Rocha, Isabel, Improving the flux distributions simulated with genome-scale metabolic models of Saccharomyces cerevisiae. Metabolic Engineering Communications, 3, 153-163, 20162214-030110.1016/j.meteno.2016.05.002http://www.journals.elsevier.com/metabolic-engineering-communicationsinfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-21T12:31:55Zoai:repositorium.sdum.uminho.pt:1822/41877Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T19:27:14.138364Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Improving the flux distributions simulated with genome-scale metabolic models of Saccharomyces cerevisiae |
title |
Improving the flux distributions simulated with genome-scale metabolic models of Saccharomyces cerevisiae |
spellingShingle |
Improving the flux distributions simulated with genome-scale metabolic models of Saccharomyces cerevisiae Pereira, R. genome-scale metabolic model Saccharomyces cerevisiae flux distribution NADH: NADPH metabolic engineering |
title_short |
Improving the flux distributions simulated with genome-scale metabolic models of Saccharomyces cerevisiae |
title_full |
Improving the flux distributions simulated with genome-scale metabolic models of Saccharomyces cerevisiae |
title_fullStr |
Improving the flux distributions simulated with genome-scale metabolic models of Saccharomyces cerevisiae |
title_full_unstemmed |
Improving the flux distributions simulated with genome-scale metabolic models of Saccharomyces cerevisiae |
title_sort |
Improving the flux distributions simulated with genome-scale metabolic models of Saccharomyces cerevisiae |
author |
Pereira, R. |
author_facet |
Pereira, R. Nielsen, Jens Rocha, Isabel |
author_role |
author |
author2 |
Nielsen, Jens Rocha, Isabel |
author2_role |
author author |
dc.contributor.none.fl_str_mv |
Universidade do Minho |
dc.contributor.author.fl_str_mv |
Pereira, R. Nielsen, Jens Rocha, Isabel |
dc.subject.por.fl_str_mv |
genome-scale metabolic model Saccharomyces cerevisiae flux distribution NADH: NADPH metabolic engineering |
topic |
genome-scale metabolic model Saccharomyces cerevisiae flux distribution NADH: NADPH metabolic engineering |
description |
Abstract Genome-scale metabolic models (GEMs) can be used to evaluate genotype-phenotype relationships and their application to microbial strain engineering is increasing in popularity. Some of the algorithms used to simulate the phenotypes of mutant strains require the determination of a wild-type flux distribution. However, the accuracy of this reference, when calculated with flux balance analysis, has not been studied in detail before. Here, the wild-type simulations of selected GEMs for Saccharomyces cerevisiae have been analysed and most of the models tested predicted erroneous fluxes in central pathways, especially in the pentose phosphate pathway. Since the problematic fluxes were mostly related to areas of the metabolism consuming or producing NADPH/NADH, we have manually curated all reactions including these cofactors by forcing the use of NADPH/NADP+ in anabolic reactions and NADH/NAD+ for catabolic reactions. The curated models predicted more accurate flux distributions and performed better in the simulation of mutant phenotypes. |
publishDate |
2016 |
dc.date.none.fl_str_mv |
2016-12 2016-12-01T00:00:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/1822/41877 |
url |
http://hdl.handle.net/1822/41877 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Pereira, R.; Nielsen, Jens; Rocha, Isabel, Improving the flux distributions simulated with genome-scale metabolic models of Saccharomyces cerevisiae. Metabolic Engineering Communications, 3, 153-163, 2016 2214-0301 10.1016/j.meteno.2016.05.002 http://www.journals.elsevier.com/metabolic-engineering-communications |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Elsevier B.V. |
publisher.none.fl_str_mv |
Elsevier B.V. |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
repository.mail.fl_str_mv |
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1799132763605958656 |