Integration and Validation of the GenomeScale Metabolic Models of Pichia pastoris

Motivation: Genome-scale metabolic models (GEMs) are tools that allow predicting a phenotype from a genotype under certain environmental conditions. GEMs have been developed in the last ten years for a broad range of organisms, and are used for multiple purposes such as discovering new properties of...

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Autores: Tomàs Gamisans, Màrius|||0000-0002-6076-6716, Ferrer, Pau|||0000-0002-5287-4127, Albiol i Sala, Joan|||0000-0001-5626-429X
Tipo de documento: artigo
Data de publicação:2016
País:España
Recursos:Universitat Autònoma de Barcelona
Repositório:Dipòsit Digital de Documents de la UAB
Idioma:inglês
OAI Identifier:oai:ddd.uab.cat:170620
Acesso em linha:https://ddd.uab.cat/record/170620
https://dx.doi.org/urn:doi:10.1371/journal.pone.0148031
Access Level:Acceso aberto
Palavra-chave:Fatty acids
Saccharomyces cerevisiae
Glucose
Metabolites
Protein metabolism
Pichia pastoris
Recombinant proteins
Metabolic pathways
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spelling Integration and Validation of the GenomeScale Metabolic Models of Pichia pastorisa Comprehensive Update of Protein Glycosylation Pathways, Lipid and Energy MetabolismTomàs Gamisans, Màrius|||0000-0002-6076-6716Ferrer, Pau|||0000-0002-5287-4127Albiol i Sala, Joan|||0000-0001-5626-429XFatty acidsSaccharomyces cerevisiaeGlucoseMetabolitesProtein metabolismPichia pastorisRecombinant proteinsMetabolic pathwaysMotivation: Genome-scale metabolic models (GEMs) are tools that allow predicting a phenotype from a genotype under certain environmental conditions. GEMs have been developed in the last ten years for a broad range of organisms, and are used for multiple purposes such as discovering new properties of metabolic networks, predicting new targets for metabolic engineering, as well as optimizing the cultivation conditions for biochemicals or recombinant protein production. Pichia pastoris is one of the most widely used organisms for heterologous protein expression. There are different GEMs for this methylotrophic yeast of which the most relevant and complete in the published literature are iPP668, PpaMBEL1254 and iLC915. However, these three models differ regarding certain pathways, terminology for metabolites and reactions and annotations. Moreover, GEMs for some species are typically built based on the reconstructed models of related model organisms. In these cases, some organism-specific pathways could be missing or misrepresented. Results: In order to provide an updated and more comprehensive GEM for P. pastoris, we have reconstructed and validated a consensus model integrating and merging all three existing models. In this step a comprehensive review and integration of the metabolic pathways included in each one of these three versions was performed. In addition, the resulting iMT1026 model includes a new description of some metabolic processes. Particularly new information described in recently published literature is included, mainly related to fatty acid and sphingolipid metabolism, glycosylation and cell energetics. Finally the reconstructed model was tested and validated, by comparing the results of the simulations with available empirical physiological datasets results obtained from a wide range of experimental conditions, such as different carbon sources, distinct oxygen availability conditions, as well as producing of two different recombinant proteins. In these simulations, the iMT1026 model has shown a better performance than the previous existing models. 22016-01-0120162016-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/170620https://dx.doi.org/urn:doi:10.1371/journal.pone.0148031reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengopen accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:1706202026-06-06T12:50:31Z
dc.title.none.fl_str_mv Integration and Validation of the GenomeScale Metabolic Models of Pichia pastoris
a Comprehensive Update of Protein Glycosylation Pathways, Lipid and Energy Metabolism
title Integration and Validation of the GenomeScale Metabolic Models of Pichia pastoris
spellingShingle Integration and Validation of the GenomeScale Metabolic Models of Pichia pastoris
Tomàs Gamisans, Màrius|||0000-0002-6076-6716
Fatty acids
Saccharomyces cerevisiae
Glucose
Metabolites
Protein metabolism
Pichia pastoris
Recombinant proteins
Metabolic pathways
title_short Integration and Validation of the GenomeScale Metabolic Models of Pichia pastoris
title_full Integration and Validation of the GenomeScale Metabolic Models of Pichia pastoris
title_fullStr Integration and Validation of the GenomeScale Metabolic Models of Pichia pastoris
title_full_unstemmed Integration and Validation of the GenomeScale Metabolic Models of Pichia pastoris
title_sort Integration and Validation of the GenomeScale Metabolic Models of Pichia pastoris
dc.creator.none.fl_str_mv Tomàs Gamisans, Màrius|||0000-0002-6076-6716
Ferrer, Pau|||0000-0002-5287-4127
Albiol i Sala, Joan|||0000-0001-5626-429X
author Tomàs Gamisans, Màrius|||0000-0002-6076-6716
author_facet Tomàs Gamisans, Màrius|||0000-0002-6076-6716
Ferrer, Pau|||0000-0002-5287-4127
Albiol i Sala, Joan|||0000-0001-5626-429X
author_role author
author2 Ferrer, Pau|||0000-0002-5287-4127
Albiol i Sala, Joan|||0000-0001-5626-429X
author2_role author
author
dc.subject.none.fl_str_mv Fatty acids
Saccharomyces cerevisiae
Glucose
Metabolites
Protein metabolism
Pichia pastoris
Recombinant proteins
Metabolic pathways
topic Fatty acids
Saccharomyces cerevisiae
Glucose
Metabolites
Protein metabolism
Pichia pastoris
Recombinant proteins
Metabolic pathways
description Motivation: Genome-scale metabolic models (GEMs) are tools that allow predicting a phenotype from a genotype under certain environmental conditions. GEMs have been developed in the last ten years for a broad range of organisms, and are used for multiple purposes such as discovering new properties of metabolic networks, predicting new targets for metabolic engineering, as well as optimizing the cultivation conditions for biochemicals or recombinant protein production. Pichia pastoris is one of the most widely used organisms for heterologous protein expression. There are different GEMs for this methylotrophic yeast of which the most relevant and complete in the published literature are iPP668, PpaMBEL1254 and iLC915. However, these three models differ regarding certain pathways, terminology for metabolites and reactions and annotations. Moreover, GEMs for some species are typically built based on the reconstructed models of related model organisms. In these cases, some organism-specific pathways could be missing or misrepresented. Results: In order to provide an updated and more comprehensive GEM for P. pastoris, we have reconstructed and validated a consensus model integrating and merging all three existing models. In this step a comprehensive review and integration of the metabolic pathways included in each one of these three versions was performed. In addition, the resulting iMT1026 model includes a new description of some metabolic processes. Particularly new information described in recently published literature is included, mainly related to fatty acid and sphingolipid metabolism, glycosylation and cell energetics. Finally the reconstructed model was tested and validated, by comparing the results of the simulations with available empirical physiological datasets results obtained from a wide range of experimental conditions, such as different carbon sources, distinct oxygen availability conditions, as well as producing of two different recombinant proteins. In these simulations, the iMT1026 model has shown a better performance than the previous existing models.
publishDate 2016
dc.date.none.fl_str_mv 2
2016-01-01
2016
2016-01-01
dc.type.none.fl_str_mv Article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://ddd.uab.cat/record/170620
https://dx.doi.org/urn:doi:10.1371/journal.pone.0148031
url https://ddd.uab.cat/record/170620
https://dx.doi.org/urn:doi:10.1371/journal.pone.0148031
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Dipòsit Digital de Documents de la UAB
instname:Universitat Autònoma de Barcelona
instname_str Universitat Autònoma de Barcelona
reponame_str Dipòsit Digital de Documents de la UAB
collection Dipòsit Digital de Documents de la UAB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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