Impact of the cultivation strategy on resveratrol production from glucose in engineered Corynebacterium glutamicum
Autor(a) principal: | |
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Data de Publicação: | 2018 |
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/1822/47754 |
Resumo: | The health benefits of polyphenols such as stilbenes and flavonoids for humans are increasingly attracting attention. Resveratrol is awell-characterized naturally-occurring stilbeneandpotentanti-oxidant, which isused as food supplement and cosmetic ingredient. Several microorganisms including Corynebacterium glutamicum were engineered for resveratrol production from glucose. Based on the cultivation of a resveratrol-producing C. glutamicum strain in shake flasks, different strategies for improving production under controlled conditions at bioreactor scale were tested. To this end, different cultivation parameters including substrate concentration and operation modes (batch and fed-batch) were evaluated. Whereas the highest biomass concentration was observed during fed-batch fermentation, the maximum resveratrol production was achieved in batch mode. The maximal titer obtained was 12 mg L−1 of resveratrol without the addition of the fatty acid synthase inhibitor cerulenin, which was previously shown to be crucial for production with C. glutamicum. The specific growth rate duringproductionseemstohaveasignificanteffectinresveratrolproductionandapparentlylowspecificgrowth rates may redirect the metabolic bottleneck from p-coumaric acid formation to malonyl-CoA or ATP availability. We also show that high oxygen concentrations in the bioreactor negatively affected the obtained resveratrol titerswithC.glutamicum,whichismost likelydueto thestrongtendency ofresveratrol tooxidizeoroligomerize. Thus, up-scaling of the resveratrol production process is technically challenging and individual process parameters have to be optimized cautiously. |
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7160 |
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Impact of the cultivation strategy on resveratrol production from glucose in engineered Corynebacterium glutamicumBatchCorynebacterium glutamicumFed-batchOxidationResveratrolScience & TechnologyThe health benefits of polyphenols such as stilbenes and flavonoids for humans are increasingly attracting attention. Resveratrol is awell-characterized naturally-occurring stilbeneandpotentanti-oxidant, which isused as food supplement and cosmetic ingredient. Several microorganisms including Corynebacterium glutamicum were engineered for resveratrol production from glucose. Based on the cultivation of a resveratrol-producing C. glutamicum strain in shake flasks, different strategies for improving production under controlled conditions at bioreactor scale were tested. To this end, different cultivation parameters including substrate concentration and operation modes (batch and fed-batch) were evaluated. Whereas the highest biomass concentration was observed during fed-batch fermentation, the maximum resveratrol production was achieved in batch mode. The maximal titer obtained was 12 mg L−1 of resveratrol without the addition of the fatty acid synthase inhibitor cerulenin, which was previously shown to be crucial for production with C. glutamicum. The specific growth rate duringproductionseemstohaveasignificanteffectinresveratrolproductionandapparentlylowspecificgrowth rates may redirect the metabolic bottleneck from p-coumaric acid formation to malonyl-CoA or ATP availability. We also show that high oxygen concentrations in the bioreactor negatively affected the obtained resveratrol titerswithC.glutamicum,whichismost likelydueto thestrongtendency ofresveratrol tooxidizeoroligomerize. Thus, up-scaling of the resveratrol production process is technically challenging and individual process parameters have to be optimized cautiously.We would like to thank the European Union Framework Program 7 "BacHBerry" (www.bachberry.eu), Project No. FP7- 613793 for financial support, the PortugueseFoundation forScience andTechnology (FCT) under the scope of the strategic funding of UID/BIO/04469/2013 unit, COMPETE 2020 (POCI-01-0145-FEDER-006684) and BioTecNorte operation (NORTE-01-0145-FEDER-000004) funded by the European Regional Development Fund under the scope of Norte2020 − Programa Operacional Regional do Norte.info:eu-repo/semantics/publishedVersionElsevierUniversidade do MinhoBraga, AdelaideOliveira, J.Silva, Rita M.Ferreira, PatríciaRocha, IsabelKallscheuer, NicolaiMarienhagen, JanFaria, N.2018-01-102018-01-10T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/47754engBraga, Adelaide; Oliveira, J.; Silva, Ana Rita; Ferreira, Patrícia; Rocha, Isabel; Kallscheuer, Nicolai; Marienhagen, Jan; Faria, N., Impact of the cultivation strategy on resveratrol production from glucose in engineered Corynebacterium glutamicum. Journal of Biotechnology, 265, 70-75, 20180168-16561873-486310.1016/j.jbiotec.2017.11.00629141192http://www.elsevier.com/locate/issn/01681656info: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:RCAAP2023-07-21T12:52:51Zoai:repositorium.sdum.uminho.pt:1822/47754Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T19:52:05.213067Repositório 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 |
Impact of the cultivation strategy on resveratrol production from glucose in engineered Corynebacterium glutamicum |
title |
Impact of the cultivation strategy on resveratrol production from glucose in engineered Corynebacterium glutamicum |
spellingShingle |
Impact of the cultivation strategy on resveratrol production from glucose in engineered Corynebacterium glutamicum Braga, Adelaide Batch Corynebacterium glutamicum Fed-batch Oxidation Resveratrol Science & Technology |
title_short |
Impact of the cultivation strategy on resveratrol production from glucose in engineered Corynebacterium glutamicum |
title_full |
Impact of the cultivation strategy on resveratrol production from glucose in engineered Corynebacterium glutamicum |
title_fullStr |
Impact of the cultivation strategy on resveratrol production from glucose in engineered Corynebacterium glutamicum |
title_full_unstemmed |
Impact of the cultivation strategy on resveratrol production from glucose in engineered Corynebacterium glutamicum |
title_sort |
Impact of the cultivation strategy on resveratrol production from glucose in engineered Corynebacterium glutamicum |
author |
Braga, Adelaide |
author_facet |
Braga, Adelaide Oliveira, J. Silva, Rita M. Ferreira, Patrícia Rocha, Isabel Kallscheuer, Nicolai Marienhagen, Jan Faria, N. |
author_role |
author |
author2 |
Oliveira, J. Silva, Rita M. Ferreira, Patrícia Rocha, Isabel Kallscheuer, Nicolai Marienhagen, Jan Faria, N. |
author2_role |
author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade do Minho |
dc.contributor.author.fl_str_mv |
Braga, Adelaide Oliveira, J. Silva, Rita M. Ferreira, Patrícia Rocha, Isabel Kallscheuer, Nicolai Marienhagen, Jan Faria, N. |
dc.subject.por.fl_str_mv |
Batch Corynebacterium glutamicum Fed-batch Oxidation Resveratrol Science & Technology |
topic |
Batch Corynebacterium glutamicum Fed-batch Oxidation Resveratrol Science & Technology |
description |
The health benefits of polyphenols such as stilbenes and flavonoids for humans are increasingly attracting attention. Resveratrol is awell-characterized naturally-occurring stilbeneandpotentanti-oxidant, which isused as food supplement and cosmetic ingredient. Several microorganisms including Corynebacterium glutamicum were engineered for resveratrol production from glucose. Based on the cultivation of a resveratrol-producing C. glutamicum strain in shake flasks, different strategies for improving production under controlled conditions at bioreactor scale were tested. To this end, different cultivation parameters including substrate concentration and operation modes (batch and fed-batch) were evaluated. Whereas the highest biomass concentration was observed during fed-batch fermentation, the maximum resveratrol production was achieved in batch mode. The maximal titer obtained was 12 mg L−1 of resveratrol without the addition of the fatty acid synthase inhibitor cerulenin, which was previously shown to be crucial for production with C. glutamicum. The specific growth rate duringproductionseemstohaveasignificanteffectinresveratrolproductionandapparentlylowspecificgrowth rates may redirect the metabolic bottleneck from p-coumaric acid formation to malonyl-CoA or ATP availability. We also show that high oxygen concentrations in the bioreactor negatively affected the obtained resveratrol titerswithC.glutamicum,whichismost likelydueto thestrongtendency ofresveratrol tooxidizeoroligomerize. Thus, up-scaling of the resveratrol production process is technically challenging and individual process parameters have to be optimized cautiously. |
publishDate |
2018 |
dc.date.none.fl_str_mv |
2018-01-10 2018-01-10T00:00:00Z |
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/1822/47754 |
url |
http://hdl.handle.net/1822/47754 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Braga, Adelaide; Oliveira, J.; Silva, Ana Rita; Ferreira, Patrícia; Rocha, Isabel; Kallscheuer, Nicolai; Marienhagen, Jan; Faria, N., Impact of the cultivation strategy on resveratrol production from glucose in engineered Corynebacterium glutamicum. Journal of Biotechnology, 265, 70-75, 2018 0168-1656 1873-4863 10.1016/j.jbiotec.2017.11.006 29141192 http://www.elsevier.com/locate/issn/01681656 |
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 |
publisher.none.fl_str_mv |
Elsevier |
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 |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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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 |
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