The epigenetic regulation in plant specialized metabolism: DNA methylation limits paclitaxel in vitro biotechnological production

Environmental conditions are key factors in the modulation of the epigenetic mechanisms regulating gene expression in plants. Specifically, the maintenance of cell cultures in optimal in vitro conditions alters methylation patterns and, consequently, their genetic transcription and metabolism. Pacli...

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Autores: Escrich Montañana, Ainoa, Cusidó Vidal, Rosa M., Bonfill Baldrich, Ma. Mercedes, Palazón Barandela, Javier, Sánchez Muñoz, Raúl, 1990-, Moyano Claramunt, Elisabet
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Universitat Pompeu Fabra
Repositorio:Repositorio Digital de la UPF
OAI Identifier:oai:repositori.upf.edu:10230/54007
Acceso en línea:http://hdl.handle.net/10230/54007
http://dx.doi.org/10.3389/fpls.2022.899444
Access Level:acceso abierto
Palabra clave:DNA methylation
Taxol
Cis-elements
Epigenetic regulation
Paclitaxel
Promotors
Taxane biosynthesis
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spelling The epigenetic regulation in plant specialized metabolism: DNA methylation limits paclitaxel in vitro biotechnological productionEscrich Montañana, AinoaCusidó Vidal, Rosa M.Bonfill Baldrich, Ma. MercedesPalazón Barandela, JavierSánchez Muñoz, Raúl, 1990-Moyano Claramunt, ElisabetDNA methylationTaxolCis-elementsEpigenetic regulationPaclitaxelPromotorsTaxane biosynthesisEnvironmental conditions are key factors in the modulation of the epigenetic mechanisms regulating gene expression in plants. Specifically, the maintenance of cell cultures in optimal in vitro conditions alters methylation patterns and, consequently, their genetic transcription and metabolism. Paclitaxel production in Taxus x media cell cultures is reduced during its maintenance in in vitro conditions, compromising the biotechnological production of this valuable anticancer agent. To understand how DNA methylation influences taxane production, the promoters of three genes (GGPPS, TXS, and DBTNBT) involved in taxane biosynthesis have been studied, comparing the methylation patterns between a new line and one of ~14 years old. Our work revealed that while the central promoter of the GGPPS gene is protected from cytosine methylation accumulation, TXS and DBTNBT promoters accumulate methylation at different levels. The DBTNBT promoter of the old line is the most affected, showing a 200 bp regulatory region where all the cytosines were methylated. This evidence the existence of specific epigenetic regulatory mechanisms affecting the last steps of the pathway, such as the DBTNBT promoter. Interestingly, the GGPPS promoter, a regulatory sequence of a non-specific taxane biosynthetic gene, was not affected by this mechanism. In addition, the relationship between the detected methylation points and the predicted transcription factor binding sites (TFBS) showed that the action of TFs would be compromised in the old line, giving a further explanation for the production reduction in in vitro cell cultures. This knowledge could help in designing novel strategies to enhance the biotechnological production of taxanes over time.This work has been carried out at the Plant Physiology Laboratory (Universitat de Barcelona). It was financially supported by the Spanish PID2020-113438RB-I00/AEI/10.13039/501100011033 and the Generalitat de Catalunya 2017SGR242. AE was supported by a fellowship from the Universitat Pompeu Fabra.Frontiers202220222022info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/54007http://dx.doi.org/10.3389/fpls.2022.899444reponame:Repositorio Digital de la UPFinstname:Universitat Pompeu FabraInglésFront Plant Sci. 2022 Jul 8;13:899444info:eu-repo/grantAgreement/ES/2PE/PID2020-113438RB-I00© 2022 Escrich, Cusido, Bonfill, Palazon, Sanchez-Muñoz and Moyano. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.http://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repositori.upf.edu:10230/540072026-06-12T07:21:37Z
dc.title.none.fl_str_mv The epigenetic regulation in plant specialized metabolism: DNA methylation limits paclitaxel in vitro biotechnological production
title The epigenetic regulation in plant specialized metabolism: DNA methylation limits paclitaxel in vitro biotechnological production
spellingShingle The epigenetic regulation in plant specialized metabolism: DNA methylation limits paclitaxel in vitro biotechnological production
Escrich Montañana, Ainoa
DNA methylation
Taxol
Cis-elements
Epigenetic regulation
Paclitaxel
Promotors
Taxane biosynthesis
title_short The epigenetic regulation in plant specialized metabolism: DNA methylation limits paclitaxel in vitro biotechnological production
title_full The epigenetic regulation in plant specialized metabolism: DNA methylation limits paclitaxel in vitro biotechnological production
title_fullStr The epigenetic regulation in plant specialized metabolism: DNA methylation limits paclitaxel in vitro biotechnological production
title_full_unstemmed The epigenetic regulation in plant specialized metabolism: DNA methylation limits paclitaxel in vitro biotechnological production
title_sort The epigenetic regulation in plant specialized metabolism: DNA methylation limits paclitaxel in vitro biotechnological production
dc.creator.none.fl_str_mv Escrich Montañana, Ainoa
Cusidó Vidal, Rosa M.
Bonfill Baldrich, Ma. Mercedes
Palazón Barandela, Javier
Sánchez Muñoz, Raúl, 1990-
Moyano Claramunt, Elisabet
author Escrich Montañana, Ainoa
author_facet Escrich Montañana, Ainoa
Cusidó Vidal, Rosa M.
Bonfill Baldrich, Ma. Mercedes
Palazón Barandela, Javier
Sánchez Muñoz, Raúl, 1990-
Moyano Claramunt, Elisabet
author_role author
author2 Cusidó Vidal, Rosa M.
Bonfill Baldrich, Ma. Mercedes
Palazón Barandela, Javier
Sánchez Muñoz, Raúl, 1990-
Moyano Claramunt, Elisabet
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv DNA methylation
Taxol
Cis-elements
Epigenetic regulation
Paclitaxel
Promotors
Taxane biosynthesis
topic DNA methylation
Taxol
Cis-elements
Epigenetic regulation
Paclitaxel
Promotors
Taxane biosynthesis
description Environmental conditions are key factors in the modulation of the epigenetic mechanisms regulating gene expression in plants. Specifically, the maintenance of cell cultures in optimal in vitro conditions alters methylation patterns and, consequently, their genetic transcription and metabolism. Paclitaxel production in Taxus x media cell cultures is reduced during its maintenance in in vitro conditions, compromising the biotechnological production of this valuable anticancer agent. To understand how DNA methylation influences taxane production, the promoters of three genes (GGPPS, TXS, and DBTNBT) involved in taxane biosynthesis have been studied, comparing the methylation patterns between a new line and one of ~14 years old. Our work revealed that while the central promoter of the GGPPS gene is protected from cytosine methylation accumulation, TXS and DBTNBT promoters accumulate methylation at different levels. The DBTNBT promoter of the old line is the most affected, showing a 200 bp regulatory region where all the cytosines were methylated. This evidence the existence of specific epigenetic regulatory mechanisms affecting the last steps of the pathway, such as the DBTNBT promoter. Interestingly, the GGPPS promoter, a regulatory sequence of a non-specific taxane biosynthetic gene, was not affected by this mechanism. In addition, the relationship between the detected methylation points and the predicted transcription factor binding sites (TFBS) showed that the action of TFs would be compromised in the old line, giving a further explanation for the production reduction in in vitro cell cultures. This knowledge could help in designing novel strategies to enhance the biotechnological production of taxanes over time.
publishDate 2022
dc.date.none.fl_str_mv 2022
2022
2022
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10230/54007
http://dx.doi.org/10.3389/fpls.2022.899444
url http://hdl.handle.net/10230/54007
http://dx.doi.org/10.3389/fpls.2022.899444
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Front Plant Sci. 2022 Jul 8;13:899444
info:eu-repo/grantAgreement/ES/2PE/PID2020-113438RB-I00
dc.rights.none.fl_str_mv http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Frontiers
publisher.none.fl_str_mv Frontiers
dc.source.none.fl_str_mv reponame:Repositorio Digital de la UPF
instname:Universitat Pompeu Fabra
instname_str Universitat Pompeu Fabra
reponame_str Repositorio Digital de la UPF
collection Repositorio Digital de la UPF
repository.name.fl_str_mv
repository.mail.fl_str_mv
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