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

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• dc.contributor.author Escrich Montañana, Ainoa
• dc.contributor.author Cusidó Vidal, Rosa M.
• dc.contributor.author Bonfill Baldrich, Ma. Mercedes
• dc.contributor.author Palazón Barandela, Javier
• dc.contributor.author Sánchez Muñoz, Raúl, 1990-
• dc.contributor.author Moyano Claramunt, Elisabet
• dc.date.accessioned 2022-09-07T06:22:03Z
• dc.date.available 2022-09-07T06:22:03Z
• dc.date.issued 2022
• dc.description.abstract 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.
• dc.description.sponsorship 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.
• dc.format.mimetype application/pdf
• dc.identifier.citation Escrich A, Cusido RM, Bonfill M, Palazon J, Sanchez-Muñoz R, Moyano E. The epigenetic regulation in plant specialized metabolism: DNA methylation limits paclitaxel in vitro biotechnological production. Front Plant Sci. 2022 Jul 8;13:899444. DOI: 10.3389/fpls.2022.899444
• dc.identifier.doi http://dx.doi.org/10.3389/fpls.2022.899444
• dc.identifier.issn 1664-462X
• dc.identifier.uri http://hdl.handle.net/10230/54007
• dc.language.iso eng
• dc.publisher Frontiers
• dc.relation.ispartof Front Plant Sci. 2022 Jul 8;13:899444
• dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PID2020-113438RB-I00
• dc.rights © 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.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword DNA methylation
• dc.subject.keyword Taxol
• dc.subject.keyword Cis-elements
• dc.subject.keyword Epigenetic regulation
• dc.subject.keyword Paclitaxel
• dc.subject.keyword Promotors
• dc.subject.keyword Taxane biosynthesis
• dc.title The epigenetic regulation in plant specialized metabolism: DNA methylation limits paclitaxel in vitro biotechnological production
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion