Improved biotechnological production of paclitaxel in Taxus media cell cultures by the combined action of coronatine and calix[8]arenes

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• dc.contributor.author Escrich Montañana, Ainoa
• dc.contributor.author Almagro, Lorena
• dc.contributor.author Moyano Claramunt, Elisabet
• dc.contributor.author Cusidó Vidal, Rosa M.
• dc.contributor.author Bonfill Baldrich, Ma. Mercedes
• dc.contributor.author Hosseini, Bahman
• dc.contributor.author Palazón, Javier
• dc.date.accessioned 2022-03-23T10:43:38Z
• dc.date.available 2022-03-23T10:43:38Z
• dc.date.issued 2021
• dc.description.abstract Paclitaxel (PTX), a widely used anticancer agent, is found in the inner bark of several Taxus species, although at such low levels that its extraction is ecologically unsustainable. Biotechnological platforms based on Taxus sp. cell cultures offer an eco-friendlier approach to PTX production, with yields that can be improved by elicitation. However, the also limited excretion of target compounds from the producer cells to the medium hampers their extraction and purification. In this context, we studied the effect of treating T. media cell cultures with the elicitor coronatine (COR) and calix[8]arenes (CAL), nanoparticles that can host lipophilic compounds within their macrocyclic scaffold. The highest taxane production (103.5 mg.L-1), achieved after treatment with COR (1 μM) and CAL (10 mg.L-1), was 15-fold greater than in the control, and PTX represented 82% of the total taxanes analyzed. Expression levels of the flux-limiting PTX biosynthetic genes, BAPT and DBTNBT, increased after the addition of COR, confirming its elicitor action, but not CAL. The CAL treatment significantly enhanced taxane excretion, especially when production levels were increased by COR; 98% of the total taxanes were found in the culture medium after COR + CAL treatment. By forming complexes with PTX, the nanoparticles facilitated its excretion to the medium, and by protecting cells from PTX toxicity, its intra-and extra-cellular degradation may have been avoided. The addition of COR and CAL to T. media cell cultures is therefore a bio-sustainable and economically viable system to improve the yield of this important anticancer compound.
• dc.description.sponsorship This work was supported by the Spanish MEIC (BIO2017-82374-R) (AEI/FEDER, UE), the Generalitat de Catalunya (2017SGR242) and the Fundación Seneca-Agencia de Ciencia y Tecnología de la Región de Murcia(19876/GERM/15). Ainoa Escrich was supported by a fellowship from the University Pompeu Fabra
• dc.format.mimetype application/pdf
• dc.identifier.citation Escrich A, Almagro L, Moyano E, Cusido RM, Bonfill M, Hosseini B et al. Improved biotechnological production of paclitaxel in Taxus media cell cultures by the combined action of coronatine and calix[8]arenes. Plant Physiol Biochem. 2021;163:68-75. DOI: 10.1016/j.plaphy.2021.03.047
• dc.identifier.doi http://dx.doi.org/10.1016/j.plaphy.2021.03.047
• dc.identifier.issn 0981-9428
• dc.identifier.uri http://hdl.handle.net/10230/52759
• dc.language.iso eng
• dc.publisher Elsevier
• dc.rights © 2021 Ainoa Escrich et al. Published by Elsevier Masson SAS. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.other Expressió gènica
• dc.subject.other Paclitaxel
• dc.subject.other Toxines
• dc.subject.other Calixarens
• dc.title Improved biotechnological production of paclitaxel in Taxus media cell cultures by the combined action of coronatine and calix[8]arenes
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion