A novel hydroxylation step in the taxane biosynthetic pathway: A new approach to paclitaxel production by synthetic biology
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- dc.contributor.author Sánchez Muñoz, Raúl, 1990-
- dc.contributor.author Pérez Mata, Edgar
- dc.contributor.author Almagro, Lorena
- dc.contributor.author Cusidó Vidal, Rosa M.
- dc.contributor.author Bonfill Baldrich, Ma. Mercedes
- dc.contributor.author Palazón Barandela, Javier
- dc.contributor.author Moyano Claramunt, Elisabet
- dc.date.accessioned 2020-06-03T06:16:31Z
- dc.date.available 2020-06-03T06:16:31Z
- dc.date.issued 2020
- dc.description.abstract Engineered plant cell lines have the potential to achieve enhanced metabolite production rates, providing a high-yielding source of compounds of interest. Improving the production of taxanes, pharmacologically valuable secondary metabolites of Taxus spp., is hindered by an incomplete knowledge of the taxane biosynthetic pathway. Of the five unknown steps, three are thought to involve cytochrome P450-like hydroxylases. In the current work, after an in-depth in silico characterization of four candidate enzymes proposed in a previous cDNA-AFLP assay, TB506 was selected as a candidate for the hydroxylation of the taxane side chain. A docking assay indicated TB506 is active after the attachment of the side chain based on its affinity to the ligand 3′N-dehydroxydebenzoyltaxol. Finally, the involvement of TB506 in the last hydroxylation step of the paclitaxel biosynthetic pathway was confirmed by functional assays. The identification of this hydroxylase will contribute to the development of alternative sustainable paclitaxel production systems using synthetic biology techniques.
- dc.description.sponsorship This work has been carried out at the Plant Physiology Laboratory (University of Barcelona) and the Plant Biology Department (University of Murcia). It was financially 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 (1987/GERM/15). RS-M was supported by a fellowship from the University Pompeu Fabra.
- dc.format.mimetype application/pdf
- dc.identifier.citation Sanchez-Muñoz R, Perez-Mata E, Almagro L, Cusido RM, Bonfill M, Palazon J, Moyano E. A novel hydroxylation step in the taxane biosynthetic pathway: A new approach to paclitaxel production by synthetic biology. Front Bioeng Biotechnol. 2020; 8:410. DOI: 10.3389/fbioe.2020.00410
- dc.identifier.doi http://dx.doi.org/10.3389/fbioe.2020.00410
- dc.identifier.issn 2296-4185
- dc.identifier.uri http://hdl.handle.net/10230/44883
- dc.language.iso eng
- dc.publisher Frontiers
- dc.relation.ispartof Front Bioeng Biotechnol. 2020; 8:410
- dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/BIO2017-82374-R
- dc.rights © 2020 Sanchez-Muñoz, Perez-Mata, Almagro, Cusido, Bonfill, Palazon 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 Taxane hydroxylase
- dc.subject.keyword Paclitaxel
- dc.subject.keyword Protoplasts transfection
- dc.subject.keyword Cytochrome P450
- dc.subject.keyword Biotechnological production
- dc.subject.keyword Biotransformation
- dc.title A novel hydroxylation step in the taxane biosynthetic pathway: A new approach to paclitaxel production by synthetic biology
- dc.type info:eu-repo/semantics/article
- dc.type.version info:eu-repo/semantics/publishedVersion