Paclitaxel: new insights into its regulation, biosynthesis and biotechnological production
The emergency to obtain effective substances against cancer, and the awareness to protect natural resources make plant biofactories a promising alternative for obtaining plant-derived compounds. In this context, the biotechnological production of the potent anticancer agent paclitaxel could be incre...
| Author: | |
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| Format: | Doctoral thesis |
| Status: | Published version |
| Publication date: | 2022 |
| Country: | España |
| Institution: | CBUC, CESCA |
| Repository: | TDR. Tesis Doctorales en Red |
| OAI Identifier: | oai:www.tdx.cat:10803/687277 |
| Online Access: | http://hdl.handle.net/10803/687277 |
| Access Level: | Open access |
| Keyword: | Biotechnological production Gene regulation Paclitaxel Taxane biosynthesis Taxus spp. Biosíntesis de taxanos Producción biotecnológica Regulación genética 577 |
| _version_ | 1878740563234127872 |
|---|---|
| author | Escrich Montañana, Ainoa |
| author_browse | Escrich Montañana, Ainoa |
| author_facet | Escrich Montañana, Ainoa |
| author_role | author |
| collection | TDR. Tesis Doctorales en Red |
| description | The emergency to obtain effective substances against cancer, and the awareness to protect natural resources make plant biofactories a promising alternative for obtaining plant-derived compounds. In this context, the biotechnological production of the potent anticancer agent paclitaxel could be increased using in vitro cell cultures of Taxus spp. The objective of this work was to provide novel knowledge related to the biosynthesis and production of paclitaxel through the implementation of optimized Taxus spp. biofactories. Our results showed that: (1) The synergistic action of coronatine and calix[8]arene significantly increases the paclitaxel synthesis. (2) There exists an epigenetic control over the paclitaxel biosynthesis pathway, adversely affected in cultures maintained long-term under in vitro conditions. (3) By increasing the level of ploidy in Taxus spp. cell cultures, the production of taxanes also increased. (4) The enzyme TB574 is the ideal candidate to carry out the hydroxylation step on the C1 carbon of the taxane skeleton. |
| eu_rights_str_mv | openAccess |
| format | doctoralThesis |
| id | ES_d552feebfeeb7bdb846cd0a82d3166bb |
| institution | CBUC, CESCA |
| instname_str | CBUC, CESCA |
| network_acronym_str | ES |
| network_name_str | España |
| oai_identifier_str | oai:www.tdx.cat:10803/687277 |
| publishDate | 2022 |
| publishDateSort | 2022 |
| publisher | Universitat Pompeu Fabra |
| publisherStr | Universitat Pompeu Fabra |
| reponame_str | TDR. Tesis Doctorales en Red |
| spelling | Paclitaxel: new insights into its regulation, biosynthesis and biotechnological production Escrich Montañana, Ainoa Biotechnological production Gene regulation Paclitaxel Taxane biosynthesis Taxus spp. Biosíntesis de taxanos Producción biotecnológica Regulación genética 577 The emergency to obtain effective substances against cancer, and the awareness to protect natural resources make plant biofactories a promising alternative for obtaining plant-derived compounds. In this context, the biotechnological production of the potent anticancer agent paclitaxel could be increased using in vitro cell cultures of Taxus spp. The objective of this work was to provide novel knowledge related to the biosynthesis and production of paclitaxel through the implementation of optimized Taxus spp. biofactories. Our results showed that: (1) The synergistic action of coronatine and calix[8]arene significantly increases the paclitaxel synthesis. (2) There exists an epigenetic control over the paclitaxel biosynthesis pathway, adversely affected in cultures maintained long-term under in vitro conditions. (3) By increasing the level of ploidy in Taxus spp. cell cultures, the production of taxanes also increased. (4) The enzyme TB574 is the ideal candidate to carry out the hydroxylation step on the C1 carbon of the taxane skeleton. La emergencia para obtener sustancias efectivas contra el cáncer, y la necesidad de proteger los recursos naturales convierten a las biofactorías vegetales en una alternativa prometedora para obtener compuestos derivados de plantas. En este contexto, la producción biotecnológica del potente agente anticancerígeno paclitaxel podría incrementarse utilizando cultivos celulares de Taxus spp. en condiciones in vitro. El objetivo de este trabajo ha sido proporcionar nuevos conocimientos sobre la biosíntesis y la producción de paclitaxel para la optimización de las biofactorías de Taxus spp. Nuestros resultados mostraron que: (1) La acción sinérgica de coronatina y calix[8]areno incrementa significativamente la síntesis de paclitaxel. (2) Existe un control epigenético sobre la ruta de biosíntesis de paclitaxel que afecta negativamente a los cultivos mantenidos a largo plazo en condiciones in vitro. (3) Al aumentar el nivel de ploidía en los cultivos celulares de Taxus spp. se incrementó la producción de taxanos. (4) El enzima TB574 es el candidato idóneo para llevar a cabo la etapa de hidroxilación sobre el carbono C1 del núcleo del taxano. Programa de doctorat en Biomedicina Universitat Pompeu Fabra http://hdl.handle.net/10803/687277 |
| spellingShingle | Paclitaxel: new insights into its regulation, biosynthesis and biotechnological production Escrich Montañana, Ainoa Biotechnological production Gene regulation Paclitaxel Taxane biosynthesis Taxus spp. Biosíntesis de taxanos Producción biotecnológica Regulación genética 577 |
| status_str | publishedVersion |
| title | Paclitaxel: new insights into its regulation, biosynthesis and biotechnological production |
| title_full | Paclitaxel: new insights into its regulation, biosynthesis and biotechnological production |
| title_fullStr | Paclitaxel: new insights into its regulation, biosynthesis and biotechnological production |
| title_full_unstemmed | Paclitaxel: new insights into its regulation, biosynthesis and biotechnological production |
| title_short | Paclitaxel: new insights into its regulation, biosynthesis and biotechnological production |
| title_sort | Paclitaxel: new insights into its regulation, biosynthesis and biotechnological production |
| topic | Biotechnological production Gene regulation Paclitaxel Taxane biosynthesis Taxus spp. Biosíntesis de taxanos Producción biotecnológica Regulación genética 577 |
| topic_facet | Biotechnological production Gene regulation Paclitaxel Taxane biosynthesis Taxus spp. Biosíntesis de taxanos Producción biotecnológica Regulación genética 577 |
| url | http://hdl.handle.net/10803/687277 |