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...
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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 |
| Summary: | 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. |
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