PACLITAXEL PATHWAY TRANSCRIPTIONAL ACTIVATORS

Paclitaxel, a molecule produced from yew tree extracts, is a leading drug for the treatment of a variety of cancers. Clinical data suggest that the number of its applications will increase in the future. However, because trees grow slowly and produce taxanes in very low quantities, supply of raw material has become an increasing problem. Fermentation using plant cell culture may be a long-term solution, since suspension cells constitute a renewable source of taxoids. However a major obstacle remains the obtention of stable and highly productive cell lines. The overall goal of this proposal is to improve the productivity of yew cells through genetic engineering, using transcription factor genes that activate the paclitaxel metabolic pathway. The specific objective of this phase I project is to identify Arabidopsis transcription factors that activate selected pathway genes. The approach we propose to express in plant cells each of the 1533 identified Arabidopsis transcription factors, together with a representative gene of the Taxol pathway. Activators identified through this primary screen will be further tested against a second pathway gene. Production and testing of transgenic yew cells containing he est candidates will be part of a future phase II project.