Community Research and Development Information Service - CORDIS

Periodic Report Summary 1 - DRUGTISSUECULT (Plant Tissue Cultures as New Production Platforms for Terpenoid Based Anti-Cancer Drugs)

The goals of WP1 are to establish Thapsia garganica in vitro tissue cultures and study the production of thapsigargins. The establishment of in vitro shoot cultures of T. garganica, containing around 0.12% of thapsigargin of the dry weight has been achieved. The final aim is to produce high levels of thapsigargins (1-2% of the dry weight) from in vitro plants, to develop a sustainable production platform of thapsigargins.

The objectives of WP2 are to produce in vitro Withania somnifera cultures with increased withaferin A content through optimisation of the growth conditions and genetic engineering. Currently, 0.15 % withaferin A has been achieved in shoot cultures. The final aim is to obtain cultures producing 2% withaferin A, leading to cost reduction of this high value pharmaceutical compound and make it affordable for cancer treatment.

The main goal of WP3 is to study the biosynthesis and regulation of thapsigargins in the in vitro tissue cultures developed in WP1 to enhance the production output. In order to achieve this, genes encoding enzymes involved in thapsigargins biosynthesis will be identified. The gene expression levels before and after induction of the first gene in the biosynthesis will also be studied.

The objective of WP4 (planned at month 30) is to elucidate at least one of the last steps in withaferin A biosynthesis pathway. Through transcriptomic approach, using RNA sequencing and testing the candidate genes in heterologous expression systems, the involved gene(s) will be identified and their products will subsequently be biochemically characterized. These findings will contribute to the production of new molecules with potential therapeutic properties through combinatorial metabolic engineering.

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