Journal article
Domesticating deadly carrots: Predicting the biosynthetic pathway of thapsigargins for the treatment of solid tumors
Planta Medica, Vol.81(S 01), pp.S1-S381
2016
Abstract
Thapsigargin, a guaianolide sesquiterpene lactone, is the active component of a pro-drug currently in phase 2 of clinical trials for the treatment of solid tumours. Thapsigargin is currently only being isolated from Thapsia garganica L. (Apiaceae); a member of the taxonomically complex genus Thapsia L. found in the Mediterranean. Thapsia species do not grow well out of their natural habitat and on-going research seeks to solve the potential resource problem for Mipsagargin, a new thapsigargin derived drug, by transferring the biosynthetic pathway to other heterologous hosts for efficient production [1]. Plant material of Thapsia garganica has been collected from around the species' Mediterranean range, as part of a revision of the genus. The amount of thapsigargin and other closely related guaianolides was quantified between individuals across its range, in planta and during the growing season. Secondly the expression levels of the terpene synthases TgTPS1 and TgTPS2, as well as a cytochrome P450, thought to be involved in the biosynthesis of thapsigargin, were investigated. These tests have also been carried out in conjunction with soil analyses to test if fluctuations in the levels of thapsigargin can be linked to environmental factors. Thapsigargin has been found to be extremely variable over its geographical distribution even over small areas. Lastly, to see whether candidates for the biosynthesis of thapsigargin could shed light on where the compound is made within the plant, root sections have been investigated from greenhouse plants provided by ThapsIbiza. Using light microscopy and MALDI-imaging epithelial cells containing thapsigargin and surrounding secretory channels within the vascular cambium were observed, indicating for the first time that this is the localisation of thapsigargin biosynthesis. It is hoped that these results will fast track the discovery of new enzymes involved in the biosynthetic pathway of thapsigargin.
Details
- Title
- Domesticating deadly carrots: Predicting the biosynthetic pathway of thapsigargins for the treatment of solid tumors
- Authors/Creators
- K. Martinez (Author/Creator) - University of CopenhagenH.T. Simonsen (Author/Creator) - Technical University of DenmarkN. Rønsted (Author/Creator) - University of CopenhagenT. Bundgaard Andersen (Author/Creator)C. Barnes (Author/Creator) - University of CopenhagenB. Boughton (Author/Creator) - The University of MelbourneF. Cozzi (Author/Creator) - University of Copenhagen
- Publication Details
- Planta Medica, Vol.81(S 01), pp.S1-S381
- Publisher
- Georg Thieme Verlag
- Identifiers
- 991005542774007891
- Murdoch Affiliation
- Murdoch University
- Language
- English
- Resource Type
- Journal article
UN Sustainable Development Goals (SDGs)
This output has contributed to the advancement of the following goals:
Source: InCites
Metrics
53 Record Views
InCites Highlights
These are selected metrics from InCites Benchmarking & Analytics tool, related to this output
- Collaboration types
- Domestic collaboration
- International collaboration
- Citation topics
- 3 Agriculture, Environment & Ecology
- 3.16 Phytochemicals
- 3.16.1270 Sesquiterpenes
- Web Of Science research areas
- Chemistry, Medicinal
- Integrative & Complementary Medicine
- Pharmacology & Pharmacy
- Plant Sciences
- ESI research areas
- Pharmacology & Toxicology