| Literature DB >> 28275147 |
Trine Bundgaard Andersen1,2,3,4,5, Karen Agatha Martinez-Swatson1,2,3,4,5, Silas Anselm Rasmussen1,2,3,4,5, Berin Alain Boughton1,2,3,4,5, Kirsten Jørgensen1,2,3,4,5, Johan Andersen-Ranberg1,2,3,4,5, Nils Nyberg1,2,3,4,5, Søren Brøgger Christensen1,2,3,4,5, Henrik Toft Simonsen6,7,8,9,10.
Abstract
The Mediterranean plant Thapsia garganica (dicot, Apiaceae), also known as deadly carrot, produces the highly toxic compound thapsigargin. This compound is a potent inhibitor of the sarcoplasmic-endoplasmic reticulum Ca2+-ATPase calcium pump in mammals and is of industrial importance as the active moiety of the anticancer drug mipsagargin, currently in clinical trials. Knowledge of thapsigargin in planta storage and biosynthesis has been limited. Here, we present the putative second step in thapsigargin biosynthesis, by showing that the cytochrome P450 TgCYP76AE2, transiently expressed in Nicotiana benthamiana, converts epikunzeaol into epidihydrocostunolide. Furthermore, we show that thapsigargin is likely to be stored in secretory ducts in the roots. Transcripts from TgTPS2 (epikunzeaol synthase) and TgCYP76AE2 in roots were found only in the epithelial cells lining these secretory ducts. This emphasizes the involvement of these cells in the biosynthesis of thapsigargin. This study paves the way for further studies of thapsigargin biosynthesis.Entities:
Mesh:
Substances:
Year: 2017 PMID: 28275147 PMCID: PMC5411132 DOI: 10.1104/pp.16.00055
Source DB: PubMed Journal: Plant Physiol ISSN: 0032-0889 Impact factor: 8.340