Journal article
Localization and in-vivo characterization of thapsia garganica CYP76AE2 indicates a role in thapsigargin biosynthesis
University of Copenhagen1
Technical University of Denmark2
Natural Product Discovery, Section for Microbial and Chemical Ecology, Department of Biotechnology and Biomedicine, Technical University of Denmark3
University of Melbourne4
University of California at Berkeley5
Bruker Biospin Scandinavia AB6
Department of Biotechnology and Biomedicine, Technical University of Denmark7
Photosynthetic Cell Factories, Section for Synthetic Biology, Department of Biotechnology and Biomedicine, Technical University of Denmark8
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.
| Language: | English |
|---|---|
| Publisher: | American Society of Plant Biologists |
| Year: | 2017 |
| Pages: | 56-72 |
| ISSN: | 15322548 and 00320889 |
| Types: | Journal article |
| DOI: | 10.1104/pp.16.00055 |
| ORCIDs: | Simonsen, Henrik Toft , 0000-0003-0942-9949 , 0000-0003-2855-7735 , 0000-0002-6597-3431 and 0000-0002-5773-6874 |
Cytochrome P-450 Enzyme System Gas Chromatography-Mass Spectrometry Gene Expression Profiling Gene Expression Regulation, Plant Models, Chemical Molecular Structure Nicotiana Phylogeny Plant Leaves Plant Proteins Plant Roots Plants, Genetically Modified Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization Thapsia Thapsigargin
