Murdoch University Research Repository

Welcome to the Murdoch University Research Repository

The Murdoch University Research Repository is an open access digital collection of research
created by Murdoch University staff, researchers and postgraduate students.

Learn more

Localization and in-Vivo Characterization of Thapsia garganica CYP76AE2 Indicates a Role in Thapsigargin Biosynthesis

Andersen, T.B., Martinez-Swatson, K.A., Rasmussen, S.A., Boughton, B.A.ORCID: 0000-0001-6342-9814, Jørgensen, K., Andersen-Ranberg, J., Nyberg, N., Christensen, S.B. and Simonsen, H.T. (2017) Localization and in-Vivo Characterization of Thapsia garganica CYP76AE2 Indicates a Role in Thapsigargin Biosynthesis. Plant Physiology, 174 (1). pp. 56-72.

Link to Published Version: https://doi.org/10.1104/pp.16.00055
*Subscription may be required

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.

Item Type: Journal Article
Publisher: American Society of Plant Biologists
Copyright: © 2017 American Society of Plant Biologists.
URI: http://researchrepository.murdoch.edu.au/id/eprint/56447
Item Control Page Item Control Page