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

T.B. Andersen; K.A. Martinez-Swatson; S.A. Rasmussen; B.A. Boughton; K. Jørgensen; J. Andersen-Ranberg; N. Nyberg; S.B. Christensen; H.T. Simonsen

doi:10.1104/pp.16.00055

Back

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

Journal article

Peer reviewed

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

T.B. Andersen, K.A. Martinez-Swatson, S.A. Rasmussen, B.A. Boughton, K. Jørgensen, J. Andersen-Ranberg, N. Nyberg, S.B. Christensen and H.T. Simonsen

Plant Physiology, Vol.174(1), pp.56-72

2017

DOI: https://doi.org/10.1104/pp.16.00055

Files and links (1)

url

Link to Published Version *Subscription may be requiredView

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.

Details

Title: Localization and in-Vivo Characterization of Thapsia garganica CYP76AE2 Indicates a Role in Thapsigargin Biosynthesis
Authors/Creators: T.B. Andersen (Author/Creator) - University of Copenhagen
K.A. Martinez-Swatson (Author/Creator) - University of Copenhagen
S.A. Rasmussen (Author/Creator) - Natural Product Discovery
B.A. Boughton (Author/Creator) - The University of Melbourne
K. Jørgensen (Author/Creator) - University of Copenhagen
J. Andersen-Ranberg (Author/Creator) - University of California, Berkeley
N. Nyberg (Author/Creator) - University of Copenhagen
S.B. Christensen (Author/Creator) - Aarhus University
H.T. Simonsen (Author/Creator) - Department of Biotechnology
Publication Details: Plant Physiology, Vol.174(1), pp.56-72
Publisher: American Society of Plant Biologists
Identifiers: 991005544998107891
Copyright: © 2017 American Society of Plant Biologists.
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

32 Record Views

32 Times Cited - Web of Science

InCites Highlights

These are selected metrics from InCites Benchmarking & Analytics tool, related to this output

Collaboration types: Industry collaboration; Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.68 Lipids; 1.68.1273 Terpenoid Biosynthesis
Web Of Science research areas: Plant Sciences
ESI research areas: Plant & Animal Science