Journal article
Localization and in-Vivo Characterization of Thapsia garganica CYP76AE2 Indicates a Role in Thapsigargin Biosynthesis
Trine Bundgaard Andersen, Karen Agatha Martinez-Swatson, Silas Anselm Rasmussen, Berin Alain Boughton, Kirsten Jorgensen, Johan Andersen-Ranberg, Nils Nyberg, Soren Brogger Christensen, Henrik Toft Simonsen
PLANT PHYSIOLOGY | AMER SOC PLANT BIOLOGISTS | Published : 2017
DOI: 10.1104/pp.16.00055
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 thapsi..
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Awarded by Danish Research Council for Independent Research \ Nature and Universe
Funding Acknowledgements
This work was supported by SpotLight, a grant from the Danish Council for Strategic Research (to T.B.A., H.T.S., and S.B.C.), by the Center for Synthetic Biology bioSYNergy, UCPH Excellence Program for Interdisciplinary Research (to J.A-R.), and by MEDPLANT, a Marie Curie Actions Initial Training Network (to K.A.M.-S.); NMR equipment used was purchased via from the Danish Research Council for Independent Research vertical bar Nature and Universe (grant no. 10-085264).