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

被引：33

作者：

Andersen, Trine Bundgaard ^{[1
]}

Martinez-Swatson, Karen Agatha ^{[2
,3
]}

Rasmussen, Silas Anselm ^{[3
]}

Boughton, Berin Alain ^{[4
]}

Jorgensen, Kirsten ^{[1
]}

Andersen-Ranberg, Johan ^{[1
,6
]}

Nyberg, Nils ^{[5
,7
]}

Christensen, Soren Brogger ^{[5
]}

Simonsen, Henrik Toft ^{[3
]}

机构：

[1] Univ Copenhagen, Dept Plant & Environm Sci, DK-1871 Frederiksberg C, Denmark

[2] Univ Copenhagen, Nat Hist Museum Denmark, DK-1350 Copenhagen K, Denmark

[3] Tech Univ Denmark, Dept Biotechnol & Biomed, DK-2800 Lyngby, Denmark

[4] Univ Melbourne, Metabol Australia, Sch BioSci, Melbourne, Vic 3010, Australia

[5] Univ Copenhagen, Dept Drug Design & Pharmacol, DK-2100 Copenhagen, Denmark

[6] Univ Calif Berkeley, 441 Koshland Hall, Berkeley, CA 94720 USA

[7] Bruker BioSpin Scandinavia AB, Vallgatan 5, SE-17067 Solna, Sweden

来源：

PLANT PHYSIOLOGY | 2017年 / 174卷 / 01期

关键词：

ESSENTIAL OIL; SESQUITERPENE LACTONES; TERPENOID BIOSYNTHESIS; PHYLOGENETIC ANALYSIS; SECRETORY STRUCTURES; GLANDULAR TRICHOMES; COPE REARRANGEMENT; MOLECULAR-CLONING; PROVIDES INSIGHTS; DIFFERENT ORGANS;

D O I：

10.1104/pp.16.00055

中图分类号：

Q94 [植物学];

学科分类号：

071001 ;

摘要：

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.

引用

页码：56 / 72

页数：17

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