CYP76AE2 的定位和体内特征表明其在 thapsigargin 生物合成中的作用。
Localization and in-Vivo Characterization of CYP76AE2 Indicates a Role in Thapsigargin Biosynthesis.
机构信息
Department of Plant and Environmental Sciences, University of Copenhagen, 1871 Frederiksberg C, Denmark (T.B.A., K.J., J.A.-R.).
Natural History Museum of Denmark, University of Copenhagen, DK-1350 Copenhagen K, Denmark (K.A.M.).
出版信息
Plant Physiol. 2017 May;174(1):56-72. doi: 10.1104/pp.16.00055. Epub 2017 Mar 8.
The Mediterranean plant (dicot, Apiaceae), also known as deadly carrot, produces the highly toxic compound thapsigargin. This compound is a potent inhibitor of the sarcoplasmic-endoplasmic reticulum Ca-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 , 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.
地中海植物（双子叶植物，伞形科），也被称为致命胡萝卜，会产生剧毒化合物 thapsigargin。这种化合物是哺乳动物肌浆内质网 Ca-ATP 酶钙泵的强抑制剂，作为抗癌药物 mipsagargin 的有效成分具有工业重要性，目前正在临床试验中。关于 thapsigargin 在植物体内储存和生物合成的知识一直有限。在这里，我们通过展示细胞色素 P450 TgCYP76AE2 （短暂表达于 ）将 epikunzeaol 转化为 epidihydrocostunolide，提出了 thapsigargin 生物合成的第二步假设。此外，我们还表明，thapsigargin 可能储存在根部的分泌道中。在根中，TgTPS2（epikunzeaol 合酶）和 TgCYP76AE2 的转录本仅在这些分泌道的上皮细胞中发现。这强调了这些细胞在 thapsigargin 生物合成中的参与。这项研究为进一步研究 thapsigargin 生物合成铺平了道路。
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