ATP-binding cassette transporter controls leaf surface secretion of anticancer drug components in Catharanthus roseus
ATP-binding cassette transporter controls leaf surface secretion of anticancer drug components in Catharanthus roseus
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DOI：
10.1073/pnas.1307504110
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发表时间：
2013-09-24
影响因子：
11.1
通讯作者：
De Luca, Vincenzo
中科院分区：
文献类型：
--
作者：
Yu, Fang;De Luca, Vincenzo
马达加斯加长春花（Catharanthus roseus）是一种高度专一的生物合成单萜类吲哚生物碱的植物，其中许多具有很强的生物活性。此类MIA包括商业上重要的化疗药物长春碱、长春新碱和衍生自长春质碱和文多灵偶联的其他合成衍生物。然而，先前的研究表明，这些MIA的生物合成涉及代谢物在特化的内部叶细胞和叶表皮之间的广泛运动，这需要未知的分泌过程的参与，以将长春质碱动员到叶表面，并将文多灵动员到内部叶细胞。文多灵和长春质碱的空间分离为完整植物中积累的低水平二聚体提供了明确的解释。目前的工作描述了一个独特的长春质转运蛋白（CrTPT 2），主要是在幼叶表皮表达的分子克隆和功能鉴定。通过用长春质碱处理激活CrTPT 2基因表达，并且其在植物中沉默重新分配长春质碱以增加叶子中长春质碱-文多灵药物二聚体的水平。系统发育分析表明，CrTPT 2是密切相关的一个关键的转运蛋白参与角质层组装在植物中，这可能是独特的MIA生产的植物物种，在那里它介导的生物碱分泌到植物表面。
The Madagascar periwinkle (Catharanthus roseus) is highly specialized for the biosynthesis of many different monoterpenoid indole alkaloids (MIAs), many of which have powerful biological activities. Such MIAs include the commercially important chemotherapy drugs vinblastine, vincristine, and other synthetic derivatives that are derived from the coupling of catharanthine and vindoline. However, previous studies have shown that biosynthesis of these MIAs involves extensive movement of metabolites between specialized internal leaf cells and the leaf epidermis that require the involvement of unknown secretory processes for mobilizing catharanthine to the leaf surface and vindoline to internal leaf cells. Spatial separation of vindoline and catharanthine provides a clear explanation for the low levels of dimers that accumulate in intact plants. The present work describes the molecular cloning and functional identification of a unique catharanthine transporter (CrTPT2) that is expressed predominantly in the epidermis of young leaves. CrTPT2 gene expression is activated by treatment with catharanthine, and its in planta silencing redistributes catharanthine to increase the levels of catharanthine-vindoline drug dimers in the leaves. Phylogenetic analysis shows that CrTPT2 is closely related to a key transporter involved in cuticle assembly in plants and that may be unique to MIA-producing plant species, where it mediates secretion of alkaloids to the plant surface.