萜类吲哚生物碱(terpeniod indole alkaloids, TIAs)是植物中产生的一类具有药理活性的次生代谢产物.药用植物长春花(Catharanthus roseus)因含有长春碱和长春新碱等重要的抗肿瘤萜类吲哚生物碱而成为研究TIAs次生代谢的主要模式植物.应用正、反向遗传学和各种代谢组学技术对长春花TIAs次生代谢途径及其调控进行了较深入的研究,相继鉴定了参与TIAs代谢途径调控的CrORCAs、CrMYCs、CrZCTs和CrWRKYs等转录因子,特别是发现茉莉素(jasmonates, JAs)介导TIAs生物合成的转录调控网络. 本文以长春花TIAs生物合成途径为模式,重点论述其代谢途径中的关键酶、参与调节的转录因子,尤其是茉莉素介导的调控网络及机制,解析植物中这些天然抗癌生物碱合成积累水平低的制约因素和组织细胞特异性,讨论基于这些新知识的长春花抗肿瘤TIAs代谢工程策略和工厂化绿色生产前景.
Terpenoid indole alkaloids(TIAs) are one of the large classes of secondary metabolites with pharmacological activity in plants. Increasing interest focuses on medicinal plant Catharanthus roseus served as a model for TIAs biosynthesis because of the presence of two antitumour alkaloids, vinblastine and vincristine. Forward and reverse genetics and various metabonomics have been employed to dissect TIAs metabolic pathway and its regulation. A number of transcriptional factors including CrORCAs, CrMYCs, CrZCTs and CrWRKYs were identified to function importantly in TIAs pathway regulation. Particularly, jasmonates(JAs) was found to be a big player in mediating this transcriptional network. This review highlights the main progress in this hotspot field of transcriptional regulation mechanism of TIAs biosynthesis in C. roseus, including the key enzymes and transcriptional factors involved in this pathway as well as JAmediated regulatory network. Furthermore, in this article we described the tissuespecific accumulation of TIAs and factors limiting plant TIAs biosynthesis. Finally, the new knowledgebased metabolic engineering approaches were comprehensively discussed for enhancing anticancer TIAs level in plant tissues, and green production of commercialization for those important TIAs.