Liu Jiaqi, Cai Junjun, Wang Rui, Yang Shihai
College of Chinese Herbal Medicine, Jilin Agricultural University, Changchun 130047, China.
Crop Research Institute, Sichuan Academy of Agricultural Sciences, Chengdu 610066, China.
Int J Mol Sci. 2016 Dec 28;18(1):53. doi: 10.3390/ijms18010053.
As one of the model medicinal plants for exploration of biochemical pathways and molecular biological questions on complex metabolic pathways, synthesizes more than 100 terpenoid indole alkaloids (TIAs) used for clinical treatment of various diseases and for new drug discovery. Given that extensive studies have revealed the major metabolic pathways and the spatial-temporal biosynthesis of TIA in plant, little is known about subcellular and inter-cellular trafficking or long-distance transport of TIA end products or intermediates, as well as their regulation. While these transport processes are indispensable for multi-organelle, -tissue and -cell biosynthesis, storage and their functions, great efforts have been made to explore these dynamic cellular processes. Progress has been made in past decades on transcriptional regulation of TIA biosynthesis by transcription factors as either activators or repressors; recent studies also revealed several transporters involved in subcellular and inter-cellular TIA trafficking. However, many details and the regulatory network for controlling the tissue-or cell-specific biosynthesis, transport and storage of serpentine and ajmalicine in root, catharanthine in leaf and root, vindoline specifically in leaf and vinblastine and vincristine only in green leaf and their biosynthetic intermediates remain to be determined. This review is to summarize the progress made in biosynthesis, transcriptional regulation and transport of TIAs. Based on analysis of organelle, tissue and cell-type specific biosynthesis and progresses in transport and trafficking of similar natural products, the transporters that might be involved in transport of TIAs and their synthetic intermediates are discussed; according to transcriptome analysis and bioinformatic approaches, the transcription factors that might be involved in TIA biosynthesis are analyzed. Further discussion is made on a broad context of transcriptional and transport regulation in order to guide our future research.
作为探索生物化学途径以及复杂代谢途径相关分子生物学问题的典型药用植物之一，它能合成100多种萜类吲哚生物碱（TIAs），这些生物碱可用于多种疾病的临床治疗以及新药研发。鉴于大量研究已揭示了植物中TIAs的主要代谢途径及其时空生物合成过程，但对于TIAs终产物或中间体的亚细胞和细胞间运输、长距离运输及其调控机制却知之甚少。尽管这些运输过程对于多细胞器、多组织和多细胞的生物合成、储存及其功能而言不可或缺，但人们已付出巨大努力来探索这些动态的细胞过程。在过去几十年中，转录因子作为激活剂或抑制剂对TIAs生物合成的转录调控方面取得了进展；最近的研究还揭示了几种参与亚细胞和细胞间TIAs运输的转运蛋白。然而，许多细节以及控制蛇根碱和阿吗碱在根中的组织或细胞特异性生物合成、运输和储存，长春质碱在叶和根中的运输和储存，文朵灵仅在叶中的运输和储存，以及长春碱和长春新碱仅在绿叶中的运输和储存及其生物合成中间体的调控网络仍有待确定。本综述旨在总结TIAs生物合成、转录调控和运输方面取得的进展。基于对细胞器、组织和细胞类型特异性生物合成的分析以及类似天然产物运输和转运方面的进展，讨论了可能参与TIAs及其合成中间体运输的转运蛋白；根据转录组分析和生物信息学方法，分析了可能参与TIAs生物合成的转录因子。并在转录和运输调控的广泛背景下进行了进一步讨论，以指导我们未来的研究。
