长春花萜类吲哚生物碱生物合成与调控研究  被引量:19

Advance in biosynthesis of terpenoid indole alkaloids and its regulation in Catharanthus roseus

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作  者:匡雪君 王彩霞[2] 邹丽秋 朱孝轩[1] 孙超[1] 

机构地区:[1]中国医学科学院北京协和医学院药用植物研究所,北京100193 [2]中国中医科学院中药研究所,北京100700

出  处:《中国中药杂志》2016年第22期4129-4137,共9页China Journal of Chinese Materia Medica

基  金:国家自然科学基金面上项目(81273485;81573704)

摘  要:长春花含有多种具有重要药理活性的萜类吲哚生物碱(TIA)。TIA的生物合成与调控及其合成生物学研究受到广泛关注。3α(S)-异胡豆苷是TIA生物合成的重要节点,由裂环马钱子苷和色胺缩合而成。前者通过环烯醚萜途径生成;后者通过吲哚途径生成。由3α(S)-异胡豆苷分别经过多步酶促反应生成文多灵和长春质碱,然后两者缩合生成α-3,4-脱水长春碱,进而生成长春碱和长春新碱。AP2/ERF和WRKY等多种转录因子参与了TIA合成的调控。长春花TIA生物合成途径的逐步解析为其合成生物学研究奠定了基础。目前已在酿酒酵母实现了3α(S)-异胡豆苷和文多灵等的异源合成。长春花TIA生物合成与调控的研究将为TIA类药物的生产和研发提供支撑。Catharanthus roseus can produce a variety of terpenoid indole alkaloids (TIA), most of which exhibit strong pharmacological activities. Hence, biosynthesis and regulation of TIA have received recent attention. 3α (S)-strictosidine is an important node in TIA biosynthesis, which is a condensation product of secologanin and tryptamine. The former is produced in iridoid pathway, and the latter is produced in indole pathway. Vindoline and catharanthine, which are produced respectively by 3α (S)-strictosidine via multi-step enzymatic reaction, can form α-3, 4-anhydrovinblastine by the condensation reaction. Then, vinblastine and vincristine are generated from α-3,4-anhydrovinblastine. Many transcription factors are involved in the regulation of TIA synthesis, such as AP2/ERF and WRKY. Illumination of biosynthetic pathway has laid a foundation for the study of synthetic biology. Today, 3α (S)-strictosidine and vindoline have been synthesized in heterologous hosts Saccharomyces cerevisiae. Research about synthetic biology and the regulation mechanisms will provide a guidance for the production and development of TIA drugs in C. rosens.

关 键 词:长春花 萜类吲哚生物碱 代谢调控 合成生物学 

分 类 号:S567.239[农业科学—中草药栽培]

 

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