长春花萜类吲哚生物碱生物合成和调控研究お.docVIP

长春花萜类吲哚生物碱生物合成和调控研究お 　　[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α3， 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。 　　[关键词] 长春花； 萜类吲哚生物碱； 代谢调控； 合成生物学 　　Advance in biosynthesis of terpenoid indole alkaloids and 　　its regulation in Catharanthus roseus 　　KUANG Xuejun1， WANG Caixia2， ZOU Liqiu1， ZHU Xiaoxuan1， SUN Chao1* 　　（1. Institute of Medicinal Plant Development， China Academy of Medical Sciences and Peking Union Medical College， Beijing 100193， China； 　　2. Institute of Chinese Materia Medica， China Academy of Chinese Medical Sciences， Beijing 100700， China） 　　[Abstract] 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 multistep enzymatic reaction， can form α3， 4anhydrovinblastine by the condensation reaction. Then， vinblastine and vincristine are generated from α3， 4anhydrovinblastine. 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. roseus. 　　[Key words] Catharanthus roseus； terpenoid i