Monoterpenoid indole alkaloids (MIAs) possess a diversity of alkaloid skeletons whose biosynthesis is poorly understood. A bioinformatic search of candidate genes, combined with their virus-induced gene silencing, targeted MIA profiling and in vitro/in vivo pathway reconstitution identified and functionally characterized six genes as well as a seventh enzyme reaction required for the conversion of 19E-geissoschizine to tabersonine and catharanthine. The involvement of pathway intermediates in the formation of four MIA skeletons is described, and the role of stemmadenine-O-acetylation in providing necessary reactive substrates for the formation of iboga and aspidosperma MIAs is described. The results enable the assembly of complex dimeric MIAs used in cancer chemotherapy and open the way to production of many other biologically active MIAs that are not easily available from nature.

单萜类吲哚生物碱（MIA）具有生物合成了解甚少的多种生物碱骨架。候选基因的生物信息学搜索，结合其病毒诱导的基因沉默，靶向的MIA分析和体外/体内途径重构，确定并功能化了6个基因，并将19 E- geissoschizine转化为7所需的第七种酶反应烟碱和黄hara碱。描述了途径中间体在四个MIA骨架形成中的参与，以及stemmadenine- O的作用描述了在提供必要的反应性底物以形成伊波加和曲霉精子MIA时的β-乙酰化作用。结果使得能够组装用于癌症化学疗法的复杂的二聚体MIA，并开辟了生产许多其他生物活性MIA的方式，而这些天然MIA很难从大自然中获得。