Monoterpenoid indole alkaloid biosynthesis

植物具有非凡的特性，能够进行复杂的生物化学创新，产生多种颜色、香味、芳香和生物活性有机分子。虽然产生的大多数分子对生存并不是直接必需的，但许多分子可能在植物适应生物和非生物环境中发挥关键作用。这种化学多样性的独特生物活性提供了药用和预防疾病的分子，被人类用来预防/治疗许多毁灭性的疾病。单萜类吲哚生物碱（MIAs）构成了最大和最多样化的一类化合物，在夹竹桃科（4700种），loganaceae（600种）和Rubiaceae（近10000种）植物家族的许多成员中都有发现。MIA化学的复杂性与它们对生物体的显著不同作用相匹配，这导致它们被用作预防疟疾（奎宁）、治疗神经系统疾病（利血平）、癌症（喜树碱、长春碱和长春新碱）、血管扩张剂（育亨宾）、治疗痛风的抗炎药（秋水秋碱）以及人类潜在的镇痛药和新型止痛药（conolidine）。在过去的25年里，我的实验室在马达加斯加长春花（Catharanthus roseus）抗癌蛋白的生物合成方面取得了许多重要发现，这些蛋白在过去的45年里被用于化疗。从这些发现中获得的遗传资源和生化知识目前正被用于提高玫瑰玫瑰中有价值的药物化合物的生产，或通过酵母或微生物工厂等其他生物的合成生物学实验。在重组生物体中生产MIA药物为降低现有MIA药物的生产成本和生产无法从天然来源获得的新的和独特的药物创造了独特的机会。在这种模式植物上的初步发现也极大地改善了在自然界中发现的其他MIA途径的基因发现工具，并有助于了解MIA在植物适应性和适应环境方面所起的生态作用。

Plantshave remarkable attributes for being able to perform complex and biologicallyinnovative biochemistry that generates a diversity of colors, fragrances, aromasand biologically active organic molecules. While the majority of the molecules produced arenot directly essential for survival, many may play key roles in plantadaptation to the biotic and abiotic environment. The unique biologicalactivities of this chemical diversity have provided medicinal and diseasepreventing molecules that have been used by humanity to prevent/cure manydevastating diseases. The monoterpenoid indole alkaloids (MIAs) makeup the largest and most diverse class of compounds that are characteristicallyfound within many members of the Apocynaceae (4700 species), the Loganiaceae(600 species) and the Rubiaceae (> 10,000 species) plant families. Thecomplexity of MIA chemistry is matched by their remarkably diverse effects onliving organisms that has led to their use as drugs for preventing malaria(quinine) and for treating neurological disorders (reserpine), cancer(camptothecin, vinblastine and vincristine), as vasodilators (yohimbine), asanti-inflammatories for gout treatments (colchicine) and as potential analgesics and novel painkillers (conolidine) in human beings. Over the past >25 years my laboratoryhas made many key discoveries about the biosynthesis ofanti-cancer MIAs of the Madagascar periwinkle (Catharanthus roseus) that have been used in chemotherapy treatmentsover the past 45 years. The genetic resources and biochemical knowledge derived from these discoveries arepresently being exploited to enhance the production of valuable medicinalcompounds in C. roseus or through synthetic biology experiments in other organisms including yeast or in microbialfactories. The production of MIA pharmaceuticals in recombinant organismscreates unique opportunities for less expensive manufacturing of existing MIA drugsand for generating new and unique medicines not available from natural sources. The initial discoveries made in this model plant have also greatly improved the tools available for gene discovery of other MIA pathways found in Nature and for learning about the ecological roles that MIAs play in plant fitness and adaptations to their environment.