Monoterpenoid indole alkaloid biosynthesis

植物 具有显著的属性，能够执行复杂的和生物学的 创新的生物化学，产生各种颜色、香气和香味 和生物活性有机分子。而产生的大多数分子都是 不是生存的直接必需品，许多可能在植物中发挥关键作用 适应生物和非生物环境。独特的生物 这种化学多样性的活动提供了药用和疾病 防止被人类用来预防/治愈许多 毁灭性的疾病。单萜类吲哚生物碱(MIA)使 最大和最多样化的化合物类别，其特点是 在罗布麻科(4700种)的许多成员中都发现了马钱科 (600种)和茜草科(&gt；10,000种)植物科。这个 MIA化学的复杂性与它们对 导致它们被用作预防疟疾药物的活的有机体 (奎宁)和治疗神经疾病(利血平)，癌症 (喜树碱、长春新碱和长春新碱)，作为血管扩张剂(育亨宾)，AS 用于痛风治疗的抗炎药(秋水仙碱)以及潜在的镇痛剂和新的疼痛 人类体内的杀人剂(刀豆素)。在过去的25年里我的实验室 已经在生物合成方面取得了许多关键发现 已用于化疗的马达加斯加长春花的抗癌MIA 在过去的45年里。从这些发现中获得的遗传资源和生化知识是 目前正在开发以提高有价值的药用植物的生产 玫瑰花中的化合物或通过在其他生物体(包括酵母或微生物)中进行的合成生物学实验 工厂。MIA药物在重组生物中的生产 为生产成本较低的现有MIA药物创造独特的机会 以及用于生产自然来源无法获得的新的独特药物。在这一模式植物中的初步发现也极大地改进了可用于发现在自然中发现的其他MIA途径的基因以及了解MIA在植物适应性和对其环境的适应中所起的生态作用的工具。

Plants have remarkable attributes for being able to perform complex and biologically innovative biochemistry that generates a diversity of colors, fragrances, aromas and biologically active organic molecules. While the majority of the molecules produced are not directly essential for survival, many may play key roles in plant adaptation to the biotic and abiotic environment. The unique biological activities of this chemical diversity have provided medicinal and disease preventing molecules that have been used by humanity to prevent/cure many devastating diseases. The monoterpenoid indole alkaloids (MIAs) make up the largest and most diverse class of compounds that are characteristically found within many members of the Apocynaceae (4700 species), the Loganiaceae (600 species) and the Rubiaceae (> 10,000 species) plant families. The complexity of MIA chemistry is matched by their remarkably diverse effects on living 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), as anti-inflammatories for gout treatments (colchicine) and as potential analgesics and novel pain killers (conolidine) in human beings. Over the past >25 years my laboratory has made many key discoveries about the biosynthesis of anti-cancer MIAs of the Madagascar periwinkle (Catharanthus roseus) that have been used in chemotherapy treatments over the past 45 years. The genetic resources and biochemical knowledge derived from these discoveries are presently being exploited to enhance the production of valuable medicinal compounds in C. roseus or through synthetic biology experiments in other organisms including yeast or in microbial factories. The production of MIA pharmaceuticals in recombinant organisms creates unique opportunities for less expensive manufacturing of existing MIA drugs and 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.