Monoterpenoid indole alkaloid biosynthesis

植物具有非凡的属性，能够进行复杂的生物创新生物化学，产生多种颜色，香味，香气和生物活性有机分子。虽然产生的大多数分子不是生存所必需的，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物和疾病预防分子，人类已经使用这些分子来预防/治疗许多毁灭性的疾病。单萜类吲哚生物碱（MIA）构成了最大和最多样化的一类化合物，其特征性地存在于夹竹桃科（4700种）、马钱科（600种）和茜草科（> 10，000种）植物家族的许多成员中。MIA化学的复杂性与它们对生物体的显著不同的作用相匹配，这导致它们被用作预防疟疾的药物（奎宁）和治疗神经系统疾病的药物（利血平），癌症的药物（喜树碱，长春碱和长春新碱），血管扩张剂（育亨宾），痛风治疗的抗炎药（秋水仙碱）以及潜在的镇痛药和新型止痛药（可诺利定）。在过去的>25年里，我的实验室 * 在马达加斯加长春花（Catharanthus roseus）的 * 抗癌MIA的生物合成方面取得了许多关键发现，这些MIA在过去的45年里一直用于化疗治疗 *。从这些发现中获得的遗传资源和生物化学知识目前正被用于提高C.玫瑰或通过合成生物学实验在其他有机体包括酵母或微生物 * 工厂。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自然来源获得的新的独特药物创造了独特的机会。在这种模式植物中的初步发现也极大地改善了可用于自然界中发现的其他MIA途径的基因发现的工具，以及了解MIA在植物适应性和适应环境中发挥的生态作用。

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.***