Monoterpenoid indole alkaloid biosynthesis

植物具有非凡的特性，能够进行复杂的、具有生物创新性的生物化学反应，产生多种颜色、香味和具有生物活性的有机分子。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物和预防疾病的分子，这些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（柔亨宾）、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（共聚物）。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年里一直用于化疗。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孢杆菌中有价值的药用化合物的生产，或通过酵母或微生物工厂等其他生物的合成生物学实验。重组生物体中MIA药物的生产*为现有MIA药物的低成本制造*和产生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

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.***