Monoterpenoid indole alkaloid biosynthesis

单萜吲哚生物碱生物合成

• 批准号: RGPIN-2017-04145
• 负责人: DeLuca, Vincenzo
• 金额: $ 5.03万
• 依托单位: Brock University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=710902
• 关键词: Monoterpenoid; indole; alkaloid; biosynthesis

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.

植物 具有卓越的特性，能够执行复杂的， 创新的生物化学，产生多种颜色，香味，香气 和生物活性有机分子。虽然产生的大部分分子是 虽然不是生存的直接必需品，但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物和疾病 防止人类用来预防/治疗许多疾病的分子 毁灭性的疾病。单萜吲哚生物碱（MIA）使 最大和最多样化的一类化合物， 发现于夹竹桃科（4700种）、马钱科 (600种）和茜草科（> 10，000种）植物科。的 MIA化学的复杂性与它们对环境的显著不同的影响相匹配。 导致它们被用作预防疟疾的药物 （奎宁）和用于治疗神经障碍（利血平）、癌症 （喜树碱、长春碱和长春新碱），作为血管扩张剂（育亨宾）， 用于痛风治疗的抗炎药（秋水仙碱）和作为潜在的镇痛药和新的疼痛 人类的杀手（康诺利定）。在过去的25年里，我的实验室 在生物合成方面有许多重要发现， 马达加斯加长春花（Catharanthus roseus）的抗癌MIA已用于化疗治疗 在过去的45年里。从这些发现中获得的遗传资源和生物化学知识是 目前正在开发，以提高生产有价值的药用 化合物C. roseus或通过合成生物学实验在其他生物体中，包括酵母或微生物 工厂在重组生物体中生产MIA药物 为现有MIA药物的低成本生产创造了独特的机会 以及产生无法从自然资源中获得的新的和独特的药物。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。