'Omics'-based approaches and synthetic biology platform to investigate valuable plant natural products.

基于“组学”的方法和合成生物学平台来研究有价值的植物天然产物。

• 批准号: RGPIN-2014-05294
• 负责人: DesgagnéPenix, Isabel
• 金额: $ 2.55万
• 依托单位: Université du Québec à Trois-Rivières
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2019
• 资助国家: 加拿大
• 起止时间: 2019-01-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=685732
• 关键词: Omics; based; approaches; synthetic; biology

Plant natural products (PNPs) have been used for treating human ailments since prehistoric times and are still the most important source for the majority of today's medicines. About 90% of the world's population relies on traditional medicinal plants, not only to meet their primary care needs but also for income generation. Although there are a vast number of medicinal plants, few are cultivated on a large scale and the majority of the world's supply is collected from the wild. Consequently, the commercial success of certain medicinal plants may lead to their over-collection, making the cultivation of these plants and production of their valuable PNPs necessary. Recently, PNPs of the alkaloid group produced by medicinal plants of the Amaryllidaceae family (e.g. Amaryllis, Galanthus and Narcissus), have been attracting increasing interest due to their multiple pharmacological activities. The properties of Amaryllidaceae alkaloids (AAs) include analgesic, anticancer and antimicrobial activities, and effects on cardiovascular and respiratory system. For example, narciclasine displays potent antimitotic activity, crinamine is reputed for its psychoactive properties whereas galanthamine, an acetylcholinesterase inhibitor, is used to treat symptoms of Alzheimer's disease. The commercial development of most AAs is restricted by their limited availabilities due to their low concentrations in planta. Only galanthamine is produced commercially. Although there are obvious interests in engineering AA production for crop improvement and development of pharmaceuticals, the lack of information on AA biosynthetic pathways and their regulation make this task very challenging. Recently, systems biology-based approaches have facilitated the discovery of biosynthetic genes involved in PNP metabolic pathways in other plant families through the integration of multiple `omics' (genomic, transcriptomic, proteomic and metabolomic) datasets. To date, no `omics' resources have been developed for the Amaryllidaceae. Consequently, several AA pathways remain hypothetical and enzymes and metabolic intermediates await discovery. The overall goal of the proposed research is to increase knowledge on the metabolism of AAs in plants through the application of innovative and modern genomics and integrated systems biology strategies. Specific aims are (i) the establishment of `omic' databases to facilitate discovery of novel AA biosynthetic genes, (ii) biochemical genomics to characterize novel genes and (iii) the development of a sustainable `green' microalgal synthetic biology platform to functionally validate genes and to produce AAs with promising medicinal value. An improved molecular understanding of AA biosynthesis is a necessary prerequisite to develop novel Amaryllidaceae cultivars with valuable AA profiles, and will pave the way for biotechnologies, such as synthetic biology, to create engineered microalgae strains for the production of high-value AAs relevant to diversifying Canadian agricultural and pharmaceutical industries.

植物天然产物（PNP）自史前时代以来一直用于治疗人类疾病，并且仍然是当今大多数药物的最重要来源。世界上约有90%的人口依赖于传统的药用植物，这不仅是为了满足他们的初级保健需求，也是为了创收。虽然有大量的药用植物，但很少有大规模种植，世界上大部分的供应都是从野外收集的。因此，某些药用植物的商业成功可能导致它们的过度采集，使得这些植物的栽培和它们有价值的PNP的生产成为必要。近年来，石蒜科（Amaryllidaceae）药用植物石蒜（Amaryllis）、雪兰莪（Galanthus）和水仙（Narcissus）等产生的生物碱类PNPs因其具有多种药理活性而引起人们越来越多的关注。石蒜科生物碱具有镇痛、抗肿瘤、抗菌、调节心血管和呼吸系统等作用。例如，那西克拉新显示出有效的抗有丝分裂活性，crinamine因其精神活性而闻名，而加兰他敏，一种乙酰胆碱酯酶抑制剂，用于治疗阿尔茨海默病的症状。由于大多数AA在植物中的浓度较低，其有限的可用性限制了其商业开发。只有加兰他敏是商业化生产的。虽然有明显的利益在工程AA生产作物改良和药物的开发，缺乏信息AA生物合成途径和他们的监管，使这项任务非常具有挑战性。最近，基于系统生物学的方法通过整合多个“组学”（基因组学、转录组学、蛋白质组学和代谢组学）数据集，促进了在其他植物科中发现参与PNP代谢途径的生物合成基因。迄今为止，尚未开发石蒜科的“组学”资源。因此，几个AA途径仍然是假设和酶和代谢中间体等待发现。拟议研究的总体目标是通过应用创新的现代基因组学和综合系统生物学策略，增加对植物中氨基酸代谢的了解。具体目标是：（一）建立“组学”数据库，以促进发现新的AA生物合成基因;（二）生物化学基因组学，以表征新基因;（三）开发可持续的“绿色”微藻合成生物学平台，以功能验证基因，并生产具有潜在药用价值的AA。AA生物合成的分子水平的提高是一个必要的先决条件，开发新的石蒜科品种有价值的AA配置文件，并将铺平道路的生物技术，如合成生物学，创造工程微藻株生产高价值的AA相关的多样化加拿大农业和制药工业。