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

植物天然产物(PNPs)自史前时代起就被用于治疗人类疾病，至今仍是当今大多数药物的最重要来源。世界上约90%的人口依赖传统药用植物，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的植物，世界上大部分的供应都是从野外采集的。因此，某些药用植物的商业成功可能会导致它们的过度采集，从而有必要种植这些植物并生产其宝贵的PNPs。近年来，由石蒜科药用植物(如石蒜科、石蒜科、水仙等)产生的生物碱类化合物PNPs因具有多种药理活性而受到越来越多的关注。石蒜科生物碱的性质包括镇痛、抗癌和抗微生物活性，以及对心血管和呼吸系统的影响。例如，那西拉辛显示出强大的抗有丝分裂活性，金雀花碱因其精神活性而闻名，而乙酰胆碱酯酶抑制剂加兰他明则用于治疗阿尔茨海默病的症状。由于其在植物中的浓度较低，限制了大多数AAs的商业发展。只有加兰他明是商业化生产的。虽然人们对工程生产AA用于作物改良和药物开发有明显的兴趣，但由于缺乏关于AA生物合成途径及其调控的信息，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、转录组、蛋白质组和代谢组学)数据集，促进了在其他植物家族中发现参与PNP代谢途径的生物合成基因。到目前为止，还没有为石蒜科开发“组学”资源。因此，几条AA途径仍然是假设的，酶和代谢中间体有待发现。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来增加对植物体内AAs代谢的了解。具体目标是(1)建立“组学”数据库，以促进发现新的氨基酸生物合成基因；(2)生化基因组学，以确定新基因的特征；(3)开发可持续的“绿色”微藻合成生物学平台，以从功能上验证基因，并生产具有良好药用价值的氨基酸。提高对AA生物合成的分子水平的了解是开发具有有价值的AA图谱的石蒜科新品种的必要前提，并将为生物技术(如合成生物学)创造工程微藻菌株铺平道路，以生产与加拿大农业和制药工业多样化相关的高价值AAs。

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.