Yellow Gold: Innovative systems for sustainable daffodil-derived galanthamine production in the uplands.

患有痴呆症的人数很多，而且还在以相当快的速度增长。2010年，全球有3560万痴呆症患者，每年确诊460万例。阿尔茨海默病(AD)占这些病例的50%到75%。自1998年以来，加兰他明已被美国食品和药物管理局、英国药品和医疗保健产品监管局和欧洲药品管理局批准为AD治疗药物。加兰他明主要是从植物中生产的，因为虽然化学合成是可能的，但难度很大，成本也很高。加兰他明是一种天然植物生物碱，用于生产医药产品加兰他明。目前正从水仙花/水仙(在中欧和西欧)、银杏(在东欧)和石蒜(在中国)中提取。然而，除了水仙花外，由于资源或研究的限制，来源植物是不适合农业开发的野生花卉。因此，水仙花是世界上唯一经济上可行的加兰他明来源。根据现有的产量水平，目前全球加兰他明的年消费量限制在3-4吨/年，但公布的数据预测，潜在的全球市场可能接近40吨/年。独立报告预测，加兰他明药物的有竞争力的活性药物成分价格在中期内将保持在15,000-18,000 GB/公斤之间。英国高原的特点是生长条件差，这些因素包括：低温；暴露在风中；高降雨量；冬季霜冻；稀薄的石质土壤；以及缺乏主要养分。因此，农业生产一般仅限于以草原为基础的牛羊系统，目前这些系统严重依赖政府支助付款才能产生经济效益。然而，之前的研究(天然产品加兰他明的可持续生产；Defra项目NF0612)证实，与高地地区相关的环境挑战导致种植在那里的水仙花的加兰他明产量比种植在低地条件下的水仙高50%。因此，为生产加兰他明而种植的水仙为英国旱地农民提供了一种新的、潜在的高价值作物，可以提供重要的新收入来源，增加他们的经济韧性。然而，要做到这一点，需要进行基础研究，以评估和克服与将水仙生产整合到现有的以牧场为基础的耕作系统中有关的任何问题。该项目将获得、重新设计、测试和评估在长期草地下种植球茎植物并有选择地收获随后的绿色水仙材料的机械。为期4年的田间农艺试验将评估成苗率和季节性变化对成苗率的影响程度。全面的生产试验将量化将水仙花生产纳入放牧牧场对动物性能和土地载畜量的影响。还将确定化肥投入对水仙花的竞争能力和所获得的加兰他明产量的影响程度，以便制定方案，以优化从丘陵和旱地农场同时生产加兰他明和牲畜。以这种方式种植水仙花将确保与高地放牧草原相关的生态系统服务得到维护。

The number of people suffering from dementia is large and growing at a considerable rate. In 2010, there were over 35.6 million dementia sufferers worldwide and 4.6 million cases are diagnosed each year. Alzheimer's Disease (AD) accounts for between 50 and 75% of these cases. Galanthamine has been approved by the US Food and Drug Administration, the UK Medicines and Healthcare Products Regulatory Authority and the European Medicines Agency as an AD treatment since 1998. Galanthamine is mainly produced from plants, as although chemical synthesis is possible, it is difficult and expensive. Galanthamine is the natural plant alkaloid used to produce the pharmaceutical product galanthamine. It is currently being extracted from daffodils/Narcissus (in central and western Europe), Leucojum (in eastern Europe) and Lycoris (in China). However, with the exception of daffodils the source plants are wild flowers not suitable for agricultural exploitation due to limitations in either resources or research. Thus daffodils are the only economically-viable world-wide source for galanthamine. The annual global consumption of galanthamine is currently constrained to 3-4 t/yr by existing production levels, but published figures predict the potential global market could be nearer 40 t/yr. Independent reports project the competitive Active Pharmaceutical Ingredient price for galanthamine drugs to remain between £15,000 - £18,000/kg in the medium term.The UK uplands are characterised by poor growing conditions brought about by a combination of factors including: low temperatures; exposure to wind; high rainfall; winter frosts; thin, stony soils; and a shortage of major nutrients. Consequently agricultural production is generally limited to grassland-based beef and sheep systems that are currently heavily reliant upon Government support payments to be economic. However, previous research ('Sustainable production of the natural product galanthamine'; Defra project NF0612) established that the environmental challenges associated with upland areas trigger a 50% higher yield of galanthamine in daffodils that are grown there when compared to those grown in lowland conditions. Daffodils grown for galanthamine production therefore offer a novel, potentially high value crop for UK upland farmers that could provide an important new income stream, increasing their economic resilience. However, for this to happen, underpinning research is required to evaluate and overcome any problems associated with integrating daffodil production into existing pastoral based farming systems. This project will acquire, re-design, test and evaluate machinery for planting bulbs under long-term grass leys and selectively harvesting the subsequent green daffodil material. Field-scale agronomy trials over a 4 year period will assess establishment rates and the extent to which these are influenced by seasonal variation. Full-scale production trials will quantify the impact of incorporating daffodil production into grazed pastures on animal performance and the stock carrying capacity of the land. The extent to which fertiliser inputs influence the competitive ability of the daffodils and the yield of galanthamine obtained will also be determined in order to develop protocols which optimise simultaneous production of galanthamine and livestock from hill and upland farms. Growing daffodils in this way will ensure that the ecosystem services associated with grazed grasslands in the uplands are maintained.