21ENGBIO: Re-engineering amino acid metabolism in wheat grain
21ENGBIO:重新设计小麦籽粒中的氨基酸代谢
基本信息
- 批准号:BB/W011999/1
- 负责人:
- 金额:$ 12.74万
- 依托单位:
- 依托单位国家:英国
- 项目类别:Research Grant
- 财政年份:2022
- 资助国家:英国
- 起止时间:2022 至 无数据
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Lysine is one of the 20 amino acids used to make proteins and most animals, including humans, cannot make it, so rely on acquiring it through their diet. Unfortunately, cereal grains contain low concentrations of lysine, resulting in nutrient deficiency in humans and farm animals, such as pigs and chickens, that are dependent on cereal grain for their nutrition. This has resulted in imported soybeans taking much of the market for pig and chicken feed manufacture in the UK and EU, while in developing countries, lysine deficiency is a major cause of malnutrition in people who are reliant on cereal grains for their protein intake. Lysine deficiency does not occur in people in developed countries because they can acquire lysine from meat, but the National Food Strategy (2021) considers current levels of meat consumption to be unsustainable. Reducing our dependence on meat for lysine intake will require the development of a sustainable and readily-available global supply of plant-sourced lysine, which will be unachievable without major changes to the structure of global agricultural production and agri-food systems, unless cereals can be re-engineered to accumulate higher concentrations of lysine in their grains. This project will use genome editing with CRISPR to produce high lysine, non-GM wheat lines. Lysine is synthesised from another amino acid, aspartate, via a multistep biochemical pathway. The key control point is a reaction catalysed by an enzyme called DHDPS. DHDPS is feedback-inhibited by lysine, which binds to the enzyme, and we will edit a wheat DHDPS gene so that the enzyme it encodes no longer binds lysine. We will do this in wheat that has already been edited and has high concentrations of aspartate in the grain, using selection agents that will enable us to identify plants containing a lysine-insensitive DHDPS. These agents include a lysine analogue that competes with lysine for incorporation into proteins, and compounds that inhibit DHDPS itself. These compounds will have to be synthesised and our team will include a synthetic chemist as well as plant molecular biologists and Rothamsted's Cereal Transformation Team, making it genuinely multidisciplinary. Crucially, the inhibitors bind DHDPS over the lysine binding site and we have designed changes that will not only render DHDPS lysine-insensitive but also make it resistant to the inhibitors. The stacking of multiple edits to re-engineer amino acid biosynthesis in wheat grain makes the project an excellent fit for the bioengineered cells and systems theme of the call. The editing will require a technique called homology-directed repair, a technology that has been applied successfully in barley and maize but has not yet been used successfully in wheat, so very much a breakthrough technology. Overall, the project is high risk but high gain, with huge potential international impact, in developed as well as developing countries, affecting human nutritional status, animal feed manufacture, bioethanol production through improved animal feed co-product, market expansion for UK wheat grain, and an increase in availability of plant-derived lysine.
赖氨酸是用于制造蛋白质的20种氨基酸之一,包括人类在内的大多数动物都不能制造它,所以依赖于通过饮食获得它。不幸的是,谷物含有低浓度的赖氨酸,导致人类和农场动物(如猪和鸡)的营养缺乏,这些动物依赖谷物获得营养。这导致进口大豆占据了英国和欧盟猪和鸡饲料生产的大部分市场,而在发展中国家,赖氨酸缺乏是依赖谷物摄入蛋白质的人营养不良的主要原因。赖氨酸缺乏症不会发生在发达国家的人群中,因为他们可以从肉类中获得赖氨酸,但国家粮食战略(2021年)认为目前的肉类消费水平是不可持续的。减少我们对肉类赖氨酸摄入的依赖将需要开发可持续和易于获得的植物来源赖氨酸全球供应,如果不对全球农业生产和农业食品系统的结构进行重大改变,这将是无法实现的,除非谷物可以重新设计,以在其谷物中积累更高浓度的赖氨酸。该项目将使用CRISPR进行基因组编辑,以生产高赖氨酸的非转基因小麦品系。赖氨酸是由另一种氨基酸天冬氨酸通过多步生化途径合成的。关键控制点是一种叫做DHDPS的酶催化的反应。DHDPS被赖氨酸反馈抑制,赖氨酸与酶结合,我们将编辑小麦DHDPS基因,使其编码的酶不再与赖氨酸结合。我们将在已经经过编辑且谷物中含有高浓度天冬氨酸的小麦中进行这项工作,使用选择剂,使我们能够识别含有对赖氨酸不敏感的DHDPS的植物。这些试剂包括与赖氨酸竞争掺入蛋白质的赖氨酸类似物,以及抑制DHDPS本身的化合物。这些化合物必须合成,我们的团队将包括合成化学家以及植物分子生物学家和Rothamsted的谷物转化团队,使其真正成为多学科。至关重要的是,抑制剂在赖氨酸结合位点上结合DHDPS,并且我们设计了不仅使DHDPS赖氨酸不敏感而且使其对抑制剂具有抗性的改变。多重编辑的叠加,以重新设计小麦籽粒中的氨基酸生物合成,使该项目非常适合生物工程细胞和系统的主题。这种编辑需要一种叫做同源定向修复的技术,这种技术已经成功地应用于大麦和玉米,但还没有成功地应用于小麦,所以这是一种突破性的技术。总的来说,该项目风险高,收益高,在发达国家和发展中国家具有巨大的潜在国际影响,影响人类营养状况,动物饲料制造,通过改进动物饲料副产品生产生物乙醇,英国小麦谷物的市场扩张,以及植物来源赖氨酸的可用性增加。
项目成果
期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Uncovering plant epigenetics: new insights into cytosine methylation in rye genomes.
- DOI:10.1093/jxb/erad144
- 发表时间:2023-06-27
- 期刊:
- 影响因子:6.9
- 作者:Kaur, Navneet;Nayakoti, Swapna;Brock, Natasha;Halford, Nigel G.
- 通讯作者:Halford, Nigel G.
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Nigel Halford其他文献
Nigel Halford的其他文献
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{{ truncateString('Nigel Halford', 18)}}的其他基金
Defining the signalling network linking pathogen infection and asparagine accumulation in wheat grain
定义连接病原体感染和小麦籽粒中天冬酰胺积累的信号网络
- 批准号:
BB/W007134/1 - 财政年份:2022
- 资助金额:
$ 12.74万 - 项目类别:
Research Grant
Field assessment of ultra-low asparagine, low acrylamide, gene edited wheat
超低天冬酰胺、低丙烯酰胺、基因编辑小麦的田间评估
- 批准号:
BB/T017007/1 - 财政年份:2021
- 资助金额:
$ 12.74万 - 项目类别:
Research Grant
Automated analysis of free amino acids for acrylamide reduction in wheat-based food matrixes: applications in food production and commercial testing
自动分析游离氨基酸以减少小麦食品基质中的丙烯酰胺:在食品生产和商业测试中的应用
- 批准号:
BB/P017541/1 - 财政年份:2016
- 资助金额:
$ 12.74万 - 项目类别:
Research Grant
BBSRC Embrapa: Temperature resilience of flowering in UK and Brazilian wheat (TempRe)
BBSRC Embrapa:英国和巴西小麦开花的温度恢复能力 (TempRe)
- 批准号:
BB/N004515/1 - 财政年份:2015
- 资助金额:
$ 12.74万 - 项目类别:
Research Grant
Establishing scientific exchange and collaboration on crop science between Rothamsted Research and the University of Colombo, Sri Lanka
洛桑研究中心与斯里兰卡科伦坡大学建立作物科学领域的科学交流与合作
- 批准号:
BB/K004476/1 - 财政年份:2012
- 资助金额:
$ 12.74万 - 项目类别:
Research Grant
Genetic improvement of wheat to reduce the potential for acrylamide formation during processing.
对小麦进行遗传改良,以减少加工过程中丙烯酰胺形成的可能性。
- 批准号:
BB/I020918/1 - 财政年份:2011
- 资助金额:
$ 12.74万 - 项目类别:
Research Grant
Producing 'low acrylamide risk' potatoes
生产“低丙烯酰胺风险”马铃薯
- 批准号:
BB/G018995/1 - 财政年份:2009
- 资助金额:
$ 12.74万 - 项目类别:
Research Grant
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