The development of a novel herbicide

新型除草剂的研制

• 批准号: BB/I003703/1
• 负责人: David Rice
• 金额: $ 76.88万
• 依托单位: University of Sheffield
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2011
• 资助国家: 英国
• 起止时间: 2011 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FI003703%2F1
• 关键词: development; novel; herbicide

In the next 50 years the global population is expected to increase by 50% and exceed 9 billion. The increased agricultural output needed to feed this growing population cannot be met by bringing more land into food production as no further suitable arable land is available. Therefore, meeting this challenge will require the adoption of highly efficient and sustainable agriculture practices. Efficient agriculture requires the removal of weeds. Current arable farming relies on ploughing to remove weeds by burying them as the soil is turned over. However, ploughing (tillage) removes vegetation cover, disrupts the soil structure and leads to soil erosion by water, wind or both. The Dust Bowl inter-war era in the mid-western United States graphically illustrated the vulnerability of plough-based agriculture as wind blew away precious topsoil from the drought ravaged southern plains whose soil structure had been weakened by ploughing. No-till farming is a branch of conservation agriculture in which the ground is permanently covered by a cover-crop that is left on the fields over winter to protect the soil. The roots of the cover crop hold the soil particles together, strengthening the structure and foliage intercepts rain water to lessen its impact on the soil. In this method of farming, herbicides, rather than the plough, are used for weed control and, prior to planting, the cover crop is degraded by the application of a broad spectrum herbicide and the dead organic matter is left on the surface to degrade naturally. Seeds are then drilled into the ground through the residue in a process that results in minimal disturbance of the soil and improved water retention. A further benefit of no-till is that the cover crop acts as a carbon sink removing CO2 from the atmosphere during photosynthesis with the non-harvested residue being converted to soil organic matter. It has been estimated that approximately half of the overall potential for U.S. croplands to sequester soil carbon comes from conservation tillage. Moreover, as no-till is less mechanised, agricultural diesel use is reduced by 50-80%. No-till therefore offers the potential to off-set fossil fuel emissions in other sectors. It has been suggested that the global introduction of no-till could result in the annual sequestration of 1 billion tons of carbon, 15% of that required to limit atmospheric CO2 to a trajectory that avoids further increases over today's levels. This saving is equivalent to that saved from the global doubling of nuclear capacity replacing coal, or to the combined annual emissions of all the road transport currently in use on the planet. Whilst the benefits of no-till in decreasing soil erosion and promoting carbon capture are clear, its practice relies on the availability of effective herbicides. More importantly, in order to avoid damage to the emerging crop, the herbicide has to have the property of being inactivated when it contacts the soil so that available residues are minimised. However, reliance on compounds that act by inhibiting a limited number of processes in plants has encouraged the emergence of herbicide resistant weeds. Sustainable agriculture therefore requires the development of herbicides having novel modes of action. The search to find new herbicides is now an important area of research. In this project we aim to examine the prospect of developing a new herbicide, that will be targeted against an enzyme, called imidazoleglycerol-phosphate dehydratase, which is responsible for a key step in the synthesis of histidine, an amino acid that is essential for plant growth. We will determine the atomic structures of a number of chemicals that bind to this enzyme, and use this information in a process of design, to chemically synthesize new compounds that will both inhibit the enzyme activity and be inactivated on soil contact. These new compounds will thus kill the weeds in a new way and facilitate sustainable agriculture practices.

未来50年，全球人口预计将增长50%，超过90亿。由于没有更多合适的可耕地，因此无法通过增加土地用于粮食生产来满足养活这一不断增长的人口所需的增加的农业产量。因此，应对这一挑战将需要采用高效和可持续的农业做法。高效农业需要清除杂草。目前的可耕地农业依靠翻耕来清除杂草，方法是在翻土时将杂草埋起来。然而，翻耕（耕作）会去除植被，破坏土壤结构，导致水、风或两者造成的土壤侵蚀。美国中西部两次世界大战之间的沙尘暴时期生动地说明了以犁为基础的农业的脆弱性，因为风从干旱肆虐的南部平原吹走了宝贵的表土，而这些平原的土壤结构已经被犁削弱了。免耕农业是保护性农业的一个分支，在这种农业中，地面被覆盖作物永久覆盖，覆盖作物在冬季留在田地里以保护土壤。覆盖作物的根部将土壤颗粒固定在一起，加强结构，叶子拦截雨水，减少对土壤的影响。在这种耕作方法中，使用除草剂而不是犁来控制杂草，并且在种植之前，通过施用广谱除草剂来降解覆盖作物，并且死亡的有机物质留在表面上自然降解。然后将种子通过残留物钻入地下，这一过程对土壤的干扰最小，并改善了保水性。免耕的另一个好处是，覆盖作物作为碳汇，在光合作用过程中从大气中去除二氧化碳，未收获的残留物转化为土壤有机质。据估计，美国农田固碳的总体潜力约有一半来自保护性耕作。此外，由于免耕机械化程度较低，农业柴油使用量减少了50- 80%。因此，免耕提供了抵消其他部门化石燃料排放的潜力。有人认为，全球采用免耕法可能导致每年封存10亿吨碳，这是将大气中的二氧化碳限制在避免进一步增加到今天水平的轨道上所需的15%。这一节省相当于全球核能取代煤炭所节省的两倍，或者相当于地球上目前使用的所有公路运输的年排放量总和。虽然免耕在减少土壤侵蚀和促进碳捕获方面的好处是显而易见的，但其实践依赖于有效除草剂的可用性。更重要的是，为了避免对正在生长的作物造成损害，除草剂必须具有当其接触土壤时被灭活的特性，以便使可用的残留物最小化。然而，依赖于通过抑制植物中有限数量的过程而起作用的化合物已经促进了除草剂抗性杂草的出现。因此，可持续农业需要开发具有新作用模式的除草剂。寻找新的除草剂现在是一个重要的研究领域。在这个项目中，我们的目标是研究开发一种新的除草剂的前景，这种除草剂将针对一种称为咪唑甘油磷酸酯酶的酶，这种酶负责合成组氨酸的关键步骤，组氨酸是植物生长所必需的氨基酸。我们将确定与这种酶结合的一些化学物质的原子结构，并在设计过程中使用这些信息，以化学方法合成新的化合物，这些化合物既能抑制酶的活性，又能在土壤接触时失活。因此，这些新化合物将以新的方式杀死杂草，并促进可持续农业实践。

项目成果

Crystal Structures Reveal that the Reaction Mechanism of Imidazoleglycerol-Phosphate Dehydratase Is Controlled by Switching Mn(II) Coordination.

• DOI: 10.1016/j.str.2015.05.012
• 发表时间: 2015-07-07
• 期刊: Structure (London, England : 1993)
• 作者: Bisson C;Britton KL;Sedelnikova SE;Rodgers HF;Eadsforth TC;Viner RC;Hawkes TR;Baker PJ;Rice DW
• 通讯作者: Rice DW

High-resolution crystal structure of human asparagine synthetase enables analysis of inhibitor binding and selectivity

• DOI: 10.1038/s42003-019-0587-z
• 发表时间: 2019-09-17
• 期刊: COMMUNICATIONS BIOLOGY
• 影响因子: 5.9
• 作者: Zhu, Wen;Radadiya, Ashish;Richards, Nigel G. J.
• 通讯作者: Richards, Nigel G. J.

Molecular basis of human asparagine synthetase inhibitor specificity

• DOI: 10.1101/428508
• 发表时间: 2018-09
• 期刊: bioRxiv
• 作者: Wen Zhu;Ashish Radadiya;C. Bisson;B. Nordin;Patrick Baumann;T. Imasaki;S. Wenzel;S. Sedelnikova;A. Berry;T. Nomanbhoy;J. Kozarich;Yi Jin;Y. Takagi;D. Rice;N. Richards

Erratum: Author Correction: High-resolution crystal structure of human asparagine synthetase enables analysis of inhibitor binding and selectivity.

勘误：作者更正：人天冬酰胺合成酶的高分辨率晶体结构可以分析抑制剂的结合和选择性。

• DOI: 10.1038/s42003-019-0690-1
• 发表时间: 2019
• 期刊: Communications biology
• 影响因子: 5.9
• 作者: Zhu W

Elucidating the structural basis for differing enzyme inhibitor potency by cryo-EM.

• DOI: 10.1073/pnas.1708839115
• 发表时间: 2018-02-20
• 期刊: Proceedings of the National Academy of Sciences of the United States of America
• 影响因子: 11.1
• 作者: Rawson S;Bisson C;Hurdiss DL;Fazal A;McPhillie MJ;Sedelnikova SE;Baker PJ;Rice DW;Muench SP
• 通讯作者: Muench SP