The development of tools and resources for the identification of inhibitors of pigment biosynthetic pathways in the chloroplast.

背景预计到2050年，全球人口将增加30%，达到92亿。为了养活这些人口，需要增加70%的粮食产量[1]。这种产量的增加必须在土地供应减少、水资源减少、能源投入减少、化肥和化学品减少的情况下实现。如果粮食生产要满足需求，除草剂仍将是农药综合管理做法的一个重要组成部分。在过去的30年里，没有新的除草剂以新的作用模式商业化[3]，因此抗性的威胁增加，并且需要能够在除草剂发现的早期阶段集中努力于作用模式（MOA）。漂白除草剂被指定为导致绿色植物叶子白色漂白的化学品。它们的有效性在于它们能够引起单线态氧的光依赖性产生，单线态氧损害脂质、叶绿素和蛋白质，导致植物死亡[4]。漂白除草剂的化学成分多种多样，这反映了不同的叶绿体生物合成途径以及它们影响的这些途径中的各个组分。漂白除草剂之间的共同表型性状往往会导致混淆指定MOAs特定的除草抑制剂。例如，Norflurazon是类胡萝卜素生物合成的抑制剂，特别是八氢番茄红素去饱和酶（PDS），[5]。PDS的抑制导致前体八氢番茄红素的积累。然而，八氢番茄红素也可以通过抑制质体醌/生育酚的生物合成而在营养组织中积累。这是因为质体醌是参与八氢番茄红素去饱和的辅助因子。科学原理和重要性。在这一培训方案中，将开发遗传资源、代谢物分析程序和体外分析，以便能够区分和验证不同的漂白除草剂。该方法将利用新技术和跨学科方法解决生物学问题，涉及化学、生物工程和高通量化合物筛选配方。这些有助于阐明除草MOA的方法对于快速评估和发展新的化学物质是必不可少的，当应用于农业工业时，可以进行大规模筛选。

Background. The global population is projected to increase by 30% to 9.2 billion in 2050. In order to feed this population a 70% increase in food production is required [1]. This increased production must occur with less land availability, less water, less energy input, fertilizers and chemicals. Herbicides will remain an essential component of integrated pesticide management practices; if food production is to meet demand. No new herbicides have been commercialised with a novel mode of action for over 30 years [3], hence the increased threat from resistance, and the need to be able to focus efforts on Modes of action (MOA) at an earlier stage in herbicide discovery.Bleaching herbicides are designated as chemicals that cause white bleaching of green plant leaves. Their effectiveness resides in their ability to cause light-dependant generation of singlet oxygen which damages lipids, chlorophyll and proteins leading to plant death [4]. Bleaching herbicides are chemically diverse, which reflects the different chloroplastic biosynthetic pathways and the individual components within these pathways they effect. The common phenotypic traits between bleaching herbicides often causes confusion in assigning MOAs to specific herbicidal inhibitors. For example, Norflurazon, is an inhibitor of carotenoid biosynthesis, specifically the enzyme phytoene desaturase (PDS), [5]. Inhibition of PDS results in the precursor phytoene accumulating. However, phytoene can also accumulate in vegetative tissues from the inhibition of plastoquinone/tocopherol biosynthesis. This is because plastoquinone acts as a cofactor involved in phytoene desaturation.Scientific rationale and importance. In this training programme, genetic resources, metabolite profiling procedures and in vitro assays will be developed to enable the differentiation and validation of different bleaching herbicides. The approach will tackle the biological question using new technologies and an interdisciplinary approach, involving chemistry, bioengineering and formulations for high-throughput compound screening. These methodologies that facilitate the elucidation of herbicidal MOA are essential for the rapid assessment and progression of novel chemistries, allowing large-scale screening when applied in the agro-industry.