ALMOND: Agriculture Living Machine of Operational Nano Droplets

农业部门的工业化对于养活不断增长的全球人口至关重要，但由于使用化学杀虫剂和杀虫剂来保护作物生长，导致生态系统的化学负担增加。2022年全球种子处理市场规模为134亿美元，预计在2030年之前每年增长约10%。美国农民每年在杀菌剂上花费5.75亿美元，为商业作物带来130亿美元的收益。这反映了目前使用的农用化学品在维持全球粮食供应方面的巨大作用。化学农药和杀虫剂的生态影响，包括环境持久性、生态系统毒性、水污染、食物链积累和新出现的抗药性，已经变得越来越明显，并已停止使用。然而，替代解决方案并不是没有挑战。人们对利用土壤中或土壤上或种衣剂内的自然产生的微生物(生物杀虫剂)来帮助保护作物越来越感兴趣，这种方法在苏云金芽孢杆菌和球形溶杆菌等物种以及昆虫活性真菌和病毒方面取得了很大成功。然而，由于担心微生物在被证明是安全的之前能够引起人或动物的感染，一些由微生物制造的能够保护农作物的高度有希望的特定农药和杀虫剂生物活性分子在实践中很难利用。同样，活性化合物本身往往不稳定或难以纯化，因此单独使用这些化合物具有挑战性。我们在伯克霍尔德氏菌中发现了新的具有生物活性的多炔类化合物--头孢菌素，并发现了它的生物合成途径。西帕星具有杀菌活性，可以保护萌发中的作物免受立枯病的侵袭，因此这些特殊的代谢物代表着很有前途的新生物活性。在这个项目中，我们将使用尖端的3D打印微流体来生产非繁殖的、环境友好的人造细胞--基于细胞膜的生物学灵感产生的人造工程材料。这些人工细胞含有由脂质双层隔开的网络隔间，很像生物细胞，可以作为生化微工厂在当地合成这些有前途的农药和杀虫剂生物化学品，以提高作物的健康。通过将这些人造细胞制成生物可降解水凝胶壳中的作物种子涂层，保护效果恰好定位在需要的地方。人造细胞将被编程，在种子萌发时对遗传信号做出反应，以激活杀虫剂保护。通过这种方式，人工细胞可以在不同的植物健康、疾病或不同昆虫捕食者存在的情况下以不同的方式做出反应。重要的是，这些系统提供了灵活性和组合能力，可以将通常找不到的途径和毒素组合在一起，而不会创造出可能被证明对许可构成挑战的转基因生物。通过这种方式，我们可以在单一的协同配方中结合使用不同的活性生物分子，也可以与现有的生物杀虫剂结合以增强功能，包括促进作物生长和土壤健康的固氮以及碳捕获和转化为能量以推动人造细胞新陈代谢。

Industrialisation of the agricultural sector has been essential for feeding the growing global population, but has resulted in increased chemical burden on ecosystems with the use of chemical pesticides and insecticides to protect crop growth.The global seed treatment market size was valued at $13.4B in 2022 and is expected to grow ~10 % annually until 2030. US farmers annually spend >$575 million on fungicides to provide a commercial crop gain of c.$13 billion. This reflects the huge role of agrichemicals in current usage to maintain global food supplies.The ecological impacts of chemical pesticides and insecticides, including environmental persistence, ecosystem toxicity, water contamination, foodchain accumulation and emerging resistance, have become increasingly apparent and have seen a move away from their use. However, alternative solutions are not without challenge. There is increasing interest in harnessing naturally occurring microorganisms (biopesticides) in or on soil or within seed-coatings to help protect crops, and this approach has seen much success with species such as Bacillus thuringiensis and Lysinbacillus sphaericus, and insect-active fungi and viruses. However, a number of highly promising specific pesticide and insecticides biocactive molecules made by micro-organisms that can protect crops are difficult to harness in practice due to potential concerns about the micro-organisms being able to cause infection in people or animals, until proven safe. Similarly, the active compounds themselves are often unstable or difficult to purify, so these are challenging to use alone. We have identified novel bioactive polyyne, cepacin in Burkholderia bacteria and discovered its biosynthetic pathway. Cepacin has fungicidal activity that protects germinating crops against damping off disease, as such these specialised metabolites represent promising novel bioactives.In this project we will use cutting edge 3D-printed microfluidics to produce non-reproducing, environmentally benign artificial cells - artificial engineered materials inspired by biology based on the cell membrane. These artificial cells contain networked compartments, separated by lipid bilayers, much like biological cells, and can serve as biochemical microfactories to synthesis these promising pesticide and insecticide biochemicals locally, to enhance crop health. By formulating these artificial cells as crop seed coatings in biodegradable hydrogel shells, the protective effects are localised exactly where needed. The artificial cells will be programmed to respond to genetic cues when the seed germinates, to activate pesticide protection. In this way the artificial cells can respond in different ways in different circumstances of plant health, disease or in the presence of different insect predators.Importantly these systems afford flexibility and a combinatorial ability to assemble pathways and toxins not normally found together, without creating transgenic organisms that that could prove challenging to license. In this way, we can use different active biomolecules in combination in a single synergistic formulation and also combine with existing biopesticides for enhanced function, that includes nitrogen fixation for enhanced crop growth and soil health and carbon capture and conversion to energy to power the artificial cell metabolism .