EBioAct: Environmentally sustainable production of bioactive triterpenes

动物、植物和其他生物产生的许多小分子或天然产品在健康和工业中都有用处。然而，接触到这些分子可能会产生负面后果，如对发现该分子的物种的过度开发，或化学制造过程对环境的影响。此外，许多天然产品结构复杂，无法通过化学合成获得，至少在商业规模上是如此。这项提案将专注于生产一组结构相关的三萜类分子，其中一些在医疗保健中有用途，另一些可能作为传粉者友好的杀虫剂替代品。它们包括：i)角鲨烯，广泛用于提高药物的有效性和对抗原的免疫反应，其中全球需求仍部分通过从鲨鱼中提取来满足；ii)用于治疗炎症和癌症的药物中的类固醇；iii)在植物中发现的三萜类化合物，可防止昆虫取食，是工业界感兴趣的环境可持续作物保护剂。在这个项目中，我们将演示如何将工厂用作生产角鲨烯和角鲨烯衍生分子的光能制造平台。我们的努力将集中在优化产量；证明生产可以扩大；展示尚未商业化的化合物的效用；以及调查大规模生产的技术和经济可行性。这项工作将与工业界的合作伙伴合作进行，并将为商业、社会和环境影响提供一条途径。该项目生产的工具和资源也将适用于许多其他分子的生产。这些资源将作为可重复使用的资源提供给研究界。

Many small molecules or natural products produced by animals, plants and other organisms have utility in health and industry. However, access to these molecules can have negative consequences such as over-exploitation of the species in which that molecule is found, or environmental impacts from chemical manufacturing processes. Furthermore, many natural products are structurally complex and cannot be accessed by chemical synthesis, at least at commercial scale. This proposal will focus on the production of a group of structurally related triterpenoid molecules, some of which have uses in healthcare and others which have potential as pollinator-friendly alternatives to pesticides. These include: i) squalene, widely used to improve the effectiveness of drugs and the immune response to antigens, of which global demand is still partly met by extraction from sharks; ii) steroids used in medicine for treating inflammation and cancer; iii) triterpenoids found in plants that prevent insect-feeding and are of interest to industry as environmentally sustainable crop protection agents. In this project, we will demonstrate how a plant can be used as a light-powered manufacturing platform for producing squalene and squalene-derived molecules. Our efforts will be focussed on optimising yields; demonstrating that production can be scaled up; demonstrating the utility of compounds that are not yet commercially available; and investigating the technical and economic feasibility of large-scale production. This work will be carried out in collaboration with partners from industry, and will provide a pathway for commercial, social and environmental impacts. The tools and resources produced in this project will also be applicable for the production of many other molecules. These will be provided to the research community as reusable resources.