Japan_IPAP: Embedding protein crystals within synthetic tissues as catalytic soft materials

Japan_IPAP：将蛋白质晶体嵌入合成组织中作为催化软材料

• 批准号: BB/X01259X/1
• 负责人: Oscar Ces
• 金额: $ 19.2万
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FX01259X%2F1
• 关键词: Japan_IPAP; Embedding; protein; crystals; within

Bottom-up synthetic biology aims to reproduce the structures and behaviours of cellular organisms by combining molecules that mimic the structural, functional and information containing roles present in biology. These structures are known as synthetic cells, and they can act as a framework to study biological processes (such as movement or replication), as well as act as miniature test-tubes, within which chemical and biochemical reactions can be carried out. Taking further inspiration from biology, the assembly of individual synthetic cells leads to the creation of synthetic tissues, where different compartment types can be integrated within a larger structure to act as optimised microscale reaction vessels, which can be activated through the exchange of molecular reactants between compartments.As synthetic cells and tissues are constructed from molecular parts, there is huge flexibility in the design of these systems, and this has been exploited to form compartments from lipids, polymers and protein-based membranes. One area that is significantly less explored is the encapsulation of novel biocatalysts structures within synthetic cells and tissues. One such catalyst are polyhedrin protein crystals, which can be used to embed co-produced enzyme catalysts via expression of crystals in cells. This exploits the high stability of polyhedrin crystals (used to protect viral capsids in the external environment in nature) to create long-lasting catalysts.Here, we propose to use microfluidic approaches to assembling synthetic tissues that i) encapsulate enzyme-embedded polyhedrin crystals within different compartments of the tissue and ii) possess a hydrogel shell to increase the durability of the tissue material. We will assemble water in oil emulsion droplets on-chip, encapsulating the crystals within the aqueous compartments of these droplets, before gelating the hydrogel around the emulsion to produce milliscale devices that can be handled in liquid and air. We will then test the catalytic activity of these tissues, with the aim of producing robust soft materials with long catalytic lifetime that can be used simply via incubation in reactant-containing solution. After reactant takeup and conversion within the synthetic tissue, we will aim to release product through washing cycles, setting up the next tissue-based catalysis cycle. This proof-of-concept work will demonstrate the potential for hybrid tissue mimics in catalysis, and this framework could be extended to design new, combined bio- and chemo-catalytic routes currently impossible in one-pot systems due to catalyst poisoning.In order to achieve this we are bringing together world leading research expertise in the UK and Japan with a view to bringing together expertise not available in concert elsewhere in the word: namely Ces (synthetic cells and microfluidics), Ueno (multiscale catalytic biomaterials) and Abe (catalytic protein crystal biomaterials).

自下而上的合成生物学旨在通过结合模仿生物学中存在的结构，功能和信息的分子来重现细胞生物的结构和行为。这些结构称为合成细胞，它们可以充当研究生物过程（例如运动或复制）的框架，并且可以作为微型测试管的作用，在其中可以进行化学和生化反应。从生物学中汲取进一步的灵感，单个合成细胞的组装导致合成组织的产生，在该组织中，可以将不同的隔室类型整合在较大的结构中，以充当优化的显微镜反应容器，可以通过在compartions之间进行分子反应物的交换来激活分子反应物，从而从组合部分中构建了这些型号，并且在其中构建了这些模式，并且在这些系统中构建了这些系统，并且在这些系统中构建了这些在这些系统中，这些是在这些系统中构建的，在这些系统中构建了这些设计，在这些系统中构建了这些设计，在这些系统中构建了这些设计。脂质，聚合物和基于蛋白质的膜。一个明显较少探索的区域是合成细胞和组织中新型生物催化剂结构的封装。一种这样的催化剂是多面蛋白蛋白晶体，可用于通过细胞中晶体的表达来嵌入共生产的酶催化剂。这可以利用多面腺蛋白晶体的高稳定性（用于保护自然界外部环境中的病毒包囊）以创建持久的催化剂。在这里，我们建议使用微流体方法来组装合成组织，以使酶壳内部固体中的固体和ii confloce in II）的持续性壳体壳构成了酶的壳体和II型固体。我们将在芯片上在油乳液液滴中组装水，将这些液滴的水舱内的晶体封装，然后将水凝胶凝固在乳液周围的水凝胶以生产可在液体和空气中处理的毫固定设备。然后，我们将测试这些组织的催化活性，目的是生产具有较长催化寿命的稳健软材料，可以通过在含反应物的溶液中孵育。在合成组织中反应物的成导和转化后，我们将通过洗涤周期释放产品，建立下一个基于组织的催化周期。这项概念概念证明的工作将证明杂交组织模仿催化中的潜力，并且该框架可以扩展到设计新的，合并的生物和化学催化途径，目前目前在催化剂中毒引起的一汤匙系统中无法实现的一口气系统中不可能。微流体），UENO（多尺度催化生物材料）和安倍（催化蛋白质晶体生物材料）。