Orthogonal Modules Engineered for Synthetic Protein- and Microbial-Networks

专为合成蛋白质和微生物网络设计的正交模块

• 批准号: EP/N023226/1
• 负责人: Mark Howarth
• 金额: $ 47.43万
• 依托单位: University of Oxford
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2016
• 资助国家: 英国
• 起止时间: 2016 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FN023226%2F1
• 关键词: Orthogonal; Modules; Engineered; Synthetic; Protein

Synthetic biology refers to an engineering approach to biology, where biological components can be assembled to function in a controlled and predictable way. Synthetic biology's growing sophistication is likely to generate major changes to society in areas including energy, healthcare and agriculture. Proteins are such powerful tools in synthetic biology because of their diverse structures and activities, including catalysing reactions and sensing changes in the environment. Nowadays engineering of individual proteins is often efficient. Nonetheless proteins usually work together in teams and it is still a major challenge to control how proteins come together into larger assemblies. The problems come from unstable or non-specific links between the different proteins. Our group has established a specific and unbreakable way to connect proteins, from harnessing bacterial protein chemistry. This proposal will adapt this principle, in order to engineer a family of different pairs, where each member of the pair sticks to its partner but does not stick to any other pair. Having such a family of "protein superglues", we will efficiently and stably link multiple proteins to create programmed protein teams. In addition we will harness this linkage technology to connect cells together. Different single-celled organisms often work in partnership in nature and in industrial processes, from fuel production to toxic waste remediation. Engineering these predictable linkages should be a valuable tool underpinning the design of molecular and cellular teams with enhanced cooperation.

合成生物学是指生物学的工程方法，可以在其中组装生物学成分以以受控且可预测的方式发挥作用。合成生物学的成熟程度越来越大，可能会在能源，医疗保健和农业等领域对社会产生重大变化。蛋白质是合成生物学中如此强大的工具，因为它们具有多种结构和活动，包括催化反应和感知环境的变化。如今，单个蛋白质的工程通常是有效的。但是，蛋白质通常在团队中共同起作用，而控制蛋白质如何将蛋白融合到更大的组件中仍然是一个主要挑战。这些问题来自不同蛋白质之间的不稳定或非特异性联系。我们的小组已经建立了一种特定且坚不可摧的方法，可以从利用细菌蛋白化学来连接蛋白质。该提案将适应此原则，以设计一个不同的对家庭，这对夫妇的每个成员都坚持其伴侣，但不遵守任何其他对。拥有这样的“蛋白质超级启动”家族，我们将有效且稳定地连接多种蛋白质以创建编程的蛋白质团队。此外，我们将利用这种连锁技术将细胞连接在一起。不同的单细胞生物通常在自然界和工业过程中与从燃料生产到有毒废物修复的合作伙伴关系。工程这些可预测的联系应该是一种有价值的工具，该工具是通过增强合作的分子和细胞团队设计的基础。

项目成果

Tunable Extracellular Self-Assembly of Multi-Protein Conjugates from Bacillus subtilis

• DOI: 10.1101/087593
• 发表时间: 2016-11
• 期刊: bioRxiv
• 作者: Charlie Gilbert;M. Howarth;C. Harwood;T. Ellis

DogCatcher allows loop-friendly protein-protein ligation.

• DOI: 10.1016/j.chembiol.2021.07.005
• 发表时间: 2022-02-17
• 期刊: Cell chemical biology
• 影响因子: 8.6
• 作者: Keeble AH;Yadav VK;Ferla MP;Bauer CC;Chuntharpursat-Bon E;Huang J;Bon RS;Howarth M
• 通讯作者: Howarth M

Evolving Accelerated Amidation by SpyTag/SpyCatcher to Analyze Membrane Dynamics.

• DOI: 10.1002/anie.201707623
• 发表时间: 2017-12-22
• 期刊: Angewandte Chemie (International ed. in English)
• 作者: Keeble AH;Banerjee A;Ferla MP;Reddington SC;Anuar INAK;Howarth M
• 通讯作者: Howarth M