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一种工程方法，其中生物成分可以以可控和可预测的方式组装并发挥作用。合成生物学的日益成熟可能会在能源、医疗保健和农业等领域给社会带来重大变化。蛋白质是合成生物学中如此强大的工具，因为它们具有不同的结构和活性，包括催化反应和感知环境变化。如今，单个蛋白质的工程化通常是有效的。尽管如此，蛋白质通常在团队中一起工作，控制蛋白质如何聚集成更大的组装体仍然是一个重大挑战。这些问题来自于不同蛋白质之间不稳定或非特异性的连接。我们的研究小组已经建立了一种特定且牢不可破的方法来连接蛋白质，即利用细菌蛋白质化学。这个建议将适应这一原则，以便设计一个不同配对的家庭，其中配对的每个成员都粘在它的伴侣上，但不粘在任何其他配对上。有了这样一个“蛋白质超胶”家族，我们将高效稳定地连接多个蛋白质，创造出程序化的蛋白质团队。此外，我们将利用这种连接技术将细胞连接在一起。不同的单细胞生物在自然界和工业过程中，从燃料生产到有毒废物治理，往往是合作伙伴。设计这些可预测的联系应该是一个有价值的工具，支持分子和细胞团队的设计，加强合作。

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