Orthogonal Modules Engineered for Synthetic Protein- and Microbial-Networks

合成生物学指的是生物学的一种工程方法，其中生物成分可以以受控和可预测的方式组装起来。合成生物学的日益复杂可能会在能源、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，因为它们具有多种结构和活动，包括催化反应和感知环境变化。如今，单个蛋白质的工程通常是高效的。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主要的挑战。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。我们的团队已经建立了一种特殊的、牢不可破的方式来连接蛋白质，利用细菌蛋白质化学。这个提议将采用这一原则，以设计一个由不同的配对组成的家庭，其中每一对成员都依附于它的伴侣，而不依附于任何其他配对。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，形成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。在自然界和工业过程中，从燃料生产到有毒废物的修复，不同的单细胞生物常常结成伙伴关系。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。

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.