Orthogonal Modules Engineered for Synthetic Protein- and Microbial-Networks

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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.