Engineering spatial segregation within bacterial hosts for bio-therapeutic protein production

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The production of bio-therapeutic proteins of industrial interest in recombinant hosts is becoming an increasingly popular alternative to production in mammalian cell culture which can be slow and expensive. The overall aim of this project is to develop a bacterial system for recombinant protein production by engineering compartmentalisation within the cytoplasm of E. coli which may allow for an environment that promotes production and purification of post-translationally modified proteins. In nature, compartmentalisation is achieved by localising enzymes inside of sophisticated proteinaceous organelles called bacterial microcompartments (BMCs). In the past decade, significant progress has been made to engineer these BMCs, to permit the construction of synthetic microcompartments within the bacterial cell. In this project the potential of these structures to be used for the production and purification of recombinant proteins is explored.The project will expand our understanding of the fundamentals of engineering synthetic compartmentalisation, the benefits and limitations of protein compartmentalisation and inform the rational design of future microcompartment-derived technologies. The project is aligned with the EPSRC centre for Doctoral Training in Bioprocess Engineering Leadership. It provides new synthetic biology approaches to the redesign of cellular chemistry and will impact in the development of cost-effective and sustainable bio-based manufacture.