A Synthetic Biology Approach to Accelerating the Engineering of Industrially-Important Organisms

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Synthetic biology and metabolic engineering are key to the development of microorganisms for sustainable chemical production in industrial biotechnology. To-date, these fields have focused on model organisms like Escherichia coli and Saccharomyces cerevisiae, in which metabolic pathways are readily optimised using current engineering approaches. However, many industrially-important properties are not found in model organisms, but only in specialist organisms. Such organisms are usually much less well studied and may grow slowly, have low transformation frequencies, or lack genetic tools; so are often not amenable to effective engineering by existing approaches. Even within model organisms, the expression profile of enzymes within biosynthetic pathways must be carefully optimised, as well characterised standard parts can behave unpredictably in new contexts.This research project will develop new synthetic biology approaches and design principles to accelerate the engineering of industrially-relevant organisms. In order to apply these approaches in non-model organisms, we will focus on Clostridium, a genus of anaerobic bacteria containing several industrially-important species, for which we have previously developed foundational genetic tools. This project will exploit and build upon these tools to implement various non-native (heterologous/synthetic) metabolic pathways in Clostridium, allowing the design rules and principles to be established and developed, and resulting in new strains which produce valuable compounds. The research will involve design, DNA synthesis, DNA assembly, and testing of metabolic pathways by the cultivation of anaerobic microorganisms and measurement of products formed.