Engineering synthetic C1 utilisation in non-conventional organisms for sustainable bioproduction

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Climate change is likely the most serious threat thus far to the continued wellbeing of humanity. Practical, applicable technologies are desperately needed to realise a truly sustainable future.On the one hand, carbon emissions from industry and methane emissions from agriculture are two key drivers of climate change. On the other hand, the inherent unsustainability of the petrochemical industry itself is a major roadblock to a circular economy. Significant efforts have been made to design microbiological systems to manufacture organic chemicals using biological systems, however these often rely on sugar feedstocks. Carbon dioxide and methane can be simply converted into microbial feedstock through electrical reduction into formic acid. This C1 compound can be consumed by formatotrophic microbes, which unfortunately are difficult to engineer to make useful products. Now, thanks to the development of synthetic biology and metabolic engineering, it is possible, though challenging, to engineer non-formatotrophic, industrial organisms to utilise formate as source of carbon and energy. In this project, the non-conventional, industrial yeast Yarrowia lipolytica will be engineered to both utilise formate as substrate and produce high-value products. This will be achieved by a combination of synthetic biology tools (Golden Gate, CRISPR, evolution engineering, metabolic models). In this strain design approach, it is expected to generate improved strains able to 1) tolerate high concentrations of formate 2) incorporate C1 substrates in their biomass 3) generate cellular energy and 4) produce high amount of industrially relevant products. In addition, the project will look into cell-to-cell variability in formate-based bioprocess, which is one of the current challenges of microbial biotechnology.