Development of new amine donors for biocatalysis

Natural and engineered biocatalysts are already having impact in the manufacture of high value pharmaceuticals by catalysing the conversion of functional groups in high yield. The use of enzymes for organic synthesis will be more routine once their limitations, such as narrow substrate range, are overcome (1). The range of chemical transformations displayed by enzymes continues to grow, fuelled by the discovery of new enzymes involved in natural product biosynthesis and accelerated by genome sequencing. Once a new enzyme is selected, modern enzyme engineering techniques (e.g. directed evolution) can be applied to generate a bespoke biocatalyst with broad synthetic utility. The impact of this technology was recognised by the award of the Nobel prize in Chemistry in 2018 to Prof. Frances Arnold (2). In these projects we will exploit members of large families of enzymes to develop efficient routes for the preparation of both commodity chemicals and high value active pharmaceutical ingredients (APIs, ref. 3).
This project will source natural enzymes from metabolic pathways and where necessary, evolve them to expand their substrate scope. We will combine these biocatalysts with compatible chemo-catalysts to expand the synthetic utility of the optimised route. We will specifically work with transaminase (TA) biocatalysts and explore novel synthetic amine donors (4). The project will provide training in modern biocatalyst methodology and analysis (recombinant DNA technology, enzyme characterisation and engineering). We will aim to collaborate with experts in x-ray crystallography to guide engineering/evolution of target enzymes. Moreover, this project will have specific links with our industrial biocatalysis partner Johnson Matthey.