PhD defence G. (Guangcai) Xu

Design and Directed Evolution of Enzymes for Iminium Biocatalysis

New enzymes developed based on a powerful catalysis mode invented by synthetic chemist: iminium catalysis. This catalysis mode has recently been awarded the Nobel prize in chemistry 2021. These new enzymes can be used for the synthesis of pharmaceuticals in a more sustainable way. Based on the recent Nobel prize results. The results of Guangcai Xu showcase the importance of interdisciplinary research in solving important problems such as environmentally friendly ways of manufacturing drugs. The application of biocatalysis in conquering challenging synthesis requires the constant input of new enzymes. This thesis used directed evolution guided by catalytic promiscuity to develop a series of enzymes to perform iminium catalysis, a powerful catalysis mode originating from organocatalysis. Three such iminium biocatalysts have been created: a cofactor-independent peroxygenase achieving enantiocomplementary epoxidation reactions, and two efficient Michaelases, one based on a class I aldolase DERA and the other one based on an artificially tandem-fused tautomerase enzyme. These developments illustrate the power of combining chemomimetic enzyme design and directed evolution to create synthetically useful new-to-natural enzymes.

Promotores Prof.dr. G.J. Poelarends and Prof.dr. W.J. Quax