Directed Evolution of Gold-based Artificial Metalloenzymes and Design of Gold-triggered Drug-Release Systems

Nature has evolved enzymes to solve the complex biochemical problems of life through directed evolution over millions of years. But, to solve the needs of today’s society, enzymes must be able to evolve more quickly and “smartly”. Artificial metalloenzymes are an elegant solution to add new functionality to enzymes while utilizing the power of genetic memory from the host protein matrix. These systems can be especially useful in establishing biorthogonal reactions in living systems and have been extensively investigated in the Ward Lab at the University of Basel.
The aim of this thesis is to expand the current repertoire of biorthogonal catalysts by synthesizing gold(I)-based artificial metalloenzymes as well as gold(I)-functionalized somastotatin analogues and optimize their catalytic potential via directed evolution or systematic screening. This includes the design of new “close-to-release” substrates for controlled uncaging of fluorophores upon reaction with gold catalysts.