Development of an Artificial Platinum(II)-Cyclase Platform

Proteins are essential biomolecules, which are ubiquitously found in all forms of life, and consist of sequences of naturally occurring amino acids. Some proteins function as enzymes by accelerating chemical transformations within our cells. These enzymes play pivotal roles, for example, in energy metabolism. Notably, enzymes typically excel through their high selectivity catalyzing only a single reaction of one specific substrate to one specific product within a complex biological environment. The principle of biocatalysis, in which the activity of enzymes is harnessed, has long been exploited by mankind. One of the earliest and most prominent examples is fermentation, where yeast is used to convert sugar into alcohol (ethanol). Such biocatalytic processes are gaining increasing popularity in various fields, for example, in the production of agrochemicals and pharmaceuticals. This is partly due to their more environmentally benign conditions compared to other chemical methodologies, as biocatalytic reactions typically proceed in water rather than in often toxic organic solvents. The aim of this study is to develop platinum-derived artificial metalloenzymes, which will be assembled from a protein core and a non-natural platinum complex. Combining the unique reactivity of platinum with the highly tunable environment of a protein is envisioned to afford novel enzymes with new-to-nature reactivity. Leveraging advances in protein engineering, we aim to create highly selective enzymes that catalyze polycyclization reactions, ultimately enabling access to valuable bioactive molecules such as steroids.