Design of artificial metalloenzymes by functional mutation of proteins : access to new enantioselective catalysts

At the industrial level, important synthons are obtained via biocatalytic processes involving whole microorganisms or isolated enzymes. In particular, these processes offer an efficient access to chiral molecules under mild, environmentally-friendly conditions. However, the repertoire of reactions catalyzed by biocatalyts remains limited to simple chemical transformations. In parallel, catalysis with transition metal complexes also allows access to chiral molecules in an enantioselective manner thanks to chiral ligands. However, even if the repertoire of reactions catalyzed by transition metal complexes is wide, reactional conditions usually involve the use of organic solvents detrimental to the environment. The proposed research project will consist in the design, characterisation and evaluation of environmentally friendly catalytic systems obtained by functional mutation of proteins resulting from the controlled introduction of metal species as artificial cofactors displaying known catalytic properties within well-chosen protein frameworks. Our strategy is thus to combine the advantages of biocatalysts and metal catalysts and possibly expect synergetic effects. With these hybrid architectures coined as artificial metalloenzymes, the synthesis of sophisticated chiral ligands is avoided as the protein framework is used as the source of chirality providing a well-defined second sphere of coordination around the catalytic metal center. The macromolecular nature of these catalysts should also facilitate their recycling. Eventually, artificial metalloenzymes should introduce a new methodology to access chiral molecules in mild conditions. This project will focus on the design and synthesis of artificial metal cofactors, their introduction in protein frameworks, the characterisation of the resulting hybrid species and eventually the study of their catalytic properties. While this project is positioned at the fundamental level of research, it takes into account in its aims the current needs of the pharmaceutical industry in terms of sustainable processes development.