A general introduction discusses the respective advantages and disadvantages of biocatalysts (enzymes) and synthesis catalysts. While the former are endowed with remarkable catalytic efficiencies and selectivities, essentially provided by the protein environment, the latter are less constrained in terms of working conditions (temperature, pressure, solvents, etc.) and usable metal ions, as synthesis enables the exploration of virtually infinite chemical spaces. The concept of the "artificial metallo-enzyme" arose from this idea of combining the two worlds, by associating a synthesis catalyst with a protein shell to achieve novel properties. This first lecture presents a number of outstanding examples of this approach. Bio-hybrid catalysts or artificial metallo-enzymes can be built :
- from a metallo-enzyme in which the natural metal is replaced by another metal (example: replacement of Zn by Rh in carbonic anhydrase leading to an enzyme catalyzing hydrogenation reactions);
- from a metalloprotein in which the cofactor is replaced by an analog, whether covalently or non-covalently bound (e.g.: replacement of the heme in myoglobin by Mn(salen) complexes, leading to monooxygenation catalytic properties);
- from a protein possessing a specific site for a ligand; a ligand-complex conjugate binds to this protein efficiently and selectively, leading to an artificial metalloprotein (example: streptavidin associated with a biotin-catalyst conjugate);
- from a protein modified to covalently bind a synthetic catalyst;
- from a protein in which a metal ion binding site is created by site-directed mutagenesis (e.g.: addition of a non-heme iron site to myoglobin, leading to a binuclear active site resembling that of NO reductase or cytochrome oxidase).
Other biological polymers can also be used. One example is DNA, to which copper complexes can be attached, leading to artificial metallo-enzymes capable of catalyzing Diels-Alder reactions in water.
