Artificial enzyme gets picky

Researchers in Switzerland have combined chemical and genetic optimisation methods to create an artificial metallo-enzyme with high substrate selectivity. 

Thomas Ward and colleagues at the University of Neuch?tel have developed their own brand of catalyst, made up of a host protein such as avidin or streptavidin, and an organometallic catalyst bound to that protein via the biotin-avidin linkage, a high-affinity connection that is widely used in molecular biology. The work builds on previous efforts to provide these artificial metallo-enzymes with high enantioselectivity¹and the researchers plan to make the system as picky as possible in its acceptance of substrate molecules. 

The team studied the reduction of a carbon-carbon double bond in amino acid derivatives. Changes were made to the protein and to the biotin-metal complex to generate a wide range of ’mutant’ catalysts. Researchers conducted the catalysis experiment with 360 possible combinations of 20 streptavidin variants (all 20 amino acids in position 112, which is thought to be closest to the metal centre) with 18 different biotinylated metal complexes, using two competing substrates each time. The resulting two-dimensional array of results allows the researchers to identify the best catalysts, and to analyse trends in the behaviour of protein-ligand combinations, which might be more widely   applicable²    .

Ward is now adding oxidation reactions to the repertoire of his chemzymes. ’We are currently looking at the catalytic oxidation of methane into methanol,’ he told Chemistry World. ’In the spirit of methane mono-oxygenase, we speculate that weak interactions between the protein and methanol will prevent its over-oxidation. In these days of high oil prices, methanol may well be an attractive fuel alternative.’ Michael Gross