Using appropriately designed coenzyme analogues, new active sites can be introduced into naturally occurring enzymes by the chemical modification of specific residues. Catalytic activities very different from those of the corresponding native enzymes can be observed in the resulting semisynthetic enzymes. Covalent modification of the SH group of the active site residue Cys-25 of papain with flavins like 8-bromoacetyl-10-methylisoalloxazine converts the enzyme into a highly effective oxidoreductase. Thus, the catalytic versatility of existing enzymes can be enhanced through 'chemical mutation' of the active site.