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A new method for the fabrication of molecular, water-soluble, and biologically active enzyme-metal hybrids was designed and its feasibility demonstrated. The method is based on the display of nucleation sites directing a subsequent electroless deposition of palladium and other metals to the enzyme's surface. The process is carried out under mild physiological conditions, enabling the preservation of enzymatic activity and water solubility. The feasibility of the new method was demonstrated by using the enzyme glucose oxidase and palladium combination as the first model system. The glucose oxidase-palladium hybrid thus obtained retained their solubility and enzymatic glucose oxidation capabilities. Hybrids immobilized on platinum electrodes exhibited ldquonanowiringrdquo and effective direct electron transfer from the enzyme catalytic site to the electrode. The new enzyme-metal hybrids thus obtained may be readily incorporated into miniaturic biosensors and biochips, used as novel antibacterial agents or as markers for improved in vivo imaging. Furthermore, the methodology developed may be readily extended to a series of metal coatings on the surface of biologically active proteins.