A new strategy for the semi-synthesis of proteins and a membrane-bound protein. Attachment of a photosensitizer has enabled us to switch the enzyme activity by means of enzymes bearing non-natural functional groups is described. In line with our proposal that the replacement of native visible light. Artificial receptors introduced in the proximity of the active site can modulate the structures and activities of cofactors by modified cofactors may represent a useful and general methodology for introducing non-natural molecules native proteins in response to specific guest molecules. This concept has been expanded to include flavoenzymes such as into cofactor-dependent proteins and enzymes, we have shown that semi-synthetic cofactors bearing non-natural glucose oxidase. An immense variety of non-natural molecules are available that are potentially useful for protein functional units can be incorporated in the proximity of the active sites of enzymes by cofactor reconstitution. A variety engineering. By combination of the present cofactor reconstitution method with other techniques such as site-of non-natural building units such as a hydrophobic alkyl chain, a polyanion cluster, metal complexes, electron donors directed mutagenesis, chemical modification, peptide semisynthesis, and non-natural amino acid incorporation using or acceptors, a photochromic moiety, peptides, and artificial receptors have successfully been introduced into suppressor t-RNA, it should be possible to artificially manipulate native protein molecules with a similar degree hemoproteins (myoglobin, hemoglobin, and cytochrome b562) and their effects on the holoproteins have been of flexibility as that with which organic chemists manipulate small molecules. examined. Incorporation of a long alkyl chain, for example, greatly facilitates conversion of a water-soluble protein into zymes, however, it is apparent that besides these 20 amino