Generation of New Enzymes via Covalent Modification of Existing ProteinsReview
Proteins are versatile molecules for catalyst design. Given the explosive development of molecular biology techniques for gene manipulation and functional selection, genetic approaches for enzyme design are currently in wide use. However, chemical methods provide a means for introducing a diverse range of functionality that does not occur in natural enzymes and cannot be easily incorporated by genetic methods. Thus, chemical modification of proteins remains a valuable tool for protein engineering. This article reviews a variety of approaches in which chemical modification has been used to alter the catalytic properties of existing enzymes to give new catalytic activities to existing enzymes or to impart catalytic activities to proteins normally devoid of enzymatic activity. Since the focus of this review is on the chemistry promoted by these systems, modifications that alter the overall stability or general physical properties of enzymes are not discussed here.