Subtilisin Enzymes: Practical Protein Engineering

Subtilisin is the most extensively studied model system for protein engineering. The primary motivating factor for the interest in subtilisin is the commercial utility of this class of proteases. The subtilisin symposium was the first international meeting to bring together a large number of groups that have focused on the subtilisins and the subtilases-the protein superfamily of subtilisin-like enzymes. The results presented at the symposium are in this way a unique compendium of a broad spectrum of work largely focused on harnessing the potential of site-directed mutagenesis to understand and deliberately alter the function of these enzymes toward a desired end. This sort of protein engineering has been extremely successful in subtilisin, with many such "engineered" enzymes now widely used in commer­ cial enterprises. In this regard the experience derived from subtilisin does represent practical protein engineering. It is becoming clear that subtilisin represents a larger class of enzymes, the subtilases, that include many of the human pro hormone-converting enzymes. As international collabo­ rative efforts to sequence entire genomes continue, we can reasonably expect that additional members of the subtilase class will be encountered. Whenever interest in a member of this class of enzyme arises, the work on subtilisin will serve as a guide to the analysis for what in bacillus, fungi, and industry is an everyday workhorse enzyme.