Enzyme technology is undergoing the most profound and exciting transformation in its history, as was made clear at the Enzyme Engineering Conference held last month in Hawaii*. Fifteenth in the venerable biennial series, the conference was organized by Frances H. Arnold (California Insitute of Technology, Pasadena CA), Robert Kelly (North Carolina State University, Raleigh, NC), and David Anton (Dupont, Wilmington, DE). In view of the recent emergence of directed evolution and a host of other tools for biocatalyst discovery, it came as no surprise that development of enzymes with remarkable physical and catalytic properties was a major theme. However, as we contemplated the successes of the past few years—namely, the unprecedented expansion in the scope and applications of new enzymes—two questions emerged that are likely to guide research in the coming years: How far can we push enzyme discovery, and what technologies must we develop to do so?
As was clear from the many examples of enzymes that had been improved by some form of DNA evolution, a remarkable array of new functions are encoded in libraries created by in vitro recombination of small pools of homologous genes, or DNA shuffling. The technique has proved extremely valuable for generating enzymes with new properties, and since the process is stochastic, virtually no information of how enzyme structure relates to function is needed. The next frontier may be "molecular breeding" for the engineering of new pathways and even entire viral and bacterial genomes (Willem P.C. Stemmer, Maxygen, Santa Clara, CA). Already Maxygen (Redwood City, CA) has engineered viruses exhibiting entirely new tropisms, a development with important implications for gene therapy.
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