Directed evolution has been successfully used to engineer proteins for basic and applied biological research. However, engineering of novel protein functions by directed evolution remains an overwhelming challenge. This challenge may come from the fact that multiple simultaneously or synergistic mutations are required for the creation of a novel protein function. Here we review the key developments in engineering of novel protein functions by using either directed evolution or a combined directed evolution and rational or computational design approach. Specific attention will be paid to a molecular evolution model for generation of novel proteins. The engineered novel proteins should not only broaden the range of applications of proteins but also provide new insights into protein structure-function relationship and protein evolution.
(c) 2007 Wiley Periodicals, Inc.