Directed evolution: the ‘rational’ basis for ‘irrational’ design

The development of powerful genetic manipulation formats has revolutionized the creation of functional biological molecules. Recent advances in directed evolution demonstrate that multiple properties of proteins can be optimized simultaneously and rapidly. Improved proteins often contain multiple and dispersed substitutions that act synergistically to improve enzyme properties and function. The benefits of such multiple changes are often not predictable from a priori structural knowledge. Furthermore, alternative solutions to gaining functional change can be obtained.