ABSTRACT
The fascinating biocatalytic properties of enzymes are briefly
introduced, taking triosephosphate isomerase (TIM) as an example.
Recent developments in computational design and directed evolu-
tion approaches for generating nonnatural enzymes are reviewed.
Many examples of successful protein engineering toward optimized
enzyme activities are discussed. Such studies done with TIM-barrel
enzymes are discussed in greater detail, including the development
of a highly proficient nonnatural Kemp eliminase. The common
active site features of Kemp eliminase and TIM, such as the catalytic
base and the oxyanion hole, are discussed. The advances in this field
suggest that other nonnatural enzymes with tailor-made catalytic
properties will become available in the near future. These enzymes
with optimal stability and substrate specificity will be of great value
in many applications.
