Site-directed mutagenesis is still a very efficient strategy to elaborate i
mproved enzymes. Recently, advances have been made in developing rational s
trategies aimed at reshaping enzyme specificities and mechanisms, and at en
gineering biocatalysts through molecular assembling. These knowledge-based
studies greatly benefit from the most recent computational analyses of enzy
me structures and functions. The combination of rational and combinatorial
methods opens up new vistas in the design of stable and efficient enzymes.