A combination of ''rational'' and ''irrational'' strategies for the cr
eation of enzymes with novel properties is proving to be a powerful co
ncept in the field of enzyme engineering. Guided by principles of phys
ical organic chemistry, rational design strategies are used to identif
y suitable target enzymes and to choose appropriate molecular biologic
al methods for engineering purposes. In contrast, irrational (or rando
m) strategies are centered around the biological paradigm of stochasti
c molecular evolution. As illustrated in this review, such a hybrid ap
proach is particularly useful for the design of new modular enzymes. (
C) 1996 John Wiley & Sons, Inc.