From kinase to cyclase: an unusual example of catalytic promiscuity modulated by metal switching.

Enzyme promiscuity is a concept that in the last years is earning prominence in different fields of enzymology like biocatalysis, enzyme engineering or enzyme evolution. Catalytic promiscuity is defined as the ability of an enzyme to catalyze more than one chemical transformation. Naturally occurring catalytic promiscuity provide the starting point for a Darwinian evolution of enzymes to new functions since this process must occur gradually, while maintaining organism fitness throughout. Tawfik and co-workers have provided experimental evidence for the plasticity and “evolvability” of promiscuous functions. These authors propose a model by which a protein acquires a new function, without losing the original one, and gene duplication may follow the emergence of a new function, rather than initiate it. Besides the intriguing implications that this theory of divergent molecular evolution has for protein evolution, its application to promiscuous enzymes allows to design enzymes with new catalytic activities.