Engineering Artificial Metalloenzymes

Artificial metalloenzymes are an emerging class of functional biomacromolecules that both provide useful information for native metalloenzymes and have the potential to catalyze important transformations in industrial biocatalysis. Metalloenzymes can be engineered by two complementary methods: rational design and directed evolution. Rational design uses predetermined knowledge of biochemical systems to design a novel protein, often with the aid of computation, while directed evolution exploits the genetic nature of proteins to select for a desired attribute, such as reactivity or stability. Both methods have resulted in the development of metalloenzymes that catalyze abiological reactions, use abiological cofactors, and produce commercially significant compounds. This chapter seeks to provide a survey of the state-of-the-art in the field of metalloenzyme engineering.