Heme proteins direct evolution

A rich source of potential industrial biocatalysts, the heme enzymes are also a superb testing ground for laboratory evolution. Directed evolution approaches are already generating customized heme enzymes and probing the limits of heme enzyme catalysis. Over the next few years, these same approaches will allow us to explore the interconversion of function among different protein scaffolds and thereby observe how the protein modulates heme chemistry and how new functions are acquired. 

The essential problem in utihzing the peroxide shimt for P450 biocatalysis seems to lie in the time-dependent degradation of the heme and in oxidation of the protein [218, 219]. Therefore, methods of directed evolution, such as random and site-specific mutagenesis have been applied to evolve P450s to enhance the efficiency of the peroxide shimt pathway [216]. 

The last systematic description of heme peroxidases was published in 1999 by Brian Dunford, from the University of Alberta in Canada. The book Heme peroxidases covers discussion on three-dimensional structure, reaction mechanism, kinetics, and spectral properties of representative enzymes from bacterial, plant, fungal, and animal origin. Since 1999, vast information on basic but also applied aspects of heme peroxidases has been generated. We believe fusion of these two aspects will benefit research of those dedicated to development of biocatalytic process. The aim of this book is to present recent advances on basic aspects such as evolution, structure-function relation, and catalytic mechanism, as well as applied aspects, such as bioreactor and protein engineering, in order to provide the tools for rational design of enhanced biocatalysts and biocatalytic processes. The book does not include an exhaustive listing of references but rather a selected collection to enrich discussion and to allow envisioning future directions for research. 

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