Heme directed evolution

Exploring the Diversity of Heme Enzymes through Directed Evolution... 

P450s are generally less stable than peroxidases. Recently a naturally thermostable P450 (stable up to 85 °C) was identified and characterized [25, 100 -103], Both P450s and peroxidases are inactivated during catalysis, via heme alkylation by terminal olefins (see Section 10.8.3) and oxidative damage by peroxides. Eukaryotic P450s are associated with cell membranes and are therefore insoluble and difficult to use outside the cell. We believe that many of these limitations can be addressed by directed 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. 

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