Self-Sufficient Class VII Cytochromes P450: From Full-Length Structure to Synthetic Biology Applications

Abstract

Members of class VII cytochromes P450 are catalytically self-sufficient enzymes containing a phthalate dioxygenase reductase-like domain fused to the P450 catalytic domain. Among these, CYP116B46 is the first enzyme for which the 3D structure of the whole polypeptide chain has been solved, shedding light on the interaction between its domains, which is crucial for catalysis. Most of these enzymes have been isolated from extremophiles or detoxifying bacteria that can carry out regio- and enantioselective oxidation of compounds of biotechnological interest. Protein engineering has generated mutants that can perform challenging organic reactions such as the anti-Markovnikov alkene oxidation. This potential, combined with the detailed 3D structure, forms the basis for further directed evolution studies aimed at widening their biotechnological exploitation.

Keywords: CYP116; biocatalysis; cytochromes P450; fine chemicals; self-sufficient enzyme; synthetic biology.