Engineered Cytochromes P 450 for Biocatalysis

Cytochrome P450 monooxygenases are a large class of enzymes, which have evolved to carry out a myriad of oxidation reactions across all kingdoms of life. Reflecting the functional diversity of naturally evolved P450s, these enzymes have proven to be remarkably pliable to protein engineering for improving or altering their substrate profile, catalytic properties, selectivity, and stability. In this chapter, major contributions made in this area are discussed with an emphasis on the different protein engineering strategies, including directed evolution, rational design, or semi-rational approaches, applied for the development of engineered P450 catalysts for biotechnological applications. This survey illustrates the diverse and growing range of applications of engineered P450s, which encompasses the synthesis of chiral building blocks, the preparation of drug metabolites, and the late-stage functionalization of natural products, highlighting their potential toward enabling the synthesis and discovery of bioactive molecules and toward developing sustainable processes for manufacturing of pharmaceuticals and other high-value compounds.