Harnessing heme chemistry: Recent advances in the biocatalytic applications of cytochrome P450 monooxgenases

Cytochrome P450 monooxygenases (CYPs/P450s) are heme-thiolate proteins with broad chemical functionality that have widespread application as powerful biocatalysts given their high stereo- and regio-selectivity. A large variety of value-added compounds, including pharmaceuticals and natural products, can be synthesized by P450s, often with superior selectivity and at milder conditions than their chemical counterparts making them ideal alternative catalysts. This review addresses the most recent advances in P450-mediated syntheses and include enzyme engineering strategies that have expanded the stereo- and regio-selectivity of P450 steroid and fatty acid hydroxylation as well as facilitated C-N bond formation and cyclization, all of which have synthetic applications to produce value-added compounds. Approaches to overcome the limitations of P450 catalysis will also be discussed, including the use of decoy molecules to expand the substrate scope and enable the use of hydrogen peroxide, self-sufficient systems, cascade reactions and cofactor alternatives to improve efficiency and biotechnological viability.