Biaryl scaffolds are prevalent in a vast array of drug molecules and natural products. The unique structures and promising bioactivities of biaryl natural products make them highly valuable compounds, however this structural feature contributes to their difficulty as synthetic targets.

To overcome the challenges associated with constructing biaryl compounds through traditional synthesis, we propose a chemoenzymatic approach toward this class of molecules. This work describes the development of P450 enzymes into tunable biocatalysts for convergent oxidative coupling reactions with catalyst-controlled selectivity. In particular, the discovery and characterization of previously unknown P450s form a diverse library of sequences has led to the site-selective generation of biaryl bonds, relevant for the total synthesis of many classes of natural products with known therapeutic potentials. This approach allows for the rapid generation of molecular complexity in natural and novel biaryl compounds, with increased accessibility and structural diversity, thereby accelerating the therapeutic development of these bioactive molecules.