Bringing out the Potential of Wild-type Cytochrome P450s using Decoy Molecules: Oxygenation of Nonnative Substrates by Bacterial Cytochrome P450s

To bring out the potential of wild‐type cytochrome P450s, we have developed a series of “decoy molecules” to change their high substrate specificity without any mutagenesis. Decoy molecules are inert dummy substrates with structures that are very similar to those of natural substrates. The decoy molecules force long‐alkyl‐chain fatty acid hydroxylases (P450BSβ, P450SPα, and P450BM3) to generate the active species and to catalyze oxidation of various substrates other than fatty acids. Interestingly, the catalytic activity was highly dependent on the structure of decoy molecules. Furthermore, the enantioselectivity of reactions catalyzed by P450BSβ and P450SPα was also dependent on the structure of decoy molecules. The decoy molecule system allows us to control reactions catalyzed by wild‐type enzymes by designing decoy molecules.