Design of artificial metalloenzymes for C-C cross-coupling reactions

Artificial metalloenzymes enable several non-natural chemical transformations by hosting a metal catalyst and providing activating microenvironments to the metal. New strategies to combine the complementary features of enzyme and transition metal catalysis are crucial for exploiting the pre-evolved selectivities of enzymes in chemical synthesis. In order to exploit the inherent selectivity of a serine protease Subtilisin (SBL) for C-C crosscoupling reactions, the interplay of natural substrate binding pockets and the nucleophilic machinery of the enzyme with the metal catalyst was central to our approach. A catalytically potent metal catalyst (palladium) was appropriately positioned to carry out oxidative Heck reaction between an alkene and arylboronic acid substrates in the active site of SBL. Further characterization of SBL-based artificial metalloenzymes and step-wise elucidation of the biotransformation pathway was accomplished through X-ray crystallography and mass-spectrometry studies. Such interlacing of the metal and the enzyme steps for cross-coupling reactions presents an attractive route for performing important organic reactions enzymatically.