Chemical Optimization of Whole-Cell Transfer Hydrogenation Using Carbonic Anhydrase as Host Protein

Abstract

Artificial metalloenzymes combine a synthetic metallocofactor with a protein scaffold and can catalyze abiotic reactions in vivo. Herein, we report on our efforts to valorize human carbonic anhydrase II as a scaffold for whole-cell transfer hydrogenation. Two platforms were tested: periplasmic compartmentalization and surface display in Escherichia coli. A chemical optimization of an IrCp∗ cofactor was performed. This led to 90 turnovers in the cell, affording a 69-fold increase in periplasmic product formation over the previously reported, sulfonamide-bearing IrCp∗ cofactor. These findings highlight the versatility of carbonic anhydrase as a promising scaffold for whole-cell catalysis with artificial metalloenzymes.