Highly Productive Oxidative Biocatalysis in Continuous-Flow by Surpassing the Aqueous Equilibrium Solubility of Oxygen.

We report a simple, mild, and synthetically clean approach to accelerate the rate of enzymatic oxidation reactions by a factor of up to 100 when compared to conventional batch gas/liquid systems. Biocatalytic decomposition of H2O2 is used to produce a soluble source of O-2 directly in reaction media, thereby enabling the concentration of aqueous O-2 to be increased beyond equilibrium solubility under safe and practical conditions. To best exploit this method, a novel flow reactor was developed to maximize productivity (g product L(-1)h(-1)). This scalable benchtop method provides a distinct advantage over conventional bio-oxidation in that no pressurized gas or specialist equipment is employed. The method is general across different oxidase enzymes and compatible with a variety of functional groups. These results culminate in record space-time yields for bio-oxidation.