Highly Productive Oxidative Biocatalysis in Continuous Flow by Enhancing the Aqueous Equilibrium Solubility of Oxygen

We report a simple, mild and synthetically clean approach to accelerate the rate of enzymatic oxidation reactions by up to a factor of 100 when compared to conventional batch gas/liquid systems. Biocatalytic decomposition of H2O2 is used to produce a soluble source of O2 directly in reaction media, enabling the ambient solubility of aqueous O2 to be increased under safe and practical conditions. To best exploit the method, a novel flow reactor was developed to maximize productivity (g product/L/h). This scalable benchtop protocol 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.