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 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 O2 directly in reaction media, thereby enabling the concentration of aqueous O2 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. Go with the flow: Decomposition of H2O2 produces a soluble source of O2 for enzymatic oxidation reactions directly in the reaction media, thereby increasing the concentration of aqueous O2 beyond equilibrium solubility. A novel multipoint‐injection flow reactor was developed to maximize productivity. This method requires no pressurized gas or specialist equipment and improves the reaction rate by up to 100‐fold compared to conventional batch gas/liquid systems.