Oxalate Oxidase for In Situ H2O2-generation in Unspecific Peroxygenase-Catalysed Drug Oxyfunctionalisations

H2O2-driven enzymes are of great interest for industrial biotransformations. Herein, we show for the first time that oxalate oxidase (OXO) is an efficient in situsource of H2O2 for one of these biocatalysts, which is known as unspecific peroxygenase (UPO). OXO is reasonably robust, produces only CO2 as a by-product and usesoxalate as a cheap sacrificial electron donor. UPO is a top-rated catalyst for selective C-H oxyfunctionalisations, as we confirm herein by testing a diverse drug panel using miniaturised high-throughput assays and mass spectrometry. 33 out of 64 drugs were converted in 5 μL-scale reactions by the UPO with OXO (conversion >70% for 11drugs). Furthermore, 84% isolated yield was achieved for the drug tolmetin on a larger scale (50 mg, TONUPO 25,664), which was excelled by implementing enzyme immobilization. This one-pot approach ensures adequate H2O2 levels, enabling rapid access to industrially relevant molecules which are difficult to obtain by other routes.