Enzymatic oxidation strategies in natural product biosynthesis and potential applications for organic synthesis

Abstract

Oxidizing enzymes are indispensable in organic synthesis, enabling transformations with unparalleled selectivity under mild conditions. This review highlights recent advances in the discovery, engineering, and synthetic application of four key oxidoreductase classes: oxygenases, dehydrogenases, oxidases, and peroxidases. We discuss strategies to overcome native enzyme limitations—including protein engineering, ancestral sequence reconstruction, and chemical mechanism-guided repurposing—and showcase their integration into multi-enzyme cascades and chemo-enzymatic platforms. By leveraging computational design and hybrid photochemical/electrochemical systems, enzymatic oxidation is poised to address long-standing challenges in C–H functionalization and offer versatile, scalable routes to high-value chemicals.

Oxidizing enzymes are indispensable in organic synthesis, enabling transformations with unparalleled selectivity under mild conditions. This review highlights recent advances in the discovery, engineering, and synthetic application of four key oxidoreductase classes: oxygenases, dehydrogenases, oxidases, and peroxidases. We discuss strategies to overcome native enzyme limitations—including protein engineering, ancestral sequence reconstruction, and chemical mechanism-guided repurposing—and showcase their integration into multi-enzyme cascades and chemo-enzymatic platforms. By leveraging computational design and hybrid photochemical/electrochemical systems, enzymatic oxidation is poised to address long-standing challenges in C–H functionalization and offer versatile, scalable routes to high-value chemicals.