Researchers have systematically investigated and reprogrammed natural copper enzymes to catalyze unnatural free-radical (pseudo)halogenation reactions with high enantioselectivity. While naturally occurring copper enzymes have remained underexploited for new-to-nature biocatalytic transformations despite their native metalloenzymology, evaluation of copper enzymes in the decarboxylative azidation of redox-active esters revealed catalytic activity across multiple copper enzyme families.
Among the investigated enzyme families, type III binuclear copper enzymes—specifically Bacillus megaterium tyrosinase (BmTyr)—displayed superior activity and enantioselectivity toward both stabilized and unstabilized alkyl radicals following targeted engineering. The strong halide binding affinity inherent to the binuclear copper system also enabled enantioconvergent bromination, chlorination, and isothiocyanation reactions that previously remained inaccessible to repurposed non-haem iron enzymes.
Electron paramagnetic resonance and ultraviolet–visible spectroscopic analyses confirmed the coupled binuclear nature of wild-type and engineered bacterial tyrosinases, providing insight into the origin of their enhanced activity and copper speciation during (pseudo)halide binding. These results establish binuclear copper enzymes as a platform for new-to-nature stereoselective radical reactions, expanding the scope of metalloenzyme biocatalysis beyond mononuclear systems.
Subject of Research: Biocatalytic enantioselective radical halogenation using engineered binuclear copper enzymes
Article Title: A binuclear copper enzyme platform for enantioconvergent radical (pseudo)halogenation
Article References: Chen, X.-W., Adeyemo, O. M., Chen, H., Chen, H., Nguyen, N., Palazzo, J., Zhao, L.-P., Lin, K., Mai, B. K., Liu, P., Tian, S., & Yang, Y. (2026). A binuclear copper enzyme platform for enantioconvergent radical (pseudo)halogenation. Nature Chemistry. https://doi.org/10.1038/s41557-026-02292-6
Image Credits: AI Generated
DOI: 10.1038/s41557-026-02292-6
Keywords: biocatalysis, copper enzymes, enantioselective catalysis, radical halogenation, tyrosinase, Bacillus megaterium, metalloenzymes, protein engineering, binuclear, copper, enzyme, platform
News Source: Bethany Barker. (November 6, 2026). Repurposed Binuclear Copper Enzymes Enable Enantioselective Radical Halogenation Reactions. Scienmag.
