Copper radical oxidases: galactose oxidase, glyoxal oxidase, and beyond!

The copper radical oxidases (CROs) are an evolutionary and functionally diverse group of enzymes established by the historically significant galactose 6-oxidase and glyoxal oxidase from fungi. Inducted in 2013, CROs now constitute Auxiliary Activity Family 5 (AA5) in the Carbohydrate-Active Enzymes (CAZy) classification. CROs catalyse the two-electron oxidation of their substrates using oxygen as the final electron acceptor and are particularly distinguished by a cross-linked tyrosine-cysteine co-factor that is integral to radical stabilization. Recently, there has been a significant increase in the biochemically and structurally characterized CROs, which has revealed an expanded natural diversity of catalytic activities in the family. This review provides a brief historical introduction to CRO biochemistry and structural biology as a foundation for an update on current advances in CRO enzymology, biotechnology, and biology across kingdoms of life.