Discovery of noncanonical cytochrome P450 enzymes in nature.

Twenty noncanonical cytochrome P450 families lacking a conserved cysteine ligand are identified in diverse microbial genomes, including the first native selenocysteine-ligated CYP.

• Why it matters: This challenges the long-standing paradigm that a proximal cysteine is essential for CYP function, opening new avenues for understanding enzyme diversity and potential biocatalytic applications.
• What they did: The study used bioinformatics to find 20 ncCYP families with alternative residues, and characterized a serine-ligated CYP with a typical fold that catalyzes azide reduction and nitrene insertion, including its crystal structure.
• The result: Findings expand the CYP enzyme family, revealing new types of metalloproteins that may enable future enzymatic and biocatalytic innovations.