Discovery of noncanonical cytochrome P450 enzymes in nature.

Noncanonical cytochrome P450 enzymes lacking the conserved cysteine are widespread, with 20 distinct families identified in diverse microbial genomes.

• Why it matters: Understanding these alternative CYPs broadens knowledge of enzyme diversity and could lead to new biocatalytic applications, addressing gaps in enzyme function and evolution.
• What they did: Researchers used bioinformatics to identify ncCYP families, then characterized a serine-ligated CYP with a typical fold and a selenocysteine-ligated CYP, revealing their structures and activities.
• The result: These discoveries expand the CYP enzyme family, opening new avenues for enzymatic and biocatalytic innovations by revealing functional diversity beyond the canonical cysteine ligand.