Cover Feature: Intramolecular Coupling and Nucleobase Transfer – How Cytochrome P450 Enzymes GymBx Establish Their Chemoselectivity (ChemCatChem 10/2024)

The Cover Feature shows an overview of the work presented in the Research Article by Shu-Ming Li, Georg Zocher, and co-workers. The authors report the structures of a new class of cyclodipeptide-modifying P450 enzymes named GymBx that are capable to transfer a nucleobase (hypoxanthine or guanine) onto cyclodipeptides (CDPs), an important class of secondary metabolites with a plethora of pharmacological impact. Structure comparison and protein engineering together with enzymatic kinetic analysis of the enzyme variants enabled the authors to redirect the specificity of the chemical reaction. A single point mutation (I227R) was sufficient to catalyse an intramolecular coupling reaction instead of the naturally occurring nucleobase transfer. More information can be found in the Research Article by J. Freytag et al. (DOI: 10.1002/cctc.202400105).