Stereodivergent atom-transfer radical cyclization by engineered cytochromes P450

Radical cyclization made easy Metalloenzymes contain metal cofactors that can sometimes be exploited to catalyze reactions distinct from their natural function. Drawing on inspiration from heme-based radical polymerizations, Zhou et al . screened a panel of metalloproteins for candidates that could catalyze an atom-transfer radical cyclization, producing a lactam from an amide substrate bearing bromoalkyl and alkene functional groups (see the Perspective by Zhang and Dydio). Cytochrome P-450 derivatives were effective catalysts, and a series of enzyme variants were generated by directed evolution to access the full range of enantiomer and diastereomer products for model substrates. Such biocatalysts are valuable additions to the synthetic chemistry toolkit and reiterate the potential of metalloenzymes in catalyzing useful unnatural reactions. —MAF