posted on 2018-10-29, 00:00authored byKai Chen, Shuo-Qing Zhang, Oliver F. Brandenberg, Xin Hong, Frances H. Arnold
We report a biocatalytic
platform of engineered cytochrome P450
enzymes to carry out carbene-transfer reactions using a lactone-based
carbene precursor. By simply altering the heme-ligating residue, we
obtained two enzymes that catalyze olefin cyclopropanation (Ser) or
S–H bond insertion (Cys). Both enzymes exhibit high catalytic
efficiency and stereoselectivity, thus enabling facile access
to structurally diverse spiro[2.4]lactones and α-thio-γ-lactones.
Computational studies revealed the mechanism of carbene S–H
insertion and explain how the axial ligand controls reactivity and
selectivity. This work expands the catalytic repertoire of hemeproteins
and offers insights into how these enzymes can be tuned for new chemistry.