Directed Evolution toward an Iron-Heme Enzyme for Asymmetric C–H Amination

Prier CK. Zhang RK. Buller AR. Brinkmann-Chen S. Arnold FH. * California Institute of Technology, Pasadena, USA
Enantioselective, Intermolecular Benzylic C–H Amination Catalysed by an Engineered Iron-Haem Enzyme
Nat. Chem. 2017, 9, 629–634.

Significance: The authors discovered that P-4, a P450BM3 variant with 17 mutations from the wildtype, catalyzes the benzylic C–H amination of 4-ethylanisole, albeit with low enantioselectivity. Through sequential rounds of site-selective mutagenesis, P-411CHA was found to dramatically improve the yield and enantioselectivity of the reaction for a wide range of electronically-differentiated substrates. X-ray crystallography showed that all of the beneficial mutations lie within the active site of the enzyme.

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