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A Promiscuous De Novo Retro‐Aldolase Catalyzes Asymmetric Michael Additions via Schiff Base Intermediates
Author(s) -
Garrabou Xavier,
Beck Tobias,
Hilvert Donald
Publication year - 2015
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201500217
Subject(s) - aldolase a , chemistry , catalysis , enantioselective synthesis , schiff base , michael reaction , active site , combinatorial chemistry , amine gas treating , imine , bifunctional , enzyme , stereochemistry , organic chemistry
Recent advances in computational design have enabled the development of primitive enzymes for a range of mechanistically distinct reactions. Here we show that the rudimentary active sites of these catalysts can give rise to useful chemical promiscuity. Specifically, RA95.5‐8, designed and evolved as a retro‐aldolase, also promotes asymmetric Michael additions of carbanions to unsaturated ketones with high rates and selectivities. The reactions proceed by amine catalysis, as indicated by mutagenesis and X‐ray data. The inherent flexibility and tunability of this catalyst should make it a versatile platform for further optimization and/or mechanistic diversification by directed evolution.