A Promiscuous De Novo Retro‐Aldolase Catalyzes Asymmetric Michael Additions via Schiff Base Intermediates |
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| Authors: | Dr Xavier Garrabou Dr Tobias Beck Prof?Dr Donald Hilvert |
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| Affiliation: | 1. Laboratory of Organic Chemistry, ETH Zürich, 8093 Zürich (Switzerland);2. Instituto de Química Avanzada de Catalu?a–CSIC, Jordi Girona 18‐26, 08034 Barcelona (Spain) |
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| Abstract: | 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. |
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| Keywords: | asymmetric catalysis biocatalysis directed evolution enzyme design enzyme promiscuity |
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