Asymmetric catalytic cascade processes offer direct access to complex chiral molecules from simple substrates and in a single step. In biocatalysis, cascades are generally designed by combining multiple enzymes, each catalyzing individual steps of a sequence. Herein, we report a different strategy for biocascades based on a single multifunctional enzyme that can promote multiple stereoselective steps of a domino process by mastering distinct catalytic mechanisms of substrate activation in a sequential way. Specifically, we have used an engineered 4-oxalocrotonate tautomerase (4-OT) enzyme with the ability to form both enamines and iminium ions and combine their mechanisms of catalysis in a complex sequence. This approach allowed us to activate aldehydes and enals toward the synthesis of enantiopure cyclohexene carbaldehydes. The multifunctional 4-OT enzymes could promote both a two-component reaction and a triple cascade characterized by different mechanisms and activation sequences.

Tseliou V., Faraone A., Kqiku L., Vilim J., Simionato G., Melchiorre P. (2022). Enantioselective Biocascade Catalysis with a Single Multifunctional Enzyme. ANGEWANDTE CHEMIE. INTERNATIONAL EDITION, 61(43), 1-9 [10.1002/anie.202212176].

Enantioselective Biocascade Catalysis with a Single Multifunctional Enzyme

Melchiorre P.
Ultimo
Supervision
2022

Abstract

Asymmetric catalytic cascade processes offer direct access to complex chiral molecules from simple substrates and in a single step. In biocatalysis, cascades are generally designed by combining multiple enzymes, each catalyzing individual steps of a sequence. Herein, we report a different strategy for biocascades based on a single multifunctional enzyme that can promote multiple stereoselective steps of a domino process by mastering distinct catalytic mechanisms of substrate activation in a sequential way. Specifically, we have used an engineered 4-oxalocrotonate tautomerase (4-OT) enzyme with the ability to form both enamines and iminium ions and combine their mechanisms of catalysis in a complex sequence. This approach allowed us to activate aldehydes and enals toward the synthesis of enantiopure cyclohexene carbaldehydes. The multifunctional 4-OT enzymes could promote both a two-component reaction and a triple cascade characterized by different mechanisms and activation sequences.
2022
Tseliou V., Faraone A., Kqiku L., Vilim J., Simionato G., Melchiorre P. (2022). Enantioselective Biocascade Catalysis with a Single Multifunctional Enzyme. ANGEWANDTE CHEMIE. INTERNATIONAL EDITION, 61(43), 1-9 [10.1002/anie.202212176].
Tseliou V.; Faraone A.; Kqiku L.; Vilim J.; Simionato G.; Melchiorre P.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/897857
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