Enantioselective Biocascade Catalysis with a Single Multifunctional Enzyme.

Tseliou, Vasilis; Faraone, Adriana; Kqiku, Laura; Vilím, Jan; Simionato, Gianluca; Melchiorre, Paolo

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.

ENANTIOSELECTIVE catalysis; ENZYMES; ENAMINES; BIOCATALYSIS; ALDEHYDES; CYCLOHEXENE

Angewandte Chemie, 2022, Vol 134, Issue 43, p1

0044-8249

Academic Journal

10.1002/ange.202212176