Integrating Enzymes with Chemocatalysts to Create New Reactions Pathways
Final Report Abstract
New processes providing direct synthetic pathways to important chemicals and materials under environmentally benign reaction conditions are of increasing importance. Amide bond synthesis is robust and well established, but current methods are inefficient and unsustainable. In this DFG funded research, we developed a next generation multi catalytic system for construction of ubiquitous amide bonds, by merging enzymatic and chemical catalysis in the same reaction vessel. Nitrile hydratase (NHase) enzymes were combined with inexpensive Cu-catalysed N-arylation reaction in one-pot under aqueous reaction conditions. This integrated chemo- and biocatalytic approach enables new amide bond disconnections using readily available feedstock chemicals. NHase containing E. coli cells were used, with the cell membrane serving to compartmentalise the two catalytic systems, avoiding mutual inactivation of catalysts and exhaustive manipulations between the subsequent reaction steps. The practical, efficient, and scalable reaction design allowed the synthesis of a broad substrate scope, including natural products, drug molecules, and challenging chiral amides, under mild and environmentally friendly reaction conditions. The combined chemo- and biocatalyst enable amide bond formation in a synergistic manner, which would be otherwise challenging using a single catalytic regime alone.
Publications
- “Merging Enzymes with Chemocatalysis for Amide Bond Synthesis”, Nat. Commun. 2022, 13, 380
L. Bering, E. J. Craven, S. A. Sowerby Thomas, S. A. Shepherd & J. Micklefield
(See online at https://doi.org/10.1038/s41467-022-28005-4) - “New Reaction Pathways by Integrating Chemo- and Biocatalysis”, Trends Chem. 2022
L. Bering, J. Thompson & J. Micklefield
(See online at https://doi.org/10.1016/j.trechm.2022.02.008)
