biostudies-literatureBering LGerman Research FoundationGlaxoSmithKlineRCUK | Biotechnology and Biological Sciences Research CouncilRCUK | Engineering and Physical Sciences Research CouncilBiotechnology and Biological Sciences Research CouncilEngineering and Physical Sciences Research Council380https://www.ebi.ac.uk/biostudies/studies/S-EPMC8770729biostudies-literatureUnknown13(1)Amides are one of the most fundamental chemical bonds in nature. In addition to proteins and other metabolites, many valuable synthetic products comprise amide bonds. Despite this, there is a need for more sustainable amide synthesis. Herein, we report an integrated next generation multi-catalytic system, merging nitrile hydratase enzymes with a Cu-catalysed N-arylation reaction in a single reaction vessel, for the construction of ubiquitous amide bonds. This synergistic one-pot combination of chemo- and biocatalysis provides an amide bond disconnection to precursors, that are orthogonal to those in classical amide synthesis, obviating the need for protecting groups and delivering amides in a manner unachievable using existing catalytic regimes. Our integrated approach also affords broad sNature communicationsMerging enzymes with chemocatalysis for amide bond synthesis.PMC8770729EP/V048929/1BB/R01034X/1EP/S023755/1Craven EJBering LSowerby Thomas SAShepherd SAMicklefield JfalseMerging enzymes with chemocatalysis for amide bond synthesis.Amides are one of the most fundamental chemical bonds in nature. In addition to proteins and other metabolites, many valuable synthetic products comprise amide bonds. Despite this, there is a need for more sustainable amide synthesis. Herein, we report an integrated next generation multi-catalytic system, merging nitrile hydratase enzymes with a Cu-catalysed N-arylation reaction in a single reaction vessel, for the construction of ubiquitous amide bonds. This synergistic one-pot combination of chemo- and biocatalysis provides an amide bond disconnection to precursors, that are orthogonal to those in classical amide synthesis, obviating the need for protecting groups and delivering amides in a manner unachievable using existing catalytic regimes. Our integrated approach also affords broad s2022-01-01T00:00:00Z2022 Jan2026-05-09T03:00:58.79Z2025-04-06T14:57:24.857ZS-EPMC87707293504642610.1038/s41467-022-28005-4