biostudies-literatureUnknown12(28)Zheng HNitriles are broadly applied to synthesize pharmaceuticals, agrochemicals, and materials because of their versatile transformation. Although various methods have been developed for introducing a nitrile group into organic molecules, most of them entail the use of highly toxic chemicals, transition metals, or harsh conditions. In this work, we reported a greener chemo-enzymatic cascade to synthesize alky and aryl nitriles from readily accessible aldehydes, that were further transformed into corresponding amides <i>via</i> an artificial enzyme cascade. A biphasic reaction system was designed to bridge chemical synthesis and enzymatic catalysis through simple phase separation. The biphasic system mainly perfectly avoided the inactivation of hydroxylamine on aldoxime dehydratase from <i>Pseudomonas putida</i> (OxdF1) and nitrile hydratase from <i>Aurantimonas manganoxydans</i> ATCC BAA-1229 (NHase1229). For the synthesis of various nitriles, moderate isolation yields of approximately 60% were obtained by the chemo-enzymatic cascade. Interestingly, two seemingly conflicting reactions of dehydration and hydration were sequentially proceeded to synthesize amides by the synergistic catalysis of OxdF1 and NHase1229 in <i>E. coli</i> cells. An isolation yield of approximately 62% was achieved for benzamide at the one-liter scale. In addition, the shuttle transport of substrates and products between two phases is convenient for the product separation and <i>n</i>-hexane recycling. Thus, the chemo-enzymatic cascade shows a potential application in the cyanide-free and large-scale synthesis of nitriles and amides.RSC advances17873-17881https://www.ebi.ac.uk/biostudies/studies/S-EPMC9201870biostudies-literaturePrograming a cyanide-free transformation of aldehydes to nitriles and one-pot synthesis of amides through tandem chemo-enzymatic cascades.PMC9201870Zheng HWang AWang QPei XMao FLi MXiao QZhang PfalsePrograming a cyanide-free transformation of aldehydes to nitriles and one-pot synthesis of amides through tandem chemo-enzymatic cascades.Nitriles are broadly applied to synthesize pharmaceuticals, agrochemicals, and materials because of their versatile transformation. Although various methods have been developed for introducing a nitrile group into organic molecules, most of them entail the use of highly toxic chemicals, transition metals, or harsh conditions. In this work, we reported a greener chemo-enzymatic cascade to synthesize alky and aryl nitriles from readily accessible aldehydes, that were further transformed into corresponding amides <i>via</i> an artificial enzyme cascade. A biphasic reaction system was designed to bridge chemical synthesis and enzymatic catalysis through simple phase separation. The biphasic system mainly perfectly avoided the inactivation of hydroxylamine on aldoxime dehydratase from <i>Pseudomonas putida</i> (OxdF1) and nitrile hydratase from <i>Aurantimonas manganoxydans</i> ATCC BAA-1229 (NHase1229). For the synthesis of various nitriles, moderate isolation yields of approximately 60% were obtained by the chemo-enzymatic cascade. Interestingly, two seemingly conflicting reactions of dehydration and hydration were sequentially proceeded to synthesize amides by the synergistic catalysis of OxdF1 and NHase1229 in <i>E. coli</i> cells. An isolation yield of approximately 62% was achieved for benzamide at the one-liter scale. In addition, the shuttle transport of substrates and products between two phases is convenient for the product separation and <i>n</i>-hexane recycling. Thus, the chemo-enzymatic cascade shows a potential application in the cyanide-free and large-scale synthesis of nitriles and amides.2022-01-01T00:00:00Z2022 Jun2025-04-21T14:19:05.867Z2025-04-21T14:19:05.867ZS-EPMC92018703576533010.1039/d2ra03256b