Pathway from N‐Alkylglycine to Alkylisonitrile Catalyzed by Iron(II) and 2‐Oxoglutarate‐Dependent Oxygenases. (10th March 2020)

• Record Type: Journal Article
• Authors: Chen, Tzu‐Yu; Chen, Jinfeng; Tang, Yijie; Zhou, Jiahai; Guo, Yisong; Chang, Wei‐chen
• Is Part Of: Angewandte Chemie. Volume 132:Number 19(2020)
• Page Start: 7437
• Page End: 7441
• Publication Date: 2020-03-10
• Subjects: Katalyse -- Decarboxylierung -- Enzyme -- Eisen -- Reaktionsmechanismen; Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.201914896
• Languages: English
• ISSNs: 0044-8249

Abstract

Abstract: N‐alkylisonitrile, a precursor to isonitrile‐containing lipopeptides, is biosynthesized by decarboxylation‐assisted ‐N≡C group (isonitrile) formation by using N‐alkylglycine as the substrate. This reaction is catalyzed by iron(II) and 2‐oxoglutarate (Fe/2OG) dependent enzymes. Distinct from typical oxygenation or halogenation reactions catalyzed by this class of enzymes, installation of the isonitrile group represents a novel reaction type for Fe/2OG enzymes that involves a four‐electron oxidative process. Reported here is a plausible mechanism of three Fe/2OG enzymes, Sav607, ScoE and SfaA, which catalyze isonitrile formation. The X‐ray structures of iron‐loaded ScoE in complex with its substrate and the intermediate, along with biochemical and biophysical data reveal that ‐N≡C bond formation involves two cycles of Fe/2OG enzyme catalysis. The reaction starts with an Fe IV ‐oxo‐catalyzed hydroxylation. It is likely followed by decarboxylation‐assisted desaturation to complete isonitrile installation. Abstract : CN‐Installation : Eine Unterklasse von Fe/2‐Oxoglutarat‐Enzymen katalysiert die decarboxylierungsunterstützte Entsättigung von N‐Alkylglycin, um die Isonitrilfunktionalität zu installieren. Mithilfe eines komplementären Ansatzes aus Strukturbestimmung, NMR‐Spektroskopie und Mößbauer‐Analysen werden das Reaktionszwischenprodukt und ein plausibler Reaktionsmechanismus etabliert.