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Elucidation of divergent desaturation pathways in the formation of vinyl isonitrile and isocyanoacrylate.

ABSTRACT: Two different types of desaturations are employed by iron- and 2-oxoglutarate-dependent (Fe/2OG) enzymes to construct vinyl isonitrile and isocyanoacrylate moieties found in isonitrile-containing natural products. A substrate-bound protein structure reveals a plausible strategy to affect desaturation and hints at substrate promiscuity of these enzymes. Analogs are synthesized and used as mechanistic probes to validate structural observations. Instead of proceeding through hydroxylated intermediate as previously proposed, a plausible carbocation species is utilized to trigger C=C bond installation. These Fe/2OG enzymes can also accommodate analogs with opposite chirality and different functional groups including isonitrile-(D)-tyrosine, N-formyl tyrosine, and phloretic acid, while maintaining the reaction selectivity.

SUBMITTER: Kim W

PROVIDER: S-EPMC9467999 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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Elucidation of divergent desaturation pathways in the formation of vinyl isonitrile and isocyanoacrylate.

Kim Wantae W Chen Tzu-Yu TY Cha Lide L Zhou Grace G Xing Kristi K Canty Nicholas Koenig NK Zhang Yan Y Chang Wei-Chen WC

Nature communications 20220912 1

Two different types of desaturations are employed by iron- and 2-oxoglutarate-dependent (Fe/2OG) enzymes to construct vinyl isonitrile and isocyanoacrylate moieties found in isonitrile-containing natural products. A substrate-bound protein structure reveals a plausible strategy to affect desaturation and hints at substrate promiscuity of these enzymes. Analogs are synthesized and used as mechanistic probes to validate structural observations. Instead of proceeding through hydroxylated intermedia ...[more]

PMID: 36097268

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