McKetta Department of Chemical Engineering, University of Texas, Austin, TX, USA.
Department of Chemistry, NC State University, Raleigh, NC, USA.
Nat Commun. 2022 Sep 12;13(1):5343. doi: 10.1038/s41467-022-32870-4.
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.
两种不同类型的去饱和作用被铁和 2-氧戊二酸依赖性（Fe/2OG）酶用于构建乙烯基异腈和异氰酸酯基团，这些基团存在于含异腈的天然产物中。一个结合底物的蛋白质结构揭示了一种影响去饱和作用的合理策略，并暗示了这些酶对底物的混杂性。合成了类似物并用作机制探针来验证结构观察结果。与之前提出的通过羟化中间产物进行反应不同，一个合理的碳正离子物种被用来触发 C=C 键的安装。这些 Fe/2OG 酶还可以适应具有相反手性和不同官能团的类似物，包括异腈-(D)-酪氨酸、N-甲酰基酪氨酸和 phloretic 酸，同时保持反应选择性。
