Department of Chemistry, North Carolina State University, Raleigh, North Carolina 27695, United States.
Department of Chemistry, Carnegie Mellon University, Pittsburgh, Pennsylvania 15213, United States.
Biochemistry. 2020 Jun 2;59(21):1961-1965. doi: 10.1021/acs.biochem.0c00289. Epub 2020 May 18.
Applying enzymatic reactions to produce useful molecules is a central focus of chemical biology. Iron and 2-oxoglutarate (Fe/2OG) enzymes are found in all kingdoms of life and catalyze a broad array of oxidative transformations. Herein, we demonstrate that the activity of an Fe/2OG enzyme can be redirected when changing the targeted carbon hybridization from sp to sp. During leucine 5-hydroxylase catalysis, installation of an olefin group onto the substrate redirects the Fe(IV)-oxo species reactivity from hydroxylation to asymmetric epoxidation. The resulting epoxide subsequently undergoes intramolecular cyclization to form the substituted piperidine, 2,5-hydroxypipecolic acid.
将酶反应应用于生产有用的分子是化学生物学的一个核心关注点。铁和 2-氧戊二酸（Fe/2OG）酶存在于所有生命领域，催化广泛的氧化转化。在此，我们证明当改变目标碳杂化从 sp 到 sp 时，Fe/2OG 酶的活性可以被重新定向。在亮氨酸 5-羟化酶催化过程中，将烯烃基团安装到底物上会使 Fe(IV)-氧物种的反应性从羟化作用转向不对称环氧化作用。所得环氧化物随后进行分子内环化形成取代的哌啶，2,5-羟基哌啶酸。
