Department of Chemistry, University of Texas at Austin, Austin, Texas 78712, United States.
Division of Chemical Biology & Medicinal Chemistry, College of Pharmacy, University of Texas at Austin, Austin, Texas 78712, United States.
J Am Chem Soc. 2023 Feb 15;145(6):3656-3664. doi: 10.1021/jacs.2c12953. Epub 2023 Jan 31.
OxsB is a B-dependent radical SAM enzyme that catalyzes the oxidative ring contraction of 2'-deoxyadenosine 5'-phosphate to the dehydrogenated, oxetane containing precursor of oxetanocin A phosphate. AlsB is a homologue of OxsB that participates in a similar reaction during the biosynthesis of albucidin. Herein, OxsB and AlsB are shown to also catalyze radical mediated, stereoselective C2'-methylation of 2'-deoxyadenosine monophosphate. This reaction proceeds with inversion of configuration such that the resulting product also possesses a C2' hydrogen atom available for abstraction. However, in contrast to methylation, subsequent rounds of catalysis result in C-C dehydrogenation of the newly added methyl group to yield a 2'-methylidene followed by radical addition of a 5'-deoxyadenosyl moiety to produce a heterodimer. These observations expand the scope of reactions catalyzed by B-dependent radical SAM enzymes and emphasize the susceptibility of radical intermediates to bifurcation along different reaction pathways even within the highly organized active site of an enzyme.
OxsB 是一种 B 依赖性自由基 SAM 酶，它催化 2'-脱氧腺苷 5'-磷酸的氧化环收缩，生成 oxetanocin A 磷酸的脱氢、氧杂环丁烷含前体。AlsB 是 OxsB 的同源物，它在 albucidin 生物合成过程中参与类似的反应。本文显示，OxsB 和 AlsB 还能催化自由基介导的、立体选择性的 2'-脱氧腺苷一磷酸的 C2'-甲基化。该反应具有构型反转，因此生成的产物也具有可用于提取的 C2'氢原子。然而，与甲基化不同的是，随后的催化循环导致新添加的甲基的 C-C 脱氢，生成 2'-亚甲基，然后是 5'-脱氧腺苷部分的自由基加成，生成杂二聚体。这些观察结果扩展了 B 依赖性自由基 SAM 酶催化的反应范围，并强调了自由基中间体在高度组织化的酶活性中心内沿着不同反应途径分叉的易感性。
