美国加利福尼亚大学Jonathan Rittle团队报道了二锰辅助因子介导的氧活化和酶C-H键活化。相关研究成果发表在2025年1月1日出版的《美国化学会杂志》。

二氧（O₂）是一种强效氧化剂，被需氧生物用于能量传递和关键的生物合成过程。许多金属酶利用O₂介导C-H键羟基化反应，但最常见的是在其活性位点辅因子中含有铁或铜离子。相比之下，许多锰激活的酶，如谷氨酰胺合成酶和异柠檬酸裂合酶，进行氧化还原中性化学转化，已知很少有酶能激活O₂或C-H键。

该文中，研究人员报告了形成单加氧酶SfbO（Mn₂-SfbO）的二锰金属化形式可以有效地介导酶促C-H键羟基化。二锰酸盐形式的SfbO对底物羟基化的活性与其异双金属Mn/Fe形式的活性相当，但表现出不同的动力学特征。动力学、光谱和结构研究了O₂活化中引入了混合价二锰酸辅因子（Mn^IIMn^III），并证明了超氧阴离子在O₂惰性Mn^II₂辅因子成熟中的化学计量作用。计算研究支持一种假设，即向Mn^II₂辅因子中添加超氧化物会安装一个关键的桥接氢氧化物配体，稳定高价锰的氧化态。

研究结果证实了蛋白质二锰辅因子在介导复杂的多步氧化还原转化中的可行性。

附：英文原文

Title: O2 Activation and Enzymatic C–H Bond Activation Mediated by a Dimanganese Cofactor

Author: Chang Liu, Guodong Rao, Jessica Nguyen, R. David Britt, Jonathan Rittle

Issue&Volume: January 1, 2025

Abstract: Dioxygen (O2) is a potent oxidant used by aerobic organisms for energy transduction and critical biosynthetic processes. Numerous metalloenzymes harness O2 to mediate C–H bond hydroxylation reactions, but most commonly feature iron or copper ions in their active site cofactors. In contrast, many manganese-activated enzymes─such as glutamine synthetase and isocitrate lyase─perform redox neutral chemical transformations and very few are known to activate O2 or C–H bonds. Here, we report that the dimanganese-metalated form of the cambialistic monooxygenase SfbO (Mn2–SfbO) can efficiently mediate enzymatic C–H bond hydroxylation. The activity of the dimanganese form of SfbO toward substrate hydroxylation is comparable to that of its heterobimetallic Mn/Fe form but exhibits distinct kinetic profiles. Kinetic, spectroscopic, and structural studies invoke a mixed-valent dimanganese cofactor (MnIIMnIII) in O2 activation and evidence a stoichiometric role for superoxide in maturing an O2-inert MnII2 cofactor. Computational studies support a hypothesis wherein superoxide addition to the MnII2 cofactor installs a critical bridging hydroxide ligand that stabilizes higher-valent manganese oxidation states. These findings establish the viability of proteinaceous dimanganese cofactors in mediating complex, multistep redox transformations.

DOI: 10.1021/jacs.4c16271

Source: https://pubs.acs.org/doi/abs/10.1021/jacs.4c16271