An S=1 Iron(IV) Intermediate Revealed in a Non-Heme Iron Enzyme-Catalyzed Oxidative C-S Bond Formation.
An S=1 Iron(IV) Intermediate Revealed in a Non-Heme Iron Enzyme-Catalyzed Oxidative C-S Bond Formation.
复制标题
DOI：
10.1002/anie.202309362
复制
发表时间：
2023-10-23
影响因子：
16.6
通讯作者：
Guo, Yisong
中科院分区：
文献类型：
--
作者：
Paris, Jared C.;Hu, Sha;Wen, Aiwen;Weitz, Andrew C.;Cheng, Ronghai;Gee, Leland B.;Tang, Yijie;Kim, Hyomin;Vegas, Arturo;Chang, Wei-chen;Elliott, Sean J.;Liu, Pinghua;Guo, Yisong
麦角硫醚(ESH)和卵硫醇A(OSHA)是两种天然的硫醇-组氨酸衍生物。ESH被认为是一种长寿维生素，OSHA可以抑制肝癌的增殖。ESH和OSHA在好氧途径中的关键生物合成步骤是由非血红素铁酶(如OvoA在Ovothiol生物合成中)催化的依赖O2的C-S键的形成，但由于缺乏关键反应中间体的鉴定，这一新反应的机理尚不清楚。在这项研究中，我们报告了一种具有动力学活性的S=1铁(IV)中间体的鉴定和表征，该中间体由四个组氨酸配体环境(三个来自蛋白质残基，一个来自底物)支持，能够在OvoA中从甲氧基万能耐热分子中形成C-S键，这是第一个实验观察到的非血红素铁酶中的中间自旋铁(IV)物种。因此，本研究结果为进一步剖析OSHA生物合成途径中酶促氧化C-S键的形成机制奠定了基础。它们也为研究富含组氨酸的配基环境支持的高价铁中间体的结构-功能关系提供了新的机会。通过瞬时动力学和光谱(穆斯堡尔谱、电子顺磁共振和X-射线光电子能谱)表征发现了第一个非血红素酶促反应中间体S=1 Fe(IV)。这一新物种是在卵硫醇A的生物合成中能够形成氧化碳-硫键的关键中间体。
Ergothioneine (ESH) and ovothiol A (OSHA) are two natural thiol-histidine derivatives. ESH has been implicated as a longevity vitamin and OSHA inhibits the proliferation of hepatocarcinoma. The key biosynthetic step of ESH and OSHA in the aerobic pathways is the O2-dependent C-S bond formation catalyzed by non-heme iron enzymes (e.g., OvoA in ovothiol biosynthesis), but due to the lack of identification of key reactive intermediate, the mechanism of this novel reaction is unresolved. In this study, we report the identification and characterization of a kinetically competent S = 1 iron(IV) intermediate supported by a four-histidine ligand environment (three from the protein residues and one from the substrate) in enabling C-S bond formation in OvoA from Methyloversatilis thermotoleran, which represents the first experimentally observed intermediate spin iron(IV) species in non-heme iron enzymes. Results reported in this study thus set the stage to further dissect the mechanism of enzymatic oxidative C-S bond formation in the OSHA biosynthesis pathway. They also afford new opportunities to study the structure-function relationship of high-valent iron intermediates supported by a histidine rich ligand environment. The first non-heme enzymatic S = 1 Fe(IV) intermediate is discovered via transient kinetics and spectroscopic (Mössbauer, EPR, and XANES) characterizations. This novel species is a key intermediate to enable the oxidative carbon-sulfur bond formation in the biosynthesis of ovothiol A.
登录
查看更多内容
使用酪氨酸类似物调节卵硫醇生物合成中非血红素铁酶 OvoA 的两种活性：半胱氨酸氧化与氧化 C-S 键形成。
影响因子：
15
作者：
Chen L;Naowarojna N;Song H;Wang S;Wang J;Deng Z;Zhao C;Liu P
通讯作者：
Liu P
影响因子：
8.4
作者：
Cheng R;Weitz AC;Paris J;Tang Y;Zhang J;Song H;Naowarojna N;Li K;Qiao L;Lopez J;Grinstaff MW;Zhang L;Guo Y;Elliott S;Liu P
通讯作者：
Liu P
影响因子：
4.4
作者：
HARAMI, T;MAEDA, Y;GONSER, U
通讯作者：
GONSER, U
影响因子：
15
作者：
Faponle, Abayomi S.;Seebeck, Florian P.;de Visser, Sam P.
通讯作者：
de Visser, Sam P.
影响因子：
13.8
作者：
Herr CQ;Hausinger RP
通讯作者：
Hausinger RP