Structural basis of enzymatic benzene ring reduction.
Structural basis of enzymatic benzene ring reduction.
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DOI：
10.1038/nchembio.1849
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发表时间：
2015-08
影响因子：
14.8
通讯作者：
T. Weinert;Simona G. Huwiler;J. Kung;S. Weidenweber;P. Hellwig;H. Stärk;Till Biskup;S. Weber;J. Cotelesage;G. George;U. Ermler;M. Boll
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文献类型：
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作者：
T. Weinert;Simona G. Huwiler;J. Kung;S. Weidenweber;P. Hellwig;H. Stärk;Till Biskup;S. Weber;J. Cotelesage;G. George;U. Ermler;M. Boll
在化学合成中，广泛使用的芳香族化合物的Birch还原为环二烯需要氨中的碱金属作为极低电势的电子供体。类似的反应是由苯甲酰辅酶A还原酶(BCR)催化的，BCR在全球重要的细菌降解缺氧部位的芳香族化合物中起着关键作用。由于缺乏结构信息，酶催化苯环还原的催化机理尚不清楚。在这里，我们介绍了一种脱芳烃BCR的结构表征，它含有一种前所未有的钨辅助因子，它在非质子腔中将电子转移到苯环上。底物结合通过排出对活性中心包裹至关重要的锌离子来诱导质子从主体溶剂转移到活性中心。我们的结果揭示了生物学中负氧化还原电势极限下电子转移过程的结构基础。它们为基本化学合成工具的生物或仿生替代品打开了大门。
In chemical synthesis, the widely used Birch reduction of aromatic compounds to cyclic dienes requires alkali metals in ammonia as extremely low-potential electron donors. An analogous reaction is catalyzed by benzoyl–coenzyme A reductases (BCRs) that have a key role in the globally important bacterial degradation of aromatic compounds at anoxic sites. Because of the lack of structural information, the catalytic mechanism of enzymatic benzene ring reduction remained obscure. Here, we present the structural characterization of a dearomatizing BCR containing an unprecedented tungsten cofactor that transfers electrons to the benzene ring in an aprotic cavity. Substrate binding induces proton transfer from the bulk solvent to the active site by expelling a Zn2+that is crucial for active site encapsulation. Our results shed light on the structural basis of an electron transfer process at the negative redox potential limit in biology. They open the door for biological or biomimetic alternatives to a basic chemical synthetic tool.