Nature's Machinery, Repurposed: Expanding the Repertoire of Iron-Dependent Oxygenases.
Nature's Machinery, Repurposed: Expanding the Repertoire of Iron-Dependent Oxygenases.
复制标题
自然的机械，重新利用：扩展铁依赖性氧酶的曲目。
DOI：
10.1021/acscatal.0c03606
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发表时间：
2020-10-16
期刊：
影响因子：
12.9
通讯作者：
Arnold FH
中科院分区：
文献类型：
--
作者：
Dunham NP;Arnold FH
铁在生物学中是一种特别重要的氧化还原活性辅助因子，因为它能够介导与大气中O2的反应。依赖铁的加氧酶利用这种地球上丰富的过渡金属将氧原子插入有机化合物中。在这些酶催化的惊人的转化多样性中，蛋白质框架引导活性中间体精确地形成产物，在许多情况下，这需要切断强碳氢键。近年来，几个铁依赖性加氧酶家族的成员已经被设计用于新的自然转化，提供比传统合成方法的优势。在这个视角中，我们首先通过回顾机制研究来探索血红素依赖性细胞色素P450加氧酶和非血红素铁依赖性加氧酶的反应性，重点是蛋白质支架如何最大化铁血红素和铁辅助因子的催化潜力。然后，我们回顾了这些辅助因子如何通过工程这些酶的蛋白质框架被重新用于非生物转化。最后，我们讨论了与工程这些平台相关的当代挑战，并评论了它们在生物催化中的作用。
Iron is an especially important redox-active cofactor in biology because of its ability to mediate reactions with atmospheric O2. Iron-dependent oxygenases exploit this earth-abundant transition metal for the insertion of oxygen atoms into organic compounds. Throughout the astounding diversity of transformations catalyzed by these enzymes, the protein framework directs reactive intermediates toward the precise formation of products, which, in many cases, necessitates the cleavage of strong C–H bonds. In recent years, members of several iron-dependent oxygenase families have been engineered for new-to-nature transformations that offer advantages over conventional synthetic methods. In this Perspective, we first explore what is known about the reactivity of heme-dependent cytochrome P450 oxygenases and nonheme iron-dependent oxygenases bearing the 2-His-1-carboxylate facial triad by reviewing mechanistic studies with an emphasis on how the protein scaffold maximizes the catalytic potential of the iron-heme and iron cofactors. We then review how these cofactors have been repurposed for abiological transformations by engineering the protein frameworks of these enzymes. Finally, we discuss contemporary challenges associated with engineering these platforms and comment on their roles in biocatalysis moving forward.
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DOI：
10.1002/anie.201810059
发表时间：
2018-11-26
期刊：
Angewandte Chemie (International ed. in English)
影响因子：
--
作者：
Chandgude AL;Fasan R
通讯作者：
Fasan R
影响因子：
62.1
作者：
Baglia RA;Zaragoza JPT;Goldberg DP
通讯作者：
Goldberg DP
影响因子：
5.6
作者：
Andersen, OA;Flatmark, T;Hough, E
通讯作者：
Hough, E
影响因子：
2.9
作者：
Basran, Jaswir;Booth, Elizabeth S.;Raven, Emma L.
通讯作者：
Raven, Emma L.
影响因子：
12.9
作者：
Carminati, Daniela M.;Fasa, Rudi
通讯作者：
Fasa, Rudi