Oxidizing intermediates in P450 catalysis: a case for multiple oxidants.
Oxidizing intermediates in P450 catalysis: a case for multiple oxidants.
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DOI：
10.1007/978-3-319-16009-2_2
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发表时间：
2015
影响因子：
--
通讯作者：
Anuja Modi;J. Dawson
中科院分区：
文献类型：
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作者：
Anuja Modi;J. Dawson
细胞色素P450（Cytochrome P450，P450）的催化作用涉及有机化合物通过一系列催化中间体的氧化反应，即铁-过氧化、铁-氢过氧化、化合物I（化合物I）和FeIII−（H2 O2）中间体。现在P450酶的结构已经很好地建立，目前P450领域研究的一个主要焦点是揭示这些活性中间体的细节和活性。一般的共识是化合物I中间体是反应循环中最具反应性的物质，特别是当反应涉及烃羟基化时。CPD I最近已通过实验表征。除了化合物I，还有大量的实验和理论证据支持其他中间体参与各种类型的氧化反应。在环氧化、杂原子氧化和脱烷基化反应中使用P450活性位点突变体已经通过实验证明了这些多种氧化剂的参与。在本章中，我们将回顾P450反应循环和每一个活性中间体，讨论它们在氧化反应中的作用。
Cytochrome P450 (P450 or CYP) catalysis involves the oxygenation of organic compounds via a series of catalytic intermediates, namely, the ferric-peroxo, ferric-hydroperoxo, Compound I (Cpd I) and FeIII−(H2O2) intermediates. Now that the structures of P450 enzymes have been well established, a major focus of current research in the P450 area has been unraveling the intimate details and activities of these reactive intermediates. The general consensus is that the Cpd I intermediate is the most reactive species in the reaction cycle, especially when the reaction involves hydrocarbon hydroxylation. Cpd I has recently been characterized experimentally. Other than Cpd I, there is a multitude of evidence, both experimental as well as theoretical, supporting the involvement of other intermediates in various types of oxidation reactions. The involvement of these multiple oxidants has been experimentally demonstrated using P450 active-site mutants in epoxidation, heteroatom oxidation and dealkylation reactions. In this chapter, we will review the P450 reaction cycle and each of the reactive intermediates to discuss their role in oxidation reactions.