Structure and function of the cytochrome P450 peroxygenase enzymes.
Structure and function of the cytochrome P450 peroxygenase enzymes.
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DOI：
10.1042/bst20170218
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发表时间：
2018-02-19
影响因子：
3.9
通讯作者：
Makris TM
中科院分区：
文献类型：
--
作者：
Munro AW;McLean KJ;Grant JL;Makris TM
细胞色素P450 （P450或CYPs）构成了一个大的血红素酶超家族，其成员催化广泛的有机底物的氧化转化，其功能对人类和其他生物的外源代谢和类固醇转化至关重要。P450过氧酶是P450过氧酶的一个亚群，在微生物中进化为催化脂肪酸的氧化代谢，使用过氧化氢作为氧化剂，而不是绝大多数其他特征P450酶典型的NAD(P) h驱动的氧化还原伙伴系统。研究表明，过氧酶（CYP152）家族的早期成员在中长链脂肪酸的α和β碳上催化羟基化。然而，最近对其他CYP152家族p450的研究表明，它具有氧化脱羧酸脂肪酸的能力，产生终端烯烃，具有作为生物燃料的潜在应用前景。其他研究揭示了它们脱羧和脱饱和羟基脂肪酸形成新产品的能力。结构数据揭示了过氧酶中底物羧酸基结合的共同活性位点基序，机制和瞬态动力学分析表明，形成了活性铁氧（化合物I和II），它们最终分别负责脂肪酸的羟基化和脱羧化。本文将重点介绍P450过加氧酶的生物化学特性及其在生产挥发性烯烃作为生物燃料以及其他精细化学品方面的生物技术应用。
The cytochromes P450 (P450s or CYPs) constitute a large heme enzyme superfamily, members of which catalyze the oxidative transformation of a wide range of organic substrates, and whose functions are crucial to xenobiotic metabolism and steroid transformation in humans and other organisms. The P450 peroxygenases are a subgroup of the P450s that have evolved in microbes to catalyze the oxidative metabolism of fatty acids, using hydrogen peroxide as an oxidant rather than NAD(P)H-driven redox partner systems typical of the vast majority of other characterized P450 enzymes. Early members of the peroxygenase (CYP152) family were shown to catalyze hydroxylation at the α and β carbons of medium-to-long-chain fatty acids. However, more recent studies on other CYP152 family P450s revealed the ability to oxidatively decarboxylate fatty acids, generating terminal alkenes with potential applications as drop-in biofuels. Other research has revealed their capacity to decarboxylate and to desaturate hydroxylated fatty acids to form novel products. Structural data have revealed a common active site motif for the binding of the substrate carboxylate group in the peroxygenases, and mechanistic and transient kinetic analyses have demonstrated the formation of reactive iron-oxo species (compounds I and II) that are ultimately responsible for hydroxylation and decarboxylation of fatty acids, respectively. This short review will focus on the biochemical properties of the P450 peroxygenases and on their biotechnological applications with respect to production of volatile alkenes as biofuels, as well as other fine chemicals.