Cytochromes P450 as versatile biocatalysts
Cytochromes P450 as versatile biocatalysts
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DOI：
10.1016/j.jbiotec.2006.01.026
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发表时间：
2006-06-25
影响因子：
4.1
通讯作者：
Bernhardt, Rita
中科院分区：
文献类型：
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作者：
Bernhardt, Rita
细胞色素P450是50年前发现的一种广泛分布的酶，具有高度的复杂性和广泛的活性范围。它们是由基因超家族编码的血红素蛋白，可转化多种底物并催化多种有趣的化学反应。该酶家族参与药物的生物转化、外源性物质的生物转化、化学致癌物的代谢、生理学上重要的化合物如类固醇、脂肪酸、类花生酸、脂溶性维生素、胆汁酸的生物合成、烷烃、萜烯和芳香族化合物的转化以及除草剂和杀虫剂的降解。细胞色素P450催化的反应也具有广泛的通用性，例如碳羟基化、杂原子氧化、脱烷基化、环氧化、芳族羟基化、还原、脱卤（Sono，M.，罗奇议员库尔特急诊科道森，J.H.，1996.含血红素加氧酶。Rev.96，2841-2888），（Werck-Reichhart，D.，Feyereisen河，2000.细胞色素P450：一个成功的故事。I（REVIEWS 3003）），（Bernhardt，R.，2004.细胞色素P-450 1，544-549），（Bernhardt，R.，2004.优化嵌合体生成;创造不同的P450功能。11，287-288），（Guengerich，F.P.，2004.细胞色素P450：我们学到了什么，未来的问题是什么？药物代谢Rev.36，159 -197）。迄今为止，已经克隆了超过5000种不同的P450基因（详情参见：http：//drnelson.utmem.edu/CytochromeP450.html）。相同基因家族的成员通常定义为与来自任何其他家族的P450蛋白具有>= 40%的序列同一性。同一亚科内的哺乳动物序列总是> 55%相同。P450酶在不同物种中的数量有很大差异，目前在植物中的数量最多。细胞色素P450的结构-功能关系还远未得到很好的理解，其催化能力迄今几乎没有用于生物技术过程。然而，这些系统催化的一系列有趣的反应以及允许异源表达它们并改善和改变它们的活性、稳定性和选择性，以及工业界对生命科学的兴趣日益增加，使它们成为未来生物技术应用的有希望的候选者。(c)2006 Elsevier B. V.保留所有权利。
Cytochromes P450 are ubiquitously distributed enzymes, which were discovered about 50 years ago and which possess high complexity and display a broad field of activity. They are hemoproteins encoded by a superfamily of genes converting a broad variety of substrates and catalysing a variety of interesting chemical reactions. This enzyme family is involved in the biotransformation of drugs, the bioconversion of xenobiotics, the metabolism of chemical carcinogens, the biosynthesis of physiologically important compounds such as steroids, fatty acids, eicosanoids, fat-soluble vitamins, bile acids, the conversion of alkanes, terpenes, and aromatic compounds as well as the degradation of herbicides and insecticides. There is also a broad versatility of reactions catalysed by cytochromes P450 such as carbon hydroxylation, heteroatom oxygenation, dealkylation, epoxidation, aromatic hydroxylation, reduction, dehalogenation (Sono, M., Roach, M.P., Coulter, E.D., Dawson, J.H., 1996. Heme-containing oxygenases. Chem. Rev. 96, 2841-2888), (Werck-Reichhart, D., Feyereisen, R., 2000. Cytochromes P450: a success story. Genome Biol. I (REVIEWS3003)), (Bernhardt, R., 2004. Cytochrome P-450. Encyclopedia Biol. Chem. 1, 544-549), (Bernhardt, R., 2004. Optimized chimeragenesis; creating diverse P450 functions. Chem. Biol. 11, 287-288), (Guengerich, F.P., 2004. Cytochrome P450: what have we learned and what are the future issues? Drug Metab. Rev. 36,159-197). More than 5000 different P450 genes have been cloned up to date (for details see: http://drnelson.utmem.edu/CytochromeP450.html). Members of the same gene family are defined as usually having >= 40% sequence identity to a P450 protein from any other family. Mammalian sequences within the same subfamily are always > 55% identical. The numbers of individual P450 enzymes in different species differ significantly, showing the highest numbers observed so far in plants.The structure-function relationships of cytochromes P450 are far from being well understood and their catalytic power has so far hardly been used for biotechnological processes.Nevertheless, the set of interesting reactions being catalysed by these systems and the availability of new genetic engineering techniques allowing to heterologously express them and to improve and change their activity, stability and selectivity as well as the increasing interest of the industry in life sciences makes them promising candidates for biotechnological application in the future. (c) 2006 Elsevier B.V. All rights reserved.