University of Missouri-Kansas City, School of Pharmacy, Division of Pharmacology and Toxicology, 2464 Charlotte St., Kansas City, MO 64108, USA.
Expert Opin Drug Metab Toxicol. 2010 Feb;6(2):115-31. doi: 10.1517/17425250903431040.
Cytochrome P450 enzymes comprise a superfamily of heme monooxygenases that are of considerable interest for the: i) synthesis of novel drugs and drug metabolites; ii) targeted cancer gene therapy; iii) biosensor design; and iv) bioremediation. However, their applications are limited because cytochrome P450, especially mammalian P450 enzymes, show a low turnover rate and stability, and require a complex source of electrons through cytochrome P450 reductase and NADPH.
In this review, we discuss the recent progress towards the use of P450 enzymes in a variety of the above-mentioned applications. We also present alternate and cost-effective ways to perform P450-mediated reaction, especially using peroxides. Furthermore, we expand upon the current progress in P450 engineering approaches describing several recent examples that are utilized to enhance heterologous expression, stability, catalytic efficiency and utilization of alternate oxidants.
The review provides a comprehensive knowledge in the design of P450 biocatalysts for potentially practical purposes. Finally, we provide a prospective on the future aspects of P450 engineering and its applications in biotechnology, medicine and bioremediation.
Because of its wide applications, academic and pharmaceutical researchers, environmental scientists and healthcare providers are expected to gain current knowledge and future prospects of the practical use of P450 biocatalysts.
细胞色素 P450 酶组成一个血红素单加氧酶超家族，具有很大的兴趣：i）合成新型药物和药物代谢物；ii）靶向癌症基因治疗；iii）生物传感器设计；和 iv）生物修复。然而，它们的应用受到限制，因为细胞色素 P450，尤其是哺乳动物 P450 酶，表现出低周转率和稳定性，并且需要通过细胞色素 P450 还原酶和 NADPH 来提供复杂的电子源。
在这篇综述中，我们讨论了在上述各种应用中使用 P450 酶的最新进展。我们还介绍了替代的、具有成本效益的方法来进行 P450 介导的反应，特别是使用过氧化物。此外，我们扩展了当前在 P450 工程方法方面的进展，描述了几个最近的例子，这些例子被用来提高异源表达、稳定性、催化效率和利用替代氧化剂的能力。
本综述提供了关于设计用于潜在实际目的的 P450 生物催化剂的全面知识。最后，我们对 P450 工程的未来方面及其在生物技术、医学和生物修复中的应用提供了展望。
由于其广泛的应用，学术和制药研究人员、环境科学家和医疗保健提供者有望获得关于 P450 生物催化剂实际应用的当前知识和未来前景。
