Department of Chemistry, BioScience Research Collaborative, Rice University, Houston, Texas 77005, United States.
Biochemistry. 2023 Jan 17;62(2):253-261. doi: 10.1021/acs.biochem.2c00336. Epub 2022 Aug 31.
The P450 superfamily comprises some of the most powerful and versatile enzymes for the site-selective oxidation of small molecules. One of the main drawbacks for the applications of the P450s in biotechnology is that the majority of these enzymes is multicomponent in nature and requires the presence of suitable redox partners to support their functions. Nevertheless, the discovery of several self-sufficient P450s, namely those from Classes VII and VIII, has served as an inspiration for fusion approaches to generate chimeric P450 systems that are self-sufficient. In this Perspective, we highlight the domain organizations of the Class VII and Class VIII P450 systems, summarize recent case studies in the engineering of catalytically self-sufficient P450s based on these systems, and outline outstanding challenges in the field, along with several emerging technologies as potential solutions.
P450 超家族包含一些最强大和多功能的酶,可用于小分子的位点选择性氧化。P450 在生物技术中的应用的主要缺点之一是,这些酶中的大多数本质上是多组分的,需要合适的氧化还原伴侣的存在来支持它们的功能。然而,几种自足 P450 的发现,即来自第 VII 类和第 VIII 类的 P450,为融合方法生成自足的嵌合 P450 系统提供了灵感。在本观点中,我们强调了第 VII 类和第 VIII 类 P450 系统的结构域组织,总结了基于这些系统的催化自足 P450 的工程设计的最新案例研究,并概述了该领域的突出挑战,以及一些新兴技术作为潜在的解决方案。