Laboratory of Organic Chemistry, ETH Zurich, 8093, Zurich, Switzerland.
School of Chemistry & Manchester Institute of Biotechnology, The University of Manchester, 131 Princess Street, Manchester, M1 7DN, UK.
Chemistry. 2018 Aug 14;24(46):11821-11830. doi: 10.1002/chem.201800975. Epub 2018 Jul 15.
Nature employs a limited number of genetically encoded, metal-coordinating residues to create metalloenzymes with diverse structures and functions. Engineered components of the cellular translation machinery can now be exploited to encode non-canonical ligands with user-defined electronic and structural properties. This ability to install "chemically programmed" ligands into proteins can provide powerful chemical probes of metalloenzyme mechanism and presents excellent opportunities to create metalloprotein catalysts with augmented properties and novel activities. In this Concept article, we provide an overview of several recent studies describing the creation of engineered metalloenzymes with interesting catalytic properties, and reveal how characterization of these systems has advanced our understanding of nature's bioinorganic mechanisms. We also highlight how powerful laboratory evolution protocols can be readily adapted to allow optimization of metalloenzymes with non-canonical ligands. This approach combines beneficial features of small molecule and protein catalysis by allowing the installation of a greater variety of local metal coordination environments into evolvable protein scaffolds, and holds great promise for the future creation of powerful metalloprotein catalysts for a host of synthetically valuable transformations.
自然界利用有限数量的遗传编码的、金属配位残基来产生具有不同结构和功能的金属酶。现在可以利用细胞翻译机制的工程组件来编码具有用户定义的电子和结构特性的非典型配体。这种将“化学编程”配体安装到蛋白质中的能力可以为金属酶机制提供强大的化学探针，并为具有增强特性和新活性的金属蛋白催化剂的创造提供极好的机会。在这篇概念文章中，我们概述了几项最近的研究，描述了具有有趣催化特性的工程金属酶的创建，并揭示了这些系统的表征如何促进了我们对自然界生物无机机制的理解。我们还强调了如何轻松地适应强大的实验室进化方案，以允许对具有非典型配体的金属酶进行优化。这种方法通过允许将更多种类的局部金属配位环境安装到可进化的蛋白质支架中，结合了小分子和蛋白质催化的有益特征，为未来创造用于一系列具有合成价值的转化的强大金属蛋白催化剂提供了巨大的前景。
