Manchester Institute of Biotechnology, School of Chemistry, University of Manchester, 131 Princess Street, Manchester M1 7DN, UK.
Manchester Institute of Biotechnology, School of Chemistry, University of Manchester, 131 Princess Street, Manchester M1 7DN, UK.
Curr Opin Chem Biol. 2020 Apr;55:136-144. doi: 10.1016/j.cbpa.2020.01.006. Epub 2020 Mar 9.
Enzyme design and engineering strategies rely almost exclusively on nature's alphabet of twenty canonical amino acids. Recent years have seen the emergence of powerful genetic code expansion methods that allow hundreds of structurally diverse amino acids to be installed into proteins in a site-selective manner. Here, we will highlight how the availability of an expanded alphabet of amino acids has opened new avenues in enzyme engineering research. Genetically encoded noncanonical amino acids have provided new tools to probe complex enzyme mechanisms, improve biocatalyst activity and stability, and most ambitiously to design enzymes with new catalytic mechanisms that would be difficult to access within the constraints of the genetic code. We anticipate that the studies highlighted in this article, coupled with the continuing advancements in genetic code expansion technology, will promote the widespread use of noncanonical amino acids in biocatalysis research in the coming years.
酶的设计和工程策略几乎完全依赖于自然界的二十个标准氨基酸。近年来，出现了强大的遗传密码扩展方法，可将数百种结构多样的氨基酸以位点选择性的方式装入蛋白质中。在这里，我们将重点介绍扩展的氨基酸字母表的可用性如何为酶工程研究开辟新途径。遗传编码的非标准氨基酸为探究复杂的酶机制、提高生物催化剂的活性和稳定性提供了新工具，最具雄心的是设计具有新催化机制的酶，而这些酶在遗传密码的限制下很难获得。我们预计，本文中强调的研究，加上遗传密码扩展技术的不断进步，将促进非标准氨基酸在未来几年的生物催化研究中的广泛应用。
