Department of Chemistry, University of Texas at Austin, 105 E. 24th St. Stop A5300, Austin, TX, 78712, USA.
Department of Chemistry, University of Texas at Austin, 105 E. 24th St. Stop A5300, Austin, TX, 78712, USA.
Curr Opin Chem Biol. 2022 Feb;66:102096. doi: 10.1016/j.cbpa.2021.102096. Epub 2021 Dec 5.
Artificial metalloenzymes (ArMs) utilize the best properties of homogenous transition metal catalysts and naturally occurring proteins. While synthetic metal complexes offer high tunability and broad-scope reactivity with a variety of substrates, enzymes further endow these complexes with enhanced aqueous stability and stereoselectivity. For these reasons, dozens of ArMs have been designed to perform catalytic asymmetric hydrogenation reactions, and hydrogenase ArMs are, in fact, the oldest class of ArMs. Herein, we report recent advances in the design of hydrogenase ArMs, including (i) the modification of natural [Fe]-hydrogenase by insertion of artificial metallocofactors, (ii) design of a novel ArM system from the tractable and inexpensive protein β-lactoglobulin to afford a high-performing transfer hydrogenase, and (iii) the design of chimeric streptavidin scaffolds that drastically alter the secondary coordination sphere of previously reported streptavidin/biotin transfer hydrogenase ArMs.
人工金属酶（ArMs）利用均相过渡金属催化剂和天然蛋白质的最佳特性。虽然合成金属配合物具有高度的可调性和广泛的反应性，可以与各种底物反应，但酶进一步赋予这些配合物更高的水稳定性和立体选择性。出于这些原因，已经设计了数十种 ArMs 来进行催化不对称氢化反应，而氢化酶 ArMs 实际上是最早的一类 ArMs。在此，我们报告了氢化酶 ArMs 设计的最新进展，包括 (i) 通过插入人工金属辅因子修饰天然 [Fe]-氢化酶，(ii) 从易于处理和廉价的蛋白质 β-乳球蛋白设计新型 ArM 系统，以提供高性能的转移氢化酶，以及 (iii) 设计嵌合链霉亲和素支架，这些支架极大地改变了之前报道的链霉亲和素/生物素转移氢化酶 ArMs 的次级配位球。
