Wang Weijin, Tachibana Ryo, Zou Zhi, Chen Dongping, Zhang Xiang, Lau Kelvin, Pojer Florence, Ward Thomas R, Hu Xile
Laboratory of Inorganic Synthesis and Catalysis, Institute of Chemical Sciences and Engineering, École Polytechnique Fédérale de Lausanne ISIC-LSCI, BCH 3305, 1015, Lausanne, Switzerland.
Department of Chemistry, University of Basel, Mattenstrasse 22, 4002, Basel, Switzerland.
Angew Chem Int Ed Engl. 2023 Oct 23;62(43):e202311896. doi: 10.1002/anie.202311896. Epub 2023 Sep 18.
Artificial (transfer) hydrogenases have been developed for organic synthesis, but they rely on precious metals. Native hydrogenases use Earth-abundant metals, but these cannot be applied for organic synthesis due, in part, to their substrate specificity. Herein, we report the design and development of manganese transfer hydrogenases based on the biotin-streptavidin technology. By incorporating bio-mimetic Mn(I) complexes into the binding cavity of streptavidin, and through chemo-genetic optimization, we have obtained artificial enzymes that hydrogenate ketones with nearly quantitative yield and up to 98 % enantiomeric excess (ee). These enzymes exhibit broad substrate scope and high functional-group tolerance. According to QM/MM calculations and X-ray crystallography, the S112Y mutation, combined with the appropriate chemical structure of the Mn cofactor plays a critical role in the reactivity and enantioselectivity of the artificial metalloenzyme (ArMs). Our work highlights the potential of ArMs incorporating base-meal cofactors for enantioselective organic synthesis.
人工（转移）氢化酶已被开发用于有机合成，但它们依赖于贵金属。天然氢化酶使用地球上储量丰富的金属，但部分由于其底物特异性，这些金属不能用于有机合成。在此，我们报告了基于生物素 - 链霉亲和素技术的锰转移氢化酶的设计与开发。通过将仿生锰（I）配合物引入链霉亲和素的结合腔，并经过化学遗传优化，我们获得了能将酮氢化的人工酶，产率接近定量，对映体过量（ee）高达98%。这些酶表现出广泛的底物范围和高官能团耐受性。根据量子力学/分子力学计算和X射线晶体学，S112Y突变与锰辅因子的适当化学结构相结合，在人工金属酶（ArMs）的反应性和对映选择性中起关键作用。我们的工作突出了包含基础膳食辅因子的ArMs在对映选择性有机合成中的潜力。
