The selective functionalization of sp³ C–H bonds is a versatile tool for the diversification of organic compounds. Combining attractive features of homogeneous and enzymatic catalysts, artificial metalloenzymes offer an ideal means to selectively modify these inert motifs. Herein, we report on a copper(I) heteroscorpionate complex embedded within streptavidin that catalyzes the intramolecular insertion of a carbene into sp³ C–H bonds. Target residues for genetic optimization of the artificial metalloenzyme were identified by quantum mechanics/molecular mechanics simulations. Double-saturation mutagenesis yielded detailed insight on the contribution of individual amino acids on the activity and the selectivity of the artificial metalloenzyme. Mutagenesis at a third position afforded a set of artificial metalloenzymes that catalyze the enantio- and regioselective formation of β- and γ-lactams with high turnovers and promising enantioselectivities.

中文翻译：

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一种基于杂蝎酸铜的人工金属酶通过分子内卡宾插入实现 sp3 C-H 功能化

^{sp 3} C-H键的选择性功能化是有机化合物多样化的通用工具。结合均相和酶催化剂的有吸引力的特征，人造金属酶提供了一种理想的方法来选择性地修饰这些惰性基序。在此，我们报道了嵌入链霉抗生物素蛋白中的铜 (I) 异蝎形酸盐复合物，该复合物催化卡宾分子内插入 sp ³C-H 键。通过量子力学/分子力学模拟确定了人工金属酶遗传优化的目标残基。双饱和诱变对单个氨基酸对人工金属酶的活性和选择性的贡献产生了详细的了解。第三个位置的诱变提供了一组人工金属酶，可催化β-和γ-内酰胺的对映选择性和区域选择性形成，具有高周转率和有希望的对映选择性。