Open AccessAn Artificial Metalloenzyme Based on a Copper Heteroscorpionate Enables sp3 C–H Functionalization via Intramolecular Carbene Insertion
Author(s) -
Corentin Rumo,
Alina Stein,
Juliane Klehr,
Ryo Tachibana,
Alessandro Prescimone,
Daniel Häußinger,
Thomas R. Ward
Publication year - 2022
Publication title -
journal of the american chemical society
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.115
H-Index - 612
eISSN - 1520-5126
pISSN - 0002-7863
DOI - 10.1021/jacs.2c03311
Subject(s) - chemistry , intramolecular force , carbene , saturated mutagenesis , surface modification , combinatorial chemistry , stereochemistry , regioselectivity , catalysis , organic chemistry , mutant , biochemistry , gene
The selective functionalization of sp 3 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 sp 3 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.