Emerging artificial metalloenzymes for asymmetric hydrogenation reactions

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 b-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.

Automated summary

Artificial metalloenzymes (ArMs) combine the best properties of homogeneous transition metal catalysts and natural proteins to exhibit high tunability, broad-scope reactivity, enhanced aqueous stability, and stereoselectivity. This study focuses on recent advances in designing hydrogenase ArMs, including modification of natural [Fe]hydrogenase, design of a novel ArM system using protein b-lactoglobulin, and development of chimeric streptavidin scaffolds.