Abiotic reduction of ketones with silanes catalysed by carbonic anhydrase through an enzymatic zinc hydride
Nat. Chem. 2021, 13, 312-318, 10.1038/s41557-020-00633-7
Enzymatic reactions through mononuclear metal hydrides are unknown in nature, despite the prevalence of such intermediates in the reactions of synthetic transition-metal catalysts. If metalloenzymes could react through abiotic intermediates like these, then the scope of enzyme-catalysed reactions would expand. Here we show that zinc-containing carbonic anhydrase enzymes catalyse hydride transfers from silanes to ketones with high enantioselectivity. We report mechanistic data providing strong evidence that the process involves a mononuclear zinc hydride. This work shows that abiotic silanes can act as reducing equivalents in an enzyme-catalysed process and that monomeric hydrides of electropositive metals, which are typically unstable in protic environments, can be catalytic intermediates in enzymatic processes. Overall, this work bridges a gap between the types of transformation in molecular catalysis and biocatalysis.
Metal: ZnLigand type: Histidine residuesHost protein: Human carbonic anhydrase II (hCAII)Optimization: ChemicalReaction: Transfer hydrogenationMax TON: 500ee: >99PDB: ---Notes: ---
A "Broad Spectrum" Carbene Transferase for Synthesis of Chiral α-Trifluoromethylated Organoborons
ACS Cent. Sci. 2019, 5, 206-208, 10.1021/acscentsci.9b00015
Directed evolution generated an enzyme for the enantioselective synthesis of α-trifluoromethylated organoborons—potentially attractive synthons for fluorinated compounds.
Metal: FeLigand type: PorphyrinHost protein: Cytochrome cOptimization: GeneticReaction: B-H insertionMax TON: 2900ee: 95PDB: ---Notes: ---
Nitrene Transfer Catalyzed by a Non-Heme Iron Enzyme and Enhanced by Non-Native Small-Molecule Ligands
J. Am. Chem. Soc. 2019, 141, 19585-19588, 10.1021/jacs.9b11608
Transition-metal catalysis is a powerful tool for the construction of chemical bonds. Here we show that Pseudomonas savastanoi ethylene-forming enzyme, a non-heme iron enzyme, can catalyze olefin aziridination and nitrene C−H insertion, and that these activities can be improved by directed evolution. The nonheme iron center allows for facile modification of the primary coordination sphere by addition of metalcoordinating molecules, enabling control over enzyme activity and selectivity using small molecules.
Metal: FeLigand type: Amino acidHost protein: Pseudomonas savastanoi ethylene-forming enzyme (PsEFE)Optimization: GeneticReaction: C-H aminationMax TON: 730ee: 61PDB: 6CBANotes: Additional reaction: aziridination