Dual-function enzyme catalysis for enantioselective carbon-nitrogen bond formation.
Nat Chem
; 13(12): 1166-1172, 2021 12.
Article
in En
| MEDLINE
| ID: mdl-34663919
ABSTRACT
Chiral amines can be made by insertion of a carbene into an N-H bond using two-catalyst systems that combine a transition metal-based carbene-transfer catalyst and a chiral proton-transfer catalyst to enforce stereocontrol. Haem proteins can effect carbene N-H insertion, but asymmetric protonation in an active site replete with proton sources is challenging. Here we describe engineered cytochrome P450 enzymes that catalyse carbene N-H insertion to prepare biologically relevant α-amino lactones with high activity and enantioselectivity (up to 32,100 total turnovers, >99% yield and 98% e.e.). These enzymes serve as dual-function catalysts, inducing carbene transfer and promoting the subsequent proton transfer with excellent stereoselectivity in a single active site. Computational studies uncover the detailed mechanism of this new-to-nature enzymatic reaction and explain how active-site residues accelerate this transformation and provide stereocontrol.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Cytochrome P-450 Enzyme System
/
Amines
Language:
En
Journal:
Nat Chem
Journal subject:
QUIMICA
Year:
2021
Document type:
Article
Affiliation country: