Shi M,
Yao Y,
Fan X,
Li K,
Yu X,
Liu Y,
Wu Z,
Wang N *.
Sichuan University, Chengdu, P. R. China
Reversing the Enantioselectivity of Enzymatic Dynamic Kinetic Asymmetric Transformations
in the Synthesis of Fused Lactones.
ACS Catal. 2024;
14: 17480-17488
DOI:
10.1021/acscatal.4c05196
Keywords
ketoreductase - lactones - kinetic resolution - protein engineering
Significance
The authors present the design of an enzyme – ketoreductase – used to obtain polycyclic
lactones from β-ketoesters by dynamic kinetic resolution. The usefulness of the method
was demonstrated on 20 examples, obtained diastereo- and enantioselectively. By changing
the enzyme mutant, the stereoselectivity of the reaction can be reversed, maintaining
decent enantioselectivity.
Comment
Since an enzyme is a complex biochemical structure, it is difficult to design it to
work enantioselectively on enantiomers opposite to the natural one. Shi et al. overcame
this limitation by developing a ketoreductase and presented two variants of the enzyme
that process both enantiomers via enantioselective dynamic kinetic resolution.
