One Enzyme – Two Variants: Enantioselective Synthesis of Fused Lactones Giving Access to Two Enantiomers

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.

 

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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.

 

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Publication History

Article published online:
28 January 2025