Intramolecular Stereoselective Stetter Reaction Catalyzed by Benzaldehyde Lyase
Xiaoyang Chen1,2, Zhiguo Wang1,3, Yujiao Lou1
1Department of Chemistry, Center of Chemistry for Frontier Technologies, Zhejiang University, Hangzhou, 310027, China.
Angewandte Chemie (International Ed. in English)
|February 9, 2021
Summary
Researchers engineered benzaldehyde lyase for a novel intramolecular Stetter reaction, achieving high yield and stereoselectivity. This work advances enzyme promiscuity for new chemical transformations.
Area of Science:
- Enzyme engineering and biocatalysis
- Organic chemistry and reaction mechanisms
Background:
- Designing enzyme promiscuity for novel chemical transformations is a significant scientific challenge.
- Thiamine diphosphate (ThDP)-dependent enzymes are versatile biocatalysts with potential for broader applications.
Purpose of the Study:
- To engineer a benzaldehyde lyase for a novel intramolecular stereoselective Stetter reaction.
- To explore enzyme promiscuity through rational enzyme structure screening and molecular dynamics simulations.
Main Methods:
- Rational structure screening of ThDP-dependent enzymes.
- Molecular dynamics (MD) simulations to guide enzyme selection and optimization.
- Optimization of reaction conditions for the novel biocatalytic transformation.
Main Results:
- First example of an intramolecular stereoselective Stetter reaction catalyzed by engineered benzaldehyde lyase.
- Achieved high productivity up to 99%.
- Demonstrated high stereoselectivity up to 99:1 enantiomeric ratio (e.r.).
Conclusions:
- Rational enzyme design using MD simulations can successfully engineer enzyme promiscuity for new reactions.
- Engineered benzaldehyde lyase provides a highly efficient and stereoselective biocatalyst for the intramolecular Stetter reaction.
- This study expands the catalytic repertoire of ThDP-dependent enzymes.
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