Enzymatic Mannich Reaction for the Synthesis of γ-Chiral Amino-Substituted α-Amino Acids
Abstract
γ-Chiral amino-substituted α-amino acids are commonly found in bioactive molecules and play a critical role in drug design and development. However, the synthesis of these compounds remains challenging, as it requires protection of the reactive amino and carboxyl groups alongside stringent control over remote stereoselectivity. In this study, we developed a biocatalytic Mannich reaction catalyzed by engineered Ap UstD, a characterized aldolase, enabling the synthesis of γ-chiral amino-substituted α-amino acids without the need for protection of the amino or carboxyl groups. Through protein engineering, the mutant Ap UstD-M3 was obtained, showing good catalytic activity and selectivity, and also performing efficiently in preparative-scale reactions.
Fields of Study & Subjects
Enzyme Catalysis and Immobilization
Cyclopropane Reaction Mechanisms
Enzyme Structure and Function
Publication details
- Journal / source
- ACS Catalysis
- Publisher
- American Chemical Society (ACS)
- Volume
- 16
- Issue
- 2
- Pages
- 1350–1357
- Publication date
- 7 January 2026
- Language
- EN