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An Engineered Enzyme Catalyzing Tandem Reductive Aminations for Synthesizing Tertiary Amines
Yaqing Ma1,2, Han Zhang1,3, Jinping Bao1,2
1State Key Laboratory of Engineering Biology For Low-Carbon Manufacturing, Chinese Academy of Sciences, Tianjin Institute of Industrial Biotechnology, Tianjin, China.
Angewandte Chemie (International Ed. in English)
|July 15, 2026
Summary
Researchers engineered a novel tandem aminase enzyme for sustainable, one-pot synthesis of diverse tertiary amines. This biocatalytic approach offers precise stereochemical control, addressing a key challenge in medicinal chemistry.
Area of Science:
- Biocatalysis and Enzyme Engineering
- Organic Synthesis
- Medicinal Chemistry
Background:
- Tertiary amines are crucial structural motifs in many bioactive molecules.
- Current chemical synthesis methods for tertiary amines often lack sustainability.
- Biocatalytic routes for synthesizing tertiary amines are underdeveloped.
Purpose of the Study:
- To develop innovative and sustainable catalytic strategies for tertiary amine synthesis.
- To engineer a novel biocatalyst capable of efficient and stereoselective tertiary amine production.
Main Methods:
- Engineering a wild-type imine reductase into a tandem aminase (AHTanAm) for consecutive intermolecular reductive aminations.
- Utilizing X-ray crystallography and mutagenesis for mechanistic dissection of enzyme activity.
- Demonstrating one-pot synthesis of a wide range of tertiary amines from primary amine precursors.
Main Results:
- The engineered tandem aminase (AHTanAm) enables the one-pot synthesis of hundreds of tertiary amines.
- The biocatalyst exhibits precise stereochemical control over multiple stereocenters.
- Enzyme-pocket alterations were identified as key to amplifying the second-step amination activity, driving tandem catalysis.
Conclusions:
- This study presents the first engineered tandem aminase for tertiary amine synthesis via imine reductase redesign.
- The developed biocatalyst offers a sustainable and stereoselective alternative to traditional chemical synthesis.
- This work addresses a critical synthetic challenge, providing access to valuable tertiary amine compounds.
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