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Published on: October 2, 2012
Reprogramming ThDP Enzymes for Z-Alkenes: Overriding Thermodynamic Preference via Noncovalent Controls
Huangong Li1,2, Tairan Yang1, Yilong Zhao1
1State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai200237, China.
Journal of the American Chemical Society
|July 30, 2026
Summary
Researchers reprogrammed a thiamine diphosphate (ThDP)-dependent enzyme for selective Z-alkene synthesis. This biocatalytic approach overcomes thermodynamic bias, offering a sustainable method for producing Z-α,β-unsaturated carboxylic acids.
Area of Science:
- Biocatalysis
- Organic Chemistry
- Enzyme Engineering
Background:
- Conventional alkene synthesis favors thermodynamically stable E-isomers, complicating direct Z-alkene production.
- Accessing Z-alkenes often requires complex substrate control or directing groups.
- Thiamine diphosphate (ThDP)-dependent enzymes are crucial in various metabolic pathways.
Purpose of the Study:
- To reprogram a ThDP-dependent enzyme for selective Z-alkene synthesis.
- To develop a biocatalytic method that overrides thermodynamic bias in alkene formation.
- To establish a sustainable alternative to conventional Z-alkene synthesis strategies.
Main Methods:
- Enzyme reprogramming of a ThDP-dependent enzyme.
- Catalysis of a formal dehalogenative elimination reaction.
- Utilizing the enzyme's active site for kinetic control via noncovalent interactions.
- Rational active-site engineering for stereochemical inversion.
Main Results:
- Achieved direct and selective synthesis of Z-α,β-unsaturated carboxylic acids.
- Demonstrated kinetic control through noncovalent interactions within the enzyme's active site.
- Successfully inverted stereochemical outcome via active-site engineering to produce E-isomers.
- Established a stereodivergent synthesis platform from a common scaffold.
Conclusions:
- The engineered enzyme provides a novel biocatalytic platform for Z-alkene synthesis.
- This approach offers a sustainable and stereoselective alternative to traditional chemical methods.
- The work expands the catalytic capabilities of ThDP-dependent enzymes beyond their native functions.
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