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Published on: September 6, 2019
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Structure-Guided Reprogramming of a Hydroxylase To Halogenate Its Small Molecule Substrate
Andrew J Mitchell, Noah P Dunham, Jonathan A Bergman
1Department of Chemistry, University of Pittsburgh , Pittsburgh, Pennsylvania 15260, United States.
Biochemistry
|December 29, 2016
Summary
Enzymatic halogenation using iron(II) and 2-(oxo)-glutarate (FeII/2OG)-dependent enzymes offers a green alternative to chemical methods. Researchers reprogrammed a hydroxylase enzyme to create a new chiral haloalkyl center, showcasing potential for stereospecific catalysis.
Area of Science:
- Biocatalysis and Enzyme Engineering
- Organic Chemistry
- Green Chemistry
Background:
- Chemical halogenation often lacks selectivity and uses harsh conditions.
- Iron(II) and 2-(oxo)-glutarate (FeII/2OG)-dependent halogenases are known biocatalysts for C-H bond functionalization.
- Enzymatic approaches offer greener and more selective alternatives for introducing halogens.
Purpose of the Study:
- To explore the potential of FeII/2OG enzymes for selective halogenation of unactivated carbon centers.
- To reprogram an N-acyl amino acid hydroxylase (SadA) for halogenation activity.
- To generate a novel chiral haloalkyl center using biocatalysis.
Main Methods:
- Utilized the structural information of the FeII/2OG halogenase WelO5.
- Identified and reprogrammed a homologous N-acyl amino acid hydroxylase, SadA.
- Investigated the substrate specificity and catalytic activity of the engineered enzyme.
Main Results:
- Successfully reprogrammed SadA to perform halogenation of its substrate.
- Generated a new chiral haloalkyl center with high stereospecificity.
- Demonstrated the versatility of FeII/2OG enzymes as platforms for catalyst development.
Conclusions:
- FeII/2OG enzymes can be engineered for novel halogenation reactions.
- Reprogrammed SadA provides a stereospecific route to chiral haloalkyl compounds.
- This work highlights the potential for developing novel biocatalysts for late-stage C-H functionalization.
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