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Unlocking a Nitrosuccinate Lyase for Decarboxylative Enzymatic Hydronitration
Matteo Aleotti1, Hannah Dreisbach1, Rémi Corlay1
1Institute of Chemistry, University of Graz, Graz, Austria.
Angewandte Chemie (International Ed. in English)
|May 28, 2026
Summary
Researchers repurposed an enzyme for biocatalytic hydronitration, a novel method for synthesizing nitro compounds. This efficient enzymatic strategy offers a green chemistry approach for creating valuable chemical motifs.
Area of Science:
- Biocatalysis
- Synthetic Chemistry
- Enzyme Engineering
Background:
- Nitro compounds are essential in synthetic chemistry.
- Mild and selective biocatalytic methods for nitro compound synthesis are lacking.
- Enzymatic strategies offer potential for green chemistry approaches.
Purpose of the Study:
- To develop a novel biocatalytic route for synthesizing nitro compounds.
- To repurpose the nitrosuccinate lyase CreD for hydronitration.
- To explore the efficiency and scope of this enzymatic strategy.
Main Methods:
- Enzyme repurposing of nitrosuccinate lyase CreD.
- Biocatalytic hydronitration using sodium nitrite.
- Comprehensive mutagenesis and computational analysis.
- QM/MM simulations for mechanism elucidation.
Main Results:
- CreD and homologues efficiently catalyze hydronitration of fumarate.
- High turnover numbers (up to 102,000) and atom economy were achieved.
- Key molecular determinants for nucleophile selectivity and enzyme assembly were identified.
- A diagnostic fingerprint for predicting hydronitration activity was defined.
Conclusions:
- Enzymatic hydronitration is a viable and efficient biocatalytic strategy.
- Repurposed enzymes offer a sustainable route to nitro compounds.
- Molecular insights pave the way for expanding biocatalytic Michael-type additions.
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