Myoglobin-Catalyzed Azide Reduction Proceeds via an Anionic Metal Amide Intermediate.
Matthias Tinzl1, Johannes V Diedrich2, Peer R E Mittl3
1Laboratory of Organic Chemistry, ETH Zürich, 8093 Zürich, Switzerland.
Journal of the American Chemical Society
|January 24, 2024
Summary
Heme proteins catalyze nitrene transfer for C-N bond formation. This study reveals how myoglobin reduces azides, detailing the ferrous amide intermediate and its rate-limiting protonation, guiding enzyme engineering for better nitrene transferases.
Area of Science:
- Biocatalysis
- Bioinorganic Chemistry
- Enzyme Mechanisms
Background:
- Heme proteins catalyze nitrene transfer for stereoselective carbon-nitrogen bond formation.
- Biocatalytic nitrene transfer is limited by competing reduction of nitrene precursors.
Purpose of the Study:
- Investigate azide reduction by myoglobin to understand factors controlling reaction intermediates.
- Gain mechanistic insights into heme protein-catalyzed azide reduction.
Main Methods:
- UV/vis and Mössbauer spectroscopies
- Quantum mechanical calculations
- X-ray crystallography
Main Results:
- Characterized a ferrous amide intermediate formed via nitrene reduction and protonation.
- Identified rate-limiting protonation of the ferrous amide to form the amine product.
- Demonstrated a chemoenzymatic cascade for substituted pyrrole synthesis.
Conclusions:
- Mechanistic understanding of heme protein-catalyzed azide reduction.
- Provides a guide for engineering more efficient nitrene transferase enzymes.
- Chemoenzymatic cascade offers a practical route to substituted pyrroles.
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