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The corrinoid protein MtaC, which is natively involved in methyl transferase catalysis, catalyzes N -alkylation of aniline using ethyl diazoacetate. Our results show how the native preference of B 12 scaffolds for radical versus polar chemistry translates to non-native catalysis, which could guide selection of B 12 -dependent proteins for biocatalysis. MtaC also has high thermal stability and organic solvent tolerance, remaining folded even in pure methanol.
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Non‐native Intramolecular Radical Cyclization Catalyzed by a B 12 ‐Dependent Enzyme**
Abstract Despite the unique reactivity of vitamin B12and its derivatives, B12‐dependent enzymes remain underutilized in biocatalysis. In this study, we repurposed the B12‐dependent transcription factor CarH to enable non‐native radical cyclization reactions. An engineered variant of this enzyme, CarH*, catalyzes the formation γ‐ and δ‐lactams through either redox‐neutral or reductive ring closure with marked enhancement of reactivity and selectivity relative to the free B12cofactor. CarH* also catalyzes an unusual spirocyclization by dearomatization of pendant arenes to produce bicyclic 1,3‐diene products instead of 1,4‐dienes provided by existing methods. These results and associated mechanistic studies highlight the importance of protein scaffolds for controlling the reactivity of B12and expanding the synthetic utility of B12‐dependent enzymes.
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- Award ID(s):
- 2154726
- PAR ID:
- 10479298
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Angewandte Chemie International Edition
- Volume:
- 62
- Issue:
- 51
- ISSN:
- 1433-7851
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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