Catalysis

Controlling Non-Native B12 Reactivity and Catalysis in the Transcription Factor CarH

Authors

Abstract

Vitamin B12 derivatives catalyze a wide range of organic transformations, but B12-dependent enzymes are underutilized in biocatalysis relative to other metalloenzymes. In this study, we engineered a variant of the transcription factor CarH, called CarH*, that catalyzes styrene C-H alkylation with improved yield and selectivity relative to B12 itself. While the native function of CarH involves transcription regulation via AdoCbl Co(III)-carbon bond cleavage and β-hydride elimination to generate 4’,5’-didehydroadenosine, CarH*-catalyzed styrene alkylation proceeds via non-native oxidative addition and olefin addition coupled with a native-like β-hydride elimination. Mechanistic studies on this reaction echo findings from earlier studies on AdoCbl homolysis under strong cage conditions to suggest that CarH* can enable non-native radical chemistry with improved selectivity relative to B12 itself. These findings lay the groundwork for the development of B12-dependent enzymes as catalysts for a wide range of non-native transformations.

Content

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Supplementary material

Thumbnail image of CarH_styrene_SI_10_13.pdf
Supporting Information for Controlling Non-Native B12 Reactivity and Catalysis in the Transcription Factor CarH
Supplemental figures, experimental and computational methods, and data for material characterization.
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