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

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 yields (2-6.5-fold) and selectivity relative to cobalamin. While the native function of CarH involves transcription regulation via adenosylcobalamin (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 ea

SUBMITTER: Yang X 

PROVIDER: S-EPMC8955669 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature