Controlling Non-Native Cobalamin Reactivity and Catalysis in the Transcription Factor CarH.
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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 -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 -hydride elimination. Mechanistic studies on this reaction echo findings from earlier studies on AdoCbl homolysis to suggest that CarH* selectivity results from its ability to impart a cage effect on radical intermediates. These findings lay the groundwork for the development of B12-dependent enzymes as catalysts for non-native transformations.
author list (cited authors)
Yang, X., Gerroll, B., Jiang, Y., Kumar, A., Zubi, Y. S., Baker, L. A., & Lewis, J. C.
complete list of authors
Yang, Xinhang||Gerroll, Benjamin HR||Jiang, Yuhua||Kumar, Amardeep||Zubi, Yasmine S||Baker, Lane A||Lewis, Jared C