An Asymmetric Hydrogen Atom Transferase with an Abiological Thiophenol Cofactor

Biocatalytic hydrogen atom transfer (HAT) holds the potential
to
help address some long-standing challenges in organic synthesis. Although
several families of enzymes rely on cysteine to perform HAT, these
enzymes are rather impractical for synthetic purposes. To circumvent
possible side reactions associated with cysteinyl radicals, we report
herein artificial hydrogen atom transferases (AHATases) with an abiological
thiophenol cofactor, capitalizing on biotin–streptavidin technology.
Chemogenetic optimization afforded an AHATase with good reactivity
and high enantioselectivity (er up to 93:7) for the photoinduced radical
hydroamination of alkenes. Crystal structures suggest that aromatic-sulfur
interactions are key contributing factors to cofactor anchoring and
enantioinduction. Mechanistic studies support H atom abstraction and
donation processes, both of which are catalyzed by the AHATase. Our
work highlights the synthetic potential of thiol-based biocatalytic
HAT and expands the repertoire of HAT biocatalysis.