Inspired by the resourcefulness of nature to expand protein and enzyme functionality through the recruitment of cofactors, protein engineers have continued to expand biomolecular functionality by designing artificial cofactors. Artificial cofactor engineering as a strategy to advance biocatalysis in collaboration with directed evolution has produced enzymes capable of efficiently performing numerous valuable chemical transformations. Contrary to the abundance of two electron metal-mediated chemistry in artificial cofactor biocatalysis, there are few examples of radical activity being engineered into enzymes. Photoinduced electron transfer events provide a facile means to generate highly reactive intermediates at ambient temperature, bypassing thermal barriers and permitting access to unique reactivity patterns making it an attractive alternative and compliment to two electron transformations. Here we report the preparation, characterization, and application of twelve novel artificial enzymes with photocatalytic redox reactivity. Two derivatives of the organic photoredox catalyst, 9-mesityl-10-phenyl acirindium (Mes-Acr+), were synthesized and covalently tethered to three thermostable protein scaffolds, which were found through a computational screening effort of the Protein Data Bank. Importantly, we first analyzed the ground and excited-state properties of the free and scaffold-bound Mes-Acr+ cofactors, as the photophysical properties of a photocatalyst govern the photocatalytic activity. The artificial photoredox enzymes were found to be efficient photoinduced sulfoxidation catalysts acting on a variety of aryl thioethers and possessed activities that correlated with the photophysical characterization data. We anticipate that the general computational platform for artificial cofactor host identification, strategy of merging photocatalytic radical chemistry with biocatalysis, as well as the specific Mes-Acr+ enzymes presented will all be informative and relevant for future artificial biocatalysis developments.

Artificial cofactors to design photoredox biocatalysts: Novel scaffolds and cofactors

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.