Photoexcitation of flavoenzymes enables a stereoselective radical cyclization

Biegasiewicz, Kyle F.; Cooper, Simon J.; Gao, Xin; Oblinsky, Daniel G.; Kim, Ji Hye; Garfinkle, Samuel E.; Joyce, Leo A.; Sandoval, Braddock A.; Scholes, Gregory D.; Hyster, Todd K.

doi:10.1126/science.aaw1143

Title: Photoexcitation of flavoenzymes enables a stereoselective radical cyclization

Journal Article · 20 June 2019 · Science

DOI: https://doi.org/10.1126/science.aaw1143 · OSTI ID:1528674

;

; Kim, Ji Hye;

; Joyce, Leo A.; Sandoval, Braddock A.; Scholes, Gregory D.;

Photoexcitation is a common strategy for initiating radical reactions in chemical synthesis. We found that photoexcitation of flavin-dependent “ene”-reductases changes their catalytic function, enabling these enzymes to promote an asymmetric radical cyclization. This reactivity enables the construction of five-, six-, seven-, and eight-membered lactams with stereochemical preference conferred by the enzyme active site. After formation of a prochiral radical, the enzyme guides the delivery of a hydrogen atom from flavin—a challenging feat for small-molecule chemical reagents. The initial electron transfer occurs through direct excitation of an electron donor-acceptor complex that forms between the substrate and the reduced flavin cofactor within the enzyme active site. Photoexcitation of promiscuous flavoenzymes has thus furnished a previously unknown biocatalytic reaction.

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Sponsoring Organization:: USDOE

Grant/Contract Number:: SC0019370

OSTI ID:: 1528674

Journal Information:: Science, Journal Name: Science Journal Issue: 6446 Vol. 364; ISSN 0036-8075

Publisher:: American Association for the Advancement of Science (AAAS)Copyright Statement

Country of Publication:: United States

Language:: English

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