Photoexcitation of flavoenzymes enables a stereoselective radical cyclization

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

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29 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1166-1169
Number of pages4
JournalScience
Volume364
Issue number6446
DOIs
StatePublished - 2019

All Science Journal Classification (ASJC) codes

  • General

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    Biegasiewicz, K. F., Cooper, S. J., Gao, X., Oblinsky, D. G., Kim, J. H., Garfinkle, S. E., Joyce, L. A., Sandoval, B. A., Scholes, G. D., & Hyster, T. K. (2019). Photoexcitation of flavoenzymes enables a stereoselective radical cyclization. Science, 364(6446), 1166-1169. https://doi.org/10.1126/science.aaw1143