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Title: Photoexcitation of flavoenzymes enables a stereoselective radical cyclization

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. As a result, photoexcitation of promiscuous flavoenzymes has thus furnished a previously unknown biocatalytic reaction.

Authors:
ORCiD logo [1]; ORCiD logo [1]; ORCiD logo [1]; ORCiD logo [1];  [1]; ORCiD logo [1];  [2];  [1];  [1]; ORCiD logo [1]
  1. Princeton Univ., Princeton, NJ (United States)
  2. Dept.of Process Research and Development, Rahway, NJ (United States)
Publication Date:
Research Org.:
Princeton Univ., NJ (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22)
OSTI Identifier:
1528674
Alternate Identifier(s):
OSTI ID: 1529103
Grant/Contract Number:  
SC0019370
Resource Type:
Published Article
Journal Name:
Science
Additional Journal Information:
Journal Volume: 364; Journal Issue: 6446; Journal ID: ISSN 0036-8075
Publisher:
AAAS
Country of Publication:
United States
Language:
English

Citation Formats

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., and Hyster, Todd K. Photoexcitation of flavoenzymes enables a stereoselective radical cyclization. United States: N. p., 2019. Web. doi:10.1126/science.aaw1143.
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. Photoexcitation of flavoenzymes enables a stereoselective radical cyclization. United States. doi:10.1126/science.aaw1143.
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., and Hyster, Todd K. Fri . "Photoexcitation of flavoenzymes enables a stereoselective radical cyclization". United States. doi:10.1126/science.aaw1143.
@article{osti_1528674,
title = {Photoexcitation of flavoenzymes enables a stereoselective radical cyclization},
author = {Biegasiewicz, Kyle F. and Cooper, Simon J. and Gao, Xin and Oblinsky, Daniel G. and Kim, Ji Hye and Garfinkle, Samuel E. and Joyce, Leo A. and Sandoval, Braddock A. and Scholes, Gregory D. and Hyster, Todd K.},
abstractNote = {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. As a result, photoexcitation of promiscuous flavoenzymes has thus furnished a previously unknown biocatalytic reaction.},
doi = {10.1126/science.aaw1143},
journal = {Science},
number = 6446,
volume = 364,
place = {United States},
year = {2019},
month = {6}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record
DOI: 10.1126/science.aaw1143

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