@article{e9087a452a1a4ea9827558ae64996cf9,
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. Photoexcitation of promiscuous flavoenzymes has thus furnished a previously unknown biocatalytic reaction.",
author = "Biegasiewicz, {Kyle F.} and Cooper, {Simon J.} and Xin Gao 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.}",
note = "Funding Information: We thank M. Souza for preparing glassware for spectroscopy studies, C. Kraml and L. Wilson at Lotus Separations for compound purification, P. Jeffrey for assistance with x-ray structure determination, K. Conover for assistance in photoNMR data acquisition, and the staff of NSLS-II beamline FMX (17-ID-2) for help with data collection. Research reported in this publication was supported by the National Institutes of Health (NIH) National Institute of General Medical Sciences (NIGMS) (R01 GM127703), the Searle Scholars Award (SSP-2017-1741), Sloan Research Fellowship, the Princeton Catalysis Initiative, and Princeton University. D.G.O. acknowledges support from the Postgraduate Scholarships Doctoral Program of the Natural Sciences and Engineering Research Council of Canada. D.G.O. and G.D.S. acknowledge support from the Division of Chemical Sciences, Geosciences, and Biosciences, Office of Basic Energy Sciences of the U.S. Department of Energy (DOE) through grant DE-SC0019370. The AMX (17-ID) beamline of The Life Science Biomedical Technology Research (LSBR) resource is primarily supported by NIH, NIGMS through a Biomedical Technology Research Resource P41 grant (P41GM111244), and by the DOE Office of Biological and Environmental Research (KP1605010). As a National Synchrotron Light Source II facility resource at Brookhaven National Laboratory, work performed at LSBR is supported in part by the DOE Office of Science, Office of Basic Energy Sciences Program under contract DE-SC0012704 (KC0401040). Publisher Copyright: {\textcopyright} 2019 American Association for the Advancement of Science. All rights reserved.",
year = "2019",
doi = "10.1126/science.aaw1143",
language = "English (US)",
volume = "364",
pages = "1166--1169",
journal = "Science",
issn = "0036-8075",
publisher = "American Association for the Advancement of Science",
number = "6446",
}