@article {70449,
	title = {Design and evolution of the tetracycline repressor into sulfonylurea herbicide-responsive gene switches for field crops.},
	journal = {Nat Commun},
	year = {2026},
	month = {2026 Jun 08},
	abstract = {<p>Chemically inducible expression systems enable transgene expression regulation in response to external small molecules. Tetracycline repressor (TetR)-based gene switches work in plants, but antibiotics are neither approved nor advisable for crop use. Here we report engineering of TetR mutants that respond to approved sulfonylurea (SU) herbicides instead of antibiotics. Designed variants show low-nanomolar EC values for ethametsulfuron-methyl (Es) or chlorsulfuron and tightly bind the Tet operator sequence, but only in the absence of corresponding SUs. Crystal structures of two repressors in complex with their respective SU ligands reveal extensive interactions explaining their strong binding. The Es repressor-based gene switch is introduced into tobacco, soybean, maize, rice, and Arabidopsis, and robust reporter gene activation is observed upon herbicide application. Addition of a repressor-regulated siRNA targeting the repressor transcript increases the magnitude and spatial distribution of the response following herbicide treatment and results in a partially bistable gene switch. The SU repressors also function well in mammalian cell culture and may enable regulation of additional genes in conjunction with TetR.</p>
},
	issn = {2041-1723},
	doi = {10.1038/s41467-026-73848-w},
	url = {https://doi.org/10.1038/s41467-026-73848-w},
	author = {McBride, Kevin E and Kakani, Naga Kishore and Bozhanova, Nina G and Fang, Jin and Lowe, Keith and Leija, Christopher and McGonigle, Brian and Schreiter, Eric R and Hermanson, Flynn and Chan, Mandy and Arling, Maren and Wang, Ning and Cho, Hyeon-Je and Richey, Christian and Hoerster, George and Marvin, Jonathan S and Lenderts, Brian and McReynolds, Maxwell R and Hastings, Craig and Madrigal, Alfredo and Falco, S Carl and Lassner, Michael W and Anand, Ajith and Gordon-Kamm, William and Looger, Loren L}
}
