An orthogonalized PYR1-based CID module with reprogrammable ligand-binding specificity
Abstract
Plants sense abscisic acid (ABA) using chemical-induced dimerization (CID) modules, including the receptor PYR1 and HAB1, a phosphatase inhibited by ligand-activated PYR1. This system is unique because of the relative ease with which ligand recognition can be reprogrammed. To expand the PYR1 system, we designed an orthogonal ‘*’ module, which harbors a dimer interface salt bridge; X-ray crystallographic, biochemical and in vivo analyses confirm its orthogonality. We used this module to create PYR1*MANDI/HAB1* and PYR1*AZIN/HAB1*, which possess nanomolar sensitivities to their activating ligands mandipropamid and azinphos-ethyl. Experiments in Arabidopsis thaliana and Saccharomyces cerevisiae demonstrate the sensitive detection of banned organophosphate contaminants using living biosensors and the construction of multi-input/output genetic circuits. Our new modules enable ligand-programmable multi-channel CID systems for plant and eukaryotic synthetic biology that can empower new plant-based and microbe-based sensing modalities.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Oct 23, 2023
- Source ID
- 10.1038/s41589-023-01447-7
Entities
People
- Aditya S. Vaidya
- Angélica V. Medina-cucurella
- Brian F Volkman
- Dmitri A. Nusinow
- Francis C. Peterson
- Ian R Wheeldon
- Jesús Beltrán
- Jingde Qiu
- Sang-Youl Park
- Sean Cutler
- Shuang Wei
- Timothy A Whitehead
- Zenan Xing
Organizations
- National Institute on Drug Abuse
- National Science Foundation
- United States Department of Defense