An orthogonalized PYR1-based CID module with reprogrammable ligand-binding specificity.

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. © 2023. The Author(s).

Citation

Sang-Youl Park, Jingde Qiu, Shuang Wei, Francis C Peterson, Jesús Beltrán, Angélica V Medina-Cucurella, Aditya S Vaidya, Zenan Xing, Brian F Volkman, Dmitri A Nusinow, Timothy A Whitehead, Ian Wheeldon, Sean R Cutler. An orthogonalized PYR1-based CID module with reprogrammable ligand-binding specificity. Nature chemical biology. 2024 Jan;20(1):103-110

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PMID: 37872402

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