Reference: Park SY, et al. (2024) An orthogonalized PYR1-based CID module with reprogrammable ligand-binding specificity. Nat Chem Biol 20(1):103-110

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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.

Reference Type
Journal Article | Research Support, N.I.H., Extramural
Authors
Park SY, Qiu J, Wei S, Peterson FC, Beltrán J, Medina-Cucurella AV, Vaidya AS, Xing Z, Volkman BF, Nusinow DA, ... Show all
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