An orthogonalized PYR1-based CID module with reprogrammable ligand-binding specificity.
Nat Chem Biol
; 20(1): 103-110, 2024 Jan.
Article
em En
| MEDLINE
| ID: mdl-37872402
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.
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MEDLINE
Assunto principal:
Arabidopsis
/
Proteínas de Arabidopsis
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article