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

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

Research output: Contribution to journalArticlepeer-review

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. [Figure not available: see fulltext.].

Original languageEnglish
Pages (from-to)103-110
Number of pages8
JournalNature Chemical Biology
Volume20
Issue number1
DOIs
StatePublished - Jan 2024

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