Rapid biosensor development using plant hormone receptors as reprogrammable scaffolds

Jesús Beltrán, Paul J. Steiner, Matthew Bedewitz, Shuang Wei, Francis C. Peterson, Zongbo Li, Brigid E. Hughes, Zachary Hartley, Nicholas R. Robertson, Angélica V. Medina-Cucurella, Zachary T. Baumer, Alison C. Leonard, Sang Youl Park, Brian F. Volkman, Dmitri A. Nusinow, Wenwan Zhong, Ian Wheeldon, Sean R. Cutler, Timothy A. Whitehead

Research output: Contribution to journalArticlepeer-review

26 Scopus citations


A general method to generate biosensors for user-defined molecules could provide detection tools for a wide range of biological applications. Here, we describe an approach for the rapid engineering of biosensors using PYR1 (Pyrabactin Resistance 1), a plant abscisic acid (ABA) receptor with a malleable ligand-binding pocket and a requirement for ligand-induced heterodimerization, which facilitates the construction of sense–response functions. We applied this platform to evolve 21 sensors with nanomolar to micromolar sensitivities for a range of small molecules, including structurally diverse natural and synthetic cannabinoids and several organophosphates. X-ray crystallography analysis revealed the mechanistic basis for new ligand recognition by an evolved cannabinoid receptor. We demonstrate that PYR1-derived receptors are readily ported to various ligand-responsive outputs, including enzyme-linked immunosorbent assay (ELISA)-like assays, luminescence by protein-fragment complementation and transcriptional circuits, all with picomolar to nanomolar sensitivity. PYR1 provides a scaffold for rapidly evolving new biosensors for diverse sense–response applications.

Original languageEnglish
Pages (from-to)1855-1861
Number of pages7
JournalNature Biotechnology
Issue number12
StatePublished - Dec 2022


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