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Publication Abstract from PubMed

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.

Rapid biosensor development using plant hormone receptors as reprogrammable scaffolds.,Beltran J, Steiner PJ, Bedewitz M, Wei S, Peterson FC, Li Z, Hughes BE, Hartley Z, Robertson NR, Medina-Cucurella AV, Baumer ZT, Leonard AC, Park SY, Volkman BF, Nusinow DA, Zhong W, Wheeldon I, Cutler SR, Whitehead TA Nat Biotechnol. 2022 Jun 20. doi: 10.1038/s41587-022-01364-5. PMID:35726092^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.