Journal
NATURE BIOTECHNOLOGY
Volume 40, Issue 12, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41587-022-01364-5
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Funding
- Defense Advanced Research Projects Agency Advanced Plant Technologies [HR001118C0137]
- National Science Foundation [NSF- 2128287, NSF-2128016, NSF-2128246]
- National Science Foundation Graduate Research Fellowship Program
- National Institutes of Health National Institute on Drug Abuse [1R21DA053496-01]
- National Science Foundation Plants3D NRT project [NSF-1922642]
- Medical College of Wisconsin
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This study presents a method for constructing biosensors using the PYR1 plant receptor and successfully evolves sensors with different sensitivities for various small molecules. The PYR1 receptor can be applied to different ligand-responsive outputs, demonstrating high sensitivity.
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. Biosensors are developed from malleable hormone receptors.
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