美国科罗拉多大学博尔德分校Timothy A. Whitehead，美国加州大学Sean R. Cutler和Ian Wheeldon共同合作，近期取得重要工作进展，他们利用植物激素受体作为可重复编程的支架快速开发生物传感器。该项研究成果2022年6月20日在线发表于《自然—生物技术》杂志上。

在这里，研究人员描述了一种使用PYR1（Pyrabactin Resistance 1）快速设计生物传感器的方法，PYR1 是一种植物脱落酸 (ABA) 受体，具有可延展的配体结合口袋，并且需要配体诱导的异二聚化，这有助于构建感觉-反应功能。研究人员应用该平台开发了21个传感器，其对一系列小分子具有纳摩尔到微摩尔的灵敏度，包括结构多样的天然和合成大麻素以及几种有机磷酸盐。X射线晶体学分析揭示了进化的大麻素受体识别新配体的机制基础。

他们证明PYR1衍生的受体很容易移植到各种配体反应输出中，包括酶联免疫吸附测定 (ELISA) 样测定、通过蛋白质片段互补的发光和转录环路，所有这些都具有皮摩尔到纳摩尔的灵敏度。PYR1为快速发展的新生物传感器提供了一个支架，用于不同的感觉-反应应用。

据介绍，一种为用户定义的分子生成生物传感器的通用方法可以为广泛的生物应用提供检测工具。

附：英文原文

Title: Rapid biosensor development using plant hormone receptors as reprogrammable scaffolds

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

Issue&Volume: 2022-06-20

Abstract: 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.

DOI: 10.1038/s41587-022-01364-5

Source: https://www.nature.com/articles/s41587-022-01364-5