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A GPCR-based yeast biosensor for biomedical, biotechnological, and point-of-use cannabinoid determination
Nature Communications ( IF 14.7 ) Pub Date : 2022-06-27 , DOI: 10.1038/s41467-022-31357-6
Karel Miettinen 1 , Nattawat Leelahakorn 1 , Aldo Almeida 1, 2 , Yong Zhao 1 , Lukas R Hansen 1 , Iben E Nikolajsen 1 , Jens B Andersen 3 , Michael Givskov 3 , Dan Staerk 4 , Søren Bak 1 , Sotirios C Kampranis 1
Affiliation  

Eukaryotic cells use G-protein coupled receptors to sense diverse signals, ranging from chemical compounds to light. Here, we exploit the remarkable sensing capacity of G-protein coupled receptors to construct yeast-based biosensors for real-life applications. To establish proof-of-concept, we focus on cannabinoids because of their neuromodulatory and immunomodulatory activities. We construct a CB2 receptor-based biosensor, optimize it to achieve high sensitivity and dynamic range, and prove its effectiveness in three applications of increasing difficulty. First, we screen a compound library to discover agonists and antagonists. Second, we analyze 54 plants to discover a new phytocannabinoid, dugesialactone. Finally, we develop a robust portable device, analyze body-fluid samples, and confidently detect designer drugs like JWH-018. These examples demonstrate the potential of yeast-based biosensors to enable diverse applications that can be implemented by non-specialists. Taking advantage of the extensive sensing repertoire of G-protein coupled receptors, this technology can be extended to detect numerous compounds.



中文翻译:

用于生物医学、生物技术和使用点大麻素测定的基于 GPCR 的酵母生物传感器

真核细胞使用 G 蛋白偶联受体来感知从化合物到光的各种信号。在这里,我们利用 G 蛋白偶联受体的显着传感能力来构建基于酵母的生物传感器,用于现实生活中的应用。为了建立概念验证,我们专注于大麻素,因为它们具有神经调节和免疫调节活性。我们构建一个 CB 2基于受体的生物传感器,对其进行优化以实现高灵敏度和动态范围,并在难度越来越大的三个应用中证明其有效性。首先,我们筛选化合物库以发现激动剂和拮抗剂。其次,我们分析了 54 种植物,以发现一种新的植物大麻素 dugesialactone。最后,我们开发了一种强大的便携式设备,分析体液样本,并自信地检测 JWH-018 等设计药物。这些示例展示了基于酵母的生物传感器在实现可由非专业人员实施的各种应用方面的潜力。利用 G 蛋白偶联受体的广泛传感库,该技术可以扩展到检测多种化合物。

更新日期:2022-06-27
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