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一种基于 G 蛋白偶联受体的酵母生物传感器,用于生物医学、生物技术和现场检测大麻素。

A GPCR-based yeast biosensor for biomedical, biotechnological, and point-of-use cannabinoid determination.

机构信息

Biochemical Engineering Group, Plant Biochemistry Section, Department of Plant and Environmental Sciences, University of Copenhagen, Thorvaldsensvej 40, 1871, Frederiksberg C, Denmark.

Bioremediation Laboratory, Faculty of Biological Sciences, Autonomous University of Coahuila, Carretera Torreón-Matamoros km. 7.5, Torreón, Coahuila, 27000, Mexico.

出版信息

Nat Commun. 2022 Jun 27;13(1):3664. doi: 10.1038/s41467-022-31357-6.

DOI:10.1038/s41467-022-31357-6
PMID:35760809
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9237071/
Abstract

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 CB 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.

摘要

真核细胞使用 G 蛋白偶联受体来感知各种信号,范围从化学化合物到光。在这里,我们利用 G 蛋白偶联受体的出色传感能力,构建基于酵母的生物传感器,用于实际应用。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。我们构建了一个基于 CB 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,并在三个难度不断增加的应用中证明其有效性。首先,我们筛选化合物文库以发现激动剂和拮抗剂。其次,我们分析 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,并自信地检测像 JWH-018 这样的设计药物。这些例子展示了基于酵母的生物传感器在使多样化的应用成为可能方面的潜力,这些应用可以由非专业人员实施。利用 G 蛋白偶联受体的广泛传感能力,这项技术可以扩展到检测许多化合物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/50fc/9237071/e18c2ee6282d/41467_2022_31357_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/50fc/9237071/d3570dae7686/41467_2022_31357_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/50fc/9237071/de0f94041b3e/41467_2022_31357_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/50fc/9237071/78b956655030/41467_2022_31357_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/50fc/9237071/5fcc3a7c8e6e/41467_2022_31357_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/50fc/9237071/fab0b4d0df44/41467_2022_31357_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/50fc/9237071/e18c2ee6282d/41467_2022_31357_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/50fc/9237071/d3570dae7686/41467_2022_31357_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/50fc/9237071/12d709143fe2/41467_2022_31357_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/50fc/9237071/1235cc4ab8b6/41467_2022_31357_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/50fc/9237071/de0f94041b3e/41467_2022_31357_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/50fc/9237071/78b956655030/41467_2022_31357_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/50fc/9237071/5fcc3a7c8e6e/41467_2022_31357_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/50fc/9237071/fab0b4d0df44/41467_2022_31357_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/50fc/9237071/e18c2ee6282d/41467_2022_31357_Fig8_HTML.jpg

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