An L-2-hydroxyglutarate biosensor based on specific transcriptional regulator LhgR.
An L-2-hydroxyglutarate biosensor based on specific transcriptional regulator LhgR.
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DOI：
10.1038/s41467-021-23723-7
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发表时间：
2021-06-15
影响因子：
16.6
通讯作者：
Xu P
中科院分区：
文献类型：
--
作者：
Kang Z;Zhang M;Gao K;Zhang W;Meng W;Liu Y;Xiao D;Guo S;Ma C;Gao C;Xu P
l-2-羟戊二酸（l-2-HG）在碳饥饿反应、肿瘤发生和缺氧适应等多种生理过程中发挥重要作用。尽管l-2-HG代谢的重要性和被广泛研究，但对其代谢的调节仍知之甚少，没有一种调节因子对l-2-HG有特异性反应。本研究通过细菌基因组邻域分析，确定了恶臭假单胞菌W619中抑制LhgO转录的l-2-HG氧化酶（LhgO）基因。LhgR被证明可以识别l-2-HG作为其特异性效应分子，然后该变构转录因子被用作生物识别元件来构建l-2-HG传感FRET传感器。l-2-HG传感器能够方便地监测各种生物样品中l-2-HG的浓度。除了细菌在碳饥饿过程中产生l-2-HG外，利用l-2-HG传感器还揭示了l-2-HG脱氢酶的生物学功能和缺氧诱导的l-2-HG积累。l -2-羟基戊二酸（L-2-HG）是一种重要的代谢物，但其调控机制尚不清楚。在这里，作者报告了一种基于变构转录因子LhgR的L-2-HG FRET生物传感器，用于监测细胞和生物样品中的L-2-HG。
l-2-Hydroxyglutarate (l-2-HG) plays important roles in diverse physiological processes, such as carbon starvation response, tumorigenesis, and hypoxic adaptation. Despite its importance and intensively studied metabolism, regulation of l-2-HG metabolism remains poorly understood and none of regulator specifically responded to l-2-HG has been identified. Based on bacterial genomic neighborhood analysis of the gene encoding l-2-HG oxidase (LhgO), LhgR, which represses the transcription of lhgO in Pseudomonas putida W619, is identified in this study. LhgR is demonstrated to recognize l-2-HG as its specific effector molecule, and this allosteric transcription factor is then used as a biorecognition element to construct an l-2-HG-sensing FRET sensor. The l-2-HG sensor is able to conveniently monitor the concentrations of l-2-HG in various biological samples. In addition to bacterial l-2-HG generation during carbon starvation, biological function of the l-2-HG dehydrogenase and hypoxia induced l-2-HG accumulation are also revealed by using the l-2-HG sensor in human cells. L-2-hydroxyglutarate (L-2-HG) is an important metabolite but its regulation is poorly understood. Here the authors report an L-2-HG FRET biosensor based on the allosteric transcription factor, LhgR, to monitor L-2-HG in cells and biological samples.
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影响因子：
16.1
作者：
Chen, Xiaoying;Zaro, Jennica L.;Shen, Wei-Chiang
通讯作者：
Shen, Wei-Chiang
DOI：
10.1073/pnas.1614102114
发表时间：
2017-02-07
影响因子：
11.1
作者：
Li, Hongde;Chawla, Geetanjali;Tennessen, Jason M.
通讯作者：
Tennessen, Jason M.
影响因子：
64.8
作者：
通讯作者：
--
利用细菌变构转录因子先前未知的能力在体外感测不同的小分子。
影响因子：
13.6
作者：
Cao J;Yao Y;Fan K;Tan G;Xiang W;Xia X;Li S;Wang W;Zhang L
通讯作者：
Zhang L
源自 CRISPR-Cas12a 的生物传感平台，用于高灵敏度检测多种小分子
影响因子：
16.6
作者：
Liang, Mindong;Li, Zilong;Zhang, Li-Xin
通讯作者：
Zhang, Li-Xin