A genetically encoded biosensor for point-of-care and live-cell detection of d-2-hydroxyglutarate
Yidong Liu,
Zhaoqi Kang,
Rong Xu,
Shuang Hou,
Lingru Gong,
Leilei Guo,
Kaiyu Gao,
Xianzhi Xu,
Xiaoxu Tan,
Dan Xiao,
Wen Zhang,
Gang Wang,
Shaowu Ou,
Jinqu Hu,
Jiyuan Liu,
Chuanjuan Lü,
Cuiqing Ma,
Ping Xu and
Chao Gao ()
Additional contact information
Yidong Liu: Shandong University
Zhaoqi Kang: Shandong University
Rong Xu: Shandong University
Shuang Hou: Shandong University
Lingru Gong: Shandong University
Leilei Guo: Shandong University
Kaiyu Gao: Shandong University
Xianzhi Xu: Shandong University
Xiaoxu Tan: Shandong University
Dan Xiao: Shandong University
Wen Zhang: Shandong University
Gang Wang: The First Hospital of China Medical University
Shaowu Ou: The First Hospital of China Medical University
Jinqu Hu: The First Hospital of China Medical University
Jiyuan Liu: The First Hospital of China Medical University
Chuanjuan Lü: Shandong University
Cuiqing Ma: Shandong University
Ping Xu: Shanghai Jiao Tong University
Chao Gao: Shandong University
Nature Communications, 2025, vol. 16, issue 1, 1-18
Abstract:
Abstract d-2-Hydroxyglutarate (d-2-HG) is a functional endogenous metabolite in various domains of life. Its abnormal accumulation promotes human tumorigenesis. Convenient d-2-HG testing for diagnosis and prognosis of d-2-HG-related diseases remains technically challenging, and there is no analytical method to directly detect d-2-HG in living cells. Here, we identify a d-2-HG-specific transcriptional activator, HgcR, and develop a d-2-HG sensor (DHOR) using HgcR as a sensing moiety. Then, we build a portable device adaptive with DHOR for rapid and low-cost point-of-care d-2-HG testing in serum, urine, and glioma tissue samples. DHOR also allow spatiotemporal resolution of d-2-HG in living bacteria and human cells. We use DHOR to identify d-2-HG transporters from Escherichia coli and human solute carrier 22 family. Overall, DHOR provides a powerful and versatile tool for in vitro and live-cell detection of d-2-HG, offering the opportunity to deepen our understanding about physiological and pathogenetic roles of d-2-HG.
Date: 2025
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-62225-8
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DOI: 10.1038/s41467-025-62225-8
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