A genetically encoded biosensor for point-of-care and live-cell detection of d-2-hydroxyglutarate
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.
Authors
- Lianggeng Gong (ORCID: https://orcid.org/0000-0002-2326-3423)
- Jinqu Hu (ORCID: https://orcid.org/0009-0003-7056-3431)
- Xiaoxu Tan
- Rong Xu (ORCID: https://orcid.org/0000-0001-5465-3566)
- Dan Xiao (ORCID: https://orcid.org/0000-0001-5295-0540)
- Zhaoqi Kang
- Kaiyu Gao
- Chuanjuan Lü (ORCID: https://orcid.org/0000-0003-4682-6089)
- Shaowu Ou (ORCID: https://orcid.org/0000-0002-9446-9576)
- Wen Zhang (ORCID: https://orcid.org/0000-0003-0821-7143)
- Shuang Hou (ORCID: https://orcid.org/0000-0001-5487-2427)
- Cuiqing Ma (ORCID: https://orcid.org/0000-0002-7468-1027)
- Chao Gao (ORCID: https://orcid.org/0000-0002-5205-0670)
- Ping Xu (ORCID: https://orcid.org/0000-0002-4418-9680)
- Jiyuan Liu (ORCID: https://orcid.org/0000-0002-3524-2064)
- Gang Wang (ORCID: https://orcid.org/0000-0003-1004-8705)
- Yidong Liu (ORCID: https://orcid.org/0000-0002-4631-0771)
- Leilei Guo (ORCID: https://orcid.org/0009-0005-3404-2115)
- Xianzhi Xu
Institutions
- Shandong University (CN)
- Shanghai Jiao Tong University (CN)
- Second Hospital of Shandong University (CN)
- First Hospital of China Medical University (CN)
- State Key Laboratory of Microbial Technology
- Shandong University of Science and Technology (CN)
- China Medical University (CN)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-07-26
- DOI
- https://doi.org/10.1038/s41467-025-62225-8
- Citations
- 2
- Primary Topic
- Amino Acid Enzymes and Metabolism
- Type
- article
- Field-Weighted Citation Impact
- 2.22
Funders
- Shandong University
- National Natural Science Foundation of China
- China Postdoctoral Science Foundation
- Natural Science Foundation of Shandong Province
- Natural Science Foundation of Qingdao