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A genetically encoded biosensor for point-of-care and live-cell detection of d-2-hydroxyglutarate

Author

Listed:
  • 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)

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.

Suggested Citation

  • 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 &, 2025. "A genetically encoded biosensor for point-of-care and live-cell detection of d-2-hydroxyglutarate," Nature Communications, Nature, vol. 16(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-62225-8
    DOI: 10.1038/s41467-025-62225-8
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