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

  • Nat Commun. 2025 Jul 26;16(1):6913. doi: 10.1038/s41467-025-62225-8.
Yidong Liu  1 ,  Zhaoqi Kang  1 ,  Rong Xu  1 ,  Shuang Hou  1 ,  Lingru Gong  1 ,  Leilei Guo  1 ,  Kaiyu Gao  1 ,  Xianzhi Xu  1 ,  Xiaoxu Tan  1 ,  Dan Xiao  1 ,  Wen Zhang  2 ,  Gang Wang  3 ,  Shaowu Ou  3 ,  Jinqu Hu  3 ,  Jiyuan Liu  3 ,  Chuanjuan Lü  1 ,  Cuiqing Ma  1 ,  Ping Xu  4 ,  Chao Gao  5
Affiliations
  • 1. State Key Laboratory of Microbial Technology, Shandong University, Qingdao, People's Republic of China.
  • 2. Institute of Medical Sciences, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, People's Republic of China.
  • 3. Department of Neurosurgery, The First Hospital of China Medical University, Shenyang, People's Republic of China.
  • 4. State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic & Developmental Sciences, and School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
  • 5. State Key Laboratory of Microbial Technology, Shandong University, Qingdao, People's Republic of China. [email protected].
PMID: 40715112 DOI: 10.1038/s41467-025-62225-8
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.

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