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

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

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. jieerbu@sdu.edu.cn.
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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