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<p><span>d</span>-2-Hydroxyglutarate (<span>d</span>-2-HG) is a functional endogenous metabolite in various domains of life. Its abnormal accumulation promotes human tumorigenesis. Convenient <span>d</span>-2-HG testing for diagnosis and prognosis of <span>d</span>-2-HG-related diseases remains technically challenging, and there is no analytical method to directly detect <span>d</span>-2-HG in living cells. Here, we identify a <span>d</span>-2-HG-specific transcriptional activator, HgcR, and develop a <Emphasis Type="UnderlineSmallCaps">d</Emphasis>-2-<Emphasis Type="Underline">H</Emphasis>G sens<Emphasis Type="Underline">or</Emphasis> (DHOR) using HgcR as a sensing moiety. Then, we build a portable device adaptive with DHOR for rapid and low-cost point-of-care <span>d</span>-2-HG testing in serum, urine, and glioma tissue samples. DHOR also allow spatiotemporal resolution of <span>d</span>-2-HG in living bacteria and human cells. We use DHOR to identify <span>d</span>-2-HG transporters from <i>Escherichia coli</i> and human solute carrier 22 family. Overall, DHOR provides a powerful and versatile tool for in vitro and live-cell detection of <span>d</span>-2-HG, offering the opportunity to deepen our understanding about physiological and pathogenetic roles of <span>d</span>-2-HG.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月26日

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  • 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,
  • Chao Gao

摘要

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.