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

by Hou, Shuang , Gong, Lingru , Guo, Leilei , Gao, Chao , Hu, Jinqu , Wang, Gang , Ma, Cuiqing , Gao, Kaiyu , Ou, Shaowu , Tan, Xiaoxu , Lü, Chuanjuan , Kang, Zhaoqi , Xu, Rong , Liu, Jiyuan , Liu, Yidong , Xiao, Dan , Zhang, Wen , Xu, Ping , Xu, Xianzhi

in 631/1647/1888/2249 / 631/1647/350/59 / 631/92/552 / 692/308/53 / 96/10 / Bioaccumulation / Biosensing Techniques - instrumentation / Biosensing Techniques - methods / Biosensors / Carbon / Chromatography / Coding / Dehydrogenases / E coli / Escherichia coli - genetics / Escherichia coli - metabolism / Genetic code / Glioma - metabolism / Glucose / Glutarates - analysis / Glutarates - blood / Glutarates - metabolism / Glutarates - urine / HEK293 Cells / Humanities and Social Sciences / Humans / Metabolism / Metabolites / multidisciplinary / Mutation / Oxidation / Physiology / Point-of-Care Systems / Portable equipment / Proteins / Science / Science (multidisciplinary) / Sensors / Tumorigenesis

2025

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2025

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2025

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Journal Article

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

Hou, Shuang,

Gong, Lingru,

Guo, Leilei,

Gao, Chao,

Hu, Jinqu,

Wang, Gang,

Ma, Cuiqing,

Gao, Kaiyu,

Ou, Shaowu,

Tan, Xiaoxu,

Lü, Chuanjuan,

Kang, Zhaoqi,

Xu, Rong,

Liu, Jiyuan,

Liu, Yidong,

Xiao, Dan,

Zhang, Wen,

Xu, Ping,

Xu, Xianzhi

2025

Overview

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- H G sens or (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. D-2-hydroxyglutarate (D-2-HG) is an endogenous metabolite that plays both physiological and pathological roles. Here, the authors report a genetically encoded D-2-HG biosensor based on the transcriptional activator HgcR, which enables rapid detection of D-2-HG in vitro and in live cells.

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Publisher

Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio

Subject

/ 96/10

/ Biosensing Techniques - instrumentation