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A d-2-hydroxyglutarate biosensor based on specific transcriptional regulator DhdR

Author

Listed:
  • Dan Xiao

    (Shandong University)

  • Wen Zhang

    (Shandong University)

  • Xiaoting Guo

    (Eye Hospital of Shandong First Medical University)

  • Yidong Liu

    (Shandong University)

  • Chunxia Hu

    (Shandong University)

  • Shiting Guo

    (Shandong University)

  • Zhaoqi Kang

    (Shandong University)

  • Xianzhi Xu

    (Shandong University)

  • Cuiqing Ma

    (Shandong University)

  • Chao Gao

    (Shandong University)

  • Ping Xu

    (Shanghai Jiao Tong University)

Abstract

d-2-Hydroxyglutarate (d-2-HG) is a metabolite involved in many physiological metabolic processes. When d-2-HG is aberrantly accumulated due to mutations in isocitrate dehydrogenase or d-2-HG dehydrogenase, it functions in a pro-oncogenic manner and is thus considered a therapeutic target and biomarker in many cancers. In this study, DhdR from Achromobacter denitrificans NBRC 15125 is identified as an allosteric transcriptional factor that negatively regulates d-2-HG dehydrogenase expression and responds to the presence of d-2-HG. Based on the allosteric effect of DhdR, a d-2-HG biosensor is developed by combining DhdR with amplified luminescent proximity homogeneous assay (AlphaScreen) technology. The biosensor is able to detect d-2-HG in serum, urine, and cell culture medium with high specificity and sensitivity. Additionally, this biosensor is used to identify the role of d-2-HG metabolism in lipopolysaccharide biosynthesis of Pseudomonas aeruginosa, demonstrating its broad usages.

Suggested Citation

  • Dan Xiao & Wen Zhang & Xiaoting Guo & Yidong Liu & Chunxia Hu & Shiting Guo & Zhaoqi Kang & Xianzhi Xu & Cuiqing Ma & Chao Gao & Ping Xu, 2021. "A d-2-hydroxyglutarate biosensor based on specific transcriptional regulator DhdR," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-27357-7
    DOI: 10.1038/s41467-021-27357-7
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