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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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    1. Chloé Grazon & R C. Baer & Uroš Kuzmanović & Thuy Nguyen & Mingfu Chen & Marjon Zamani & Margaret Chern & Patricia Aquino & Xiaoman Zhang & Sébastien Lecommandoux & Andy Fan & Mario Cabodi & Catherine, 2020. "A progesterone biosensor derived from microbial screening," Nature Communications, Nature, vol. 11(1), pages 1-10, December.
    2. Mindong Liang & Zilong Li & Weishan Wang & Jiakun Liu & Leshi Liu & Guoliang Zhu & Loganathan Karthik & Man Wang & Ke-Feng Wang & Zhong Wang & Jing Yu & Yuting Shuai & Jiaming Yu & Lu Zhang & Zhiheng , 2019. "A CRISPR-Cas12a-derived biosensing platform for the highly sensitive detection of diverse small molecules," Nature Communications, Nature, vol. 10(1), pages 1-9, December.
    3. C. K. Stover & X. Q. Pham & A. L. Erwin & S. D. Mizoguchi & P. Warrener & M. J. Hickey & F.S. L. Brinkman & W. O. Hufnagle & D. J. Kowalik & M. Lagrou & R. L. Garber & L. Goltry & E. Tolentino & S. We, 2000. "Complete genome sequence of Pseudomonas aeruginosa PAO1, an opportunistic pathogen," Nature, Nature, vol. 406(6799), pages 959-964, August.
    4. Supriya K. Saha & Christine A. Parachoniak & Krishna S. Ghanta & Julien Fitamant & Kenneth N. Ross & Mortada S. Najem & Sushma Gurumurthy & Esra A. Akbay & Daniela Sia & Helena Cornella & Oriana Milti, 2014. "Mutant IDH inhibits HNF-4α to block hepatocyte differentiation and promote biliary cancer," Nature, Nature, vol. 513(7516), pages 110-114, September.
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