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An l-2-hydroxyglutarate biosensor based on specific transcriptional regulator LhgR

Author

Listed:
  • Zhaoqi Kang

    (State Key Laboratory of Microbial Technology, Shandong University)

  • Manman Zhang

    (Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Department of Radiobiology, Institute of Radiation Medicine of Chinese Academy of Medical Science and Peking Union Medical College)

  • Kaiyu Gao

    (State Key Laboratory of Microbial Technology, Shandong University)

  • Wen Zhang

    (Center for Gene and Immunotherapy, The Second Hospital of Shandong University)

  • Wensi Meng

    (State Key Laboratory of Microbial Technology, Shandong University)

  • Yidong Liu

    (State Key Laboratory of Microbial Technology, Shandong University)

  • Dan Xiao

    (State Key Laboratory of Microbial Technology, Shandong University)

  • Shiting Guo

    (State Key Laboratory of Microbial Technology, Shandong University)

  • Cuiqing Ma

    (State Key Laboratory of Microbial Technology, Shandong University)

  • Chao Gao

    (State Key Laboratory of Microbial Technology, Shandong University)

  • Ping Xu

    (State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic and Developmental Sciences, and School of Life Sciences and Biotechnology, Shanghai Jiao Tong University)

Abstract

l-2-Hydroxyglutarate (l-2-HG) plays important roles in diverse physiological processes, such as carbon starvation response, tumorigenesis, and hypoxic adaptation. Despite its importance and intensively studied metabolism, regulation of l-2-HG metabolism remains poorly understood and none of regulator specifically responded to l-2-HG has been identified. Based on bacterial genomic neighborhood analysis of the gene encoding l-2-HG oxidase (LhgO), LhgR, which represses the transcription of lhgO in Pseudomonas putida W619, is identified in this study. LhgR is demonstrated to recognize l-2-HG as its specific effector molecule, and this allosteric transcription factor is then used as a biorecognition element to construct an l-2-HG-sensing FRET sensor. The l-2-HG sensor is able to conveniently monitor the concentrations of l-2-HG in various biological samples. In addition to bacterial l-2-HG generation during carbon starvation, biological function of the l-2-HG dehydrogenase and hypoxia induced l-2-HG accumulation are also revealed by using the l-2-HG sensor in human cells.

Suggested Citation

  • Zhaoqi Kang & Manman Zhang & Kaiyu Gao & Wen Zhang & Wensi Meng & Yidong Liu & Dan Xiao & Shiting Guo & Cuiqing Ma & Chao Gao & Ping Xu, 2021. "An l-2-hydroxyglutarate biosensor based on specific transcriptional regulator LhgR," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-23723-7
    DOI: 10.1038/s41467-021-23723-7
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