Journal
NATURE COMMUNICATIONS
Volume 12, Issue 1, Pages -Publisher
NATURE RESEARCH
DOI: 10.1038/s41467-021-23723-7
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Funding
- National Key R&D Program of China [2018YFA0901200]
- National Natural Science Foundation of China [31970055]
- Shandong Provincial Funds for Distinguished Young Scientists [JQ 201806]
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l-2-Hydroxyglutarate (l-2-HG) is a key metabolite involved in various physiological processes, but its regulation remains poorly understood. A novel l-2-HG FRET biosensor based on the allosteric transcription factor LhgR has been developed to monitor l-2-HG levels in cells and biological samples, revealing new insights into its roles in bacterial and human cells.
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. L-2-hydroxyglutarate (L-2-HG) is an important metabolite but its regulation is poorly understood. Here the authors report an L-2-HG FRET biosensor based on the allosteric transcription factor, LhgR, to monitor L-2-HG in cells and biological samples.
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