An l-2-hydroxyglutarate biosensor based on specific transcriptional regulator LhgR
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 non...
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Published in | Nature communications Vol. 12; no. 1; p. 3619 |
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Main Authors | , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
London
Nature Publishing Group
15.06.2021
Nature Publishing Group UK Nature Portfolio |
Subjects | |
Online Access | Get full text |
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Summary: | 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. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 2041-1723 2041-1723 |
DOI: | 10.1038/s41467-021-23723-7 |