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A d-2-hydroxyglutarate biosensor based on specific transcriptional regulator DhdR
- Source :
- Nature Communications, Vol 12, Iss 1, Pp 1-14 (2021), Nature Communications
- Publication Year :
- 2021
- Publisher :
- Nature Portfolio, 2021.
-
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.<br />d-2-hydroxyglutarate (d-2-HG) is a metabolite that can be aberrantly accumulated and acts as a biomarker in many cancers. Here the authors report a d-2-HG biosensor based on the allosteric transcription factor DhdR which they use for detection in serum and urine.
- Subjects :
- Metabolite
Science
Allosteric regulation
General Physics and Astronomy
Dehydrogenase
Biosensing Techniques
General Biochemistry, Genetics and Molecular Biology
Article
Glutarates
chemistry.chemical_compound
Neoplasms
Transcriptional regulation
Humans
Transcription factor
Multidisciplinary
Bacteria
biology
Biological techniques
Achromobacter denitrificans
General Chemistry
biology.organism_classification
Isocitrate Dehydrogenase
Alcohol Oxidoreductases
HEK293 Cells
Gene Expression Regulation
chemistry
Biochemistry
Metabolic pathways
Cell culture
Mutation
Biosensor
Metabolic Networks and Pathways
Transcription Factors
Subjects
Details
- Language :
- English
- ISSN :
- 20411723
- Volume :
- 12
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Nature Communications
- Accession number :
- edsair.doi.dedup.....24226a46efe0463773477c5b13b84513