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A d-2-hydroxyglutarate biosensor based on specific transcriptional regulator DhdR
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Journal Article
A d-2-hydroxyglutarate biosensor based on specific transcriptional regulator DhdR
2021
Overview
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.
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.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
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/ 38/43
/ 45/77
/ 45/88
/ 45/90
/ 49/22
/ 631/1647
/ 82/29
/ 82/80
/ 82/83
/ 9/10
/ 96/44
/ 96/95
/ Achromobacter denitrificans - enzymology
/ Achromobacter denitrificans - genetics
/ Achromobacter denitrificans - metabolism
/ Alcohol Oxidoreductases - genetics
/ Alcohol Oxidoreductases - metabolism
/ Cancer
/ Humanities and Social Sciences
/ Humans
/ Metabolic Networks and Pathways
/ Mutation
/ Science
