A d-2-hydroxyglutarate biosensor based on specific transcriptional regulator DhdR

Dan Xiao, Wen Zhang, Xiaoting Guo, Yidong Liu, Chunxia Hu, Shiting Guo, Zhaoqi Kang, Xianzhi Xu, Cuiqing Ma, Chao Gao () and Ping Xu ()
Additional contact information
Dan Xiao: Shandong University
Wen Zhang: Shandong University
Xiaoting Guo: Eye Hospital of Shandong First Medical University
Yidong Liu: Shandong University
Chunxia Hu: Shandong University
Shiting Guo: Shandong University
Zhaoqi Kang: Shandong University
Xianzhi Xu: Shandong University
Cuiqing Ma: Shandong University
Chao Gao: Shandong University
Ping Xu: Shanghai Jiao Tong University

Nature Communications, 2021, vol. 12, issue 1, 1-14

Abstract: 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.

Date: 2021
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-021-27357-7 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-27357-7

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-021-27357-7

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().