TY - JOUR
T1 - An l-2-hydroxyglutarate biosensor based on specific transcriptional regulator LhgR
AU - Kang, Zhaoqi
AU - Zhang, Manman
AU - Gao, Kaiyu
AU - Zhang, Wen
AU - Meng, Wensi
AU - Liu, Yidong
AU - Xiao, Dan
AU - Guo, Shiting
AU - Ma, Cuiqing
AU - Gao, Chao
AU - Xu, Ping
N1 - Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12/1
Y1 - 2021/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85108169709&partnerID=8YFLogxK
U2 - 10.1038/s41467-021-23723-7
DO - 10.1038/s41467-021-23723-7
M3 - Article
C2 - 34131130
AN - SCOPUS:85108169709
SN - 2041-1723
VL - 12
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 3619
ER -