Liu Yidong, Kang Zhaoqi, Xu Rong, Hou Shuang, Gong Lingru, Guo Leilei, Gao Kaiyu, Xu Xianzhi, Tan Xiaoxu, Xiao Dan, Zhang Wen, Wang Gang, Ou Shaowu, Hu Jinqu, Liu Jiyuan, Lü Chuanjuan, Ma Cuiqing, Xu Ping, Gao Chao
State Key Laboratory of Microbial Technology, Shandong University, Qingdao, People's Republic of China.
Institute of Medical Sciences, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, People's Republic of China.
Nat Commun. 2025 Jul 26;16(1):6913. doi: 10.1038/s41467-025-62225-8.
D-2-Hydroxyglutarate (D-2-HG) is a functional endogenous metabolite in various domains of life. Its abnormal accumulation promotes human tumorigenesis. Convenient D-2-HG testing for diagnosis and prognosis of D-2-HG-related diseases remains technically challenging, and there is no analytical method to directly detect D-2-HG in living cells. Here, we identify a D-2-HG-specific transcriptional activator, HgcR, and develop a d-2-HG sensor (DHOR) using HgcR as a sensing moiety. Then, we build a portable device adaptive with DHOR for rapid and low-cost point-of-care D-2-HG testing in serum, urine, and glioma tissue samples. DHOR also allow spatiotemporal resolution of D-2-HG in living bacteria and human cells. We use DHOR to identify D-2-HG transporters from Escherichia coli and human solute carrier 22 family. Overall, DHOR provides a powerful and versatile tool for in vitro and live-cell detection of D-2-HG, offering the opportunity to deepen our understanding about physiological and pathogenetic roles of D-2-HG.
D-2-羟基戊二酸(D-2-HG)是生命各个领域中的一种功能性内源性代谢物。其异常积累会促进人类肿瘤发生。对D-2-HG相关疾病进行诊断和预后的便捷D-2-HG检测在技术上仍然具有挑战性,并且尚无直接检测活细胞中D-2-HG的分析方法。在此,我们鉴定出一种D-2-HG特异性转录激活因子HgcR,并开发了一种以HgcR作为传感部分的D-2-HG传感器(DHOR)。然后,我们构建了一种与DHOR适配的便携式设备,用于在血清、尿液和胶质瘤组织样本中进行快速且低成本的即时D-2-HG检测。DHOR还能对活细菌和人类细胞中的D-2-HG进行时空分辨。我们利用DHOR从大肠杆菌和人类溶质载体22家族中鉴定出D-2-HG转运蛋白。总体而言,DHOR为体外和活细胞检测D-2-HG提供了一种强大且通用的工具,为加深我们对D-2-HG的生理和致病作用的理解提供了契机。