Citation: Junbin Li, Min Dai, Tianxin Zhang, Xindi Sun, Du Lian, Mengyi Xiong, Yibo Zhou, Zhihe Qing. Activable chimeric bioluminescent sensors via electrostatic protein engineering for field-deployable imaging of wound infection[J]. Chinese Chemical Letters, ;2026, 37(9): 112449. doi: 10.1016/j.cclet.2026.112449 shu

Activable chimeric bioluminescent sensors via electrostatic protein engineering for field-deployable imaging of wound infection

Junbin Li ^a ,
Min Dai ^a ,
Tianxin Zhang ^a ,
Xindi Sun ^b ,
Du Lian ^a ,
Mengyi Xiong ^{b, *,} ,
Yibo Zhou ^a ,
Zhihe Qing ^{a, *,}

a.
Hunan Provincial Key Laboratory of Cytochemistry, School of Chemistry and Pharmaceutical Engineering, Changsha University of Science and Technology, Changsha 410114, China
b.
Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, China

xiongmy@hnu.edu.cn

qingzhihe@hnu.edu.cn

Received Date: 21 July 2025
Revised Date: 27 November 2025
Accepted Date: 22 January 2026
Available Online: 23 January 2026

Figures(5)

Genetically encoded sensors have been extensively utilized for the analysis of biomarkers. However, their applications remain limited by the scarcity of analyte-binding proteins or peptides and the challenges associated with translating analyte recognition into a quantifiable signal. Herein, we report a novel class of activable chimeric sensors that harness bioluminescent resonance energy transfer (BRET) between nanoluciferase proteins and fluorescent small-molecule probes. We demonstrated that the responsiveness of these hybrid sensors can be significantly enhanced by modulating the electrostatic surface potential of the fusion protein in the vicinity of the recognition site. As proof of concept, we engineered two chimeric bioluminescent sensors, Bp7-pH and Bp7-NO, for the detection of pH and nitric oxide (NO), respectively. Both sensors exhibited strong BRET signal modulation upon exposure to their target analytes, leading to distinct and quantifiable shifts in luminescence color. Importantly, we successfully applied these sensors for field-deployable imaging of pH and NO dynamics in a murine wound infection model. Given the vast array of existing fluorescent molecular sensors, the detection targets of these chimeric bioluminescent sensors can be easily modified by altering the recognition moieties. Collectively, this work establishes a generalizable and tunable design strategy for developing highly sensitive chimeric bioluminescent sensors, with broad applicability in physiological and pathological monitoring.
- Fluorescent probe,
- Bioluminescent sensor,
- Protein engineering,
- Wound infection,
- Field-deployable imaging
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