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ORIGINAL RESEARCH article

Front. Bioeng. Biotechnol.

Sec. Biosensors and Biomolecular Electronics

Systematic evaluation of pigment-based whole-cell lead biosensors: Challenges in genetic circuit engineering and critical considerations for background noise control

Provisionally accepted
Chang-ye  HuiChang-ye Hui1*Yan  GuoYan Guo1Li-dan  DengLi-dan Deng1Wen-wu  GongWen-wu Gong1Juan  ZhangJuan Zhang2
  • 1Shenzhen Prevention and Treatment Center for occupational Diseases, 深圳市, China
  • 2Jilin University, Changchun, China

The final, formatted version of the article will be published soon.

To develop whole-cell biosensors for Pb(II) detection by engineering bacteria with diverse pbr operons and optimizing their biosensing performance through genetic circuit engineering. We constructed a series of biosensors using pbr operons from different bacterial species. The pbr operon from Klebsiella pneumoniae CG43 plasmid pLVPK showed optimal performance, with high specificity for Pb(II) and a broad detection range (0.0061-50 μM). Strategies such as incorporating transcription terminators and modulating the expression levels of regulatory proteins were explored to reduce background noise and optimize the dynamic range. Introducing a transcription terminator in the pKp-DV construct resulted in a lower detection limit of 0.0002 μM. However, other strategies, such as adjusting the regulator dosage and integrating a hybrid genetic circuit, did not significantly enhance the biosensing performance. Engineering diverse pbr operons improved Pb(II) sensitivity, yet elevated background signals limited dynamic range. Future optimization should reduce basal leakage, strengthen circuits, and enhance matrix tolerance for field-ready sensors.

Keywords: background noise control, genetic circuit engineering, Lead (II) detection, pigment signal, Whole-cell biosensor

Received: 12 Nov 2025; Accepted: 17 Dec 2025.

Copyright: © 2025 Hui, Guo, Deng, Gong and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Chang-ye Hui

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