基于转录因子生物传感器的构建与应用进展
Construction and advances in the applications of transcription factor-based biosensors
- 合成生物学 2025年6卷第4期 页码：829-845
- 作者机构：
1.天津大学化工学院，天津 300350
2.宁夏大学生命科学学院，宁夏 银川 750021
- 作者简介：
[ "王宏（1999—），男，硕士研究生。研究方向为代谢工程与合成生物学。 E-mail：wh17826529977@163.com" ]
[ "陆孔泳（1989—），女，博士，副教授，硕士生导师。研究方向为合成生物学、生物发酵与代谢调控、微藻生物技术、工业微生物技术等。E-mail：lky@nxu.edu.cn" ]
[ "王智文（1981—），男，博士，教授，博士生导师。研究方向为基因组编辑与合成生物学元件开发、基因组尺度网络模型构建与途径模拟设计、合成高附加值生物医药与生物基化学品人工细胞工厂构建、微生物资源挖掘与利用等。E-mail：zww@tju.edu.cn" ]
- 基金信息：宁夏重点研发基金资助项目(2024BEE02005)
DOI：10.12211/2096-8280.2025-030
中图分类号： Q81收稿：2025-03-28，
修回：2025-05-29，
纸质出版：2025-08-31
- 稿件说明：
移动端阅览
王宏， 陆孔泳， 郑洋洋， 陈涛， 王智文. 基于转录因子生物传感器的构建与应用进展［J］. 合成生物学， 2025， 6（4）： 829-845
WANG Hong， LU Kongyong， ZHENG Yangyang， CHEN Tao， WANG Zhiwen. Construction and advances in the applications of transcription factor-based biosensors［J］. Synthetic Biology Journal， 2025， 6（4）： 829-845
王宏， 陆孔泳， 郑洋洋， 陈涛， 王智文. 基于转录因子生物传感器的构建与应用进展［J］. 合成生物学， 2025， 6（4）： 829-845 DOI： 10.12211/2096-8280.2025-030.
WANG Hong， LU Kongyong， ZHENG Yangyang， CHEN Tao， WANG Zhiwen. Construction and advances in the applications of transcription factor-based biosensors［J］. Synthetic Biology Journal， 2025， 6（4）： 829-845 DOI： 10.12211/2096-8280.2025-030.
摘要
微生物细胞工厂作为绿色生物制造的重要实现形式，广泛应用于食品、化工、医药和能源等领域。然而，利用传统代谢工程策略改造微生物细胞工厂生产目标产品时，仍面临静态代谢调控的局限性与代谢通量实时监测的滞后性等问题，制约着生物基产品的高效生物合成。基于转录因子生物传感器通过实时感知代谢物浓度信号或环境信号，自动调控目的基因表达，为微生物细胞工厂的高效构建与智能化调控提供了创新性解决方案。本文介绍了基于转录因子生物传感器的组成、分类及作用机制，围绕传感器配体识别模块的设计和信号输出模块的元件重构，总结了基于转录因子生物传感器的构建策略，对基于转录因子生物传感器在微生物细胞工厂中的应用进展进行了综述，包括高通量筛选、代谢工程靶点挖掘以及动态调控。聚焦目前基于转录因子生物传感器面临的代谢物响应元件匮乏、检测范围受限、配体识别特异性不足、转录依赖的耗时性和传感器元件鲁棒性缺陷等挑战，对未来的研究方向进行展望，为未来基于转录因子生物传感器的构建与应用提供借鉴。
Abstract
Microbial cell factories are pivotal in green biomanufacturing
with applications spanning various sectors
including food production
chemical engineering
pharmaceuticals
and energy. However
traditional metabolic engineering strategies
which reply on static regulation and are hindered by the inherent latency in real-time metabolic flux monitoring
face significant limitations in constructing microbial systems that efficiently synthesize target products. These constraints severely hinder the high-yield biosynthesis of bio-based compounds. Transcription factor-based biosensors (TFBs)
which are cornerstone tools in synthetic biology and metabolic engineering
offer innovative solutions by dynamically linking real-time perception of metabolite concentration signals or environmental cues with autonomous regulation of target gene expression. This integration allows for intelligent optimization and efficient construction of microbial production systems. This review systematically examines the molecular architecture
functional classification
and signal transduction mechanisms of TFBs
focusing on the rational design of ligand-recognition modules and the reconfiguration of signal-output components. Key strategies for constructing TFBs are summarized
including directed evolution and rational redesign of transcription factor ligand-binding domains (LBD)
modular engineering of responsive promoters
and optimization of ribosome binding sites (RBS) for reporter genes. The review also highlights cutting-edge applications of TFBs in microbial cell factories
such as high-throughput screening platforms
identification of metabolic engineering targets
and dynamic regulation of metabolic pathways. Despite their transformative potential
several challenges remain
including the scarcity of metabolite-responsive elements
narrow ligand detection ranges
insufficient substrate recognition specificity
time-consuming transcription-dependent processes
and poor robustness of sensor components under industrial conditions. To address these bottlenecks
future research must prioritize the integration of synthetic biology with artificial intelligence (AI)-driven big data modeling. Such interdisciplinary efforts will accelerate the development of customizable
standardized plug-and-play modular components to overcome limitations like the shortage of responsive elements. Concurrently
the establishment of scalable validation platforms across “lab-scale
pilot-scale
and industrial production” stages is essential to validate system scalability
laying the foundation for next-generation TFBs capable of supporting large-scale industrial biomanufacturing. These advancements are set to enhance the efficiency and intelligence of microbial cell factories while expanding their applications in critical areas such as food safety testing
environmental monitoring
and medical diagnostics and therapeutics. By offering critical insights into the design and application of TFBs
this review aims to drive the evolution of microbial cell factories into multifunctional
smart bioproduction systems that integrate precision
adaptability
and industrial robustness
ultimately fostering sustainable innovation in the bioeconomy.
2
关键词
Keywords
references
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