Design, optimization and application of whole-cell microbial biosensors with engineered genetic circuits

YANG Lu; WU Nan; BAI Rongrong; DONG Weiliang; ZHOU Jie; JIANG Min

doi:10.12211/2096-8280.2021-021

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Design, optimization and application of whole-cell microbial biosensors with engineered genetic circuits

Invited Review | 更新时间：2026-01-19

- Design, optimization and application of whole-cell microbial biosensors with engineered genetic circuits
  封面论文
- Synthetic Biology Journal Vol. 3, Issue 6, Pages: 1061-1080(2022)
- 作者机构：
  
  1.南京工业大学生物与制药工程学院，江苏南京 211816
  2.南京工业大学材料化学工程国家重点实验室，江苏南京 211816
- 作者简介：
- 基金信息：
- DOI：10.12211/2096-8280.2021-021
  CLC： Q812
- Received：07 February 2021，
  
  Revised：2021-04-23，
  
  Published：31 December 2022
- 稿件说明：
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杨璐，吴楠，白茸茸，董维亮，周杰，姜岷. 基因回路型全细胞微生物传感器的设计、优化与应用［J］. 合成生物学， 2022， 3（6）： 1061-1080

YANG Lu， WU Nan， BAI Rongrong， DONG Weiliang， ZHOU Jie， JIANG Min. Design， optimization and application of whole-cell microbial biosensors with engineered genetic circuits［J］. Synthetic Biology Journal， 2022， 3（6）： 1061-1080
杨璐，吴楠，白茸茸，董维亮，周杰，姜岷. 基因回路型全细胞微生物传感器的设计、优化与应用［J］. 合成生物学， 2022， 3（6）： 1061-1080 DOI： 10.12211/2096-8280.2021-021.

YANG Lu， WU Nan， BAI Rongrong， DONG Weiliang， ZHOU Jie， JIANG Min. Design， optimization and application of whole-cell microbial biosensors with engineered genetic circuits［J］. Synthetic Biology Journal， 2022， 3（6）： 1061-1080 DOI： 10.12211/2096-8280.2021-021.

摘要

基于合成生物学理念构建的基因回路型全细胞微生物传感器作为生物传感器的一大重要分支，能够感知环境中特定的待测物质，并按照一定规律将其转换成特定的信号输出，在生物制造过程监控、环境监测与食品安全、医疗诊断与监护等领域的检测应用中显现出巨大的潜力。随着合成生物学各项技术的日益完善和遗传元件的逐渐丰富，越来越多的基于不同响应机制、不同逻辑门与逻辑回路的全细胞微生物传感器已被陆续开发。然而，目前基因回路型全细胞微生物传感器的设计与构建仍主要依靠假设-试错循环的经验性方法。如何设计与构建具有高响应特性的基因回路型全细胞传感器，以及如何对元件、基因回路的优化提高其传感检测性能以满足不同实际应用场景的检测需求，是目前亟需解决的瓶颈问题。本文将主要对基因回路型全细胞生物传感器的原理、分类以及发展历程进行综述，着重介绍全细胞微生物传感器基因回路的设计与构建原则、传感检测性能的优化策略以及在不同检测领域的应用进展，最后剖析了目前全细胞微生物传感器面临的生物安全性、设计构建烦琐、缺乏高效便捷性、难以进入传感器市场等诸多挑战，以及对人工智能、合成生物学、液滴微流控等新兴技术将加速遗传传感元件的开发和生物传感器的人工设计与构建进行了展望。

Abstract

Whole-cell microbial biosensors with engineered genetic circuits constructed based on the concept of synthetic biology is an important branch of the biosensor. Whole-cell microbial biosensor is mainly composed of the sensing module

the computing module and the output actuating module. It can sense the concentration of specific substances in the environment and then transfer it to specific signal outputs in time according to certain rules

which shows great potential in bioengineering process control

environmental monitoring

food safety

environmental quality monitoring and disease diagnosis and control

etc. With the improvement of various technologies in synthetic biology and the enrichment of genetic elements

more and more whole-cell microbial sensors based on different response mechanisms

different logic gates and logic circuits have been developed. However

the design and construction of genetically engineered whole-cell microbial biosensor still mainly rely on the empirical method of trial-and error-learning. Therefore

how to design and construct high performance genetically engineered microbial whole-cell biosensors and how to tune its response curves by optimizing genetic elements or circuits to meet the detection requirements of different practical application scenarios is the new and important challenge. Here we reviewed the principle

classification and development process of genetically engineered whole-cell biosensor. We also focused on the design and construction of genetic circuit based on transcription factors and riboswitches

discussed optimization strategies for improving biosensor detection performance including dynamic range

specificity and working range

and then summarized its application progress in different detection fields. The optimization strategies are mainly involved in changing the expression level of genetic elements

adjusting the binding affinity between metabolites and genetic elements

restructuring the position of functional domains

etc. Finally

some challenges

such as biological safety

cumbersome design and construction

and inconvenience to enter the sensor market were discussed. It is expected that emerging technologies such as artificial intelligence

synthetic biology

and droplet microfluidics

will accelerate the development of genetic regulatory elements and the design and construction of novel biosensors.

关键词

Keywords

references

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