合成生物学研究中的微生物启动子工程策略

于慧敏; 郑煜堃; 杜岩; 王苗苗; 梁有向

doi:10.12211/2096-8280.2020-092

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合成生物学研究中的微生物启动子工程策略

特约评述 | 更新时间：2026-03-05

- 合成生物学研究中的微生物启动子工程策略
- Microbial promoter engineering strategies in synthetic biology
- 合成生物学 2021年2卷第4期页码：598-611
- 作者机构：
  
  清华大学化学工程系，教育部工业生物催化重点实验室，北京 100084
- 作者简介：
  
  [ "于慧敏（1973—），女，博士，教授，博士生导师。研究方向为工业生物催化、合成生物学与生物纳米技术等。E-mail：yuhm@tsinghua.edu.cn" ]
- 基金信息：
  
  国家重点研发计划(2018YFA0902200);国家自然科学基金面上项目(21776157;22078173)
- DOI：10.12211/2096-8280.2020-092
  中图分类号： Q812
- 收稿：2020-12-30，
  
  修回：2021-02-06，
  
  纸质出版：2021-08-31
- 稿件说明：
移动端阅览
于慧敏，郑煜堃，杜岩，王苗苗，梁有向. 合成生物学研究中的微生物启动子工程策略［J］. 合成生物学， 2021， 2（4）： 598-611

YU Huimin， ZHENG Yukun， DU Yan， WANG Miaomiao， LIANG Youxiang. Microbial promoter engineering strategies in synthetic biology［J］. Synthetic Biology Journal， 2021， 2（4）： 598-611
于慧敏，郑煜堃，杜岩，王苗苗，梁有向. 合成生物学研究中的微生物启动子工程策略［J］. 合成生物学， 2021， 2（4）： 598-611 DOI： 10.12211/2096-8280.2020-092.

YU Huimin， ZHENG Yukun， DU Yan， WANG Miaomiao， LIANG Youxiang. Microbial promoter engineering strategies in synthetic biology［J］. Synthetic Biology Journal， 2021， 2（4）： 598-611 DOI： 10.12211/2096-8280.2020-092.

摘要

合成生物学研究对于我国绿色生物制造产业和可持续发展战略至关重要。启动子是合成生物学核心元件，是在转录水平上实现基因高效、精准表达调控的最关键因素之一。本文重点对原核微生物启动子工程研究的基本内容、研究进展及发展趋势进行了综述。首先概述了启动子序列基本特征及其受RNA聚合酶σ因子识别调控的一般规律；并以大肠杆菌乳糖操纵子为例简要介绍了诱导型启动子的负调控与正调控诱导机制。其次，分别从对靶基因自身内源启动子进行突变改造以及采用高效外源启动子进行替换改造这两个方面入手，阐述了启动子改造的常用策略。进一步对近年来公开报道的不同类型诱导型启动子进行了梳理，小结了代表性化学分子诱导剂以及物理信号诱导方式的种类及基本特征。简述了非模式和模式微生物组成型启动子的研究进展及研究侧重点。结合动态代谢调控技术及人工智能工具的突破性发展，提出具有动态调控功能的特殊启动子的发现与改造、全新性能启动子元件的人工智能设计与改造等将成为启动子工程研究的新方向与新前沿。最后分析了启动子工程领域存在的挑战性问题，展望了今后的研究重点，并结合合成生物学的发展，进一步强调了微生物启动子工程的重要作用。

Abstract

Synthetic biology is of vital importance to the green biomanufacturing industry and sustainable development strategies of our country. Promoter is the core-component of synthetic biology

playing a significant role in highly efficient and fine-tuning expression and regulation of target genes at the transcriptional level. Herein we summarized and discussed the key progress and future frontiers of microbial promoter engineering

particularly for prokaryotic microorganisms. Firstly

we introduced the basic DNA sequence characteristics of promoters and the regular mechanism for promoter recognition and transcription-initiation by RNA polymerase sigma factors. Inducible mechanisms for both negative and positive regulation were particularly highlighted with the typical

lac

operator of

Escherichia coli

as an example. Then

effective strategies for obtaining improved-promoters were summarized

which were roughly divided into two categories: endogenous promoter mutation and heterologous promoter replacement. For the endogenous promoter mutation

the following strategies

e.g.

point mutation toward sigma factor consensus sequence

coupling optimization of -35 and -10 regions with RBS sequence

random mutation or saturation mutagenesis of UP element or spacer sequences accompanying with promoter library construction and high-throughput screening were emphasized. For the heterologous promoter replacement

strategies such as substituting the native promoter into stronger ones from other microorganisms

introducing phage-source chimeric promoters

tuning the constitutive promoter into inducible pattern and integrating positive regulator(s)

were mainly discussed. We further sorted out the representative inducers for inducible promoters reported so far

including both chemical molecules and physical signals. Progress in constitutive promoters of non-model and model microbial organisms were simply summarized as well. Next

arising from

the breakthrough development of dynamic metabolic regulation and artificial intelligence (AI)

we proposed that the innovative research on identification and evolution of new and unique promoters with dynamic-response features and AI

de novo

design for promoters with novel/superior functions will be the new frontiers of promoter engineering. Finally

we analyzed the challenging scientific issues in the microbial promoter engineering

from the viewpoint of both basic research and large-scale applications; and further discussed the research priority coupling with the vigorous development of synthetic biology.

关键词

Keywords

references

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