Progress in the regulatory tools of gene expression for model microorganisms

doi:10.12211/2096-8280.2020-026

Abstract

Abstract:

Model microorganisms, such as Escherichia coli, Bacillus subtilis, and Saccharomyces cerevisiae, are important cellular chassis in synthetic biology. The development and application of new tools for the regulation of gene expression in model microorganisms has enabled precise and sophisticated design and engineering of metabolic pathways and genetic circuits, which greatly promotes research in synthetic biology and metabolic engineering. In this review, we systematically summarized and discussed the recent advances of gene regulation toolbox in model microorganisms, focusing on artificial genetic parts with fine-tuning capabilities. Starting with classical approaches, we proceeded to the new tools for gene regulations, including those created based on the central dogma, global regulatory proteins, and genetic machinery that respond to specific signals. Discovery of novel regulatory elements for gene expression and developments of stress-responsive gene expression system of cellular state are expected to further expand the dynamic range and increase the sensitivity of the regulation of gene expression. By combining systems biology with computational analysis, the standardization and diversification of the regulatory elements for gene expression can be further promoted, which will certainly facilitate improved efficiency of the regulation for gene expression in synthetic biology.

Key words: model microorganisms, gene expression, regulatory tools, artificial gene expression tools, global regulation, synthetic biology, metabolic engineering

摘要：

以大肠杆菌、枯草芽孢杆菌和酿酒酵母等为代表的典型模式微生物是合成生物学研究中的重要底盘细胞。典型模型微生物的新型基因表达调控工具开发与应用实现了细胞代谢途径的精确工程设计和新型遗传回路的设计，极大促进了合成生物学和代谢工程的发展。本文针对典型模式微生物基因表达精细调控工具，特别是人工基因表达调控元件和精确调控的工具进行了系统总结和讨论。首先总结了经典的基因表达调控元件，然后介绍和讨论了基于中心法则创建的新型基因表达调控元件、基于全局调控蛋白的基因表达全局调控工具，以及响应特定信号的基因表达调控工具三个方面的最新研究进展，最后展望了如何通过新型天然基因表达调控元件的发现和响应代谢压力等细胞生理特性的基因表达调控系统的开发，进一步提升基因表达精细调控的范围和精度。通过将系统生物学数据与生物信息学相结合，能够进一步促进基因表达调控元件的标准化和多元化，提升基因表达精细调控的效率。

关键词: 典型模式微生物, 基因表达精细调控工具, 基因表达全局调控工具, 合成生物学, 代谢工程

CLC Number:

Rongzhen TIAN, Yanfeng LIU, Jianghua LI, Long LIU, Guocheng DU. Progress in the regulatory tools of gene expression for model microorganisms[J]. Synthetic Biology Journal, 2020, 1(4): 454-469.

田荣臻, 刘延峰, 李江华, 刘龙, 堵国成. 典型模式微生物基因表达精细调控工具的研究进展[J]. 合成生物学, 2020, 1(4): 454-469.

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[3]	Zhonghu BAI, He REN, Jianqi NIE, Yang SUN. The recent progresses and applications of in-parallel fermentation technology [J]. Synthetic Biology Journal, 2023, 4(5): 904-915.
[4]	Yujie WU, Xinxin LIU, Jianhui LIU, Kaiguang Yang, Zhigang SUI, Lihua ZHANG, Yukui ZHANG. Research progress of strain screening and quantitative analysis of key molecules based on high-throughput liquid chromatography and mass spectrometry [J]. Synthetic Biology Journal, 2023, 4(5): 1000-1019.
[5]	Zhehui HU, Juan XU, Guangkai BIAN. Application of automated high-throughput technology in natural product biosynthesis [J]. Synthetic Biology Journal, 2023, 4(5): 932-946.
[6]	Huan LIU, Qiu CUI. Advances and applications of ambient ionization mass spectrometry in screening of microbial strains [J]. Synthetic Biology Journal, 2023, 4(5): 980-999.
[7]	Yannan WANG, Yuhui SUN. Base editing technology and its application in microbial synthetic biology [J]. Synthetic Biology Journal, 2023, 4(4): 720-737.
[8]	Wanqiu LIU, Xiangyang JI, Huiling XU, Yicong LU, Jian LI. Cell-free protein synthesis system enables rapid and efficient biosynthesis of restriction endonucleases [J]. Synthetic Biology Journal, 2023, 4(4): 840-851.
[9]	Meili SUN, Kaifeng WANG, Ran LU, Xiaojun JI. Rewiring and application of Yarrowia lipolytica chassis cell [J]. Synthetic Biology Journal, 2023, 4(4): 779-807.
[10]	Zhenzhen CHENG, Jian ZHANG, Cong GAO, Liming LIU, Xiulai CHEN. Progress in metabolic engineering of microorganisms for the utilization of formate [J]. Synthetic Biology Journal, 2023, 4(4): 756-778.
[11]	Zhi SUN, Ning YANG, Chunbo LOU, Chao TANG, Xiaojing YANG. Rational design for functional topology and its applications in synthetic biology [J]. Synthetic Biology Journal, 2023, 4(3): 444-463.
[12]	Qilong LAI, Shuai YAO, Yuguo ZHA, Hong BAI, Kang NING. Microbiome-based biosynthetic gene cluster data mining techniques and application potentials [J]. Synthetic Biology Journal, 2023, 4(3): 611-627.
[13]	Qiaozhen MENG, Fei GUO. Applications of foldability in intelligent enzyme engineering and design: take AlphaFold2 for example [J]. Synthetic Biology Journal, 2023, 4(3): 571-589.
[14]	Sheng WANG, Zechen WANG, Weihua CHEN, Ke CHEN, Xiangda PENG, Fafen OU, Liangzhen ZHENG, Jinyuan SUN, Tao SHEN, Guoping ZHAO. Design of synthetic biology components based on artificial intelligence and computational biology [J]. Synthetic Biology Journal, 2023, 4(3): 422-443.
[15]	Hailong LV, Jian WANG, Hao LV, Jin WANG, Yong XU, Dayong GU. Synthetic biology for next-generation genetic diagnostics [J]. Synthetic Biology Journal, 2023, 4(2): 318-332.