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中国生物工程杂志

CHINA BIOTECHNOLOGY
中国生物工程杂志  2021, Vol. 41 Issue (9): 101-109    DOI: 10.13523/j.cb.2104006
综述     
光遗传学在细菌生产调控中的应用进展
马宁,王汉杰()
天津大学生命科学学院 天津市微纳生物材料与检疗技术工程中心天津市生物大分子结构功能与应用重点实验室 天津 300072
Advances of Optogenetics in the Regulation of Bacterial Production
MA Ning,WANG Han-jie()
School of Life Sciences, Tianjin University, Tianjin Engineering Center of Micro-Nano Biomaterials and Detection-Treatment Technology, Tianjin Key Laboratory of Function and Application of Biological, Tianjin 300072, China
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摘要:

合成生物学的发展使得人们可以根据需求对微生物进行改造,作为“工厂”高效地合成催化所需物质,并通过添加化学诱导物的方式对生命过程进行调控。然而,化学诱导的潜在毒性以及不可逆性等限制其应用。光遗传学技术利用特定波长的光信号实现对细胞生命过程的调控,具有特异性、可逆性、高时空分辨率等特点。近年来,人们对不同来源的光敏蛋白进行改造,开发出各种不同波长、不同效应的光遗传元件用于基因回路的构建,进而实现对细菌蛋白合成、代谢过程的调控。光遗传技术在人与细菌之间搭起了实时的信号沟通桥梁,实现更为精准的物质生产调控:(1)通过光控治疗因子的合成分泌进行药物递送;(2)通过代谢通路的控制提高目的产物的催化效率;(3)通过光诱导控制生物活材料的形成。随着探索的深入,更小体积、更多波长、更高效率的光遗传元件将被开发出来,实现多输入的细菌生命活动调控。

关键词: 光遗传学合成生物学光敏蛋白工程菌生物材料代谢工程    
Abstract:

Advances in synthetic biology made it possible to engineer microorganisms to serve as “factories” to synthesize substances efficiently, and regulate cell activity by adding chemical inducers. However, the toxicity and irreversibility of chemical inducers limited their applications. Optogenetics, which uses light signals of specific wavelengths to regulate the process of cell life, has the characteristics of specificity, reversibility and high spatial and temporal resolution. In recent years, people have modified photosensitive proteins from different sources and developed various optogenetic elements with different wavelengths for the construction of gene circuits, and thus realized the regulation of bacterial protein synthesis and metabolism. Optogenetics technology builds a real-time signal communication between human and bacteria, making the production process more precise and controllable:(1) Drug delivery through bacteria synthesizes therapeutic factors controlled by light;(2) Improve the catalytic efficiency of the target product by controlling the metabolic pathway;(3) Control the formation of living biomaterials under light induction. With further exploration, optogenetic elements with smaller size, more wavelengths and higher efficiency will be developed to realize multi-input regulation of bacterial life activities.

Key words: Optogenetic    Synthetic biology    Photosensitive protein    Engineered bacteria    Biomaterial    Metabolic engineering
收稿日期: 2021-04-06 出版日期: 2021-09-30
ZTFLH:  Q819  
通讯作者: 王汉杰     E-mail: wanghj@tju.edu.cn
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引用本文:

马宁,王汉杰. 光遗传学在细菌生产调控中的应用进展[J]. 中国生物工程杂志, 2021, 41(9): 101-109.

MA Ning,WANG Han-jie. Advances of Optogenetics in the Regulation of Bacterial Production. China Biotechnology, 2021, 41(9): 101-109.

链接本文:

https://manu60.magtech.com.cn/biotech/CN/10.13523/j.cb.2104006        https://manu60.magtech.com.cn/biotech/CN/Y2021/V41/I9/101

图1  细菌光敏色素家族成员及其结构域
图2  双组分系统构成及其工作原理示意图
图3  光遗传细菌的工程应用
底盘 光控系统 代谢物质 产量
Yeast OptoEXP/OptoINVRT Isobutanol and 2-methyl-1-butanol (8.49±0.31) g/L /(2.38±0.06) g/L[47]
E.coil MG1655 CcaS/CcaR highly-reduced metabolites (i.e.
mevalonate,fatty acids, isobutanol, and
isopropyl alcohol)[48]
-
E.coil JM109 EL222 Acetoin and lactate-co-3-hydroxybutyrate 67.2 g/L, 39.19 %wt/14.31 g/L, 137.71 %wt[49]
E.coil MG1655 OptoLAC mevalonate and isobutanol (6.4±0.2) g/L, 24 %wt/(2.5±0.1) g/L, 27 %wt[50]
表1  光遗传用于微生物发酵调控
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