调控工程在光合蓝细菌中的应用

doi:10.12211/2096-8280.2022-012

合成生物学 ›› 2022, Vol. 3 ›› Issue (5): 966-984.DOI: 10.12211/2096-8280.2022-012

调控工程在光合蓝细菌中的应用

董正鑫¹^,³^,⁴^,⁵, 孙韬¹^,²^,⁴, 陈磊¹^,³^,⁴^,⁵, 张卫文¹^,²^,³^,⁴^,⁵

^1.天津大学化工学院合成微生物学实验室，天津 300072
^2.天津大学生物安全战略研究中心，天津 300072
^3.教育部系统生物工程重点实验室，天津 300072
^4.教育部合成生物学前沿科学中心，天津 300072
^5.化学化工协同创新中心，天津 300072

收稿日期:2022-02-11 修回日期:2022-04-01 出版日期:2022-10-31 发布日期:2022-11-16
通讯作者: 孙韬,张卫文
作者简介:董正鑫（1997—），男，博士研究生。主要研究方向为微生物合成生物学。 E-mail：dongxin7122@foxmail.com
孙韬（1990—），博士，讲师，硕士生导师。从事微生物合成生物学及生物安全相关研究。 E-mail：tsun@tju.edu.cn
张卫文（1967—），男，博士，教授，博士生导师，生物安全战略研究中心主任。长期从事光合微生物的合成生物学，以及生物安全相关研究，牵头中美合成生物学生物安全“二轨”战略对话。 E-mail：wwzhang8@tju.edu.cn
基金资助:
国家重点研发计划(2018YFA0903000)

Applications of regulatory engineering in photosynthetic cyanobacteria

Zhengxin DONG¹^,³^,⁴^,⁵, Tao SUN¹^,²^,⁴, Lei CHEN¹^,³^,⁴^,⁵, Weiwen ZHANG¹^,²^,³^,⁴^,⁵

^1.Laboratory of Synthetic Microbiology，School of Chemical Engineering & Technology，Tianjin University，Tianjin 300072，China
^2.Center for Biosafety Research and Strategy，Tianjin University，Tianjin 300072，China
^3.Key Laboratory of Systems Bioengineering，Ministry of Education of China，Tianjin 300072，China
^4.Frontier Science Center for Synthetic Biology，Ministry of Education of China，Tianjin 300072，China
^5.Collaborative Innovation Center of Chemical Science and Engineering，Tianjin 300072，China

Received:2022-02-11 Revised:2022-04-01 Online:2022-10-31 Published:2022-11-16
Contact: Tao SUN, Weiwen ZHANG

摘要/Abstract

摘要：

能源短缺与环境污染问题限制着人类发展，光合蓝细菌因能够利用太阳能将CO₂固定生成燃料和化学品而受到广泛关注。迄今为止，在光合蓝细菌中已实现近百种燃料和化学品由CO₂的生物合成，有望促进CO₂的资源化利用并助力“碳中和”。调控工程能够实现基因表达多层次调控及代谢网络的全局性调控，是提高光合蓝细菌CO₂固定效率的有效手段。本文首先归纳了光合蓝细菌底盘中的双组分信号转导系统、调控小RNA和σ因子等3种主要调控系统的分类、作用过程以及功能；介绍了光合蓝细菌调控系统中的调控元件功能研究，系统总结了光合蓝细菌中通过调控系统元件改造，提高底盘鲁棒性、优化产品生产所进行的调控工程；最后，讨论了光合蓝细菌中调控工程的未来研究方向，重点包括调控系统功能阐明、工具开发、多基因调控、调控系统蛋白工程改造和系统调控工程等。总之，有望通过系统调控工程，实现对光合蓝细菌底盘细胞全局代谢网络的精确调控。

关键词: 光合蓝细菌, 自养型细胞工厂, 碳中和, 调控工程, 双组分系统, 小RNA, σ因子

Abstract:

Energy shortage and environmental pollution are the limiting factors for the development of human society. Photosynthetic cyanobacteria have attracted increasing attention due to their ability to use solar energy for the fixation of CO₂ for green production of biofuels and chemicals under low nutrient conditions. So far, nearly 100 kinds of fuels and chemicals have been synthesized in photosynthetic cyanobacteria directly from CO₂, which is expected to promote CO₂ utilization and contribute to “carbon neutrality”. However, the industrial applications of photosynthetic cyanobacteria are restricted by factors such as their slow growth rate, low biomass, low product yield, and poor environmental robustness. Regulatory engineering, enabling global regulation of metabolic networks and multi-level regulation of genes expression, is a powerful tool to address these challenges. In this paper, we firstly introduce the classification, mechanism, and function of three major regulatory systems, including two-component signal transduction systems (TCS), regulatory small RNAs (sRNAs), and σ factor in photosynthetic cyanobacteria. Subsequently, we briefly discuss the functions of regulatory elements in the regulatory systems of photosynthetic cyanobacteria related to the tolerance against high salt, short-chain alcohols, light stress, metal ions, oxidative stress, as well as heat and drought, and the regulation of carbon metabolism in the production of the target components. We systematically review the applications of regulatory engineering, based on engineered regulatory system elements, in improving the robustness of photosynthetic cyanobacteria under the above stress conditions and in optimizing the carbon fluxes towards product biosynthesis. Finally, we conclude with the future research focuses of regulatory engineering in photosynthetic cyanobacteria, highlighting research areas such as functional elucidation of the regulatory systems, toolbox development, multi-gene regulations, protein engineering of the regulatory systems, and systematic regulatory engineering. In a word, the regulatory systems are expected to be artificially designed through regulatory engineering to achieve accurate control of the global metabolic network to improve the robustness and cell growth of photosynthetic cyanobacteria, and more importantly the titer, yield, and productivity of the target components for industry-scale applications.

Key words: photosynthetic cyanobacteria, autotrophic cell factory, carbon neutrality, regulatory engineering, two-component systems, small RNAs, sigma factors

中图分类号:

Q819

董正鑫, 孙韬, 陈磊, 张卫文. 调控工程在光合蓝细菌中的应用[J]. 合成生物学, 2022, 3(5): 966-984.

Zhengxin DONG, Tao SUN, Lei CHEN, Weiwen ZHANG. Applications of regulatory engineering in photosynthetic cyanobacteria[J]. Synthetic Biology Journal, 2022, 3(5): 966-984.

图/表 6

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调控工程在光合蓝细菌中的应用

Applications of regulatory engineering in photosynthetic cyanobacteria

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菌株	调控系统单元	所属调控系统	功能
PCC 6803	Hik31-Rre34	TCS	维持Cu²⁺稳态^[75]
PCC 6803	Sll0649	TCS	维持Cu²⁺、Cd²⁺、Fe²⁺、Mn²⁺、Zn²⁺稳态^[76]
Nostocflagelliforme CCNUN1	OrrA	TCS	调控MAA合成，抵抗UV-B和干旱^[78]
PCC 6803	Slr1037、Sll0039	TCS	丁醇耐受^[37]
PCC 6803	Hik33、Hik34、Hik16、Hik41	TCS	NaCl耐受^[81]
PCC 6803	Hik2-Rre1 Hik34-Rre1	TCS	NaCl耐受^[84]
PCC 6803	Hik36-Hik43-Rre6	TCS	NaCl耐受，生物膜生成^[86]
PCC 7942	Synpcc7942_1125、Synpcc7942_1404	TCS	NaCl耐受^[87]
PCC 7102	OrrA	TCS	NaCl耐受、干旱^[88-89]
PCC 6803	Rre37	TCS	氮缺乏、三羧酸循环、丙酮酸代谢、琥珀酸合成^[91]
PCC 7102	SigB2	σ因子	NaCl耐受^[88]
PCC 6803	SigE	σ因子	琥珀酸合成^[91]
PCC 6803	SigB	σ因子	盐耐受、热耐受、丁醇耐受、氧化耐受^{[51, 92-93]}
PCC 6803	SigD	σ因子	氧化耐受^[51]
PCC 6803	SigE	σ因子	糖原降解、光系统蛋白丰度、琥珀酸合成、聚羟基丁酸酯合成^{[91, 94-95]}
PCC 7120	SigE	σ因子	氮固定^[96]
PCC 6803	CoaR	sRNA	丁醇耐受^[60]
PCC 6803	IsrR	sRNA	铁离子缺乏、氧化耐受^[99]
PCC 6803	IsaR1	sRNA	铁离子缺乏、盐耐受^[101-102]
PCC 6803	PsbA2R、PsbA3R	sRNA	光适应^[103]
PCC 6803	PsrR1	sRNA	光适应^[104]
PCC 6803	RblR	sRNA	光适应、碳固定^[61]
PCC 6803	Yfr1	sRNA	碳固定、氧化耐受、盐耐受、活性氧耐受^[105]
PCC 6803	Nc117	sRNA	醇类耐受^[62]