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中国生物工程杂志

CHINA BIOTECHNOLOGY
中国生物工程杂志
中国生物工程杂志  2021, Vol. 41 Issue (4): 55-63    DOI: 10.13523/j.cb.2012048
综述     
利用转录因子工程重塑代谢网络实现细胞工厂高效生产
董曙馨1,秦磊2,李春1,2,李珺1,*()
1 北京理工大学化学与化工学院 北京 100081
2 清华大学化学工程系 北京 100084
Transcription Factor Engineering Harnesses Metabolic Networks to Meet Efficient Production in Cell Factories
DONG Shu-xin1,QIN Lei2,LI Chun1,2,LI Jun1,*()
1 School of Chemistry and Chemical Engineering, Beijing Institute of Technology, Beijing 100081, China
2 Department of Chemical Engineering,Tsinghua University, Beijing 100084, China
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摘要：

酿酒酵母已被广泛用作生产精细化学品的典型细胞工厂。但在生产过程中,各种环境胁迫以及异常的细胞代谢严重制约了生产成本降低和收益提高。解决此类瓶颈问题的一种有效方法是利用转录因子工程,通过重塑关键基因的转录水平来提高菌株的耐受性和生产效率。从运用转录因子工程提高耐受性、产量和基于人工转录因子设计在优化代谢通量、定量分析中的应用两方面综述转录因子工程的价值,讨论转录因子工程的开发以及应用于生产大宗化学品方面的挑战和解决方案。
关键词： 酿酒酵母;  转录因子工程;  应激;  代谢网络;  合成生物学    
Abstract:

Yeast has been well used as a typical microbial platform to make fermented fine chemicals. However, various stress conditions and abnormal metabolic milieu severely restrict the production costs and benefits. One effective way to resolve such bottlenecks is to engineer transcription factors (TFs) to enhance strain tolerance and production efficiency through remodeling the transcript levels of different stress resistant genes. The value of TFs engineering is reviewed from two aspects: novel strategies for the enhancement of both tolerance and yield by TFs engineering are examined. In addition, the applications of artificial transcription factors (ATFs)-based fabricating in metabolic fluxes optimization and quantitative evaluation are discussed. Lastly, we discuss challenges and potential solutions in exploiting TFs engineering for bio-based economic products.
Key words: Yeast    Transcription factors engineering    Stress    Metabolic networks    Synthetic biology
收稿日期: 2020-12-23 出版日期: 2021-04-30
ZTFLH:  Q819  
通讯作者: 李珺     E-mail: junlibiotech@bit.edu.cn
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董曙馨
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引用本文:

董曙馨,秦磊,李春,李珺. 利用转录因子工程重塑代谢网络实现细胞工厂高效生产[J]. 中国生物工程杂志, 2021, 41(4): 55-63.

DONG Shu-xin,QIN Lei,LI Chun,LI Jun. Transcription Factor Engineering Harnesses Metabolic Networks to Meet Efficient Production in Cell Factories. China Biotechnology, 2021, 41(4): 55-63.

链接本文:

https://manu60.magtech.com.cn/biotech/CN/10.13523/j.cb.2012048    或    https://manu60.magtech.com.cn/biotech/CN/Y2021/V41/I4/55

图1  微生物细胞工厂生产高附加值化学品
图2  利用传统转录因子工程构建工程菌株
转录因子 来源 应用 参考文献
TaWRKY49
TaWRKY92
TaWRKY112
TaWRKY142		 水稻 提高了拟南芥抵抗盐、渗透压、真菌病原体的能力 [45]
GmRR34 大豆 提高拟南芥抗干旱能力 [46]
VqERF112
VqERF114
VqERF072		 葡萄 增强拟南芥抵抗丁香假单胞菌能力 [47]
CsbZIP18 茶树 拟南芥植物对ABA敏感性降低;负调控拟南芥抗冻性 [48]
NAC2/3 马齿草 降低小麦根部,枝条中有害的重金属镉含量 [49]
AtCBF3 拟南芥 提高茄子抗冻性 [50]
LcMYB2 羊草 增加植物对干旱和渗透压的耐受性 [51]
表1  转录因子在植物中的异源表达
图3  人工转录因子调控基因表达
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