智能抗逆微生物细胞工厂与绿色生物制造
Intelligent microbial cell factory with tolerance for green biological manufacturing
- 合成生物学 2020年1卷第4期 页码：427-439
- 作者机构：
1.清华大学化学工程系，工业生物催化教育部重点实验室，北京 100084
2.北京理工大学化学与化工学院，生物化工研究所，北京 100081
- 作者简介：
[ "许可（1983— ），男，博士，助理研究员，研究方向为代谢工程与合成生物学。E-mail: xuke528@tsinghua.edu.cn" ]
[ "李春（1970— ），男，博士生导师，教授，研究方向为代谢工程与合成生物学。E-mail: lichun@tsinghua.edu.cn" ]
- 基金信息：国家自然科学基金(22078171)
DOI：10.12211/2096-8280.2020-045
中图分类号： Q 819收稿：2020-04-09，
修回：2020-05-02，
纸质出版：2020-08-31
- 稿件说明：
移动端阅览
许可, 王靖楠, 李春. 智能抗逆微生物细胞工厂与绿色生物制造[J]. 合成生物学, 2020, 1(4): 427-439
XU Ke, WANG Jingnan, LI Chun. Intelligent microbial cell factory with tolerance for green biological manufacturing[J]. Synthetic Biology Journal, 2020, 1(4): 427-439
许可, 王靖楠, 李春. 智能抗逆微生物细胞工厂与绿色生物制造[J]. 合成生物学, 2020, 1(4): 427-439 DOI： 10.12211/2096-8280.2020-045.
XU Ke, WANG Jingnan, LI Chun. Intelligent microbial cell factory with tolerance for green biological manufacturing[J]. Synthetic Biology Journal, 2020, 1(4): 427-439 DOI： 10.12211/2096-8280.2020-045.
摘要
绿色生物制造作为新的工业模式，在其发酵过程中，生物转化效率往往被环境变化或代谢失衡引起的一系列逆境胁迫所限制，导致细胞工厂生长缓慢、产量下降、生产能耗大幅升高等，严重制约着产业的发展。构建在多重胁迫因子条件下具有良好表现的智能抗逆微生物细胞工厂，为绿色生物制造迎来了新的机遇。本文介绍了绿色生物制造过程中微生物细胞工厂面临的胁迫因子及其胁迫机理，综述了提高微生物细胞工厂耐受性的主要策略，包括非理性技术增强细胞自身防御系统及以工程化思维、借助合成生物学技术有针对性地设计并集成抗逆基因线路，重编程微生物细胞工厂提高其抗逆能力，最后对智能抗逆微生物细胞工厂在生物医药、大宗化学品、食品等绿色生物制造涉及领域的应用进行展望。期待本文为实现细胞工厂对环境胁迫的应答与智能调节提供新的研究思路。
Abstract
The current development model has led to an unsustainable supply of petroleum and global climate change
which present an urgent need for switching the traditional 'take-make-dispose' economy to a renewable one with a reduced carbon footprint by introducing biological systems into the traditional chemical manufacturing to develop green
renewable and safe biological manufacturing. Green biological manufacturing is a new industrial model
and the bio-transformation efficiency is often limited by a series of stresses caused by environmental changes or metabolic imbalance
which lead to the slow growth of cells
decline of production
and increase of energy consumption. All these ultimately make biological manufacturing less competitive economically. How to minimize the impact of stresses on microbial cell factory is of great significance
which creates a new opportunity for building an intelligent microbial cell factory with tolerance under multiple stress conditions for green biological manufacturing. This review not only introduces stress factors and their action mechanism to microbial cell factories in the process of biological manufacturing
but also summarizes commonly used strategies to improve the tolerance of microbial cells
including the random and semirational technologies to improve the self-defense system of cells. With the help of engineering thinking and synthetic biology technology to design and integrate tolerant gene circuits for reprogramming metabolism
in particular the development of intelligent microbial cell factory
stress tolerance can be further improved. It is expected that this review can provide new ideas for the intelligent response and regulation of microbial cells to environmental stresses.
2
关键词
Keywords
references
LIU Zihe , WANG Kai , CHEN Yun , et al . Third-generation biorefineries as the means to produce fuels and chemicals from CO 2 [J ] . Nature Catalysis , 2020 , 3 ( 3 ): 274 - 288 .
XU Ke , LYU Bo , HUO Yixin , et al . Toward the lowest energy consumption and emission in biofuel production: combination of ideal reactors and robust hosts [J ] . Current Opinion in Biotechnology , 2017 , 50 : 19 - 24 .
谭天伟 , 苏海佳 , 陈必强 , 等 . 绿色生物制造 [J ] . 北京化工大学学报(自然科学版) , 2018 , 45 ( 5 ): 107 - 118 .
TAN Tianwei , SU Haijia , CHEN Biqiang , et al . Green bio-manufacturing [J ] . Journal of Beijing University of Chemical Technology (Natural Science Edition) , 2018 , 45 ( 5 ): 107 - 118 .
DEPARIS Q , CLAES A , FOULQUIÉ-MORENO M R , et al . Engineering tolerance to industrially relevant stress factors in yeast cell factories [J ] . FEMS Yeast Research , 2017 , 17 ( 4 ): fox036 .
赵美琳 , 诸葛斌 , 陆信曜 , 等 . 工业酵母抗逆机理研究进展 [J ] . 微生物学通报 , 2019 ( 5 ): 1155 - 1164 .
ZHAO Meilin , ZHUGE bin , LU Xinyao , et al . Research progress in stress tolerance of industrial yeasts [J ] . Microbiology China , 2019 ( 5 ): 1155 - 1164 .
LAM F H , GHADERI A , FINK G R , et al . Biofuels. Engineering alcohol tolerance in yeast [J ] . Science , 2014 , 346 ( 6205 ): 71 - 75 .
UNREAN P . Flux control-based design of furfural-resistance strains of Saccharomyces cerevisiae for lignocellulosic biorefinery [J ] . Bioprocess and Biosystems Engineering , 2017 , 40 ( 4 ): 611 - 623 .
GUBICZA K , NIEVES I U , SAGUES W J , et al . Techno-economic analysis of ethanol production from sugarcane bagasse using a Liquefaction plus Simultaneous Saccharification and co-Fermentation process [J ] . Bioresource Technology , 2016 , 208 : 42 - 48 .
QIN Lei , LI Wenchao , LIU Li , et al . Inhibition of lignin-derived phenolic compounds to cellulase [J ] . Biotechnology for Biofuels , 2016 , 9 ( 1 ): 70 .
MAITY S K . Opportunities, recent trends and challenges of integrated biorefinery: part I [J ] . Renewable and Sustainable Energy Reviews , 2015 , 43 : 1427 - 1445 .
张克俞 , 张明明 , 赵心清 , 等 . 关键基因过表达提高酿酒酵母抑制剂耐受性及乙醇发酵性能 [J ] . 应用与环境生物学报 , 2018 , 24 ( 3 ): 541 - 546 .
ZHANG Keyu , ZHANG Mingming , ZHAO Xinqing , et al . Improvement of inhibitor stress tolerance and ethanol fermentation of Saccharomyces cerevisiae by overexpression of novel key genes [J ] . Chinese Journal of Applied and Environmental Biology , 2018 , 24 ( 3 ): 541 - 546 .
CLOMBURG J M , CRUMBLEY A M , GONZALEZ R . Industrial biomanufacturing: the future of chemical production [J ] . Science , 2017 , 355 ( 6320 ): aag0804 .
ABBOTT D A , INGLEDEW W M . Buffering capacity of whole corn mash alters concentrations of organic acids required to inhibit growth of Saccharomyces cerevisiae and ethanol production [J ] . Biotechnology Letters , 2004 , 26 ( 16 ): 1313 - 1316 .
AUESUKAREE C . Molecular mechanisms of the yeast adaptive response and tolerance to stresses encountered during ethanol fermentation [J ] . Journal of Bioscience and Bioengineering , 2017 , 124 ( 2 ): 133 - 142 .
XU Ke , YU Liping , BAI Wenxin , et al . Construction of thermo-tolerant yeast based on an artificial protein quality control system (APQC) to improve the production of bio-ethanol [J ] . Chemical Engineering Science , 2018 , 177 : 410 - 416 .
CASPETA L , NIELSEN J . Thermotolerant yeast strains adapted by laboratory evolution show trade-off at ancestral temperatures and preadaptation to other stresses [J ] . mBio , 2015 , 6 ( 4 ): e00431-15 .
GAO Liman , LIU Yueqin , SUN Hun , et al . Advances in mechanisms and modifications for rendering yeast thermotolerance [J ] . Journal of Bioscience and Bioengineering , 2016 , 121 ( 6 ): 599 - 606 .
LUHE A L , TAN L , WU J C , et al . Increase of ethanol tolerance of Saccharomyces cerevisiae by error-prone whole genome amplification [J ] . Biotechnology Letters , 2011 , 33 ( 5 ): 1007 - 1011 .
DIVATE N R , CHEN G H , WANG P M , et al . Engineering Saccharomyces cerevisiae for improvement in ethanol tolerance by accumulation of trehalose [J ] . Bioengineered , 2016 , 7 ( 6 ): 445 - 458 .
朱宝生 , 刘功良 , 白卫东 , 等 . 耐高糖酵母筛选及其高糖胁迫机制的研究进展 [J ] . 中国酿造 , 2016 , 35 ( 6 ): 11 - 14 .
ZHU Baosheng , LIU Gongliang , BAI Weidong , et al . Screening of high-sugar-tolerant yeast and research on its high sugar stress [J ] . China Brewing , 2016 , 35 ( 6 ): 11 - 14 .
毕新煜 , 刘功良 , 姜弘佳 , 等 . 酵母菌高糖耐受机制的研究进展 [J ] . 中国酿造 , 2017 ( 10 ): 1 - 4 .
BI Xinyu , LIU Gongliang , JIANG Hongjia , et al . Research progress on high sugar tolerance mechanism of yeast [J ] . China Brewing , 2017 ( 10 ): 1 - 4 .
SHI Xinchi , ZOU Yanan , CHEN Yong , et al . Overexpression of THI4 and HAP4 improves glucose metabolism and ethanol production in Saccharomyces cerevisiae [J ] . Frontiers in Microbiology , 2018 , 9 : 1444 .
岳国君 , 武国庆 , 郝小明 . 我国燃料乙醇生产技术的现状与展望 [J ] . 化学进展 , 2007 , 19 ( 7 ): 1084 - 1090 .
YUE Guojun , WU Guoqing , HAO Xiaoming . The status quo and prospects of fuel ethanol process technology in China [J ] . Progress in Chemistry , 2007 , 19 ( 7 ): 1084 - 1090 .
赵心清 , 张明明 , 徐桂红 , 等 . 酿酒酵母乙酸耐性分子机制的功能基因组进展 [J ] . 生物工程学报 , 2014 , 30 ( 3 ): 368 - 380 .
ZHAO Xinqing , ZHANG Mingming , XU Guihong , et al . Advances in functional genomics studies underlying acetic acid tolerance of Saccharomyces cerevisiae [J ] . Chinese Journal of Biotechnology , 2014 , 30 ( 3 ): 368 - 380 .
ZI Z K , WOLFRAM L , EDDA K . A quantitative study of the Hog1 MAPK response to fluctuating osmotic stress in Saccharomyces cerevisiae [J ] . PLoS One , 2010 , 5 ( 3 ): e9522 .
KIM Daehee , HAHN Ji-Sook . Roles of the Yap1 transcription factor and antioxidants in Saccharomyces cerevisiae 's tolerance to furfural and 5-hydroxymethylfurfural, which function as thiol-reactive electrophiles generating oxidative stress [J ] . Applied and Environmental Microbiology , 2013 , 79 ( 16 ): 5069 - 5077 .
WOJDA I , ALONSO-MONGE R , BEBELMAN J P , et al . Response to high osmotic conditions and elevated temperature in Saccharomyces cerevisiae is controlled by intracellular glycerol and involves coordinate activity of MAP kinase pathways [J ] . Microbiology , 2003 , 149 ( 5 ): 1193 - 1204 .
CHAROENBHAKDI S , DOKPIKUL T , BURPHAN T , et al . Vacuolar H + -ATPase protects Saccharomyces cerevisiae cells against ethanol-induced oxidative and cell wall stresses [J ] . Applied & Environmental Microbiology , 2016 , 82 ( 16 ): 5057 .
HERRERO E , ROS J , BELLÍ G , et al . Redox control and oxidative stress in yeast cells [J ] . BBA - General Subjects , 2008 , 1780 ( 11 ): 1217 - 1235 .
MORANO K A , GRANT C M , MOYE-ROWLEY W S . The response to heat shock and oxidative stress in Saccharomyces cerevisiae [J ] . Genetics , 2012 , 190 ( 4 ): 1157 - 1195 .
LIU Yueqin , ZHANG Genli , SUN Huan , et al . Enhanced pathway efficiency of Saccharomyces cerevisiae by introducing thermo-tolerant devices [J ] . Bioresource Technology , 2014 , 170 ( 5 ): 38 - 44 .
XU K , GAO L M , HASSAN J U , et al . Improving the thermo-tolerance of yeast base on the antioxidant defense system [J ] . Chemical Engineering Science , 2018 , 175 : 335 - 342 .
MORANO K A , GRANT C M , MOYE-ROWLEY W S . The resp onse to heat shock and oxidative stress in Saccharomyces cerevisiae [J ] . Genetics , 2012 , 190 ( 4 ): 1157 - 1195 .
FINLEY D , ULRICH H D , SOMMER T , et al . The ubiquitin-proteasome system of Saccharomyces cerevisiae [J ] . Genetics , 192 ( 2 ): 319 - 360 .
HIPP M S , PARK S H , HARTL F U . Proteostasis impairment in protein-misfolding and-aggregation diseases [J ] . Trends in Cell Biology , 2014 , 24 ( 9 ): 506 - 514 .
BENYAIR R , RON E , LEDERKREMER G Z , et al . Protein quality control, retention, and degradation at the endoplasmic reticulum [J ] . 2011, 292 : 197 - 280 .
SANDOVAL N R , PAPOUTSAKIS E T . Engineering membrane and cell-wall programs for tolerance to toxic chemicals: beyond solo genes [J ] . Current Opinion in Microbiology , 2016 , 33 : 56 - 66 .
RAY S , KASSAN A , BUSIJA A R , et al . The plasma membrane as a capacitor for energy and metabolism [J ] . American Journal of Physiology - Cell Physiology , 2016 , 310 ( 3 ): C181 - C192 .
QI Yanli , LIU Hui , CHEN Xiulai , et al . Engineering microbial membranes to increase stress tolerance of industrial strains [J ] . Metabolic Engineering , 2019 , 53 : 24 - 34 .
方华 , 李灏 . 海藻糖与热激蛋白在酿酒酵母耐受乙醇胁迫中的作用 [J ] . 中国生物工程杂志 , 2014 , 34 ( 6 ): 84 - 89 .
FANG Hua , LI Hao . The roles of trehalose and heat shock proteins for enhancing ethanol tolerance of Saccharomyces cerevisiae [J ] . China Biotechnology , 2014 , 34 ( 6 ): 84 - 89 .
LEITE F C , LEITE D V , PEREIRA L F , et al . High intracellular trehalase activity prevents the storage of trehalose in the yeast Dekkera bruxellensis [J ] . Letters in Applied Microbiology , 2016 , 63 ( 3 ): 210 - 214 .
ELEUTHERIO E , PANEK A , MESQUITA J F D , et al . Revisiting yeast trehalose metabolism [J ] . Current Genetics , 2015 , 61 ( 3 ): 263 - 274 .
PETITJEAN M , TESTE M A , FRANCOIS J M , et al . Yeast tolerance to various stresses relies on the trehalose-6P synthase (Tps1) protein, not on trehalose [J ] . Journal of Biological Chemistry , 2015 , 290 ( 26 ): 16177 - 16190 .
BUSTI S , MAPELLI V , TRIPODI F , et al . Respiratory metabolism and calorie restriction relieve persistent endoplasmic reticulum stress induced by calcium shortage in yeast [J ] . Scientific Reports , 2016 , 6 : 27942 .
CASPETA L , CASTILLO T , NIELSEN J . Modifying yeast tolerance to inhibitory conditions of ethanol production processes [J ] . Frontiers in Bioengineering and Biotechnology , 2015 , 3 : 184 .
CASPETA L , CHEN Y , NIELSEN J . Thermotolerant yeasts selected by adaptive evolution express heat stress response at 30 ℃ [J ] . Scientific Reports , 2016 , 6 : 27003 .
ALPER H , MOXLEY J , NEVOIGT E , et al . Engineering yeast transcription machinery for improved ethanol tolerance and production [J ] . Science , 2006 , 314 ( 5805 ): 1565 .
SI Tong , CHAO Ran , MIN Yuhao , et al . Automated multiplex genome-scale engineering in yeast [J ] . Nature Communications , 2017 , 8 : 15187 .
SHEN M J , WU Y , YANG K , et al . Heterozygous diploid and interspecies SCRaMbLEing [J ] . Nature Communications , 2018 , 9 ( 1 ): 1934 .
SNOEK T , NICOLINO M P , VAN DEN BREMT S , et al . Large-scale robot-assisted genome shuffling yields industrial Saccharomyces cerevisiae yeasts with increased ethanol tolerance [J ] . Biotechnology for Biofuels , 2015 , 8 ( 1 ): 32 .
PARENTEAU J , MAIGNON L , BERTHOUMIEUX M , et al . Introns are mediators of cell response to starvation [J ] . Nature , 2019 , 565 : 612 - 617 .
赵学明 , 王庆昭 . 合成生物学: 学科基础, 研究进展与前景展望 [J ] . 前沿科学 , 2007 ( 3 ): 56 - 66 .
ZHAO Xueming , WANG Qingzhao . Synthetic biology: fundamentals, advances and prospect [J ] . Frontier Science , 2007 ( 3 ): 56 - 66 .
CAMERON D E , BASHOR C J , COLLINS J J . A brief history of synthetic biology [J ] . Nature Reviews Microbiology , 2014 , 12 ( 5 ): 381 - 390 .
张先恩 . 中国合成生物学发展回顾与展望 [J ] . 中国科学(生命科学) , 2019 ( 12 ): 1543 - 1572 .
ZHANG X-E . Synthetic biology in China: review and prospects [J ] . SCIENTIA SINICA Vitae , 2019 ( 12 ): 1543 - 1572 .
杜鹤童 , 赵倚晴 , 陈金春 , 等 . 基于嗜盐微生物合成生物学的下一代工业生物技术 [J ] . 生命科学 , 2019 , 31 ( 4 ): 385 - 390 .
DU Hetong , ZHAO Yiqing , CHEN Jinchun , et al . Next generation industrial biotechnology based on synthetic biology of halophiles [J ] . Chinese Bulletin of Life Sciences , 2019 , 31 ( 4 ): 385 - 390 .
SIBANDA T , SELVARAJAN R , TEKERE M J M B . Synthetic extreme environments: overlooked sources of potential biotechnologically relevant microorganisms [J ] . Microbial Biotechnology , 2017 , 10 ( 3 ): 570 - 585 .
GONG Z W , NIELSEN J , ZHOU Y J J . Engineering robustness of microbial cell factories [J ] . Biotechnology Journal , 2017 , 12 ( 10 ): 1700014 .
JIA Haiyang , FAN Yanshuang , FENG Xudong , et al . Enhancing stress-resistance for efficient microbial biotransformations by synthetic biology [J ] . Frontiers in Bioengineering and Biotechnology , 2014 , 2 : 44 .
XU Ke , LEE Yun Seo , LI Jun , et al . Resistance mechanisms and reprogramming of microorganisms for efficient biorefinery under multiple environmental stresses [J ] . Synthetic and Systems Biotechnology , 2019 , 4 ( 2 ): 92 - 98 .
JIA Haiyang , SUN Xiangying , SUN Huan , et al . Intelligent microbial heat-regulating engine (IMHeRE) for improved thermo-robustness and efficiency of bioconversion [J ] . ACS Synthetic Biology , 2016 , 5 ( 4 ): 312 - 320 .
TAN Z G , KHAKBAZ P , CHEN Y X , et al . Engineering Escherichia coli membrane phospholipid head distribution improves tolerance and production of biorenewables [J ] . Metabolic Engineering , 2017 , 44 : 1 - 12 .
PHAM H L , WONG A , CHUA N Y , et al . Engineering a riboswitch-based genetic platform for the self-directed evolution of acid-tolerant phenotypes [J ] . Nature Communications , 2017 , 8 ( 1 ): 411 .
XU Ke , QIN Lei , BAI Wenxin , et al . Multilevel defense system (MDS) relieves multiple stresses for economically boosting ethanol production of industrial Saccharomyces cerevisiae [J ] . ACS Energy Letters , 2020 , 5 ( 2 ): 572 - 582 .
QIN L , DONG S , YU J , et al . Stress-driven dynamic regulation of multiple tolerance genes improves robustness and productive capacity of Saccharomyces cerevisiae in industrial lignocellulose fermentation [J ] . Metabolic Engineering , 2020 , 61 : 160 - 170 .
0
浏览量
1
下载量
0
CSCD
- 网络PDF下载
- WORD下载
- Meta-XML下载
- BibTeX下载
- Endnote下载
- RefMan 下载
- NoteExpress下载
- NoteFirst下载
关联资源
相关文章
相关作者
相关机构
- 地址：北京市东城区青年湖南街13号 邮编：100000
- 联系电话：010-64519339
- 技术支持由北京北大方正电子有限公司提供 京ICP备09064830号-19
京公网安备11010802024621 - 本系统建议在Chrome、 IE9+ 以上版本浏览器阅读本站内容，360浏览器请切换至极速模式
- Cookies帮助我们提供服务并提供个性化体验。使用本网站，即表示您同意我们使用Cookies