马红武,陈修来,袁倩倩,刘立明,孙际宾.面向生物合成的代谢工程策略设计[J].中国科学院院刊,2018,33(11):1166-1173.
面向生物合成的代谢工程策略设计
Design of Metabolic Engineering Strategies for Biosynthesis of Valuable Products
面向生物合成的代谢工程策略设计
Design of Metabolic Engineering Strategies for Biosynthesis of Valuable Products
作者
马红武
中国科学院天津工业生物技术研究所 天津 300308
MA Hongwu
Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin 300308, China
陈修来
江南大学 食品科学与技术国家重点实验室 无锡 214122;江南大学 工业生物技术教育部重点实验室 无锡 214122
CHEN Xiulai
State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China;Key Laboratory of Industrial Biotechnology(Ministry of Education), Jiangnan University, Wuxi 214122, China
袁倩倩
中国科学院天津工业生物技术研究所 天津 300308
YUAN Qianqian
Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin 300308, China
刘立明
江南大学 食品科学与技术国家重点实验室 无锡 214122;江南大学 工业生物技术教育部重点实验室 无锡 214122;江南大学 粮食发酵工艺与技术国家工程实验室 无锡 214122
LIU Liming
State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China;Key Laboratory of Industrial Biotechnology(Ministry of Education), Jiangnan University, Wuxi 214122, China;National Engineering Laboratory for Cereal Fermentation Technology, Jiangnan University, Wuxi 214122, China
孙际宾
中国科学院天津工业生物技术研究所 天津 300308
SUN Jibin
Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin 300308, China
中国科学院天津工业生物技术研究所 天津 300308
MA Hongwu
Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin 300308, China
陈修来
江南大学 食品科学与技术国家重点实验室 无锡 214122;江南大学 工业生物技术教育部重点实验室 无锡 214122
CHEN Xiulai
State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China;Key Laboratory of Industrial Biotechnology(Ministry of Education), Jiangnan University, Wuxi 214122, China
袁倩倩
中国科学院天津工业生物技术研究所 天津 300308
YUAN Qianqian
Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin 300308, China
刘立明
江南大学 食品科学与技术国家重点实验室 无锡 214122;江南大学 工业生物技术教育部重点实验室 无锡 214122;江南大学 粮食发酵工艺与技术国家工程实验室 无锡 214122
LIU Liming
State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China;Key Laboratory of Industrial Biotechnology(Ministry of Education), Jiangnan University, Wuxi 214122, China;National Engineering Laboratory for Cereal Fermentation Technology, Jiangnan University, Wuxi 214122, China
孙际宾
中国科学院天津工业生物技术研究所 天津 300308
SUN Jibin
Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin 300308, China
中文关键词
计算设计;代谢工程;生物合成;动态调控;代谢网络;合成生物学
英文关键词
computational design;metabolic engineering;biosynthesis;dynamic regulation;metabolic network;synthetic biology
中文摘要
代谢工程研究的主要目的是通过改造菌株代谢网络，高效地合成目的产品。由于细胞代谢网络的复杂性，从数千个代谢反应及其调控回路中找到合适的改造靶点非常困难，往往要经过反复试差才能成功。通过对大规模代谢网络的计算分析，设计出特定生物产品的最优合成途径，可以帮助人们找出合适的代谢工程改造策略，减少改造过程的盲目性，更快更好地得到生物合成菌株。文章重点讨论两个问题：（1）如何设计代谢网络来合成原来不能合成的产品并提高产品得率，介绍了基于代谢网络计算分析的代谢工程设计方法；（2）如何设计菌株实现酶反应的精准调控，介绍了通过设计基因回路动态调控代谢途径流向的动态代谢工程研究新进展。
英文摘要
One main objective of metabolic engineering is to rewire the metabolic network for efficient production of biochemicals. Due to the complexity of cellular metabolic networks, it is often not straightforward to identify the proper modification targets from thousands of metabolic genes. Therefore, a time-consuming trial & error process is often required for the successful development. Aided by computational modeling of large-scale metabolic networks, one can design optimal pathways for synthesis of objective products, reducing the uncertainty of development and thus accelerating the strain construction process. In this short text, we give brief introduction to metabolic engineering design methods from two aspects:how to modify an organism to produce new chemicals with higher yields, and how to improve the cellular adaptation to the changing process conditions by integrating gene circuits. The computer aided design approach together with automated genome edition technologies, will greatly enhance the efficiency of the construction of artificial cell factories.
DOI10.16418/j.issn.1000-3045.2018.11.004
作者简介
马红武 中国科学院天津工业生物技术研究所"百人计划"研究员。2001年在天津大学获得生物化工博士学位。2001-2011年先后在德国和英国从事研究工作。主要研究方向为大规模生物网络的计算分析与设计及相关计算方法工具的开发。在Bioinformatics、Molecular Systems Biology等刊物上发表学术论文30余篇,SCI引用千余次,2014年获汤森路透高被引科学家奖。
E-mail:ma_hw@tib.cas.cn
MA Hongwu Professor at Tianjin Institute of Industrial Biotechnology,Chinese Academy of Sciences (CAS) and winner of the Hundred Talents Program of CAS.He got his Ph.D.from Tianjin University,China in 2001.He then worked in German Research Centre for Biotechnology (GBF) and University of Edinburgh for ten years.His researches mainly focus on the computation analysis of large scale biological networks and the development of relevant computational tools.He has published more 30 papers at Bioinformatics,Molecular Systems Biology,etc.,of which have been cited over a thousand times.He won the Thomson-Reuters highly cited researcher award in 2014.
E-mail:ma_hw@tib.cas.cn
刘立明 江南大学食品科学与技术国家重点实验室教授。2006年获江南大学发酵工程专业工学博士学位。2009-2010年于瑞典查尔姆斯理工大学从事博士后研究工作,研究方向为系统生物学。主要从事系统生物学、代谢工程和酶工程方面的研究。已获得"万人计划"科技创新领军人才和国家自然科学基金支持。
E-mail:mingll@jiangnan.edu.cn
LIU Liming Professor at Jiangnan University.He received his Ph.D.in fermentation engineering from Jiangnan University in 2006.From 2009 to 2010,he worked at Chalmers University of Technology as a postdoctoral fellow,focusing on the research of systems biology.His group focuses on the research of systems biology,metabolic engineering,and enzyme engineering.He was supported by the Scientific and Technological Innovation Leading Talents of National "Ten Thousand Talents Program" of Ministry of Science and Technology of China and the National Natural Science Foundation of China.
E-mail:mingll@jiangnan.edu.cn
孙际宾 中国科学院天津工业生物技术研究所研究员,中国科学院"百人计划"入选者,中国科学院特聘研究员。2004年从German Research Centre for Biotechnology/Technical University of Braunschweig获得博士学位。2008年到中国科学院天津工业生物技术研究所工作。研究方向为工业微生物的系统与合成生物技术。
E-mail:sunjibin@tib.cas.cn
SUN Jibin Professor at Tianjin Institute of Industrial Biotechnology,CAS since 2008,winner of the Hundred Talents Program of CAS.He got his Ph.D.from German Research Centre for Biotechnology/Technical University of Braunschweig in 2004.His researches mainly focus on systems and synthetic biotechnology of industrial microorganisms in terms of tools development and industrial application.
E-mail:sunjibin@tib.cas.cn
E-mail:ma_hw@tib.cas.cn
MA Hongwu Professor at Tianjin Institute of Industrial Biotechnology,Chinese Academy of Sciences (CAS) and winner of the Hundred Talents Program of CAS.He got his Ph.D.from Tianjin University,China in 2001.He then worked in German Research Centre for Biotechnology (GBF) and University of Edinburgh for ten years.His researches mainly focus on the computation analysis of large scale biological networks and the development of relevant computational tools.He has published more 30 papers at Bioinformatics,Molecular Systems Biology,etc.,of which have been cited over a thousand times.He won the Thomson-Reuters highly cited researcher award in 2014.
E-mail:ma_hw@tib.cas.cn
刘立明 江南大学食品科学与技术国家重点实验室教授。2006年获江南大学发酵工程专业工学博士学位。2009-2010年于瑞典查尔姆斯理工大学从事博士后研究工作,研究方向为系统生物学。主要从事系统生物学、代谢工程和酶工程方面的研究。已获得"万人计划"科技创新领军人才和国家自然科学基金支持。
E-mail:mingll@jiangnan.edu.cn
LIU Liming Professor at Jiangnan University.He received his Ph.D.in fermentation engineering from Jiangnan University in 2006.From 2009 to 2010,he worked at Chalmers University of Technology as a postdoctoral fellow,focusing on the research of systems biology.His group focuses on the research of systems biology,metabolic engineering,and enzyme engineering.He was supported by the Scientific and Technological Innovation Leading Talents of National "Ten Thousand Talents Program" of Ministry of Science and Technology of China and the National Natural Science Foundation of China.
E-mail:mingll@jiangnan.edu.cn
孙际宾 中国科学院天津工业生物技术研究所研究员,中国科学院"百人计划"入选者,中国科学院特聘研究员。2004年从German Research Centre for Biotechnology/Technical University of Braunschweig获得博士学位。2008年到中国科学院天津工业生物技术研究所工作。研究方向为工业微生物的系统与合成生物技术。
E-mail:sunjibin@tib.cas.cn
SUN Jibin Professor at Tianjin Institute of Industrial Biotechnology,CAS since 2008,winner of the Hundred Talents Program of CAS.He got his Ph.D.from German Research Centre for Biotechnology/Technical University of Braunschweig in 2004.His researches mainly focus on systems and synthetic biotechnology of industrial microorganisms in terms of tools development and industrial application.
E-mail:sunjibin@tib.cas.cn
