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面向生物合成的代谢工程策略设计
引用本文: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.
作者姓名:马红武  陈修来  袁倩倩  刘立明  孙际宾
作者单位:中国科学院天津工业生物技术研究所 天津 300308,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,中国科学院天津工业生物技术研究所 天津 300308,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,中国科学院天津工业生物技术研究所 天津 300308
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。

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
收稿时间:2018/10/29 0:00:00

Design of Metabolic Engineering Strategies for Biosynthesis of Valuable Products
MA Hongwu,CHEN Xiulai,YUAN Qianqian,LIU Liming and SUN Jibin.Design of Metabolic Engineering Strategies for Biosynthesis of Valuable Products[J].Bulletin of the Chinese Academy of Sciences,2018,33(11):1166-1173.
Authors:MA Hongwu  CHEN Xiulai  YUAN Qianqian  LIU Liming and SUN Jibin
Institution:Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin 300308, China,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,Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin 300308, China,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 and Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin 300308, China
Abstract: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.
Keywords:computational design  metabolic engineering  biosynthesis  dynamic regulation  metabolic network  synthetic biology
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