Analysis and Design of a Genetic Circuit for Dynamic Metabolic Engineering

被引:55
作者
Anesiadis, Nikolaos [1 ]
Kobayashi, Hideki
Cluett, William R. [1 ]
Mahadevan, Radhakrishnan [1 ,2 ]
机构
[1] Univ Toronto, Dept Chem Engn & Appl Chem, Toronto, ON M5S 3E5, Canada
[2] Univ Toronto, Inst Biomat & Biomed Engn, Toronto, ON M5S 3G9, Canada
来源
ACS SYNTHETIC BIOLOGY | 2013年 / 2卷 / 08期
关键词
global sensitivity analysis; quorum sensing; toggle switch; metabolic engineering; GLOBAL SENSITIVITY-ANALYSIS; SYNTHETIC BIOLOGY; BALANCE; MODELS; CONSTRUCTION; OPTIMIZATION; STRATEGIES; FRAMEWORK; NETWORKS; BINDING;
D O I
10.1021/sb300129j
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Recent advances in synthetic biology have equipped us with new tools for bioprocess optimization at the genetic level. Previously, we have presented an integrated in silico design for the dynamic control of gene expression based on a density-sensing unit and a genetic toggle switch. In the present paper, analysis of a serine-producing Escherichia coli mutant shows that an instantaneous ON-OFF switch leads to a maximum theoretical productivity improvement of 29.6% compared to the mutant. To further the design, global sensitivity analysis is applied here to a mathematical model of serine production in E. coli coupled with a genetic circuit. The model of the quorum sensing and the toggle switch involves 13 parameters of which 3 are identified as having a significant effect on serine concentration. Simulations conducted in this reduced parameter space further identified the optimal ranges for these 3 key parameters to achieve productivity values close to the maximum theoretical values. This analysis can now be used to guide the experimental implementation of a dynamic metabolic engineering strategy and reduce the time required to design the genetic circuit components.
引用
收藏
页码:442 / 452
页数:11
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