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通过动态控制来设计代谢

Engineering metabolism through dynamic control.

作者信息

Venayak Naveen, Anesiadis Nikolaos, Cluett William R, Mahadevan Radhakrishnan

机构信息

Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, Ontario, Canada.

Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, Ontario, Canada; Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada.

出版信息

Curr Opin Biotechnol. 2015 Aug;34:142-52. doi: 10.1016/j.copbio.2014.12.022. Epub 2015 Jan 20.

Abstract

Metabolic engineering has proven crucial for the microbial production of valuable chemicals. Due to the rapid development of tools in synthetic biology, there has been recent interest in the dynamic regulation of flux through metabolic pathways to overcome some of the issues arising from traditional strategies lacking dynamic control. There are many diverse implementations of dynamic control, with a range of metabolite sensors and inducers being used. Furthermore, control has been implemented at the transcriptional, translational and post-translational levels. Each of these levels have unique sets of engineering tools, and allow for control at different dynamic time-scales. In order to extend the applications of dynamic control, new tools are required to improve the dynamics of regulatory circuits. Further study and characterization of circuit robustness is also needed to improve their applicability to industry. The successful implementation of dynamic control, using technologies that are amenable to commercialization, will be a fundamental step in advancing metabolic engineering.

摘要

代谢工程已被证明对微生物生产有价值的化学品至关重要。由于合成生物学工具的快速发展,最近人们对通过代谢途径的通量动态调节产生了兴趣,以克服传统策略缺乏动态控制所产生的一些问题。动态控制有许多不同的实现方式,使用了一系列代谢物传感器和诱导剂。此外,控制已在转录、翻译和翻译后水平上得以实施。这些水平中的每一个都有独特的工程工具集,并允许在不同的动态时间尺度上进行控制。为了扩展动态控制的应用,需要新的工具来改善调节回路的动态性能。还需要对回路稳健性进行进一步研究和表征,以提高其在工业中的适用性。使用适合商业化的技术成功实施动态控制,将是推进代谢工程的一个基本步骤。

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