Dynamic control in metabolic engineering: Theories, tools, and applications.
Dynamic control in metabolic engineering: Theories, tools, and applications.
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DOI：
10.1016/j.ymben.2020.08.015
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发表时间：
2021-01
影响因子：
8.4
通讯作者：
Zhang F
中科院分区：
文献类型：
--
作者：
Hartline CJ;Schmitz AC;Han Y;Zhang F
代谢工程允许利用微生物生产多种有价值的化学物质。改善生物生产存在许多生物学挑战，这些挑战限制了代谢工程系统的性能并减缓了其商业化。动态代谢工程是一个快速发展的领域，旨在通过设计基因编码的代谢控制系统来解决这些挑战，该系统允许细胞根据其外部和内部代谢状态自主调节其通量。本文首先讨论了动态控制系统的理论工作，包括两阶段、连续和种群行为控制策略的机理见解和设计选择。接下来，我们总结了各种传感器和致动器的分子机制，这些传感器和致动器可以实现微生物系统中的动态代谢控制。最后，重点介绍了动态控制在几种代谢物生产中的重要应用，包括脂肪酸、芳烃和萜烯化合物。总之，本文综述了代谢工程中用于提高效价、速率和产量指标的动态控制系统设计的进展、进展和前景。
Metabolic engineering has allowed the production of a diverse number of valuable chemicals using microbial organisms. Many biological challenges for improving bio-production exist which limit performance and slow the commercialization of metabolically engineered systems. Dynamic metabolic engineering is a rapidly developing field that seeks to address these challenges through the design of genetically encoded metabolic control systems which allow cells to autonomously adjust their flux in response to their external and internal metabolic state. This review first discusses theoretical works which provide mechanistic insights and design choices for dynamic control systems including two-stage, continuous, and population behavior control strategies. Next, we summarize molecular mechanisms for various sensors and actuators which enable dynamic metabolic control in microbial systems. Finally, important applications of dynamic control to the production of several metabolite products are highlighted, including fatty acids, aromatics, and terpene compounds. Altogether, this review provides a comprehensive overview of the progress, advances, and prospects in the design of dynamic control systems for improved titer, rate, and yield metrics in metabolic engineering.
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