Department of Energy, Environmental and Chemical Engineering, Washington University in St. Louis, Saint Louis, MO, 63130, USA.
Department of Energy, Environmental and Chemical Engineering, Washington University in St. Louis, Saint Louis, MO, 63130, USA; Division of Biological & Biomedical Sciences, Washington University in St. Louis, Saint Louis, MO, 63130, USA; Institute of Materials Science & Engineering, Washington University in St. Louis, Saint Louis, MO, 63130, USA.
Metab Eng. 2021 Jan;63:126-140. doi: 10.1016/j.ymben.2020.08.015. Epub 2020 Sep 11.
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.
代谢工程使人们能够利用微生物生产出大量有价值的化学物质。在提高生物生产性能方面存在许多生物挑战，这些挑战限制了代谢工程系统的性能和商业化进程。动态代谢工程是一个快速发展的领域，它试图通过设计遗传编码的代谢控制系统来解决这些挑战，这些系统允许细胞根据其外部和内部代谢状态自主调整其通量。本综述首先讨论了为动态控制系统提供机制见解和设计选择的理论工作，包括两阶段、连续和群体行为控制策略。接下来，我们总结了微生物系统中实现动态代谢控制的各种传感器和执行器的分子机制。最后，重点介绍了动态控制在几种代谢产物生产中的重要应用，包括脂肪酸、芳烃和萜烯化合物。总的来说，本综述全面概述了设计动态控制系统以提高代谢工程中产物得率、速率和产量的相关进展、进步和前景。
