Journal of Bioscience and Bioengineering ( IF 2.8 ) Pub Date : 2021-09-08 , DOI: 10.1016/j.jbiosc.2021.08.002 Hiroshi Shimizu 1 , Yoshihiro Toya 1
Microorganisms are widely used to produce valuable compounds. Because thousands of metabolic reactions occur simultaneously and many metabolic reactions are related to target production and cell growth, the development of a rational design method for metabolic pathway modification to optimize target production is needed. In this paper, recent advances in metabolic engineering are reviewed, specifically considering computational pathway modification design and experimental evaluation of metabolic fluxes by 13C-metabolic flux analysis. Computational tools for seeking effective gene deletion targets and recruiting heterologous genes are described in flux balance analysis approaches. A kinetic model and adaptive laboratory evolution were applied to identify and eliminate the rate-limiting step in metabolic pathways. Data science-based approaches for process monitoring and control are described to maximize the performance of engineered cells in bioreactors.
中文翻译:
代谢工程的最新进展——集成计算机设计和代谢途径的实验分析
微生物被广泛用于生产有价值的化合物。由于数以千计的代谢反应同时发生,并且许多代谢反应与靶标的产生和细胞生长有关,因此需要开发一种合理的代谢途径修饰设计方法来优化靶标的产生。本文综述了代谢工程的最新进展,特别考虑了计算途径修改设计和代谢通量的实验评估13C-代谢通量分析。在通量平衡分析方法中描述了用于寻找有效基因缺失目标和招募异源基因的计算工具。应用动力学模型和适应性实验室进化来识别和消除代谢途径中的限速步骤。描述了基于数据科学的过程监测和控制方法,以最大限度地提高生物反应器中工程细胞的性能。