Li Jia-Wei, Zhang Xiao-Yan, Wu Hui, Bai Yun-Peng
State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, China.
Front Bioeng Biotechnol. 2020 Feb 19;8:98. doi: 10.3389/fbioe.2020.00098. eCollection 2020.
Metabolic regulation of gene expression for the microbial production of fine chemicals, such as organic acids, is an important research topic in post-genomic metabolic engineering. In particular, the ability of transcription factors (TFs) to respond precisely in time and space to various small molecules, signals and stimuli from the internal and external environment is essential for metabolic pathway engineering and strain development. As a key component, TFs are used to construct many biosensors using synthetic biology methods, which can be used to monitor the concentration of intracellular metabolites in organic acid production that would otherwise remain "invisible" within the intracellular environment. TF-based biosensors also provide a high-throughput screening method for rapid strain evolution. Furthermore, TFs are important global regulators that control the expression levels of key enzymes in organic acid biosynthesis pathways, therefore determining the outcome of metabolic networks. Here we review recent advances in TF identification, engineering, and applications for metabolic engineering, with an emphasis on metabolite monitoring and high-throughput strain evolution for the organic acid bioproduction.
用于微生物生产精细化学品（如有机酸）的基因表达代谢调控是后基因组代谢工程中的一个重要研究课题。特别是，转录因子（TFs）能够在时间和空间上精确响应来自内部和外部环境的各种小分子、信号和刺激，这对于代谢途径工程和菌株开发至关重要。作为关键组成部分，转录因子被用于利用合成生物学方法构建许多生物传感器，这些传感器可用于监测有机酸生产中细胞内代谢物的浓度，否则这些代谢物在细胞内环境中会保持“不可见”状态。基于转录因子的生物传感器还为快速菌株进化提供了一种高通量筛选方法。此外，转录因子是重要的全局调节因子，可控制有机酸生物合成途径中关键酶的表达水平，从而决定代谢网络的结果。在此，我们综述了转录因子鉴定、工程改造及其在代谢工程中的应用方面的最新进展，重点是用于有机酸生物生产的代谢物监测和高通量菌株进化。
