Graf Michaela, Haas Thorsten, Teleki Attila, Feith André, Cerff Martin, Wiechert Wolfgang, Nöh Katharina, Busche Tobias, Kalinowski Jörn, Takors Ralf
Institute of Biochemical Engineering, University of Stuttgart, Stuttgart, Germany.
Institute of Bio- and Geosciences, IBG-1: Biotechnology, Forschungszentrum Jülich GmbH, Jülich, Germany.
Front Bioeng Biotechnol. 2020 Oct 15;8:584614. doi: 10.3389/fbioe.2020.584614. eCollection 2020.
Increasing the growth rate of the industrial host is a promising target to rise productivities of growth coupled product formation. As a prerequisite, detailed knowledge about the tight regulation network is necessary for identifying promising metabolic engineering goals. Here, we present comprehensive metabolic and transcriptional analysis of ATCC 13032 growing under glucose limited chemostat conditions with μ = 0.2, 0.3, and 0.4 h. Intermediates of central metabolism mostly showed rising pool sizes with increasing growth. C-metabolic flux analysis (C-MFA) underlined the fundamental role of central metabolism for the supply of precursors, redox, and energy equivalents. Global, growth-associated, concerted transcriptional patterns were not detected giving rise to the conclusion that glycolysis, pentose-phosphate pathway, and citric acid cycle are predominately metabolically controlled under glucose-limiting chemostat conditions. However, evidence is found that transcriptional regulation takes control over glycolysis once glucose-rich growth conditions are installed.
提高工业宿主的生长速率是提高耦合产物形成生长生产力的一个有前景的目标。作为前提条件,对于识别有前景的代谢工程目标而言,详细了解紧密的调控网络是必要的。在此,我们展示了在葡萄糖限制恒化器条件下(μ = 0.2、0.3和0.4 h)生长的ATCC 13032的全面代谢和转录分析。随着生长增加,中心代谢的中间产物大多显示出池大小增加。碳代谢通量分析(C-MFA)强调了中心代谢在提供前体、氧化还原和能量等价物方面的基础作用。未检测到全局的、与生长相关的、协同的转录模式,从而得出结论:在葡萄糖限制恒化器条件下,糖酵解、磷酸戊糖途径和柠檬酸循环主要受代谢控制。然而,有证据表明,一旦建立了富含葡萄糖的生长条件,转录调控就会控制糖酵解。