Dynamic response of Aspergillus niger to periodical glucose pulse stimuli in chemostat cultures
Dynamic response of Aspergillus niger to periodical glucose pulse stimuli in chemostat cultures
复制标题
恒化器培养物中黑曲霉对周期性葡萄糖脉冲刺激的动态响应
DOI：
10.1002/bit.27739
复制
发表时间：
2021-04-01
影响因子：
3.8
通讯作者：
Noorman，Henk
中科院分区：
文献类型：
--
作者：
Liu，Peng;Wang，Shuai;Noorman，Henk
在工业大型生物反应器中，微生物会遇到异质底物浓度条件，这可能会影响生长或产物形成。在这里，我们进行了一项延长（12小时）的实验，以10分钟的周期重复葡萄糖脉冲，以模拟黑曲霉产生的葡糖淀粉酶的葡萄糖浓度波动，并通过快速采样和定量代谢组学研究其动态响应。 10 分钟周期代表最坏情况，因为在工业生物反应器中，平均循环持续时间通常约为 1 分钟。我们发现，尽管代谢组动力学显着，但细胞生长和葡糖淀粉酶生产力并未受到显着影响。在所有中心碳代谢途径中都发现了不同时间尺度的周期性动态响应，并且经常报道的 ATP 悖论也得到了证实。动态条件下的 nigerstrain。热力学分析表明，即使在周期性动态条件下，中心碳代谢的几个反应仍保持平衡。细胞内代谢物的动态响应曲线在脉冲暴露期间没有变化，表明应变对所施加的 60 多个扰动循环没有显着的适应。产生葡糖淀粉酶的明显高耐受性。葡萄糖利用率极端变化的 nigerstrain 为强大的工业微生物宿主的设计提供了有价值的信息。
In industrial large‐scale bioreactors, microorganisms encounter heterogeneous substrate concentration conditions, which can impact growth or product formation. Here we carried out an extended (12 h) experiment of repeated glucose pulsing with a 10‐min period to simulate fluctuating glucose concentrations withAspergillus nigerproducing glucoamylase, and investigated its dynamic response by rapid sampling and quantitative metabolomics. The 10‐min period represents worst‐case conditions, as in industrial bioreactors the average cycling duration is usually in the order of 1 min. We found that cell growth and the glucoamylase productivity were not significantly affected, despite striking metabolomic dynamics. Periodical dynamic responses were found across all central carbon metabolism pathways, with different time scales, and the frequently reported ATP paradox was confirmed for thisA. nigerstrain under the dynamic conditions. A thermodynamics analysis revealed that several reactions of the central carbon metabolism remained in equilibrium even under periodical dynamic conditions. The dynamic response profiles of the intracellular metabolites did not change during the pulse exposure, showing no significant adaptation of the strain to the more than 60 perturbation cycles applied. The apparent high tolerance of the glucoamylase producingA. nigerstrain for extreme variations in the glucose availability presents valuable information for the design of robust industrial microbial hosts.