文献类型：期刊文献

英文题名：Dynamic metabolic response of Aspergillus niger to glucose perturbation: evidence of regulatory mechanism for reduced glucoamylase production

作者：Li, Chao[1];Shu, Wei[1];Wang, Shuai[1];Liu, Peng[1];Zhuang, Yingpping[1];Zhang, Siliang[1];Xia, Jianye[1]

机构：[1]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China

年份：2018

卷号：287

起止页码：28

外文期刊名：JOURNAL OF BIOTECHNOLOGY

收录：;EI(收录号：20184205952543);WOS:【SCI-EXPANDED(收录号:WOS:000449076300004)】；

基金：This work was supported by National Natural Science Foundation of China [grant number 21506052, 21776082] and the Fundamental Research Funds for the Central Universities [grant number 22221818014].

语种：英文

外文关键词：Aspergillus niger; Glucose stimulus; Dynamic metabolic response; Glucoamylase; In vivo kinetics

摘要：Environmental gradient is an important common issue during scale-up process for protein production. To address the dynamic regulatory mechanism of Aspergillus niger being exposed to inhomogeneous glucose concentrations, glucose perturbation were experimented on the steady state of A. niger chemostat culture, and dynamic profiles of the intracellular metabolites in central carbon metabolism were tracked in a time scale of seconds. The upper glycolysis and pentose phosphate pathway showed sharp variations after glucose perturbation, while the lower glycolysis, TCA cycle and amino acid pools represented a moderate and prolonged response due to the allosteric regulation of enzymes and buffering function of metabolites with large pool sizes. Improved glucose-6-phosphate enhanced the metabolic flux to PP pathway remarkably, which provided not only more redox cofactors (NADPH) for protein synthesis but also more precursors (phosphoribosyl pyrophosphate and ribose-5-phosphate) for cell growth. Moreover, reduction of the total adenine nucleotides and major precursor amino acids indicated the upregulated RNA synthesis was required to produce stress proteins, and partially explained the drop of glucoamylase production when A. niger experienced a fluctuated glucose concentration environment. These findings would be valuable for improving bioreactor operation, design, and scaleup from engineering or genetic aspects.