Abstract:
: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 scale-up from engineering or genetic aspects.
journal_name
J Biotechnoljournal_title
Journal of biotechnologyauthors
Li C,Shu W,Wang S,Liu P,Zhuang Y,Zhang S,Xia Jdoi
10.1016/j.jbiotec.2018.08.005subject
Has Abstractpub_date
2018-12-10 00:00:00pages
28-40eissn
0168-1656issn
1873-4863pii
S0168-1656(18)30604-7journal_volume
287pub_type
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