Dynamic response of Aspergillus niger to periodical glucose pulse stimuli in chemostat cultures

Abstract

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 with Aspergillus niger producing 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 this A. niger strain 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 producing A. niger strain for extreme variations in the glucose availability presents valuable information for the design of robust industrial microbial hosts.

Temporal dynamics of stress response in Halomonas elongata to NaCl shock: physiological, metabolomic, and transcriptomic insights

“…Intracellular AMP, ADP, and ATP were quantified using liquid chromatographymass spectrometry (LC-MS)/MS (Ultimate 3000 & TSQ Quantum Ultra, ThermoFisher Scientific Co., Ltd). The assays were consistent with the previous study [47,48].…”

Research progress of glucoamylase with industrial potential

“…To study the effect of substrate glucose concentration on the glucoamylase production by A. niger , the glucoamylase of A. niger responding to extracellular glucose concentration was researched by Chao et al (2018), but it only determined the effect of a single change of glucose concentration on A. niger . Subsequently, based on this, the experiment was improved by Liu et al (2021, Wang et al (2019), simulated the fluctuation of glucose concentration in industrial production, and found that the fluctuation of glucose concentration on the content of amino acids in A. niger and microbial growth and glucoamylase yields were not significantly affected, indicating that A. niger had some reversibility in the production.…”

Changes in Oxygen Availability during Glucose-Limited Chemostat Cultivations of Penicillium chrysogenum Lead to Rapid Metabolite, Flux and Productivity Responses

“…To our knowledge, there have been numerous scale-down studies on the substrate concentration gradient for a wide range of industrial cell factories. These studies have provided valuable insights into cellular metabolism and suggested methods for process intensification [8][9][10][11][12][13][14]. However, unlike substrates, e.g., glucose, which can be added directly to the broth, the dissolution and consumption of oxygen involves more mass transfer and a more involved mixing process.…”