Comparative performance of different scale-down simulators of substrate gradients inPenicillium chrysogenumcultures: the need of a biological systems response analysis
| Autor: | Amit T. Deshmukh, Joseph J. Heijnen, Jianye Xia, Henk J. Noorman, Yingping Zhuang, Ju Chu, Cees Haringa, Siliang Zhang, Junfei Zhao, Guan Wang, Wenjun Tang, Walter M. van Gulik |
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| Rok vydání: | 2018 |
| Předmět: |
0106 biological sciences
0301 basic medicine Bioengineering Penicillins Penicillium chrysogenum 01 natural sciences Applied Microbiology and Biotechnology Biochemistry 03 medical and health sciences chemistry.chemical_compound Bioreactors Arabitol 010608 biotechnology Bioreactor medicine Research Articles biology Strain (chemistry) Substrate (chemistry) biology.organism_classification Carbon Culture Media 030104 developmental biology chemistry Fermentation Biophysics Carbohydrate Metabolism Mannitol Scale down Research Article Biotechnology medicine.drug |
| Zdroj: | Microbial Biotechnology, 11(3) Microbial Biotechnology |
| ISSN: | 1751-7915 1751-7907 |
| DOI: | 10.1111/1751-7915.13046 |
| Popis: | In a 54 m3 large-scale penicillin fermentor, the cells experience substrate gradient cycles at the timescales of global mixing time about 20–40 s. Here, we used an intermittent feeding regime (IFR) and a two-compartment reactor (TCR) to mimic these substrate gradients at laboratory-scale continuous cultures. The IFR was applied to simulate substrate dynamics experienced by the cells at full scale at timescales of tens of seconds to minutes (30 s, 3 min and 6 min), while the TCR was designed to simulate substrate gradients at an applied mean residence time ((Formula presented.)) of 6 min. A biological systems analysis of the response of an industrial high-yielding P. chrysogenum strain has been performed in these continuous cultures. Compared to an undisturbed continuous feeding regime in a single reactor, the penicillin productivity (qPenG) was reduced in all scale-down simulators. The dynamic metabolomics data indicated that in the IFRs, the cells accumulated high levels of the central metabolites during the feast phase to actively cope with external substrate deprivation during the famine phase. In contrast, in the TCR system, the storage pool (e.g. mannitol and arabitol) constituted a large contribution of carbon supply in the non-feed compartment. Further, transcript analysis revealed that all scale-down simulators gave different expression levels of the glucose/hexose transporter genes and the penicillin gene clusters. The results showed that qPenG did not correlate well with exposure to the substrate regimes (excess, limitation and starvation), but there was a clear inverse relation between qPenG and the intracellular glucose level. |
| Databáze: | OpenAIRE |
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