文献类型：期刊文献

英文题名：Comparative performance of different scale-down simulators of substrate gradients in Penicillium chrysogenum cultures: the need of a biological systems response analysis

作者：Wang, Guan[1];Zhao, Junfei[1];Haringa, Cees[2];Tang, Wenjun[1];Xia, Jianye[1];Chu, Ju[1];Zhuang, Yingping[1];Zhang, Siliang[1];Deshmukh, Amit T.[3];van Gulik, Walter[4];Heijnen, Joseph J.[4];Noorman, Henk J.[3,5]

机构：[1]ECUST, State Key Lab Bioreactor Engn, Shanghai, Peoples R China;[2]Delft Univ Technol, Dept Chem Engn, Transport Phenomena, Delft, Netherlands;[3]DSM Biotechnol Ctr, Delft, Netherlands;[4]Delft Univ Technol, Dept Biotechnol, Cell Syst Engn, Delft, Netherlands;[5]Delft Univ Technol, Dept Biotechnol, Bio Proc Engn, Delft, Netherlands

年份：2018

卷号：11

期号：3

起止页码：486

外文期刊名：MICROBIAL BIOTECHNOLOGY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000430183300007)】；

基金：This work was financially subsidized by NWO-MoST Joint Program (2013DFG32630) and partially supported by National Basic Research Program (973 Program 2013CB733600).

语种：英文

摘要：In a 54m(3) large-scale penicillin fermentor, the cells experience substrate gradient cycles at the timescales of global mixing time about 20-40s. 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 (30s, 3min and 6min), while the TCR was designed to simulate substrate gradients at an applied mean residence time (c) of 6min. 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 (q(PenG)) 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 q(PenG) did not correlate well with exposure to the substrate regimes (excess, limitation and starvation), but there was a clear inverse relation between q(PenG) and the intracellular glucose level.