文献类型：期刊文献

英文题名：Impact of Altered Trehalose Metabolism on Physiological Response of Penicillium chrysogenum Chemostat Cultures during Industrially Relevant Rapid Feast/Famine Conditions

作者：Wang, Xinxin[1];Zhao, Jiachen[1];Xia, Jianye[1];Wang, Guan[1];Chu, Ju[1];Zhuang, Yingping[1]

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

年份：2021

卷号：9

期号：1

外文期刊名：PROCESSES

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000610751400001)】；

基金：This research was funded by the National Natural Science Foundation of China grant number [31900073, 21978085], the Science and Technology Commission of Shanghai Municipality grant number [19ZR1413600] and the 111 Project grant number [B18022].

语种：英文

外文关键词：feast; famine conditions; industrial-scale bioreactor; metabolomics; metabolic response; penicillin; Penicillium chrysogenum; scale-down

摘要：Due to insufficient mass transfer and mixing issues, cells in the industrial-scale bioreactor are often forced to experience glucose feast/famine cycles, mostly resulting in reduced commercial metrics (titer, yield and productivity). Trehalose cycling has been confirmed as a double-edged sword in the Penicillium chrysogenum strain, which facilitates the maintenance of a metabolically balanced state, but it consumes extra amounts of the ATP responsible for the repeated breakdown and formation of trehalose molecules in response to extracellular glucose perturbations. This loss of ATP would be in competition with the high ATP-demanding penicillin biosynthesis. In this work, the role of trehalose metabolism was further explored under industrially relevant conditions by cultivating a high-yielding Penicillium chrysogenum strain, and the derived trehalose-null strains in the glucose-limited chemostat system where the glucose feast/famine condition was imposed. This dynamic feast/famine regime with a block-wise feed/no feed regime (36 s on, 324 s off) allows one to generate repetitive cycles of moderate changes in glucose availability. The results obtained using quantitative metabolomics and stoichiometric analysis revealed that the intact trehalose metabolism is vitally important for maintaining penicillin production capacity in the Penicillium chrysogenum strain under both steady state and dynamic conditions. Additionally, cells lacking such a key metabolic regulator would become more sensitive to industrially relevant conditions, and are more able to sustain metabolic rearrangements, which manifests in the shrinkage of the central metabolite pool size and the formation of ATP-consuming futile cycles.