文献类型：期刊文献

英文题名：An industrial perspective on metabolic responses of Penicillium chrysogenum to periodic dissolved oxygen feast-famine cycles in a scale-down system

作者：Wang, Xueting[1];Yang, Qi[1];Haringa, Cees[2];Wang, Zejian[1];Chu, Ju[1,3];Zhuang, Yingping[1,3];Wang, Guan[1,3,4]

机构：[1]East China Univ Sci & Technol ECUST, State Key Lab Bioreactor Engn, Shanghai, Peoples R China;[2]Delft Univ Technol, Dept Biotechnol, Delft, Netherlands;[3]East China Univ Sci & Technol, Qingdao Innovat Inst, Qingdao, Peoples R China;[4]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, 130 Meilong Rd, Shanghai 200237, Peoples R China

年份：2024

卷号：121

期号：10

起止页码：3076

外文期刊名：BIOTECHNOLOGY AND BIOENGINEERING

收录：;EI(收录号：20242616314753);WOS:【SCI-EXPANDED(收录号:WOS:001252323300001)】；

基金：This research was funded by the National Key R&D Program of China (Grant no. 2021YFC2101000), National Natural Science Foundation of China (Grant no. 31900073, 21978085), Shanghai Rising-Star Program (Grant no. 21QA1402400), Natural Science Foundation of Shanghai (Grant no. 19ZR1413600) and the Fundamental Research Funds for the Central Universities (Grant No. JKF01221709).

语种：英文

外文关键词：dissolved oxygen; flux analysis; industrial; metabolomics; Penicillium chrysogenum; scale down

摘要：While traveling through different zones in large-scale bioreactors, microbes are most likely subjected to fluctuating dissolved oxygen (DO) conditions at the timescales of global circulation time. In this study, to mimic industrial-scale spatial DO gradients, we present a scale-down setup based on dynamic feast/famine regime (150 s) that leads to repetitive cycles with rapid changes in DO availability in glucose-limited chemostat cultures of Penicillium chrysogenum. Such DO feast/famine regime induced a stable and repetitive pattern with a reproducible metabolic response in time, and the dynamic response of intracellular metabolites featured specific differences in terms of both coverage and magnitude in comparison to other dynamic conditions, for example, substrate feast/famine cycles. Remarkably, intracellular sugar polyols were considerably increased as the hallmark metabolites along with a dynamic and higher redox state nicotinamide adenine dinucleotide hydrogen/nicotinamide adenine dinucleotide of the cytosol. Despite the increased availability of NADPH for penicillin production under the oscillatory DO conditions, this positive effect may be counteracted by the decreased adenosine triphosphate supply. Moreover, it is interesting to note that not only the penicillin productivity was reduced under such oscillating DO conditions, but also that of the unrecyclable byproduct ortho-hydroxyphenyl acetic acid and degeneration of penicillin productivity. Furthermore, dynamic flux profiles showed the most pronounced variations in central carbon metabolism, amino acid (AA) metabolism, energy metabolism and fatty acid metabolism upon the DO oscillation. Taken together, the metabolic responses of P. chrysogenum to DO gradients reported here are important for elucidating metabolic regulation mechanisms, improving bioreactor design and scale-up procedures as well as for constructing robust cell strains to cope with heterogenous industrial culture conditions.