Oscillation is a special cell behavior in microorganisms during continuous fermentation, which poses threats to the output stability for industrial productions of biofuels and biochemicals. In previous study, a spontaneous oscillatory behavior was observed in Clostridium butyricum-intensive microbial consortium in continuous fermentation for 1,3-propanediol (1,3-PDO) production from glycerol, which led to the discovery of oscillation in species C. butyricum. Spontaneous oscillations by C. butyricum tended to occur under glycerol-limited conditions at low dilution rates. At a glycerol feed concentration of 88 g/L and a dilution rate of 0.048 h−1, the oscillatory behavior of C. butyricum was observed after continuous operation for 146 h and was sustained for over 450 h with an average oscillation period of 51 h. During oscillations, microbial glycerol metabolism exhibited dramatic periodic changes, in which productions of lactate, formate and hydrogen significantly lagged behind that of other products including biomass, 1,3-PDO and butyrate. Analysis of extracellular oxidation–reduction potential and intracellular ratio of NAD+/NADH indicated that microbial cells experienced distinct redox changes during oscillations, from oxidized to reduced state with decreasing of growth rate. Meanwhile, C. butyricum S3 exhibited periodic morphological changes during oscillations, with aggregates, elongated shape, spores or cell debris at the trough of biomass production. Transcriptome analysis indicated that expression levels of multiple genes were up-regulated when microbial cells were undergoing stress, including that for pyruvate metabolism, conversion of acetyl-CoA to acetaldehyde as well as stress response. This study for the first time systematically investigated the oscillatory behavior of C. butyricum in aspect of occurrence condition, metabolism, morphology and transcriptome. Based on the experimental results, two hypotheses were put forward to explain the oscillatory behavior: disorder of pyruvate metabolism, and excessive accumulation of acetaldehyde.

中文翻译：

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酪酸梭菌长期连续发酵生产1,3-丙二醇过程中的振荡行为的代谢，形态和转录组分析

振荡是微生物在连续发酵过程中的一种特殊细胞行为，这对生物燃料和生物化学物质的工业生产的输出稳定性构成了威胁。在先前的研究中，在持续发酵的酪酸梭状芽孢杆菌密集型微生物联盟中，观察到甘油自发产生1,3-丙二醇（1,3-PDO）的自发振荡行为，从而导致了丁酸梭菌种中振荡的发现。丁酸梭菌的自发振荡倾向于在甘油限制的条件下以低稀释率发生。在甘油进料浓度为88 g / L，稀释率为0.048 h-1的情况下，连续运转146 h后观察到丁酸梭菌的振荡行为，并持续超过450 h，平均振荡周期为51 h 。在振荡期间 微生物甘油代谢表现出显着的周期性变化，其中乳酸，甲酸和氢的产生显着落后于其他产物，包括生物质，1，3-PDO和丁酸盐。对细胞外氧化还原电位和NAD + / NADH细胞内比率的分析表明，微生物细胞在振荡过程中经历了明显的氧化还原变化，从氧化状态到还原状态随着生长速率的降低。同时，丁酸梭菌S3在振荡过程中表现出周期性的形态变化，在生物质生产的谷部具有聚集体，细长的形状，孢子或细胞碎片。转录组分析表明，当微生物细胞承受压力（包括丙酮酸代谢）时，多个基因的表达水平上调，乙酰辅酶A向乙醛的转化以及应激反应。这项研究首次系统地从发生条件，代谢，形态和转录组方面研究了丁酸梭菌的振荡行为。根据实验结果，提出了两种假设来解释振荡行为：丙酮酸代谢紊乱和乙醛过度积累。