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动态建模揭示了酿酒酵母对高 CO2 水平的三步反应,伴随着不断增加的 ATP 需求。

Dynamic modeling reveals a three-step response of Saccharomyces cerevisiae to high CO2 levels accompanied by increasing ATP demands.

出版信息

FEMS Yeast Res. 2017 Jan 1;17(1). doi: 10.1093/femsyr/fox008.

DOI:10.1093/femsyr/fox008
PMID:28175306
Abstract

Saccharomyces cerevisiae is often applied in large-scale bioreactors where gradients of dissolved CO2 exist. Under high CO2 pressure, the dissolved gas enters the microbe, causing multifold intracellular responses such as decrease of pH, increase of HCO3- and changes of ion balance. Effects of varying CO2 concentrations are multifold, hard to scale and hardly investigated. Hence, the multi-level response to CO2 shifts was summarized in a predicting ODE model with mass action kinetics, balancing electrochemical charges in steady-state growth conditions. Compared to experimental observations, the simulated dynamics of ion concentrations were found to be consistent. During CO2 shifts, the model predicts the initial depolarization of the membrane potential, the temporal pH drop and the activation of countermeasures such as Pma1-mediated H+ export and Trk1,2-mediated K+ import. In conclusion, extracellular cation concentrations and the cellular pH regulation are critical factors that determine physiology and cellular energy management. Consequently, pressure-induced CO2 gradients cause peaks of ATP demand which may occur in cells circulating in large-scale industrial bioreactors.

摘要

酿酒酵母常用于存在溶解二氧化碳浓度梯度的大规模生物反应器中。在高二氧化碳压力下,溶解气体进入微生物体内,导致细胞内多种反应,如 pH 值下降、HCO3-增加和离子平衡变化。二氧化碳浓度变化的影响是多方面的,难以规模化,也难以研究。因此,采用质量作用动力学的微分方程模型对 CO2 转移的多级反应进行了总结,在稳态生长条件下平衡电化学电荷。与实验观察相比,模拟的离子浓度动态与实验观察一致。在 CO2 转移过程中,该模型预测了膜电位的初始去极化、pH 值的暂时下降以及 Pma1 介导的 H+外排和 Trk1、2 介导的 K+内流等对策的激活。总之,细胞外阳离子浓度和细胞内 pH 值调节是决定生理和细胞能量管理的关键因素。因此,压力诱导的二氧化碳浓度梯度会导致在大规模工业生物反应器中循环的细胞中出现 ATP 需求峰值。

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