Institute of Chemical Engineering, Swiss Federal Institute of Technology, CH-1015 Lausanne, Switzerland.
Biotechnol Bioeng. 1992 Dec 5;40(10):1243-55. doi: 10.1002/bit.260401014.
Yeasts degrade glucose through different metabolic pathways, where the choice of the pathway is dependent on the nature of the limitation in the various substrates. When oxygen is limiting in addition to glucose, yeasts often grow according to a mixture of oxidative and reductive metabolism. Oxygen may be limiting either by supply or by inherent biological restrictions such as the respiratory bottleneck in Saccharomyces cerevisiae or by both. A unified model incorporating both supply and biological limitations is proposed for the quantitative prediction of growth rates, consumption and production rates, as well as key metabolite concentrations during mixed oxidoreductive metabolism occurring as a result of such oxygen limitations. This simple unstructured model can be applied to different yeast strains while at the same time requiring a minimum number of measured parameters. "Estimators" are utilized in order to predict the presence of supply-side or biological limitations. The values of these estimators also characterize the relative importance of oxidative to total metabolism. Results from the aerobic and oxygen-limited chemostat cultures were used to corroborate the model predictions. During these experiments, the heat released by the yeast cultures was also monitored on-line. The model correctly predicted the overall stoichiometry, steady-state concentrations, and rates including heat dissipation rates measured in the various situations of oxygen limitations. Direct continuous measurements such as heat can be used in conjunction with the unified model for on-line process control.
酵母通过不同的代谢途径降解葡萄糖，而途径的选择取决于各种基质中限制因素的性质。当除葡萄糖外氧也受到限制时，酵母通常根据氧化和还原代谢的混合方式生长。氧的限制可能是由于供应不足，也可能是由于内在的生物学限制，如酿酒酵母中的呼吸瓶颈，或者两者兼而有之。本文提出了一个统一的模型，将供应和生物学限制都包括在内，用于定量预测混合氧化还原代谢过程中由于这种氧限制而导致的生长速率、消耗和生产速率以及关键代谢物浓度。这个简单的非结构化模型可以应用于不同的酵母菌株，同时只需要最少数量的实测参数。“估计器”用于预测供应侧或生物学限制的存在。这些估计器的值还表征了氧化代谢与总代谢的相对重要性。来自需氧和氧限制恒化器培养的结果用于验证模型预测。在这些实验中，酵母培养物释放的热量也在线监测。该模型正确预测了在各种氧限制情况下的整体化学计量、稳态浓度和速率，包括测量的耗散速率。可以将直接连续测量（如热量）与统一模型结合用于在线过程控制。
