Heijnen J J, Roels J A, Stouthamer A H
Biotechnol Bioeng. 1979 Dec;21(12):2175-201. doi: 10.1002/bit.260211204.
This paper shows the application of elementary balancing methods in combination with simple kinetic equations in the formulation of an unstructured model for the fed-batch process for the production of penicillin. The rate of substrate uptake is modeled with a Monod-type relationship. The specific penicillin production rate is assumed to be a function of growth rate. Hydrolysis of penicillin to penicilloic acid is assumed to be first order in penicillin. In simulations with the present model it is shown that the model, although assuming a strict relationship between specific growth rate and penicillin productivity, allows for the commonly observed lag phase in the penicillin concentration curve and the apparent separation between growth and production phase (idiophase-trophophase concept). Furthermore it is shown that the feed rate profile during fermentation is of vital importance in the realization of a high production rate throughout the duration of the fermentation. It is emphasized that the method of modeling presented may also prove rewarding for an analysis of fermentation processes other than the penicillin fermentation.
本文展示了基本平衡方法与简单动力学方程相结合在构建青霉素分批补料生产非结构化模型中的应用。底物摄取速率采用莫诺德型关系进行建模。特定青霉素生产速率假定为生长速率的函数。青霉素水解为青霉酸假定为青霉素的一级反应。在使用当前模型进行的模拟中表明,该模型尽管假定特定生长速率与青霉素生产力之间存在严格关系,但仍能解释青霉素浓度曲线中常见的延迟期以及生长和生产阶段(分化期-营养期概念)之间的明显分离。此外还表明,发酵过程中的进料速率曲线对于在整个发酵期间实现高生产率至关重要。需要强调的是,所提出的建模方法对于分析除青霉素发酵之外的其他发酵过程也可能具有重要价值。