生物合成调控的青霉素发酵数学模型与过程优化

Modeling and optimization of biosynthesis regulation for penicillin fermentation

青霉素生物合成受溶解氧、溶解二氧化碳、p H、氨氮、碳源 (特别是葡萄糖 )等的调控 ,这些调控反应的产生不仅与基础培养基配方有关 ,更受发酵过程通气、搅拌条件及补料方案的影响。为此 ,笔者通过把握发酵过程中产生菌生长和青霉素生物合成代谢流的元素平衡、能量平衡以及传递与反应速度平衡的方法 ,结合生产经验和数据资料 ,建立了一种能够模拟青霉素发酵过程工艺学参数和经济学参数变化的数学模型。应用这一模型 ,在充分考虑生物合成代谢调控的基础上 ,对青霉素发酵过程进行优化 ,即通过补水维持上述平衡 ,避免因环境条件、初始条件和约束条件的变化及人为的失误造成的过程波动 ,使生产不断趋向最优状态。模拟运行表明 ,这种优化可显著提高发酵生产的经济效益。

The penicillin biosynthesis was regulated by a series of pivotal factors such as dissolved oxygen, dissolved carbon dioxide, pH, ammonia-N, and carbon source (e.g. glucose) etc. The regulatory reaction related to medium composition, aeration condition, agitation rate, and a scheme for feed. By regulating the balances between element, energies, transfer, and reaction velocities in the metabolic flux of organism growth and penicillin biosynthesis, along with a great deal of experience and data, a mathematical model of penicillin fermentation which involved technical and economic parameter was established. On the basis of the model as well as in consideration of biosynthesis regulation, an optimization penicillin production was proposed. Through simulated running it was indicated that the optimization could improve significantly economic efficiency in penicillin fermentation.