Abstract The microbial production of polyhydroxyalkanoates (PHAs) has attracted huge scientific and industrial interest. However, prerequisite to the economically feasible transition from the research scale towards industrial and highly competitive processes is the optimal production of PHAs in a consistent and systematic manner. The use of rigorous, experimentally verified mathematical models enabling the optimal dynamic operation of the fermentative production of PHAs is a promising alternative route against any low-yield empirical handling implemented so far. The present study investigates the model-based dynamic optimization of poly-3-hydroxybutyrate (PHB) production in Azohydromonas lata cultures through discontinuous and continuous bioreactor configurations. A detailed and validated macroscopic, kinetic and oxygen mass transfer mathematical model that relates state variables with operating strategies is used as a tool for the design of various dynamic optimization scenarios under fed-batch and continuous bioreactor policies. A notable improvement on the performance of fed-batch optimal operating bioreactors against heuristically designed operating strategies is proved concerning final polymer concentration, productivity, intracellular content and substrate to polymer yield, under four different strategies resulting in the following maximum values respectively, 27 g/l, 1.40 g/(l h), 95 % wt. and 0.7. In a continuously operating PHB production process of two stirred tank bioreactors in series, a dynamic optimization problem is formulated and solved for the first time in the literature to ameliorate substantially the polymer productivity and provide the means for a truly sustainable PHB production. A comparison of the fed-batch and continuous operating strategies is finally effected to support studies for process economic feasibility evaluation.

中文翻译：

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基于模型的动态优化聚羟基链烷酸酯 (PHA) 在连续运行的生物反应器的分批和顺序中的发酵生产

摘要 聚羟基链烷酸酯 (PHA) 的微生物生产引起了巨大的科学和工业兴趣。然而，从研究规模向工业化和竞争激烈的过程在经济上可行的过渡的先决条件是以一致和系统的方式优化生产 PHA。使用严格的、经过实验验证的数学模型能够实现 PHA 发酵生产的最佳动态操作，是对抗迄今为止实施的任何低产量经验处理的有前途的替代途径。本研究调查了通过不连续和连续生物反应器配置在 Azohydromonas lata 培养物中聚 3-羟基丁酸酯 (PHB) 生产的基于模型的动态优化。详细且经过验证的宏观，将状态变量与操作策略相关联的动力学和氧传质数学模型用作在补料分批和连续生物反应器策略下设计各种动态优化方案的工具。在最终聚合物浓度、生产率、细胞内含量和底物与聚合物产率方面，补料分批最佳操作生物反应器的性能相对于启发式设计的操作策略的显着改进被证明，在四种不同的策略下分别产生以下最大值，27 g/ l, 1.40 g/(lh), 95 % wt. 和 0.7。在连续运行的两个串联搅拌釜生物反应器的PHB生产过程中，在文献中首次制定并解决了动态优化问题，以显着改善聚合物生产率并为真正可持续的 PHB 生产提供手段。最后对补料分批和连续操作策略进行比较，以支持工艺经济可行性评估的研究。