Cupriavidus necator DSM 545 can utilise glycerol to synthesise poly(3-hydroxybutyric acid) under unbalanced growth conditions, i.e., nitrogen limitation. To improve poly(3-hydroxybutyric acid) (PHB) batch production by C. necator through model-guided bioprocessing or genetic engineering, insights into the dynamic effect of the fermentation conditions on cell metabolism are crucial. In this work, we have used dynamic flux balance analysis (DFBA), a constrained-based stoichiometric modelling approach, to study the metabolic change associated with PHB synthesis during batch cultivation. The model employs the ‘minimisation of all fluxes’ as cellular objectives and measured extracellular fluxes as additional constraints. The mass balance constraints are further adjusted based on thermodynamic considerations. The resultant flux distribution profiles characterise the evolution of metabolic states due to adaptation to dynamic extracellular conditions and provide further insights towards improvements that can be implemented to enhance PHB productivity.

中文翻译：

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甘油生成铜（3-羟基丁酸）的杯形铜硝虫DSM545的动态代谢分析

杯形硝化菌DSM 545可在不平衡的生长条件（即氮限制）下利用甘油合成聚（3-羟基丁酸）。改善C. necator的聚（3-羟基丁酸）（PHB）批生产通过模型指导的生物加工或基因工程，洞悉发酵条件对细胞代谢的动态影响至关重要。在这项工作中，我们使用了动态通量平衡分析（DFBA）（一种基于约束的化学计量建模方法）来研究分批培养过程中与PHB合成相关的代谢变化。该模型将“所有通量的最小化”用作细胞目标，并将测得的细胞外通量用作附加约束。基于热力学考虑，进一步调节质量平衡约束。所得通量分布图表征了由于适应动态细胞外条件而导致的代谢状态的演变，并提供了进一步的见解，可以实现可提高PHB生产率的改进。