Model-based dynamic optimization of the fermentative production of polyhydroxyalkanoates (PHAs) in fed-batch and sequence of continuously operating bioreactors

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 fedbatch 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/(1 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.