Dynamic mathematical models of batch experiments and fed-batch cultures for cyclic adenosine monophosphate production by Arthrobacter A302

Abstract

A glucose utilizing strain, Arthrobacter A302 was used for cyclic adenosine monophosphate (cAMP) production in batch modes. The non-structured model in a 5 l stirred tank bioreactor for understanding, controlling, and optimizing the fermentation process was proposed using the logistic equation for microbial growth, the Luedeking-Piret equation for product formation and Luedeking-Piret-like equation for substrate uptake, respectively. The production of cAMP was a mixed-growth-associated pattern. Based on model prediction, a comparison of calculated value using the parameters evaluated above with another experimental data in 30 l bioreactor was used to test the model. The results predicted from the model were in good agreement with the experimental observations in 30 l bioreactor, which demonstrated that the model might be useful for the development and optimization of production of cAMP in industrial scale. Based on estimated kinetic parameters, three different fed-batch modes, constant rate and intermittent (once and repeated), were adopted in order to obtain more cAMP accumulation. Furthermore, the final production of cAMP reached 11.24 g l−1 after 72 h incubation using three stages feeding strategy. In particular, the cAMP productivity (0.156 g l−1 h−1) was successfully improved by 22.83, 11.43 and 9.86%, respectively, compared with the modes of the batch, constant rate fed-batch and intermittent fed-batch once.