Model-based prediction of substrate conversion and protein synthesis and excretion in recombinant Aspergillus niger biopellets

Aspergillus niger grown as biopellets in a submerged culture has been used as an expression system for glucose oxidase (GOD). With regard to mass transfer, substrate utilization and the formation and excretion of the product GOD, the behavior of aggregated cells such as biopellets differed significantly from that of systems with suspended cells. A one-dimensional pellet model has been developed which is capable to describe the relevant processes in the pellet. Experimental results showed a phase with a highly dynamic pellet size distribution during the first 20 h of the cultivation. A stable number of pellets were usually found after this first period. In the model presented this initial process was described by assuming both suspended hyphae and a fixed number of pellets. The suspended hyphae were attached to the pellets and the substrate conversion and product formation was than described with the pellet model. The model predicted the production of GOD by A. niger in a bioreactor very well. The pellet density was identified as a key parameter which has to be provided as input parameter for the simulation runs. A sensitivity analysis with three different classes of pellet sizes showed that the influence of the final pellet size distribution on the simulation result was neglectable. On the other hand, it can be shown that the total pellet number, and thus the average pellet size was an important parameter. The pellet number influenced mainly the pellet surface area and, consequently, the turnover of substrate and formation and excretion of the product.