2012|13 Annual Report Fraunhofer IGB

95 Dipl.-Ing. Tino Elter Phone +49 3461-43 9118 tino.elter@igb.fraunhofer.de Dr. Wolfgang Krischke Phone +49 711 970-4218 wolfgang.krischke@igb.fraunhofer.de References [1] U. S. Department of Health and Human Services Food and Drug Administration (2004) Guidance for Industry PAT – A Framework for Innovative Pharmaceutical Development, Manu- facturing and Quality Assurance, http://www.fda.gov/About- FDA/CentersOfﬁces/OfﬁceofMedicalProductsandTobacco/CDER/ ucm088828.htm Funding We would like to thank the German Federation of Industrial Re- search Associations (registered as Arbeitsgemeinschaft industriel- ler Forschungsvereinigungen “Otto von Guericke” e. V.) for fund- ing the Gibberellin Project, IGF project no. 16001 N, the Ministry of Science, Research and the Arts of the State of Baden-Würt- temberg for funding the DLR@UniST project and the German En- vironmental Foundation (DBU) for granting Ph.D. bursaries. Project partner Institute of Plant Biology and Biotechnology, work group Molecular Biology and Biotechnology of Fungi, University of Münster ﬁlamentous fungi is that only a part of the entire biomass is metabolically active. For one, hyphae die off during the fer- mentation process (Fig. 2). Furthermore, the fungus accumu- lates storage lipids and carbohydrates that increase the bio- mass (Fig. 3). We have been able to successfully estimate the concentration of active biomass on the basis of the base con- sumption (Fig. 4). This facilitates the calculation of other pro- cess variables, for example of substrate and product concen- trations during the fermentation process. Moreover, we have developed a mathematical model based on ﬁrst-principles which predicts the biomass, substrate and product concentra- tions. Fig. 5 shows the course of 19 fermentations and the rel- evant simulation. It becomes apparent that the model repre- sents the measured data very well. Outlook The combination of parallel fermentation technology, online measurement and control technology and mathematical mod- eling forms the basis for the understanding of a biotechno- logical process and thus facilitates a more efﬁcient process optimization and transfer to production scale. This approach is mainly demanded by the pharmaceutical industry. In 2004 the U.S. Food and Drug Administration started the Process Ana- lytical Technology initiative, PAT [1] for short. The work of the Fraunhofer IGB shows that this is also groundbreaking for the white biotechnology. 1 Screening of various ethanol producers in the multifermenter. 2 Microscope image of intact (green) and damaged cells (red). 3 Cells with lipid deposits. 4 Estimation of the biomass concentration based on base consumption. 5 Modeling the gibberellin production with Fusarium fujikuroi. 4 5 15 30 10 20 5 10 0 0 0 50 100 150 200 Concentrationofbiomass[g/L] Baseconsumption[ml] Time [h] Entire biomass Base consumption Estimation Active biomass 20 100 500 300 15 400 200 10 50 300 100 300 5 100 0 0 0 0 0 0 0 0 100 100 100 100 200 200 200 200 300 300 300 300 Concentrationof biomass[g/L] Glucoseconsumption [g/L] NH4 + -concentration [mg/L] Gibberellinconcentration [mg/L] Time [h] Time [h] Time [h] Time [h] Measured data Simulation Conﬁdence region Contacts

2012|13 Annual Report Fraunhofer IGB

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