Research profile
Cultivation of Microorganisms | Downstream Processing | Enzyme Engineering |
Process Monitoring | Completed PhD Theses

Fermentation engineering, downstream processing of proteins and plasmid DNA as well as enzyme engineering and biocatalysis, respectively, are in the focus of research. The production of extracellular proteins by means of Gram negative bacteria is one of the main aims. For these purposes methods of genetic engineering, bioengineering and reaction engineering are applied. In addition, methods of pattern recognition are being developed in order to evaluate the state of cells from microscopic images without staining. Novel research areas are represented by the aerobic microbial degradation of oil and fat, the development of phototrophic processes as well as the generation of biogas.

I Cultivation of Microorganisms

Gram-negative and Gram-positive bacteria as well as different eukaryotes have been grown in submerse culture systems. These organisms include Escherichia coli, Klebsiella planticola, diverse Bacillus sp., Dictyostelium discoideum, and Euglena gracilis. Cultivation conditions and operating strategies have been optimized in order to obtain maximal concentrations of products like recombinant proteins, plasmid DNA or polysaccharides. Oxygen supply for aerobic cultivations by other means than by pressurised air has been studied as well as the degradation of oils and fats during aerobic cultivation of microorganisms. Biorefinery concepts are current research targets. The production of high-value materials in phototrophic cultivation systems like algae is in the focus of present research efforts. Residues thereof are offered to special microorganism communities in biogas processes.



II Downstream Processing

Research targets in this area are the separation and purification of, primarily, recombinant proteins and plasmid-DNA, but also of special polysaccharides. Recombinant proteins include the whole range from industrial enzymes for use in biofuel processes to human transcription factors of interest in stem cell research. The main aim consists in achieving secretion of recombinant proteins into the extracellular space with Gram-negative bacteria. This is achieved by coexpressing bacteriocin release proteins which lead to rendering the outer membrane permeable. Different pseudo-affinity interactions are used for adsorptive as well as extractive downstream processes. Extraction processes are of particular interest even in the case of plasmid DNA separation. Plasmid DNA is processed for being applicable as vectors in gene therapy and genetic vaccination.



III Enzyme Engineering

Multiphase reaction systems like those of the type liquid-liquid-solid have been studied in different reactors. Modelling of reactions with pH-shift in the presence of partitioning reactants in liquid-liquid two-phase systems was one of the main aims. Stereospecific synthetic reactions of aldolases as well as the enzymic synthesis of precursors have been studied extensively. Fluidized-bed reactors are still in the focus of research for the application of immobilized enzymes.

IV Process Monitoring

Methods of pattern recognition are applied in order to simultaneously count cells and analyse their state with respect to viability. This concept has successfully been applied for the analysis of yeast cultures on the basis of images from standard microscopes as well as from in situ-microscopes. The results have been successfully transferred to the analysis of submerse cultures of animal and human cell lines. Thus, the history of cell death by necrosis and apoptosis can be distinguished without cell staining. Microscopic images are obtained with darkfield illumination.




Completed PhD Theses
  • Carsten Stiegelmeier: Gewinnung schwer exprimierbarer, heterologer Proteine durch Nutzung verschiedener Zellkompartimente von Escherichia coli (1995).
  • Frank-Udo Huneke: Biokatalyse im Flüssig-Flüssig-Fest-Dreiphasen-Festbettreaktor - Reaktionstechnische Untersuchungen des Reaktorverhaltens (1995).
  • Ludger Poppenborg: Hisactophilin als Affinitätsträger in Trennverfahren mit Metallchelat-Affinitätsliganden (1996)
  • Miriam Stephan: Untersuchungen zur Kultivierung von Dictyostelium discoideum (1997)
  • Marianne Dohmen: Herstellung eines Hydrolysats aus Restfleisch an Truthahnknochen - unter besonderer Berücksichtigung des Geschmacks - (1998)
  • Usama Beshay: Continuous cultivation with immobilized Dictyostelium discoideum (1998)
  • Hendrik Oldenburg: Kinetische Untersuchungen und Prozeßoptimierung der Produktion von Dihydroxyacetonphosphat mit Hilfe von Glycerinphosphat-Oxidase (1998)
  • Torsten Schmidt : Production und Analytik von Plasmid-DNA für die Gentherapie (1998)
  • Jörg Hettwer : Kinetik aldolasekatalysierter Aldolkondensationen und Prozeßoptimierung der Glycerin-3-phosphat Synthese (1998)
  • Thomas Niemann : Neue Synthesewege zur Darstellung von Dihydroxyacetonphosphat und L-Glycerin-3-phosphat (1999)
  • Ralf Neitzel : Verfahren zur extrazellulären Produktion rekombinanter Proteine mit Gram-negativen Bakterien (1999)
  • Justine Wittler: Aufarbeitung heterologer extra- und intrazellulärer Proteine mit Hilfe der Metallchelat-Protein-Affinitätswechselwirkung (2000)
  • Carsten Voß: Neue Verfahren zur Produktion von Plasmid-DNA als Biopharmazeutikum (2001)
  • Joe Max Risse: Produktion und Analytik von N-Acetylphosphinothricin sowie N-Acetylphosphinothricyl-alanyl-alanin (2001)
  • Bodo Kohring: Kultivierung von Bodenbakterien der Spezies Sinorhizobium meliloti und die Aufarbeitung ihrer Signalmoleküle (2001)
  • Sang-In Han: Kultivierung von Dictyostelium discoideum auf synthetischen Medien und Analyse des Proteoms (2001)
  • Soumia Darwish: Characterization of Protein Fractions from Potato Fruit Juice and their Use for the Production of Protein Gels by means of a Microbial Transglutaminase (2002)
  • Yinghua Lu: Technische Maßnahmen zur Verbesserung der Züchtung von Dictyostelium discoideum (2002)
  • Kleist, Sophia: Optimierung eines fermentativen Verfahrens zur Herstellung einer bakteriellen Phytase (2002)
  • Felski, Michael: Fermentative Gewinnung von Paramylon durch Euglena gracilis in konditioniertem Kartoffelfruchtwasser (2004)
  • Bettenworth, Frank: Bibliotheken von Stationärphasen-Promotoren in gramnegativen Bakterien : Erzeugung, Screening und verfahrenstechnische Analyse(2005)
  • Blaesen, Markus: Untersuchungen zur Lyse und Rückführung bakterieller Biomasse als Medienbestandteil in den Fermentationsprozess (2006)
  • Wei, Ning: A machine vision based in situ probe for automated on-line measurement of cell density and viability by dark field microscopy, image processing and pattern recognition (2007)
  • Vijayendran, Chandran: Proteome, transcriptome and metabolome plasticity in closely related strains of Escherichia coli-K12 and its diversity during molecular evolution processes (2007)
  • Sommer, Benjamin: Neue Strategien zur extrazellulären Produktion rekombinanter Proteine mit Escherichia coli (2008)
  • Streitner, Nadine: Extraktion pharmazeutisch einsetzbarer Plasmid-DNA und Integration in einen skalierbaren Aufarbeitungsprozess (2008)