TY - JOUR A1 - Werner, Frederik A1 - Krumbe, Christoph A1 - Schumacher, Katharina A1 - Groebel, Simone A1 - Spelthahn, Heiko A1 - Stellberg, Michael A1 - Wagner, Torsten A1 - Yoshinobu, Tatsuo A1 - Selmer, Thorsten A1 - Keusgen, Michael A1 - Baumann, Marcus A1 - Schöning, Michael Josef T1 - Determination of the extracellular acidification of Escherichia coli by a light-addressable potentiometric sensor JF - Physica status solidi (a) : applications and material science. 208 (2011), H. 6 Y1 - 2011 SN - 1862-6319 SP - 1340 EP - 1344 PB - Wiley CY - Weinheim ER - TY - JOUR A1 - Öhlschläger, Peter A1 - Quetting, Michael A1 - Alvarez, Gerardo A1 - Dürst, Matthias A1 - Gissmann, Lutz A1 - Kaufmann, Andreas M. T1 - Enhancement of immunogenicity of a therapeutic cervical cancer DNA-based vaccine by co-application of sequence-optimized genetic adjuvants JF - International Journal of Cancer Y1 - 2009 SN - 1097-0215 VL - 125 IS - 1 SP - 189 EP - 198 PB - Wiley CY - Weinheim ER - TY - JOUR A1 - Oosterhuis, Koen A1 - Öhlschläger, Peter A1 - Berg, Joost H. van den A1 - Toebes, Mireille A1 - Gomez, Raquel A1 - Schumacher, Ton N. A1 - Haanen, John B. T1 - Preclinical development of highly effective and safe DNA vaccines directed against HPV 16 E6 and E7 JF - International Journal of Cancer Y1 - 2011 SN - 1097-0215 VL - 129 IS - 2 SP - 397 EP - 406 PB - Wiley CY - Weinheim ER - TY - JOUR A1 - Öhlschläger, Peter A1 - Spies, Elmar A1 - Alvarez, Gerardo A1 - Quetting, Michael A1 - Groettrup, Marcus T1 - The combination of TLR-9 adjuvantation and electroporation-mediated delivery enhances in vivo antitumor responses after vaccination with HPV-16 E7 encoding DNA JF - International Journal of Cancer. 128 (2011), H. 2 Y1 - 2011 SN - 1097-0215 SP - 473 EP - 481 PB - Wiley CY - Weinheim ER - TY - JOUR A1 - Leurs, Ulrike A1 - Mezo, Gabor A1 - Öhlschläger, Peter A1 - Orban, Erika A1 - Marquard, Andrea A1 - Manea, Marilena T1 - Design, synthesis, in vitro stability and cytostatic effect of multifunctional anticancer drug-bioconjugates containing GnRH-III as a targeting moiety JF - Peptide Science N2 - Bioconjugates containing the GnRH-III hormone decapeptide as a targeting moiety are able to deliver chemotherapeutic agents specifically to cancer cells expressing GnRH receptors, thereby increasing their local efficacy while limiting the peripheral toxicity. However, the number of GnRH receptors on cancer cells is limited and they desensitize under continuous hormone treatment. A possible approach to increase the receptor mediated tumor targeting and consequently the cytostatic effect of the bioconjugates would be the attachment of more than one chemotherapeutic agent to one GnRH-III molecule. Here we report on the design, synthesis and biochemical characterization of multifunctional bioconjugates containing GnRH-III as a targeting moiety and daunorubicin as a chemotherapeutic agent. Two different drug design approaches were pursued. The first one was based on the bifunctional [4Lys]-GnRH-III (Glp-His-Trp-Lys-His-Asp-Trp-Lys-Pro-Gly-NH2) containing two lysine residues in positions 4 and 8, whose ϵ-amino groups were used for the coupling of daunorubicin. In the second drug design, the native GnRH-III (Glp-His-Trp-Ser-His-Asp-Trp-Lys-Pro-Gly-NH2) was used as a scaffold; an additional lysine residue was coupled to the ϵ-amino group of 8Lys in order to generate two free amino groups available for conjugation of daunorubicin. The in vitro stability/degradation of all synthesized compounds was investigated in human serum, as well as in the presence of rat liver lysosomal homogenate. Their cellular uptake was determined on human breast cancer cells and the cytostatic effect was evaluated on human breast, colon and prostate cancer cell lines. Compared with a monofunctional compound, both drug design approaches resulted in multifunctional bioconjugates with increased cytostatic effect. Y1 - 2012 U6 - http://dx.doi.org/10.1002/bip.21640 SN - 1097-0282 VL - 98 IS - 1 SP - 1 EP - 10 PB - Wiley CY - New York, NY ER - TY - JOUR A1 - Bongaerts, Johannes A1 - Esser, Simon A1 - Lorbach, Volker A1 - Al-Momani, Lóay A1 - Müller, Michael A. A1 - Franke, Dirk A1 - Grondal, Christoph A1 - Kurutsch, Anja A1 - Bujnicki, Robert A1 - Takors, Ralf A1 - Raeven, Leon A1 - Wubbolts, Marcel A1 - Bovenberg, Roel A1 - Nieger, Martin A1 - Schürmann, Melanie A1 - Trachtmann, Natalie A1 - Kozak, Stefan A1 - Sprenger, Georg A. A1 - Müller, Michael T1 - Diversity-oriented production of metabolites derived from chorismate and their use in organic synthesis JF - Angewandte Chemie International Edition Y1 - 2011 SN - 1521-3773 (E-Journal); 0570-0833 (Print); 1433-7851 (Print) VL - Vol. 50 IS - Iss. 34 SP - 7781 EP - 7786 PB - Wiley CY - Weinheim ER - TY - JOUR A1 - Voigt, Birgit A1 - Schroeter, Rebecca A1 - Jürgen, Britta A1 - Albrecht, Dirk A1 - Evers, Stefan A1 - Bongaerts, Johannes A1 - Maurer, Karl-Heinz A1 - Schweder, Thomas A1 - Hecker, Michael T1 - The response of Bacillus licheniformis to heat and ethanol stress and the role of the SigB regulon JF - Proteomics Y1 - 2013 SN - 1615-9861 (E-Journal); 1615-9853 (Print) VL - Vol. 13 IS - Iss. 14 SP - 2140 EP - 2146 PB - Wiley CY - Weinheim ER - TY - JOUR A1 - Heinze, Daniel A1 - Mang, Thomas A1 - Peter, Karin A1 - Möller, Martin A1 - Weichold, Oliver T1 - Synthesis of low molecular weight poly(vinyl acetate) and its application as plasticizer JF - Journal of applied polymer science N2 - Poly(vinyl acetate), PVAc, with a degree of polymerization Xn = 10 was prepared by chain-transfer radical polymerization using carbon tetrachloride and used as oligomeric plasticizer for commercial PVAc. However, the chlorinated chain ends cause a low thermal stability requiring mild Cl/H substitution. The product exhibits high thermal stability and excellent melt-compounding properties. Blends of oligomeric and commercial PVAc show single glass transition temperatures which decrease with higher oligomer content and exhibit small negative deviations from Fox' linear additivity rule. This indicates plasticization and miscibility being mainly due to entropic effects. Injection-moulded thick specimens show ductile behaviour at oligomer contents >10 wt %, while sheets with a thickness of 0.2–0.5 mm appear flexible already at 7.5 wt %. The oxygen permeability coefficients are an order of magnitude lower than those of low-density polyethylene. Due to the sum of their properties, the plasticized sheets present a promising alternative in the preparation of barrier materials. Y1 - 2014 U6 - http://dx.doi.org/10.1002/app.40226 SN - 1097-4628 (E-Journal); 0021-8995 (Print) VL - 131 IS - 9 SP - Article No. 40226 PB - Wiley CY - New York ER - TY - JOUR A1 - Wang, Ren-Qi A1 - Druckenmüller, Katharina A1 - Elbers, Gereon A1 - Guenther, Klaus A1 - Croué, Jean-Philippe T1 - Analysis of aquatic-phase natural organic matter by optimized LDI-MS method JF - Journal of mass spectrometry N2 - The composition and physiochemical properties of aquatic-phase natural organic matter (NOM) are most important problems for both environmental studies and water industry. Laser desorption/ionization (LDI) mass spectrometry facilitated successful examinations of NOM, as humic and fulvic acids in NOM are readily ionized by the nitrogen laser. In this study, hydrophobic NOMs (HPO NOMs) from river, reservoir and waste water were characterized by this technique. The effect of analytical variables like concentration, solvent composition and laser energy was investigated. The exact masses of small molecular NOM moieties in the range of 200–1200 m/z were determined in reflectron mode. In addition, spectra of post-source-decay experiments in this range showed that some compounds from different natural NOMs had the same fragmental ions. In the large mass range of 1200–15 000 Da, macromolecules and their aggregates were found in HPO NOMs from natural waters. Highly humic HPO exhibited mass peaks larger than 8000 Da. On the other hand, the waste water and reservoir water mainly had relatively smaller molecules of about 2000 Da. The LDI-MS measurements indicated that highly humic river waters were able to form large aggregates and membrane foulants, while the HPO NOMs from waste water and reservoir water were unlikely to form large aggregates. Copyright © 2014 John Wiley & Sons, Ltd. Y1 - 2014 U6 - http://dx.doi.org/10.1002/jms.3321 SN - 1096-9888 VL - 49 IS - 2 SP - 154 EP - 160 PB - Wiley CY - Bognor Regis ER - TY - JOUR A1 - Martinez, Ronny A1 - Jakob, Felix A1 - Tu, Ran A1 - Siegert, Petra A1 - Maurer, Karl-Heinz A1 - Schwaneberg, Ulrich T1 - Increasing activity and thermal resistance of Bacillus gibsonii alkaline protease (BgAP) by directed evolution JF - Biotechnology and bioengineering Y1 - 2013 SN - 1097-0290 (E-Journal); 0006-3592 (Print); 0368-1467 (Print) VL - Vol. 110 IS - Iss. 3 SP - 711 EP - 720 PB - Wiley CY - Weinheim ER - TY - JOUR A1 - Pilas, Johanna A1 - Iken, Heiko A1 - Selmer, Thorsten A1 - Keusgen, Michael A1 - Schöning, Michael Josef T1 - Development of a multi‐parameter sensor chip for the simultaneous detection of organic compounds in biogas processes JF - Physica status solidi (a) N2 - An enzyme-based multi-parameter biosensor is developed for monitoring the concentration of formate, d-lactate, and l-lactate in biological samples. The sensor is based on the specific dehydrogenation by an oxidized β-nicotinamide adenine dinucleotide (NAD+)-dependent dehydrogenase (formate dehydrogenase, d-lactic dehydrogenase, and l-lactic dehydrogenase, respectively) in combination with a diaphorase from Clostridium kluyveri (EC 1.8.1.4). The enzymes are immobilized on a platinum working electrode by cross-linking with glutaraldehyde (GA). The principle of the determination scheme in case of l-lactate is as follows: l-lactic dehydrogenase (l-LDH) converts l-lactate into pyruvate by reaction with NAD+. In the presence of hexacyanoferrate(III), the resulting reduced β-nicotinamide adenine dinucleotide (NADH) is then regenerated enzymatically by diaphorase. The electrochemical detection is based on the current generated by oxidation of hexacyanoferrate(II) at an applied potential of +0.3 V vs. an Ag/AgCl reference electrode. The biosensor will be electrochemically characterized in terms of linear working range and sensitivity. Additionally, the successful practical application of the sensor is demonstrated in an extract from maize silage. Y1 - 2015 U6 - http://dx.doi.org/10.1002/pssa.201431894 SN - 1862-6319 VL - 212 IS - 6 SP - 1306 EP - 1312 PB - Wiley CY - Weinheim ER - TY - JOUR A1 - Breuer, Lars A1 - Raue, Markus A1 - Kirschbaum, M. A1 - Mang, Thomas A1 - Schöning, Michael Josef A1 - Thoelen, R. A1 - Wagner, Torsten T1 - Light-controllable polymeric material based on temperature-sensitive hydrogels with incorporated graphene oxide JF - Physica status solidi (a) N2 - Poly(N-isopropylacrylamide) (PNIPAAm) hydrogel films with incorporated graphene oxide (GO) were developed and tested as light-stimulated actuators. GO dispersions were synthesized via Hummers method and characterized toward their optical properties and photothermal energy conversion. The hydrogels were prepared by means of photopolymerization. In addition, the influence of GO within the hydrogel network on the lower critical solution temperature (LCST) was investigated by differential scanning calorimetry (DSC). The optical absorbance and the response to illumination were determined as a function of GO concentration for thin hydrogel films. A proof of principle for the stimulation with light was performed. Y1 - 2015 U6 - http://dx.doi.org/10.1002/pssa.201431944 SN - 1862-6319 VL - 212 IS - 6 SP - 1368 EP - 1374 PB - Wiley CY - Weinheim ER - TY - JOUR A1 - Schiffels, Johannes A1 - Selmer, Thorsten T1 - A flexible toolbox to study protein-assisted metalloenzyme assembly in vitro JF - Biotechnology and Bioengineering Y1 - 2015 U6 - http://dx.doi.org/10.1002/bit.25658 SN - 1097-0290 VL - 112 IS - 11 SP - 2360 EP - 2372 PB - Wiley CY - Weinheim ER - TY - JOUR A1 - Voigt, Birgit A1 - Albrecht, Dirk A1 - Sievers, Susanne A1 - Becher, Dörte A1 - Bongaerts, Johannes A1 - Evers, Stefan A1 - Schweder, Thomas A1 - Maurer, Karl-Heinz A1 - Hecker, Michael T1 - High-resolution proteome maps of Bacillus licheniformis cells growing in minimal medium JF - Proteomics Y1 - 2015 U6 - http://dx.doi.org/10.1002/pmic.201400504 SN - 1615-9861 VL - 15 IS - 15 SP - 2629 EP - 2633 PB - Wiley CY - Weinheim ER - TY - JOUR A1 - Takenaga, Shoko A1 - Schneider, Benno A1 - Erbay, E. A1 - Biselli, Manfred A1 - Schnitzler, Thomas A1 - Schöning, Michael Josef A1 - Wagner, Torsten T1 - Fabrication of biocompatible lab-on-chip devices for biomedical applications by means of a 3D-printing process JF - Physica status solidi (a) N2 - A new microfluidic assembly method for semiconductor-based biosensors using 3D-printing technologies was proposed for a rapid and cost-efficient design of new sensor systems. The microfluidic unit is designed and printed by a 3D-printer in just a few hours and assembled on a light-addressable potentiometric sensor (LAPS) chip using a photo resin. The cell growth curves obtained from culturing cells within microfluidics-based LAPS systems were compared with cell growth curves in cell culture flasks to examine biocompatibility of the 3D-printed chips. Furthermore, an optimal cell culturing within microfluidics-based LAPS chips was achieved by adjusting the fetal calf serum concentrations of the cell culture medium, an important factor for the cell proliferation. Y1 - 2015 U6 - http://dx.doi.org/10.1002/pssa.201532053 SN - 1862-6319 VL - 212 IS - 6 SP - 1347 EP - 1352 PB - Wiley CY - Weinheim ER - TY - JOUR A1 - Tippkötter, Nils A1 - Wollny, Steffen A1 - Suck, Kirstin A1 - Sohling, Ulrich A1 - Ruf, Friedrich A1 - Ulber, Roland T1 - Recycling of spent oil bleaching earth as source of glycerol for the anaerobic production of acetone, butanol, and ethanol with Clostridium diolis and lipolytic Clostridium lundense JF - Engineering in Life Sciences N2 - A major part of edible oil is subjected to bleaching procedures, primarily with minerals applied as adsorbers. Their recycling is currently done either by regaining the oil via organic solvent extraction or by using the spent bleaching earth (SBE) as additive for animal feed, etc. As a new method, the reutilization of the by-product SBE for the microbiologic formation of acetone, butanol, and ethanol (ABE) is presented as proof-of-concept. The SBE was taken from a palm oil cleaning process. The recycling concept is based on the application of lipolytic clostridia strains. Due to considerably long fermentation times, co-fermentation with Candida rugosa and enzymatic hydrolyses of the bound oil with a subsequent clostridia fermentation are shown as alternative routes. Anaerobic fermentations under comparison of different clostridia strains were performed with glycerol media, enzymatically hydrolyzed palm oil and SBE. Solutes, side product compositions and productivities were quantified via HPLC. A successful production of ABE solutes from SBE has been done with a yield of 0.15 g butanol per gram of bound glycerol. Thus, the biotechnological recycling of the waste stream is possible in principle. Inhibition of the substrate suspension has been observed. A chromatographic ion-exchange of substrates increased the biomass concentration. Y1 - 2014 U6 - http://dx.doi.org/10.1002/elsc.201300113 SN - 1618-2863 VL - 14 IS - 4 SP - 425 EP - 432 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Thiel, Alexander A1 - Tippkötter, Nils A1 - Suck, Kirstin A1 - Sohling, Ulrich A1 - Ruf, Friedrich A1 - Ulber, Roland T1 - New zeolite adsorbents for downstream processing of polyphenols from renewable resources JF - Engineering in Life Sciences N2 - Commercial materials with polyvinylpolypyrrolidone and polymeric amberlites (XAD7HP, XAD16) are commonly used for the adsorptive downstream processing of polyphenols from renewable resources. In this study, beta-zeolite-based adsorbent systems were examined, and their properties were compared to organic resins. Batch adsorption experiments were conducted with synthetic solutions of major polyphenols. Adsorption isotherms and desorption characteristics of individual adsorbent were determined based on these results. Maximum adsorption capacities were calculated using the Langmuir model. For example, the zeolites had capacities up to 203.2 mg/g for ferulic acid. To extend these results to a complex system, additional experiments were performed on rapeseed meal and wheat seed extracts as representative renewable resources. HPLC analysis showed that with 7.5% w/v, which is regarded as the optimum amount of zeolites, zeolites A and B could bind 100% of the major polyphenols as well as release polyphenols at high yields. Additionally, regeneration experiments were performed with isopropyl alcohol at 99°C to evaluate how zeolites regenerate under mild conditions. The results showed only a negligible loss of adsorption capacity and no loss of desorption capacity. In summary, it was concluded that beta-zeolites were promising adsorbents for developing new processes to isolate polyphenols from renewable resources. Y1 - 2013 U6 - http://dx.doi.org/10.1002/elsc.201200188 VL - 13 IS - 3 SP - 239 EP - 246 PB - Wiley CY - Weinheim ER - TY - JOUR A1 - Tippkötter, Nils A1 - Al-Kaidy, Huschyar A1 - Wollny, Steffen A1 - Ulber, Roland T1 - Functionalized magnetizable particles for downstream processing in single-use systems JF - Chemie Ingenieur Technik N2 - Biotechnological downstream processing is usually an elaborate procedure, requiring a multitude of unit operations to isolate the target component. Besides the disadvantageous space-time yield, the risks of cross-contaminations and product loss grow fast with the complexity of the isolation procedure. A significant reduction of unit operations can be achieved by application of magnetic particles, especially if these are functionalized with affinity ligands. As magnetic susceptible materials are highly uncommon in biotechnological processes, target binding and selective separation of such particles from fermentation or reactions broths can be done in a single step. Since the magnetizable particles can be produced from iron salts and low priced polymers, a single-use implementation of these systems is highly conceivable. In this article, the principles of magnetizable particles, their synthesis and functionalization are explained. Furthermore, applications in the area of reaction engineering, microfluidics and downstream processing are discussed focusing on established single-use technologies and development potential. Y1 - 2013 U6 - http://dx.doi.org/10.1002/cite.201200130 VL - 85 IS - 1-2: Special Issue: Single-Use Technology SP - 76 EP - 86 PB - Wiley CY - Weinheim ER - TY - JOUR A1 - Sieker, Tim A1 - Neuner, Andreas A1 - Dimitrova, Darina A1 - Tippkötter, Nils A1 - Muffler, Kai A1 - Bart, Hans-Jörg A1 - Heinzle, Elmar A1 - Ulber, Roland T1 - Ethanol production from grass silage by simultaneous pretreatment, saccharification and fermentation: First steps in the process development JF - Engineering in Life Sciences N2 - Grass silage provides a great potential as renewable feedstock. Two fractions of the grass silage, a press juice and the fiber fraction, were evaluated for their possible use for bioethanol production. Direct production of ethanol from press juice is not possible due to high concentrations of organic acids. For the fiber fraction, alkaline peroxide or enzymatic pretreatment was used, which removes the phenolic acids in the cell wall. In this study, we demonstrate the possibility to integrate the enzymatic pretreatment with a simultaneous saccharification and fermentation to achieve ethanol production from grass silage in a one-process step. Achieved yields were about 53 g ethanol per kg silage with the alkaline peroxide pretreatment and 91 g/kg with the enzymatic pretreatment at concentrations of 8.5 and 14.6 g/L, respectively. Furthermore, it was shown that additional supplementation of the fermentation medium with vitamins, trace elements and nutrient salts is not necessary when the press juice is directly used in the fermentation step. Y1 - 2011 U6 - http://dx.doi.org/10.1002/elsc.201000160 N1 - Special Issue "Bioprocess‐oriented plant design" VL - 11 IS - 4 SP - 436 EP - 442 PB - Wiley CY - Weinheim ER - TY - JOUR A1 - Al-Kaidy, Huschyar A1 - Duwe, Anna A1 - Huster, Manuel A1 - Muffler, Kai A1 - Schlegel, Christin A1 - Tim, Sieker A1 - Stadtmüller, Ralf A1 - Tippkötter, Nils A1 - Ulber, Roland T1 - Biotechnology and bioprocess engineering – from the first ullmann's article to recent trends JF - ChemBioEng Reviews N2 - For several thousand years, biotechnology and its associated technical processes have had a great impact on the development of mankind. Based on empirical methods, in particular for the production of foodstuffs and daily commodities, these disciplines have become one of the most innovative future issues. Due to the increasing detailed understanding of cellular processes, production strains can now be optimized. In combination with modern bioprocesses, a variety of bulk and fine chemicals as well as pharmaceuticals can be produced efficiently. In this article, some of the current trends in biotechnology are discussed. Y1 - 2015 U6 - http://dx.doi.org/10.1002/cben.201500008 VL - 2 IS - 3 SP - 175 EP - 184 PB - Wiley CY - Weinheim ER -