TY - GEN A1 - Roth, J. A1 - Tippkötter, Nils T1 - New Approach for Enzymatic Hydrolysis of Lignocellulose with Selective Diffusion Separation of the Monosaccharide Products T2 - Chemie Ingenieur Technik N2 - Enzymatic hydrolysis of lignocellulosic material plays an important role in the classical biorefinery approach. Apart from the pretreatment of the raw material, hydrolysis is the basis for the conversion of the cellulose and hemicellulose fraction into fermentable sugars. After hydrolysis, usually a solid-liquid separation takes place, in order to separate the residual plant material from the sugar-rich fraction, which can be subsequently used in a fermentation step. In order to factor out the separation step, the usage of in alginate immobilized crude cellulose fiber beads (CFBs) were evaluated. Pretreated cellulose fibers are incorporated in an alginate matrix together with the relevant enzymes. In doing so, sugars diffuse trough the alginate matrix, allowing a simplified delivery into the surrounding fluid. This again reduces product inhibition of the glucose on the enzyme catalysts. By means of standardized bead production the hydrolysis in lab scale was possible. First results show that liberation of glucose and xylose is possible, allowing a maximum total sugar yield of 75 %. Y1 - 2016 U6 - https://doi.org/10.1002/cite.201650301 SN - 0009-286X SN - 1522-2640 (eISSN) N1 - ProcessNet-Jahrestagung 2016 und 32. DECHEMA-Jahrestagung der Biotechnologen 2016, 12. - 15. September 2016, Eurogress Aachen VL - 88 IS - 9 SP - 1237 PB - Wiley-VCH CY - Weinheim ER - TY - GEN A1 - Capitain, C. A1 - Hering, T. A1 - Tippkötter, Nils T1 - Enzymatische Polymerisation von Ligninmodellkomponenten und Organosolv-Lignin mit aromatischen Aminosäuren T2 - Chemie Ingenieur Technik N2 - Die stoffliche Nutzung von Lignin aus Bioraffinerien ist ein wichtiger Bestandteil für den Wertschöpfungsprozess von nachwachsenden, pflanzlichen Rohstoffen. Lignin zählt zu den wenigen erneuerbaren Quellen für phenolische Bestandteile, wird aber derzeit meist nur thermisch verwertet. Ziel dieses Forschungsvorhabens ist die Funktionalisierung von Lignin zur Verbesserung der Adhäsionseigenschaften. Als funktionelle Gruppe wird die aromatische Aminosäure L-DOPA verwendet, die charakteristisch für die Adhäsionskraft von Muscheln ist. Lignin ist ein geeignetes Stützgerüst, da es ein Polymer ist, das durch enzymkatalysierte Polymerisation gebildet wird. Essenziell für die Entwicklung ist ein besseres Verständnis über die Bildung von Lignin-Polymeren und deren verschiedene Eigenschaften. Um die Einflussfaktoren auf Kettenlänge und Polymerisationseffizienz zu untersuchen, werden zurzeit sowohl Ligninmodellkomponenten (LMK) als auch gelöstes Organosolv-Lignin verwendet. Laufende Untersuchungen werden zeigen, ob sich die enzymatische Polymerisationsreaktion auf ein gelöstes Ligninpolymer aus einem Organosolv-Aufschluss übertragen lässt. Y1 - 2016 U6 - https://doi.org/10.1002/cite.201650374 SN - 0009-286X SN - 1522-2640 (eISSN) N1 - ProcessNet-Jahrestagung 2016 und 32. DECHEMA-Jahrestagung der Biotechnologen 2016, 12. - 15. September 2016, Eurogress Aachen VL - 88 IS - 9 SP - 1236 PB - Wiley-VCH CY - Weinheim ER - TY - CHAP A1 - Tippkötter, Nils ED - Kaltschmidt, Martin T1 - Grundlagen der bio-chemischen Umwandlung T2 - Energie aus Biomasse : Grundlagen, Techniken und Verfahren Y1 - 2016 SN - 978-3-662-47437-2 (Print) SN - 978-3-662-47438-9 (Online) U6 - https://doi.org/10.1007/978-3-662-47438-9 SP - 1447 EP - 1500 PB - Springer Vieweg CY - Berlin ; Heidelberg ET - 3., aktualisierte, erweiterte Auflage ER - TY - GEN A1 - Kuthan, K. A1 - Al-Kaidy, Huschyar A1 - Tippkötter, Nils T1 - Tropfenbasierte Enzymreaktionen auf Glasoberflächen im μL-Maßstab mit ortsaufgelöster pL-Dosierung der Reaktanden T2 - Chemie Ingenieur Technik N2 - Mit der Entwicklung wässriger Tropfen, die mit einer schützenden Hülle magnetisierbarer, hydrophober Partikel umgeben sind, ergeben sich neue Möglichkeiten im Bereich der Mikrofluidik. So können die Tropfen als flüssige Mikroreaktoren eingesetzt werden. Der wässrige Kern dieser Mikroreaktoren besteht aus einer Substratlösung für enzymatische Umsetzungen. Durch Bewegen der Mikroreaktoren können diese über immobilisierten Enzymen positioniert werden, um so einen enzymatischen Umsatz innerhalb der Mikroreaktoren zu realisieren. Hierfür wurde eine neue Mikroreaktorplattform-Technologie etabliert. Die Mikroreaktoren können aufgrund ihrer magnetisierbaren Hüllenpartikel über elektromagnetische Spulen bewegt werden. Die Bewegung erfolgt dabei mit einer automatisierten Aktuatorplattform, bestehend aus einer 3x3 Doppelspulenmatrix mit Magnetkernen. Als modellhaftes Reaktionssystem wird eine Enzymkaskade eingesetzt, die sich aus einer b-Glucosidase, Glucose-Oxidase und Meerrettichperoxidase zusammensetzt. Primär untersuchte Substrate sind Fluorescein-di-b-D-glucopyranoside, und 1-(3,7-Dihydroxy-10H-phenoxazin-10-yl)-ethanon, bei deren Umsatz fluoreszierende Produkte entstehen. Y1 - 2016 U6 - https://doi.org/10.1002/cite.201650117 N1 - ProcessNet-Jahrestagung 2016 und 32. DECHEMA-Jahrestagung der Biotechnologen 2016, 12. - 15. September 2016, Eurogress Aachen VL - 88 IS - 9 SP - 1336 EP - 1337 PB - Wiley-VCH CY - Weinheim ER - TY - CHAP A1 - Samuelsson, K. A1 - Scheer, Nico A1 - Wilson, I. A1 - Wolf, C.R. A1 - Henderson, C.J. ED - Chackalamannil, Samuel T1 - Genetically Humanized Animal Models T2 - Comprehensive Medicinal Chemistry III. 3rd Edition N2 - Genetically humanized mice for proteins involved in drug metabolism and toxicity and mice engrafted with human hepatocytes are emerging as promising in vivo models for improved prediction of the pharmacokinetic, drug–drug interaction, and safety characteristics of compounds in humans. This is an overview on the genetically humanized and chimeric liver-humanized mouse models, which are illustrated with examples of their utility in drug metabolism and toxicity studies. The models are compared to give guidance for selection of the most appropriate model by highlighting advantages and disadvantages to be carefully considered when used for studies in drug discovery and development. KW - Chimeric liver-humanized mice KW - Drug distribution KW - Drug metabolism KW - Toxicology KW - Knockout mice Y1 - 2017 SN - 978-0-12-803201-5 U6 - https://doi.org/10.1016/B978-0-12-409547-2.12376-5 SP - 130 EP - 149 PB - Elsevier CY - Saint Louis ER - TY - JOUR A1 - Liu, Z. A1 - Schaap, K. S. A1 - Ballemans, L. A1 - de Blois, E. A1 - Rohde, M. A1 - Paulßen, Elisabeth T1 - Measurement of reaction kinetics of [177Lu]Lu-DOTA-TATE using a microfluidic system JF - Dalton Transactions Y1 - 2017 U6 - https://doi.org/10.1039/C7DT01830D SN - 1477-9234 VL - 46 IS - 42 SP - 14669 EP - 14676 ER - TY - JOUR A1 - Röhlen, Desiree A1 - Pilas, Johanna A1 - Schöning, Michael Josef A1 - Selmer, Thorsten T1 - Development of an amperometric biosensor platform for the combined determination of l-Malic, Fumaric, and l-Aspartic acid JF - Applied Biochemistry and Biotechnology N2 - Three amperometric biosensors have been developed for the detection of L-malic acid, fumaric acid, and L -aspartic acid, all based on the combination of a malate-specific dehydrogenase (MDH, EC 1.1.1.37) and diaphorase (DIA, EC 1.8.1.4). The stepwise expansion of the malate platform with the enzymes fumarate hydratase (FH, EC 4.2.1.2) and aspartate ammonia-lyase (ASPA, EC 4.3.1.1) resulted in multi-enzyme reaction cascades and, thus, augmentation of the substrate spectrum of the sensors. Electrochemical measurements were carried out in presence of the cofactor β-nicotinamide adenine dinucleotide (NAD+) and the redox mediator hexacyanoferrate (III) (HCFIII). The amperometric detection is mediated by oxidation of hexacyanoferrate (II) (HCFII) at an applied potential of + 0.3 V vs. Ag/AgCl. For each biosensor, optimum working conditions were defined by adjustment of cofactor concentrations, buffer pH, and immobilization procedure. Under these improved conditions, amperometric responses were linear up to 3.0 mM for L-malate and fumarate, respectively, with a corresponding sensitivity of 0.7 μA mM−1 (L-malate biosensor) and 0.4 μA mM−1 (fumarate biosensor). The L-aspartate detection system displayed a linear range of 1.0–10.0 mM with a sensitivity of 0.09 μA mM−1. The sensor characteristics suggest that the developed platform provides a promising method for the detection and differentiation of the three substrates. Y1 - 2017 U6 - https://doi.org/10.1007/s12010-017-2578-1 SN - 1559-0291 VL - 183 SP - 566 EP - 581 PB - Springer CY - Berlin ER - TY - JOUR A1 - Pilas, Johanna A1 - Yazici, Yasemen A1 - Selmer, Thorsten A1 - Keusgen, Michael A1 - Schöning, Michael Josef T1 - Optimization of an amperometric biosensor array for simultaneous measurement of ethanol, formate, d- and l-lactate JF - Electrochimica Acta N2 - The immobilization of NAD+-dependent dehydrogenases, in combination with a diaphorase, enables the facile development of multiparametric sensing devices. In this work, an amperometric biosensor array for simultaneous determination of ethanol, formate, d- and l-lactate is presented. Enzyme immobilization on platinum thin-film electrodes was realized by chemical cross-linking with glutaraldehyde. The optimization of the sensor performance was investigated with regard to enzyme loading, glutaraldehyde concentration, pH, cofactor concentration and temperature. Under optimal working conditions (potassium phosphate buffer with pH 7.5, 2.5 mmol L-1 NAD+, 2.0 mmol L-1 ferricyanide, 25 °C and 0.4% glutaraldehyde) the linear working range and sensitivity of the four sensor elements was improved. Simultaneous and cross-talk free measurements of four different metabolic parameters were performed successfully. The reliable analytical performance of the biosensor array was demonstrated by application in a clarified sample of inoculum sludge. Thereby, a promising approach for on-site monitoring of fermentation processes is provided. KW - Simultaneous determination KW - Enzymatic biosensor KW - Diaphorase KW - Dehydrogenase Y1 - 2017 U6 - https://doi.org/10.1016/j.electacta.2017.07.119 SN - 0013-4686 VL - 251 SP - 256 EP - 262 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Breuer, Lars A1 - Mang, Thomas A1 - Schöning, Michael Josef A1 - Thoelen, Ronald A1 - Wagner, Torsten T1 - Investigation of the spatial resolution of a laser-based stimulation process for light-addressable hydrogels with incorporated graphene oxide by means of IR thermography JF - Sensors and Actuators A: Physical Y1 - 2017 U6 - https://doi.org/10.1016/j.sna.2017.11.031 SN - 0924-4247 VL - 268 SP - 126 EP - 132 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Demmer, Julius K. A1 - Chowdhury, Nilanjan Pal A1 - Selmer, Thorsten A1 - Ermler, Ulrich A1 - Buckel, Wolfgang T1 - The semiquinone swing in the bifurcating electron transferring flavoprotein/butyryl-CoA dehydrogenase complex from Clostridium difficile JF - Nature Communications Y1 - 2017 U6 - https://doi.org/10.1038/s41467-017-01746-3 SN - 2041-1723 N1 - Article number 1577 VL - 8 IS - 1 SP - 1 EP - 10 ER - TY - JOUR A1 - Werkhausen, Amelie A1 - Albracht, Kirsten A1 - Cronin, Neil J. A1 - Meier, Rahel A1 - Mojsen-Moeller, Jens A1 - Seynnes, Olivier R. T1 - Modulation of muscle-tendon interaction in the human triceps surae during an energy dissipation task JF - Journal of Experimental Biology Y1 - 2017 U6 - https://doi.org/10.1242/jeb.164111 SN - 0022-0949 VL - 220 IS - 22 SP - 4141 EP - 4149 ER - TY - JOUR A1 - Meyer, Jan A1 - Hentschke, Reinhard A1 - Hager, Jonathan A1 - Hojdis, Nils A1 - Karimi-Varzaneh, Hossein Ali T1 - Molecular Simulation of Viscous Dissipation due to Cyclic Deformation of a Silica–Silica Contact in Filled Rubber JF - Macromolecules Y1 - 2017 U6 - https://doi.org/10.1021/acs.macromol.7b00947 SN - 1520-5835 VL - 50 IS - 17 SP - 6679 EP - 6689 ER - TY - JOUR A1 - Mayer, Jan A1 - Hentschke, Reinhard A1 - Hager, Jonathan A1 - Hojdis, Nils A1 - Karimi-Varnaneh, Hossein Ali T1 - A Nano-Mechanical Instability as Primary Contribution to Rolling Resistance JF - Scientific Reports Y1 - 2017 SN - 2045-2322 VL - 7 IS - Article number 11275 PB - Springer CY - Berlin ER - TY - JOUR A1 - Muschallik, Lukas A1 - Molinnus, Denise A1 - Bongaerts, Johannes A1 - Pohl, Martina A1 - Wagner, Torsten A1 - Schöning, Michael Josef A1 - Siegert, Petra A1 - Selmer, Thorsten T1 - (R,R)-Butane-2,3-diol Dehydrogenase from Bacillus clausii DSM 8716T: Cloning and Expression of the bdhA-Gene, and Initial Characterization of Enzyme JF - Journal of Biotechnology N2 - The gene encoding a putative (R,R)-butane-2,3-diol dehydrogenase (bdhA) from Bacillus clausii DSM 8716T was isolated, sequenced and expressed in Escherichia coli. The amino acid sequence of the encoded protein is only distantly related to previously studied enzymes (identity 33–43%) and exhibited some uncharted peculiarities. An N-terminally StrepII-tagged enzyme variant was purified and initially characterized. The isolated enzyme catalyzed the (R)-specific oxidation of (R,R)- and meso-butane-2,3-diol to (R)- and (S)-acetoin with specific activities of 12 U/mg and 23 U/mg, respectively. Likewise, racemic acetoin was reduced with a specific activity of up to 115 U/mg yielding a mixture of (R,R)- and meso-butane-2,3-diol, while the enzyme reduced butane-2,3-dione (Vmax 74 U/mg) solely to (R,R)-butane-2,3-diol via (R)-acetoin. For these reactions only activity with the co-substrates NADH/NAD+ was observed. The enzyme accepted a selection of vicinal diketones, α-hydroxy ketones and vicinal diols as alternative substrates. Although the physiological function of the enzyme in B. clausii remains elusive, the data presented herein clearly demonstrates that the encoded enzyme is a genuine (R,R)-butane-2,3-diol dehydrogenase with potential for applications in biocatalysis and sensor development. Y1 - 2017 U6 - https://doi.org/10.1016/j.jbiotec.2017.07.020 SN - 0168-1656 VL - 258 SP - 41 EP - 50 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Seifarth, Volker A1 - Grosse, Joachim O. A1 - Grossmann, Matthias A1 - Janke, Heinz Peter A1 - Arndt, Patrick A1 - Koch, Sabine A1 - Epple, Matthias A1 - Artmann, Gerhard A1 - Temiz Artmann, Aysegül T1 - Mechanical induction of bi-directional orientation of primary porcine bladder smooth muscle cells in tubular fibrin-poly(vinylidene fluoride) scaffolds for ureteral and urethral repair using cyclic and focal balloon catheter stimulation JF - Journal of Biomaterials Applications Y1 - 2017 U6 - https://doi.org/10.1177/0885328217723178 SN - 1530-8022 VL - 32 IS - 3 SP - 321 EP - 330 PB - Sage CY - London ER - TY - JOUR A1 - Wilson, Ian D. A1 - Wilson, Claire E. A1 - Scheer, Nico A1 - Dickie, A.P. A1 - Schreiter, K. A1 - Wilson, E. M. A1 - Riley, R. J. A1 - Wehr, R. A1 - Bial, J. T1 - The Pharmacokinetics and Metabolism of Lumiracoxib in Chimeric Humanized and Murinized FRG Mice JF - Biochemical pharmacology Y1 - 2017 U6 - https://doi.org/10.1016/j.bcp.2017.03.015 SN - 1873-2968 VL - Volume 135 SP - 139 EP - 150 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Müller, Janina A1 - Beckers, Mario A1 - Mußmann, Nina A1 - Bongaerts, Johannes A1 - Büchs, Jochen T1 - Elucidation of auxotrophic deficiencies of Bacillus pumilus DSM 18097 to develop a defined minimal medium JF - Microbial Cell Factories N2 - Background Culture media containing complex compounds like yeast extract or peptone show numerous disadvantages. The chemical composition of the complex compounds is prone to significant variations from batch to batch and quality control is difficult. Therefore, the use of chemically defined media receives more and more attention in commercial fermentations. This concept results in better reproducibility, it simplifies downstream processing of secreted products and enable rapid scale-up. Culturing bacteria with unknown auxotrophies in chemically defined media is challenging and often not possible without an extensive trial-and-error approach. In this study, a respiration activity monitoring system for shake flasks and its recent version for microtiter plates were used to clarify unknown auxotrophic deficiencies in the model organism Bacillus pumilus DSM 18097. Results Bacillus pumilus DSM 18097 was unable to grow in a mineral medium without the addition of complex compounds. Therefore, a rich chemically defined minimal medium was tested containing basically all vitamins, amino acids and nucleobases, which are essential ingredients of complex components. The strain was successfully cultivated in this medium. By monitoring of the respiration activity, nutrients were supplemented to and omitted from the rich chemically defined medium in a rational way, thus enabling a systematic and fast determination of the auxotrophic deficiencies. Experiments have shown that the investigated strain requires amino acids, especially cysteine or histidine and the vitamin biotin for growth. Conclusions The introduced method allows an efficient and rapid identification of unknown auxotrophic deficiencies and can be used to develop a simple chemically defined tailor-made medium. B. pumilus DSM 18097 was chosen as a model organism to demonstrate the method. However, the method is generally suitable for a wide range of microorganisms. By combining a systematic combinatorial approach based on monitoring the respiration activity with cultivation in microtiter plates, high throughput experiments with high information content can be conducted. This approach facilitates media development, strain characterization and cultivation of fastidious microorganisms in chemically defined minimal media while simultaneously reducing the experimental effort. Y1 - 2018 U6 - https://doi.org/10.1186/s12934-018-0956-1 SN - 1475-2859 VL - 17 IS - 1 SP - Article No. 106 PB - BioMed Central ER - TY - BOOK A1 - Artmann, Gerhard A1 - Temiz Artmann, Aysegül A1 - Zhubanova, Azhar A. A1 - Digel, Ilya ED - Artmann, Gerhard ED - Temiz Artmann, Aysegül ED - Zhubanova, Azhar A. ED - Digel, Ilya T1 - Biological, physical and technical basics of cell engineering Y1 - 2018 SN - 978-981-10-7903-0 PB - Springer CY - Singapore ER - TY - JOUR A1 - Engel, Mareike A1 - Holtmann, Dirk A1 - Ulber, Roland A1 - Tippkötter, Nils T1 - Increased Biobutanol Production by Mediator‐Less Electro‐Fermentation JF - Biotechnology Journal N2 - A future bio-economy should not only be based on renewable raw materials but also in the raise of carbon yields of existing production routes. Microbial electrochemical technologies are gaining increased attention for this purpose. In this study, the electro-fermentative production of biobutanol with C. acetobutylicum without the use of exogenous mediators is investigated regarding the medium composition and the reactor design. It is shown that the use of an optimized synthetic culture medium allows higher product concentrations, increased biofilm formation, and higher conductivities compared to a synthetic medium supplemented with yeast extract. Moreover, the optimization of the reactor system results in a doubling of the maximum product concentrations for fermentation products. When a working electrode is polarized at −600 mV vs. Ag/AgCl, a shift from butyrate to acetone and butanol production is induced. This leads to an increased final solvent yield of Yᴀᴃᴇ = 0.202 gg⁻¹ (control 0.103 gg⁻¹), which is also reflected in a higher carbon efficiency of 37.6% compared to 23.3% (control) as well as a fourfold decrease in simplified E-factor to 0.43. The results are promising for further development of biobutanol production in bioelectrochemical systems in order to fulfil the principles of Green Chemistry. Y1 - 2018 U6 - https://doi.org/10.1002/biot.201800514 SN - 1860-7314 VL - 14 IS - 4 PB - Wiley-VCH CY - Weinheim ER - TY - CHAP A1 - Duwe, A. A1 - Tippkötter, Nils A1 - Ulber, Roland T1 - Lignocellulose-Biorefinery: Ethanol-Focused T2 - Biorefineries N2 - The development prospects of the world markets for petroleum and other liquid fuels are diverse and partly contradictory. However, comprehensive changes for the energy supply of the future are essential. Notwithstanding the fact that there are still very large deposits of energy resources from a geological point of view, the finite nature of conventional oil reserves is indisputable. To reduce our dependence on oil, the EU, the USA, and other major economic zones rely on energy diversification. For this purpose, alternative materials and technologies are being sought, and is most obvious in the transport sector. The objective is to progressively replace fossil fuels with renewable and more sustainable fuels. In this respect, biofuels have a pre-eminent position in terms of their capability of blending with fossil fuels and being usable in existing cars without substantial modification. Ethanol can be considered as the primary renewable liquid fuel. In this chapter enzymes, micro-organisms, and processes for ethanol production based on renewable resources are described. KW - Bioethanol KW - Biorefinery KW - Lignocellulose feedstook Y1 - 2018 U6 - https://doi.org/10.1007/10_2016_72 N1 - Part of the Advances in Biochemical Engineering/Biotechnology book series (ABE,volume 166) SP - 177 EP - 215 PB - Springer CY - Cham ER -