120 Advances in Biochemical Engineering/Biotechnology

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1 120 Advances in Biochemical Engineering/Biotechnology Series Editor: T. Scheper Editorial Board: S. Belkin l I. Endo l S.-O. Enfors l W.-S. Hu l B. Mattiasson l J. Nielsen l G. Stephanopoulos l G. T. Tsao R. Ulber l A.-P. Zeng l J.-J. Zhong l W. Zhou

2 Advances in Biochemical Engineering/Biotechnology Series Editor: T. Scheper Recently Published and Forthcoming Volumes Biosystems Engineering I Volume Editors: Wittmann, C., Krull, R. Vol. 120, 2010 Whole Cell Sensing Systems II Volume Editors: Belkin, S., Gu, M.B. Vol. 118, 2010 Whole Cell Sensing Systems I Volume Editors: Belkin, S., Gu, M.B. Vol. 117, 2010 Optical Sensor Systems in Biotechnology Volume Editor: Rao, G. Vol. 116, 2009 Disposable Bioreactors Volume Editor: Eibl, R., Eibl, D. Vol. 115, 2009 Engineering of Stem Cells Volume Editor: Martin, U. Vol. 114, 2009 Biotechnology in China I From Bioreaction to Bioseparation and Bioremediation Volume Editors: Zhong, J.J., Bai, F.-W., Zhang, W. Vol. 113, 2009 Bioreactor Systems for Tissue Engineering Volume Editors: Kasper, C., van Griensven, M., Poertner, R. Vol. 112, 2008 Food Biotechnology Volume Editors: Stahl, U., Donalies, U. E. B., Nevoigt, E. Vol. 111, 2008 Protein Protein Interaction Volume Editors: Seitz, H., Werther, M. Vol. 110, 2008 Biosensing for the 21st Century Volume Editors: Renneberg, R., Lisdat, F. Vol. 109, 2007 Biofuels Volume Editor: Olsson, L. Vol. 108, 2007 Green Gene Technology Research in an Area of Social Conflict Volume Editors: Fiechter, A., Sautter, C. Vol. 107, 2007 White Biotechnology Volume Editors: Ulber, R., Sell, D. Vol. 105, 2007 Analytics of Protein-DNA Interactions Volume Editor: Seitz, H. Vol. 104, 2007 Tissue Engineering II Basics of Tissue Engineering and Tissue Applications Volume Editors: Lee, K., Kaplan, D. Vol. 103, 2007 Tissue Engineering I Scaffold Systems for Tissue Engineering Volume Editors: Lee, K., Kaplan, D. Vol. 102, 2006 Cell Culture Engineering Volume Editor: Hu, W.-S. Vol. 101, 2006 Biotechnology for the Future Volume Editor: Nielsen, J. Vol. 100, 2005 Gene Therapy and Gene Delivery Systems Volume Editors: Schaffer, D.V., Zhou, W. Vol. 99, 2005

3 Biosystems Engineering I Creating Superior Biocatalysts Volume Editors: Christoph Wittmann Rainer Krull With contributions by R. Biedendieck K. Buchholz B. Bunk E. Franco-Lara T. Fürch A. Ghaderi H. Gröger W. Hummel D. Jahn M. Jahn H.-J. Jördening D. Klein-Marcuschamer S.Y. Lee J. Nielsen M. Papini J.H. Park M. Salazar J. Seibel G.N. Stephanopoulos A. Weckbecker C. Wittmann V.G. Yadav

4 Editors Prof. Dr. Christoph Wittmann Technische Universität Braunschweig Biochemical Engineering Institute Gaußstraße Braunschweig Germany Prof. Dr. Rainer Krull Technische Universität Braunschweig Biochemical Engineering Institute Gaußstraße Braunschweig Germany ISSN e-issn ISBN e-isbn DOI / Springer Heidelberg Dordrecht London New York Library of Congress Control Number: # Springer-Verlag Berlin Heidelberg 2010 This work is subject to copyright. All rights are reserved, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilm or in any other way, and storage in data banks. Duplication of this publication or parts thereof is permitted only under the provisions of the German Copyright Law of September 9, 1965, in its current version, and permission for use must always be obtained from Springer. Violations are liable to prosecution under the German Copyright Law. The use of general descriptive names, registered names, trademarks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. Cover design: WMXDesign GmbH, Heidelberg, Germany Printed on acid-free paper Springer is part of Springer Science+Business Media (

5 Series Editor Prof. Dr. T. Scheper Institute of Technical Chemistry University of Hannover Callinstraße Hannover, Germany scheper@iftc.uni-hannover.de Volume Editors Prof. Dr. Christoph Wittmann Technische Universität Braunschweig Biochemical Engineering Institute Gaußstraße Braunschweig Germany c.wittmann@tu-braunschweig.de Prof. Dr. Rainer Krull Technische Universität Braunschweig Biochemical Engineering Institute Gaußstraße Braunschweig Germany r.krull@tu-braunschweig.de Editorial Board Prof. Dr. S. Belkin Interfaculty Biotechnology Program Institute of Life Sciences The Hebrew University of Jerusalem Jerusalem 91904, Israel shimshon@vms.huji.ac.il Prof. Dr. I. Endo Saitama Industrial Technology Center , Kamiaoki Kawaguchi-shi Saitama, , Japan a @pref.saitama.lg.jp Prof. Dr. S.-O. Enfors Department of Biochemistry and Biotechnology Royal Institute of Technology Teknikringen 34, Stockholm, Sweden enfors@biotech.kth.se Prof. Dr. W.-S. Hu Chemical Engineering and Materials Science University of Minnesota 421Washington Avenue SE Minneapolis, MN , USA wshu@cems.umn.edu Prof. Dr. B. Mattiasson Department of Biotechnology Chemical Center, Lund University P.O. Box 124, Lund, Sweden bo.mattiasson@biotek.lu.se Prof. Dr. J. Nielsen Center for Process Biotechnology Technical University of Denmark Building Lyngby, Denmark jn@biocentrum.dtu.dk

6 vi Editorial Board Prof. Dr. G. Stephanopoulos Department of Chemical Engineering Massachusetts Institute of Technology Cambridge, MA , USA Prof. Dr. G. T. Tsao Professor Emeritus Purdue University West Lafayette, IN 47907, USA Prof. Dr. Roland Ulber FB Maschinenbau und Verfahrenstechnik Technische Universität Kaiserslautern Gottlieb-Daimler-Straße Kaiserslautern, Germany Prof. Dr. J.-J. Zhong Bio-Building #3-311 College of Life Science & Biotechnology Key Laboratory of Microbial Metabolism, Ministry of Education Shanghai Jiao Tong University 800 Dong-Chuan Road Minhang, Shanghai , China Dr. W. Zhou Sr. Director, BioProcess Engineering Technology Development Genzyme Corporation 45 New York Avenue Framingham, MA , USA Prof. Dr. A.-P. Zeng Technische Universität Hamburg-Harburg Institut für Bioprozess- und Biosystemtechnik Denickestrasse Hamburg, Germany aze@tu-harburg.de Honorary Editors Prof. Dr. A. Fiechter Institute of Biotechnology Eidgenössische Technische Hochschule ETH-Hönggerberg 8093 Zürich, Switzerland ae.fiechter@bluewin.ch Prof. Dr. K. Schügerl Institute of Technical Chemistry University of Hannover, Callinstraße Hannover, Germany schuegerl@iftc.uni-hannover.de

7 Advances in Biochemical Engineering/ Biotechnology Also Available Electronically Advances in Biochemical Engineering/Biotechnology is included in Springer s ebook package Chemistry and Materials Science. If a library does not opt for the whole package the book series may be bought on a subscription basis. Also, all back volumes are available electronically. For all customers who have a standing order to the print version of Advances in Biochemical Engineering/Biotechnology, we offer the electronic version via SpringerLink free of charge. If you do not have access, you can still view the table of contents of each volume and the abstract of each article by going to the SpringerLink homepage, clicking on Chemistry and Materials Science, under Subject Collection, then Book Series, under Content Type and finally by selecting Advances in Biochemical Bioengineering/Biotechnology You will find information about the Editorial Board Aims and Scope Instructions for Authors Sample Contribution at springer.com using the search function by typing in Advances in Biochemical Engineering/Biotechnology. Color figures are published in full color in the electronic version on SpringerLink. vii

8 viii Advances in Biochemical Engineering/Biotechnology Aims and Scope Advances in Biochemical Engineering/Biotechnology reviews actual trends in modern biotechnology. Its aim is to cover all aspects of this interdisciplinary technology where knowledge, methods and expertise are required for chemistry, biochemistry, microbiology, genetics, chemical engineering and computer science. Special volumes are dedicated to selected topics which focus on new biotechnological products and new processes for their synthesis and purification. They give the state-of-the-art of a topic in a comprehensive way thus being a valuable source for the next 3-5 years. It also discusses new discoveries and applications. In general, special volumes are edited by well known guest editors. The series editor and publisher will however always be pleased to receive suggestions and supplementary information. Manuscripts are accepted in English. In references Advances in Biochemical Engineering/Biotechnology is abbreviated as Adv. Biochem. Engin./Biotechnol. and is cited as a journal. Special volumes are edited by well known guest editors who invite reputed authors for the review articles in their volumes. Impact Factor in 2009: 4.165; Section Biotechnology and Applied Microbiology : Rank 23 of 150

9 Attention all Users of the Springer Handbook of Enzymes Information on this handbook can be found on the internet at springeronline.com A complete list of all enzyme entries either as an alphabetical Name Index or as the EC-Number Index is available at the above mentioned URL. You can download and print them free of charge. A complete list of all synonyms (more than 57,000 entries) used for the enzymes is available in print form (ISBN ) and electronic form (ISBN ). Save 15% We recommend a standing order for the series to ensure you automatically receive all volumes and all supplements and save 15% on the list price. ix

10 Laudatio This special volume Biosystems Engineering is dedicated to Professor Dr.-Ing. Dietmar Christian Hempel on the occasion of his 65th birthday, whereby the different contributions display an excellent reflection of his research during the past 30 years, bridging engineering and life sciences. Prof. Hempel, born in Königsberg, studied Construction and Process Engineering in Dortmund and Berlin ( ). After his PhD work on Heterogeneous catalytic fixed bed reactors he became the head for Reaction and Biochemical Engineering at the Bayer AG in Leverkusen, where he started to apply chemical engineering principles to biological systems ( ). This was obviously stimulating his later research as Professor of Technical Chemistry and Chemical Engineering at the University of Paderborn ( ) and as Professor and Director of the Institute of Biochemical Engineering at the Technische Universität Braunschweig ( ) where he kept his research interest on biological systems in technical applications covering various aspects process engineering of biological and biochemical processes. As impressive outcome of his career, Dietmar Christian Hempel authored and co-authored about 300 publications and supervised 70 PhD students as a Doktorvater. From 2001 to 2008 he was head and speaker of the still successfully continued interdisciplinary DFG-collaborate research centre SFB 578 Development of biotechnological processes by integrating genetic and engineering methods From gene to product. This collaborate research centre displays a landmark in the German biochemical engineering community and serves as important link between cellular biology and bioprocess engineering.

11 Preface The special volume Biosystems Engineering reflects an emerging field of applied research that aims at a system-level understanding of biological systems toward their targeted design and improvement. To obtain system-wide insight, interdisciplinary approaches are applied, which integrate expertise from biologists, engineers, and computer scientists, who have developed powerful analytical methods, modelling concepts, and information technologies for this challenging task. With the increasing need for sustainable production of fuels and chemicals from renewable resources, a major focus in this area is on the optimization of biotechnological production strains and processes. Of specific importance hereby is the consideration of the microorganism as a part of the bioprocess in its entirety. In this regard, the different contributions of this volume provide an outstanding review of novel tools, methods, and concepts in the field of biosystems engineering, a still young, but yet powerful direction of interdisciplinary research. Part I Creating Superior biocatalysts of this volume highlights how system-wide analysis, modelling and understanding of gene regulation, metabolic networks, and fluxes open a new era for rational design and optimization of superior production strains, one of the key pre-requisites for bio-based production of pharmaceuticals, chemicals, materials, and fuels. This includes the introduction of systems and synthetic metabolic engineering approaches as well as industrial application examples. Part II Linking Cellular Networks and Bioprocesses illustrates concepts and tools which are based on models and experiments to investigate metabolic networks in correlation with the cell environment. In addition to the introduction of fundamental strategies introducing thermodynamic principles as well as different modelling approaches to metabolic network simulation, different examples directly address the link of cells and bioreactors providing fascinating and valuable insights into the interaction between cellular metabolism and process environment. Braunschweig, Summer 2010 Christoph Wittmann Rainer Krull xi

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13 Contents Integration of Systems Biology with Bioprocess Engineering: L-Threonine Production by Systems Metabolic Engineering of Escherichia Coli... 1 Sang Yup Lee and Jin Hwan Park Analysis and Engineering of Metabolic Pathway Fluxes in Corynebacterium glutamicum Christoph Wittmann Systems Biology of Industrial Microorganisms Marta Papini, Margarita Salazar, and Jens Nielsen De Novo Metabolic Engineering and the Promise of Synthetic DNA Daniel Klein-Marcuschamer, Vikramaditya G. Yadav, Adel Ghaderi, and Gregory N. Stephanopoulos Systems Biology of Recombinant Protein Production in Bacillus megaterium Rebekka Biedendieck, Boyke Bunk, Tobias Fürch, Ezequiel Franco-Lara, Martina Jahn, and Dieter Jahn Extending Synthetic Routes for Oligosaccharides by Enzyme, Substrate and Reaction Engineering Jürgen Seibel, Hans-Joachim Jördening, and Klaus Buchholz Regeneration of Nicotinamide Coenzymes: Principles and Applications for the Synthesis of Chiral Compounds Andrea Weckbecker, Harald Gröger, and Werner Hummel Index xiii