Biot echnology Second Edition Volume 2 Genetic Fundamentals and Genetic Engineering Biotechnology Second Edition Fundamentals Special Topics Volume 1 Volume 9 Biological Fundamentals Enzymes, Biomass, Food and Feed Volume 2 Volume 10 Genetic Fundamentals and Special Processes Genetic Engineering Volume 11 Volume 3 Environmental Processes Bioprocessing Volume 12 Volume 4 Modern Biotechnology: Measuring, Modelling, and Control Legal, Economic and Social Dimensions Products Volume 5 Genetically Engineered Proteins and Monoclonal Antibodies Volume 6 Products of Primary Metabolism Volume 7 Products of Secondary Metabolism Volume 8 Biotransformations 0 VCH Verlagsgesellschaft mbH, D-6940 Weinheim (Federal Republic of Germany), 1993 Distribution: VCH, P.O. Box 101161, D-6940 Weinheim (Federal Republic of Germany) Switzerland: VCH, P. 0. Box, CH-4020 Basel (Switzerland) United Kingdom and Ireland: VCH (UK) Ltd., 8 Wellington Court, Cambridge CB1 1HZ (Eqgland) USA and Canada: VCH, 220 East 23rd Street, New York, NY 10010-4606 (USA) ISBN 3-527-28312-9 (VCH, Weinheim) ISBN 1-56081-152-8( VCH, New York) Set ISBN 3-527-28310-2 (VCH, Weinheim) Set ISBN 1-56081-602-3( VCH, New York) A Multi-Volume Comprehensive Treatise Biotechnology Second, Completely Revised Edition Edited by H.-J. Rehm and G. Reed in cooperation with A. Puhler and F? Stadler Volume 2 Genetic Fundamentals and Genetic Engineering Edited by A. Puhler VCH - - - Weinheim New York Base1 Cambridge Series Editors: Volume Editor: Prof. Dr. H.-J. Rehm Dr. G. Reed Prof. Dr. A. Puhler Institut fur Mikrobiologie 2131 N. Summit Ave. Biologie VI (Genetik) Universitat Munster Apartment #304 Universitat Bielefeld CorrensstraBe 3 Milwaukee, WI 53202-1347 PO. Box 100131 D-4400 Munster USA D-4800 Bielefeld 1 Prof. Dr. A. Puhler Dr. P. J-. W. Stadler Biologie VI (Genetik) Bayer'AG Universitat Bielefeld Verfahrensentwicklung Biochemie P.O. Box 100131 Leitung D-4800 Bielefeld 1 Friedrich-Ebert-StraRe 217 D-5600 Wuppertal 1 This book was carefully produced. Nevertheless, authors. editors and publisher do not warrant the information con- tained therein to be free of errors. Readers are advised to keepin mind that statements, data, illustrations, procedural details or other items may inadvertently be inaccurate. Published jointly by VCH Verlagsgesellschaft mbH. Weinheim (Federal Republic of Germany) VCH Publishers Inc., New York, NY (USA) Editorial Director: Dr. Hans-Joachim Kraus Editorial Manager: Christa Maria Schultz Copy Editor: Karin Dembowsky Production Director: Maximilian Montkowski Production Manager: Dipl. Wirt.-Ing. (FH) Hans-Jochen Schmitt Library of Congress Card No.: applied for British Library Cataloguing-in-Publication Data: A catalogue record for this book is available from the British Library Die Deutsche Bibliothek - CIP-Einheitsaufnahme Biotechnology : a multi volume comprehensive treatise / ed. by H.-J. Rehm and G. Reed. In cooperation with A. Piihler and P. Stadler. - 2., completely rev. ed. - Weinheim; New York; Basel; Cambridge: VCH. NE: Rehm, Hans J. [Hrsg.] Z., completely rev. ed. Vol. 2. Genetic fundamentals and genetic engineering / ed. by A. Piihler - 1993 ISBN 3-527-28312-9 (Weinheim) ISBN 1-56081-152-8 (New York) NE: Piihler, Alfred [Hrsg.] OVCH Verlagsgesellschaft mbH, D-6940 Weinheim (Federal Republic of Germany), 1993 Printed on acid-free and low-chlorine paper. Nopart ofthisbookmay be reproducedinany form Allrightsreserved(inc1udingthoseoftranslationintootherlanguages). -by photoprinting, microfilm, or any other means -nor transmitted or translated into a machine language without written permission from the publishers. Registered names, trademarks, etc. used in this book, even when not specifically marked as such, are not to be considered unprotected by law. Composition and Printing: Zechnersche Buchdruckerei, D-6720 Speyer. Bookbinding: Klambt-Druck GmbH, D-6720 Speyer Printed in the Federal Republic of Germany Preface In recognition of the enormous advances in A carefully selected and distinguished Scien- biotechnology in recent years, we are pleased tific Advisory Board stands behind the series. to present this Second Edition of “Biotechno- Its members come from key institutions repre- logy” relatively soon after the introduction of senting scientific input from about twenty the First Edition of this multi-volume compre- countries. hensive treatise. Since this series was extremely The volume editors and the authors of the well accepted by the scientific community, we individual chapters have been chosen for their have maintained the overall goal of creating a recognized expertise and their contributions to number of volumes, each devoted to a certain the various fields of biotechnology. Their will- topic, which provide scientists in academia, in- ingness to impart this knowledge to their col- dustry, and public institutions with a well-bal- leagues forms the basis of “Biotechnology” anced and comprehensive overview of this and is gratefully acknowledged. Moreover, growing field. We have fully revised the Sec- this work could not have been brought to frui- ond Edition and expanded it from ten to tion without the foresight and the constant and twelve volumes in order to take all recent de- diligent support of the publisher. We are velopments into account. grateful to VCH for publishing “Biotechnolo- These twelve volumes are organized into gy” with their customary excellence. Special three sections. The first four volumes consider thanks are due Dr. Hans-Joachim Kraus and the fundamentals of biotechnology from bio- Christa Schultz, without whose constant ef- logical, biochemical, molecular biological, and forts the series could not be published. Finally, chemical engineering perspectives. The next the editors wish to thank the members of the four volumes are devoted to products of indus- Scientific Advisory Board for their encourage- trial relevance. Special attention is given here ment, their helpful suggestions, and their con- to products derived from genetically engi- structive criticism. neered microorganisms and mammalian cells. The last four volumes are dedicated to the de- H.-J. Rehm scription of special topics. G. Reed The new “Biotechnology” is a reference A. Puhler work, a comprehensive description of the P. Stadler state-of-the-art, and a guide to the original literature. It is specifically directed to micro- biologists, biochemists, molecular biologists, bioengineers, chemical engineers, and food and pharmaceutical chemists working in indus- try, at universities or at public institutions. Scientific Advisory Board Prof. Dr. M. J. Beker Prof. Dr. T. K. Ghose August Kirchenstein Institute of Microbiology Biochemical Engineering Research Centre Latvian Academy of Sciences Indian Institute of Technology Riga, Latvia New Delhi, India Prof, Dr. J. D. Bu’Lock Prof. Dr. I. Goldberg Weizmann Microbial Chemistry Laboratory Department of Applied Microbiology Department of Chemistry The Hebrew University University of Manchester Jerusalem, Israel Manchester, UK Prof. Dr. C. L. Cooney Prof. Dr. G. Goma Department of Chemical Engineering Departement de Genie Biochimique et Massachusetts Institute of Technology Alimentaire Cambridge, MA, USA Institut National des Sciences Appliquees Toulouse, France Prof. Dr. H. W. Doelle Prof. Dr. D. A. Hopwood Department of Microbiology Department of Genetics University of Queensland John Innes Institute St. Lucia, Australia Norwich, UK Prof, Dr. J. Drews Prof. Dr. E. H. Houwink F. Hoffmann-La Roche AG Organon International bv Basel, Switzerland Scientific Development Group Oss, The Netherlands Prof. Dr. A, Fiech ter Prof. Dr. A. E. Humphrey Institut fur Biotechnologie Center for Molecular Bioscience and Eidgenossische Technische Hochschule Biotechnology Zurich, Switzerland Lehigh University Bethlehem, PA, USA VIII Scientific Advisory Board Prof. Dr. I. Karube Prof. Dr. K. Schugerl Research Center for Advanced Science Institut fur Technische Chemie and Technology Universitat Hannover University of Tokyo Hannover, Germany Tokyo, Japan Prof. Dr. M. A. Lachance Prof. Dr. P. Sensi Department of Plant Sciences Chair of Fermentation Chemistry University of Western Ontario and Industrial Microbiology London, Ontario, Canada Lepetit Research Center Gerenzano, Italy Prof. Dr. Y.L iu Prof. Dr. Y. H. Tan China National Center for Biotechnology Institute of Molecular and Cell Biology Development National University of Singapore Beijing, China Singapore Prof, Dr. J. F. Martin Prof. Dr. D. Thomas Department of Microbiology Laboratoire de Technologie Enzymatique University of Leon Universite de Compiegne Leon, Spain Compiegne, France Prof, Dr. B. Mattiasson Prof. Dr. W. Verstraefe Department of Biotechnology Laboratory of Microbial Ecology Chemical Center Rijksuniversiteit Gent University of Lund Gent, Belgium Lund, Sweden Prof. Dr. M. Rohr Prof. Dr. E.-L. Winnacker Institut fur Biochemische Technologie Institut fur Biochemie und Mikrobiologie Universitat Munchen Technische Universitat Wien Munchen, Germany Wien, Austria Prof. Dr. H. Sahm Institut fur Biotechnologie Forschungszentrum Julich Julich, Germany Contents Introduction 1 11 Genetic Engineering of Gram Negative Bacteria 427 A. Puhler U. B. Priefer I. Classical Genetics 12 Genetic Engineering of Gram Positive Bacteria 455 1 Mutagenesis 5 W. Wohlleben, G. Muth, J. Kalinowski A. Crueger 13 Genetic Engineering of Yeast 507 2 Genetic Exchange Processes for P. E. Sudbery Prokaryotes 47 14 Genetic Engineering of Filamentous B. W. Holloway Fungi 529 3 Genetic Exchange Processes in Lower G. Turner Eukaryotes 73 U. Stahl, K. Esser 4 Cell Fusion 93 IV. Genetic Engineering of Plants J. Anne 5 Gene Mapping in Animals and 15 Genetic Engineering of Plant Cells 547 Plants 141 G. Kahl, K. Weising G. Wricke, H. Geldermann, W. E. Weber 16 Transgenic Plants 627 . L Willmi tzer 11. Molecular Genetics 6 Structure and Function of DNA 191 V. Genetic Engineering of Animals F. Gotz 7 Principles of Gene Expression 233 17 Genetic Engineering of Animal Cells 663 R. Mattes M. Wirth, H. Hauser 8 DNA Sequencing 257 18 Transgenic Animals 745 G. Volckaert, P. Verhasselt, M. Voet, G. Brem J. Robben 9 DNA Synthesis 317 J. W. Engels, B. Sprunkel, E. Uhlmann VI. Biosafety Concepts 111. Genetic Engineering of 19 Safety Aspects in Biotechnology 835 Microorganisms R. Simon, W.F rommer 10 Principles of Genetic Engineering for Escherichia coli 373 H. Schwab Index 855 Contributors Prof. Dr. Jozef Anne Prof. Dr. mult. Karl Esser Rega Instituut Lehrstuhl fur Allgemeine Botanik Katholieke Universiteit Leuven Ruhr-Universitgt Bochum Minderbroedersstraat 10 P.O. Box 102148 B-3000 Leuven D-4630 Bochum 1 Belgium Federal Republic of Germany Chapter 4 Chapter 3 Prof. Dr. Gottfried Brem Prof. Dr. Werner Frommer Lehrstuhl fur Molekulare Tierzuchtforschung Claudiusweg 17 Universitat Munchen D-5600 Wuppertal 1 Veteringrstrane 13 Federal Republic of Germany D-8000 Munchen 22 Chapter 19 Federal Republic of Germany Chapter 18 Dr . Anneliese Crueger Prof. Dr. Hermann Geldermann Bayer AG Institut fur Tierhaltung und Tierzuchtung Verfahrensentwicklung Biochemie Universitat Stuttgart Friedrich-Ebert-StraRe 217 GarbenstraRe 17 D-5600 Wuppertal 1 D-7000 Stuttgart 70 Federal Republic of Germany Federal Republic of Germany Chapter 1 Chapter 5 Prof. Dr. Joachim W. Engels Prof. Dr. Friedrich Gotz Institut fur Organische Chemie Lehrstuhl fur Mikrobielle Genetik Universitat Frankfurt Universitat Tiibingen Niederurseler Hang Auf der Morgenstelle 28 D-6000 Frankfurt am Main 50 D-7400 Tubingen Federal Republic of Germany Federal Republic of Germany Chapter 9 Chapter 6 XI1 Contributors Dr. Hansjorg Hauser Priv.-Doz. Dr. Ursula B. Priefer Gesellschaft fur Biotechnologische Forschung Biologie VI (Genetik) mbH Universitat Bielefeld Mascheroder Weg 1 P.O. Box 100131 D-3300 Braunschweig D-4800 Bielefeld 1 Federal Republic of Germany Federal Republic of Germany Chapter I7 Chapter I1 Prof. Dr. Bruce W. Holloway Dr. Johan Robben Department of Genetics and Developmental Faculteit Landbouwwetenschappen Biology Laboratorium voor Gentechnologie Monash University Katholieke Universiteit Leuven Wellington Road Willem de Croylaan, 42 Clayton, Victoria, 3168 B-3001 Leuven Australia Belgium Chapter 2 Chapter 8 Prof. Dr. Giinter Kahl Dr. Helmut Schwab Fachbereich Biologie Institut fur Biotechnologie Universitat Frankfurt Arbeitsgruppe Genetik Siesmayerstrarje 70 Technische Universitat Graz D-6000 Frankfurt am Main 1 Petersgasse 12 Federal Republic of Germany A-8010 Graz Chapter 15 Austria Chapter 10 Dr. Jorn Kalinowski Dr. Reinhard Simon Biologie VI (Genetik) TUV Sudwestdeutschland e. V. Universitat Bielefeld Fachgruppe Biologische Sicherheit P.O. Box 100131 Robert-Bunsen-StraRe 1 D-4800 Bielefeld 1 D-7800 Freiburg i. Br. Federal Republic of Germany Federal Republic of Germany Chapter 12 Chapter 19 Prof. Dr. Ralf Mattes Dip1.-Chem. Belinda Sprunkel Institut fur Industrielle Genetik Institut fur Organische Chemie Universitat Stuttgart Universitat Frankfurt Azenbergstrarje 18 Niederurseler Hang D-7000 Stuttgart 1 D-6000 Frankfurt am Main 50 Federal Republic of Germany Federal Republic of Germany Chapter 7 Chapter 9 Dr. Giinther Muth Prof. Dr. Ulf Stahl Institut fur Angewandte Molekularbiologie Fachbereich 13 der Universitat des Saarlandes Institut fur Biotechnologie Im Stadtwald Technische Universitat Berlin D-6600 Saarbrucken Gustav-Meyer-Allee 25 Federal Republic of Germany D-1000 Berlin 65 Chapter 12 Federal Republic of Germany Chapter 3