Basic Biotechnology, 3rd Edition
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Contents
List of contributors page ix
Preface to the second edition xiii
Preface to the third edition xv
Part I Fundamentals and principles
Chapter 1 Public perception of biotechnology 3
J. E. Smith
Chapter 2 Biochemistry and physiology of growth
and metabolism 25
Colin Ratledge
Chapter 3 Stoichiometry and kinetics of microbial
growth from a thermodynamic perspective 55
J. J. Heijnen
Chapter 4 Genome management and analysis:
prokaryotes 73
Colin R. Harwood and Anil Wipat
Chapter 5 Genetic engineering: yeasts and
filamentous fungi 119
David B. Archer, Donald A. MacKenzie and
David J. Jeenes
Chapter 6 Microbial process kinetics 155
Jens Nielsen
Chapter 7 Bioreactor design 181
Yusuf Chisti
Chapter 8 Mass transfer 201
Henk J. Noorman
Chapter 9 Downstream processing 219
Marcel Ottens, Johannes A. Wesselingh and
Luuk A. M. van der Wielen
vi CONTENTS
Chapter 10 Measurement, monitoring, modelling
and control 251
Bernhard Sonnleitner
Chapter 11 Process economics 271
Bjørn Kristiansen
Part II Practical applications
Chapter 12 High-throughput screening and process
optimisation 289
Steven D. Doig, Frank Baganz and Gary J. Lye
Chapter 13 The business of biotechnology 307
Jason Rushton and Christopher Evans
Chapter 14 Amino acids 335
L. Eggeling, W. Pfefferle and H. Sahm
Chapter 15 Organic acids 359
Christian P. Kubicek and Levente Karaffa
Chapter 16 Microbial polysaccharides and single
cell oils 381
James P. Wynn and Alistair J. Anderson
Chapter 17 Environmental applications 403
Philippe Vandevivere and Willy Verstraete
Chapter 18 Production of antibiotics by fermentation 433
Derek J. Hook
Chapter 19 Strategies of cultivation 457
Sven-Olof Enfors
Chapter 20 Enzyme biotechnology 477
Randy M. Berka and Joel R. Cherry
Chapter 21 Recombinant proteins of high value 499
Georg-B. Kresse
CONTENTS vii
Chapter 22 Insect and mammalian cell culture 523
C. J. Hewitt, B. Isailovic, N. T. Mukwena and
A. W. Nienow
Chapter 23 Plant cell biotechnology 549
Robert Verpoorte and Hens J. G. ten Hoopen
Chapter 24 Biotransformations 579
Pedro Fernandes and Joaquim M. S. Cabral
Chapter 25 Immunochemical applications 627
Mike Clarke
Index 657
Contributors
Alistair J. Anderson
Department of Biological Sciences, University of Hull, Hull, HU6
7RX, UK
David B. Archer
School of Biology, University of Nottingham, University Park,
Nottingham, NG7 2RD, UK
Frank Baganz
The Advanced Centre for Biochemical Engineering, Department of
Biochemical Engineering, University College London, Torrington
Place, London, WC1E 7JE, UK
Randy M. Berka
Research Fellow, Core Technology Department, Novozymes Biotech,
Inc., 1445 Drew Avenue, Davis, CA 95616, USA
Joaquim M. S. Cabral
Centro de Engenharia, Bioquimica e Quimica, Av Rovisco Pais,
Instituto Superior Technico, 1049--001 Lisboa, Portugal
Joel R. Cherry
Novozymes Biotech, Inc., 1445 Drew Avenue, Davis, CA 95616, USA
Yusuf Chisti
Institute of Technology and Engineering, Massey University, Private
Bag 11 222, Palmerston North, New Zealand
Mike Clark
Division of Immunology, Department of Pathology, University of
Cambridge, Tennis Court Road, Cambridge, CB2 1QP, UK
Steven D. Doig
The Advanced Centre for Biochemical Engineering, Department of
Biochemical Engineering, University College London, Torrington
Place, London, WC1E 7JE, UK
L. Eggeling
Research Centre Jülich, Biotechnologie 1, 52425 Jülich, Germany
Sven-Olof Enfors
Department of Biochemistry and Biotechnology, Riayl Institute of
Technology, S-100 44 Stockholm, Sweden
Sir Christopher Evans
Merlin Biosciences Ltd, 33 King Street, St James, London, SW1Y
6RJ, UK
Pedro Fernandes
Centro de Engenharia, Bioquimica e Quimica, Av Rovisco Pais,
Instituto Superior Technico, 1049--001 Lisboa, Portugal
x LIST OF CONTRIBUTORS
Colin R. Harwood
Department of Microbiology and Immunology, The Medical School,
University of Newcastle, Framlington Place, Newcastle upon Tyne,
NE2 4HH, UK
J. J. Heijnen
TU Delft, Julianalaan 67, 2628 BC Delft, The Netherlands
C. J. Hewitt
Department of Chemical Engineering (Biochemical Engineering),
The University of Birmingham, Edgbaston, B15 2TT, UK
Derek J. Hook
Senior Research Specialist, 3M Pharmaceuticals, Pharmacology,
Building 0270-03-A10, 3M Center, St Paul, MN 55144-1000, USA
B. Isailovic
Department of Chemical Engineering (Biochemical Engineering),
The University of Birmingham, Edgbaston, B15 2TT, UK
David J. Jeenes
Institute of Food Research, Norwich Research Park, Colney, Norwich,
NR4 7UA, UK
Levente Karaffa
Department of Microbiology and Biotechnology, Faculty of Sciences,
University of Debrecen, H-4010, PO Box 63, Debrecen, Hungary
Georg-B. Kresse, Head of Protein Discovery, Pharma Research, Roche
Diagnostics GmbH, D-82372 Penzberg, Germany
Bjørn Kristiansen
EU Biotech Consulting, Gluppeveien 15, 1614 Fredrikstad, Norway
Christian P. Kubicek
Division of Gene Technology, Institut fur Verfahrenstechnik,
Umwelttechnik und Techn, Biowissenschaften, Getreidemarkt 9/166,
A-Vienna 1060, Austria
Gary J. Lye
The Advanced Centre for Biochemical Engineering, Department of
Biochemical Engineering, University College London, Torrington
Place, London, WC1E 7JE, UK
Donald A. MacKenzie
Institute of Food Research, Norwich Research Park, Colney, Norwich,
NR4 7UA, UK
N. T. Mukwena
Department of Chemical Engineering (Biochemical Engineering),
The University of Birmingham, Edgbaston, B15 2TT, UK
Jens Nielsen
Center for Process Biotechnology, Building 223, BioCentrum-DTU,
Technical University of Denmark, DK-2800 Lyngby, Denmark
LIST OF CONTRIBUTORS xi
A. W. Nienow
Department of Chemical Engineering (Biochemical Engineering),
The University of Birmingham, Edgbaston, B15 2TT, UK
Henk J. Noorman
DSM Anti-Infectives, PO Box 425, 2600 AK Delft, The Netherlands
Marcel Ottens
Department of Biotechnology, Delft University of Technology,
Julianalaan 67, 2628 BC Delft, The Netherlands
W. Pfefferle
Degussa AG, Feed Additives Division, R&D, Kantstraese 2, 33790
Halle-Kuensebeck, Germany
Colin Ratledge
Department of Biological Sciences, University of Hull, Hull, HU6
7RX, UK
Jason Rushton
Merlin Biosciences Ltd, 33 King Street, St James, London,
SW1Y 6RJ, UK
H. Sahm
Research Centre Jülich, Biotechnologie 1, D-52425 Jülich, Germany
J. E. Smith
Department of Bioscience and Biotechnology, University of
Strathclyde, 204 George Street, Glasgow, G1 1XW, UK
Bernhard Sonnleitner
Zürich University of Applied Sciences, Winterthur, Institute for
Chemistry and Biotechnology, Postfach 805, 8401 Winterthur,
Switzerland
Hens J. G. ten Hoopen
Department of Biotechnology, Delft University of Technology, Delft,
The Netherlands
Luuk A. M. van der Wielen
Department of Biotechnology, Delft University of Technology,
Julianalaan 67, 2628 BC Delft, The Netherlands
Philippe Vandevivere
The Seawater Foundation, 4230E. Whittier Street,
Tucson, AZ 85711, USA
Robert Verpoorte
Department of Pharmacognosy, Section Metabolomics, IBL, Leiden
University, Leiden, The Netherlands
Willy Verstraete
Laboratory for Microbial Ecology and Technology, Ghent University,
Coupure L653, Belgium
xii LIST OF CONTRIBUTORS
Johannes A. Wesselingh
University of Groningen, Department of Chemical Engineering,
Nijenborgh 4, Groningen, NL-9747 AG, The Netherlands
Anil Wipat
Department of Microbiology and Immunology, The Medical School,
University of Newcastle, Framlington Place, Newcastle upon Tyne,
NE2 4HH, UK
James P. Wynn
Martek Biosciences Corp., 6480 Dobbin Road, Columbia, Maryland,
MD 21045, USA
Preface to the second edition
It is some 14 years since the first edition of this book appeared. Much
has happened to biotechnology in these intervening years. Recombi-
nant DNA technology, which was just beginning in the mid 1980s, is
now one of the major cornerstones of modern biotechnology. Devel-
opments in this area have radically altered our concepts of health-
care with the arrival of numerous products that were unthinkable
20 years ago. Such is the pace of biotechnology that it can be antici-
pated in the next 14 years that even greater developments will occur
thanks to such programmes as the Human Genome Project which
will open up opportunities for treatment of diseases at the individ-
ual level. All such advances though rely on the application of basic
knowledge and the appreciation of how to translate that knowledge
into products that can be produced safely and as cheaply as possible.
The fundamentals of biotechnology remain, as always, production of
goods and services that are needed and can be provided with safety
and reasonable cost.
Biotechnology is not just about recombinant DNA, of cloning and
genetics; it is equally about producing more prosaic materials, like
citric acid, beer, wine, bread, fermented foods such as cheese and
yoghurts, antibiotics and the like. It is also about providing clean
technology for a new millennium; of providing means of waste dis-
posal, of dealing with environmental problems. It is, in short, one of
the two major technologies of the twenty-first century that will sus-
tain growth and development in countries throughout the world for
several decades to come. It will continue to improve the standard of
all our lives, from improved medical treatments, through its effects
on foods and food supply and into the environment. No aspect of our
lives will be unaffected by biotechnology.
This book has been written to provide an overview of many of
the fundamental aspects that underpin all biotechnology and to pro-
vide examples of how these principles are put into operation: from the
starting substrate or feedstock through to the final product. Because
biotechnology is now such a huge, multi-everything activity we have
not been able to include every single topic, every single product or
process: for that an encyclopedia would have been needed. Instead
we have attempted to provide a mainstream account of the cur-
rent state of biotechnology that, we hope, will provide the reader
with insight, inspiration and instruction in the skills and arts of the
subject.
Since the first edition of this book, we sadly have to record the
death of our colleague and friend, John Bu’Lock, whose perspicacity
had led to the first edition of this book being written. John, at the
time of his death in 1996, was already beginning to plan this second
xiv PREFACE TO THE SECOND EDITION
edition and it has been a privilege for us to have been able to continue
in his footsteps to see it through into print. John was an inspiring
figure in biotechnology for many of us and it is to the memory of a
fine scientist, dedicated biotechnologist and a remarkable man that
we dedicate this book to JDB.
Preface to the third edition
From antibiotics and production of other health-care products to
waste treatment and disposal, biotechnology continues to hold our
attention. The breadth and scope of biotechnology continues to
increase: each decade sees significant new advances across a wide
range of topics. From the first edition of this book to the second edi-
tion took 14 years; from the second edition to this one has taken only
five. The rapid pace of developments in molecular biology and genet-
ics, and in their applications to biotechnology, ensures that progress
in microbiology, animal and plant cell technology for the further-
ance of our well-being never slackens. Biotechnology continues to be
a world-driving force for the production of a whole range of prod-
ucts as well as being vitally important as a process technology for the
care of the environment. The expectations are that biotechnology
will remain as one of the leading scientific and industrially linked
endeavours for at least the first half of this present century. Its con-
tribution to our health, welfare, food and drink will, in fact, con-
tinue for as long as civilisation continues, such is the importance of
biotechnology.
This new edition of Basic Biotechnology reflects these key develop-
ments in our subject but, at the same time, this new edition consoli-
dates our knowledge of those fundamental principles of science and
engineering that are vital to an understanding of the subject at its
basic level. New chapters have been included on several topics both
in the fundamentals and principles section as well as in the practical
applications section; most of the other chapters have been extensively
revised and all have been up-dated.
All our authors are internationally known for their contributions
to biotechnology; all are exceptionally busy people and we therefore
thank them most sincerely for taking time out to write their various
chapters -- both new and revised. Our task as editors has therefore
been a rather easy one: curtailing a little too much detail here, or
asking for clarification of a point, is about all we have had to do.
Equally important is the enthusiasm of the publishers for this new
edition. Their input in helping to produce a highly improved for-
mat, for what is already a highly regarded and popular book, is to
be applauded. Obviously our publishers, like the purchasers of this
book, know a good book when they see one.
We trust that this new edition adequately reflects the current sta-
tus and trends in mainstream biotechnology. Given the diversity of
biotechnology it will be an impossible task to cover every aspect of
the field in one volume. Nevertheless, we feel that the major aspects
of the subject are covered herein.
Part I
Fundamentals and
principles
