Biotechnology is an expansive field incorporating expertisein both the life science and engineering disciplines. Inbiotechnology, the life scientist is concerned with developingthe most favourable biocatalysts, while the engineer isdirected towards process performance, defining conditionsand strategies that will maximise the production potential ofthe biocatalyst. Increasingly, the synergistic effect of thecontributions of engineering and life sciences is recognised askey to the translation of new bioproducts from the laboratorybench to commercial bioprocess.
Fundamental to the successful realisation of the bioprocessthen, is a need for process engineers and life scientistscompetent to evaluate biological systems from a cross-disciplinary viewpoint. This book aims to generate corecompetencies through an understanding of the complementarybiotechnology disciplines and their interdependence, andan appreciation of the challenges associated with theapplication of engineering principles in a life science context.Its ultimate goal is to maximise the potential of theengineering approach when addressing concepts as diverseas process manipulation for enhancement of bioproductaccumulation, reactor design and scale up for peak process performance and the development of downstream protocolsfor optimal purification of biomaterials.
This book is primarily, but not exclusively, intended as atextbook for postgraduate or senior undergraduate students and covers material suitable for a comprehensive semestercourse in Bioprocess Engineering. Initial chapters focus onthe microbiology, biochemistry and molecular biology thatunderpin biocatalyst potential for product accumulation.The following chapters develop kinetic and mass transferprinciples that quantify optimum process performance.The text is wide in scope, relating to bioprocesses usingbacterial, fungal and enzymic biocatalysts, batch, fed-batchand continuous strategies and free and immobilisedconfigurations.
Finally, I would like to acknowledge and thank the manywho have provided invaluable insights during my travelsthrough the field of Bioprocess Engineering. The lateProfessor Geoffrey Hansford (University of Cape Town,South Africa), Dr John Wase (University of Birmingham,United Kingdom) and Dr Terrence Watson (Centre forScientific and Industrial Research, South Africa) deservespecial mention. And to my graduate students over the years,thank you all for your hard work and dedication in movingthe boundaries of current knowledge.

List of figures xi

List of plates XV

Preface xvii

About the author xix

1 Historical development：from ethanol to biopharm e ceutical s 1

1.1 Notes 5

2 Microbiology 7

2.1 Microorganisms：the core of cellular bio processes 8

2.2 Cellular structure and sites of metabolic reactions 15

2.3 Classification according to carbon and energy requirements 18

2.4 Nutrient requirements 21

2.5 Notes 23

3 Metabolic macromolecules 25

3.1 Carbohydrates 26

3.2 Lipids 30

3.3 Proteins 31

3.4 Nucleosides， nucleotides and nucleic acids 33

3.5 Notes 38

4 Molecular biology 39

4.1 Replication， transcription and translation 40

4.2 Genetic regulation 44

4.3 Genetic modification 49

4.4 Notes 50

5 Carbon metabolism 53

5.1 Energy generation， storage and transfer 54

5.2 Catabolic pathways：energy generation 59

5.3 Anabolic pathways：energy utilisation 71

5.4 Notes 73

6 Enzymes as biocatalysts 75

6.1 Enzyme kinetics with no inhibition 76

6.2 Enzyme kinetics with inhibition 78

6.3 Enzyme reactors with soluble enzymes 84

6.4 Enzyme reactors with immobilised enzymes 86

6.5 Notes 96

7 Microbial kinetics during batch， continuous and fed-batch processes 97

7.1 The nutrient medium 98

7.2 Batch process design equations 101

7.3 Continuous process design equations 116

7.4 Fed-batch bioprocess design equations 140

7.5 Notes 145

8 The oxygen transfer rate and overall volumetric oxygen transfer coefficient 147

8.1 Oxygen transfer design equations 149

8.2 Measurement of the oxygen transfer rate 157

8.3 Notes 168

9 Bioprocess scale up 171

9.1 Scale up with constant oxygen transfer rate 173

9.2 Scale up with constant mixing 180

9.3 Scale up with constants hear stress 182

9.4 Scale up with constant flow regime 185

9.5 Notes 187

10 Bioprocess asepsis and sterility 189

10.1Heat sterilisation of media and equipment 190

10.2 Filter sterilisation of air 203

10.3 Notes 207

11 Downstream processing 209

11.1 Overview of potential recovery operations 211

11.2 Separation of cells and extracellular fluid 213

11.3 Cell rupture and separation of cell extract 217

11.4 Concentration and purification of soluble products 219

11.5 Notes 232

Index 235

Professor Kim Clarke is an academic in the Department of Process Engineering, University of Stellenbosch, and a registered Professional Engineer. She holds a PhD and BSc (Chemical Engineering), both from the University of Cape Town, South Africa, and an MSc (Biological and Chemical Engineering) from the University of Birmingham, United Kingdom. She has developed and lectured university courses in bioprocess engineering for over IS years and has twice been a recipient of the University of Stellenbosch Award for Excellence in Education (2007 and 2010). In addition, she heads a research group in bioprocess engineering where her research profile focuses on the application of chemical engineering principles in the development and optimisation of biological processes. Her research is specifically directed towards fundamental kinetic and mass transfer studies which quantify the principles governing process performance and define process strategies for optimisation of the production potential of the biocatalyst.

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