Preface xvii
About the Authors xxi
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Part 1: The Basics of Biology: An Engineer’s Perspective 1
Chapter 1: What Is a Bioprocess Engineer? 1
1.1 Biotechnology and Bioprocess Engineering 2
1.2 Differing Approaches to Research for Biologists and Engineers 3
1.3 The Story of Penicillin: How Biologists and Engineers Work Together 4
1.4 Bioprocesses: Regulatory Constraints 9
Suggestions for Further Reading 11
Questions 11
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Chapter 2: An Overview of Biological Basics 13
2.1 Microbial Diversity 13
2.2 Cell Construction 28
2.3 Cell Nutrients 51
2.4 Summary 56
Suggestions for Further Reading 58
Questions 58
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Chapter 3: Enzymes 61
3.1 How Enzymes Work 62
3.2 Enzyme Kinetics 63
3.3 Immobilized Enzyme Systems 86
3.4 Large-Scale Production of Enzymes 98
3.5 Medical and Industrial Utilization of Enzymes 100
3.6 Summary 103
Suggestions for Further Reading 104
Problems 104
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Chapter 4: How Cells Work 113
4.1 The Central Dogma 114
4.2 DNA Replication: Preserving and Propagating the Message 117
4.3 Transcription: Sending the Message 119
4.4 Translation: Going from Message to Product 123
4.5 Metabolic Regulation 130
4.6 How the Cell Senses its Extracellular Environment 135
4.7 Summary 139
4.8 Appendix: Example Regulation of Complex Pathways 140
Suggestions for Further Reading 142
Problems 143
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Chapter 5: Major Metabolic Pathways 145
5.1 Bioenergetics 146
5.2 Glucose Metabolism: Glycolysis and the TCA Cycle 149
5.3 Respiration 152
5.4 Control Sites in Aerobic Glucose Metabolism 154
5.5 Metabolism of Nitrogenous Compounds 155
5.6 Nitrogen Fixation 156
5.7 Metabolism of Hydrocarbons 156
5.8 Biodegradation of Xenobiotics 157
5.9 Overview of Biosynthesis 158
5.10 Overview of Anaerobic Metabolism 161
5.11 Overview of Autotrophic Metabolism 163
5.12 Summary 165
Suggestions for Further Reading 166
Questions 168
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Chapter 6: How Cells Grow 169
6.1 Batch Growth 170
6.2 Quantifying Growth Kinetics 191
6.3 Cell Growth in Continuous Culture 208
6.4 Summary 219
Suggestions for Further Reading 219
Problems 220
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Chapter 7: Stoichiometry of Microbial Growth and Product Formation 227
7.1 Coefficients for ATP Consumption and Oxygen 227
7.2 Stoichiometric Calculations 229
7.3 Theoretical Predictions of Yield Coefficients 235
7.4 Estimation of Elemental Cell Composition 236
7.5 Stoichiometry by Oxidation-Reduction Half-Reactions 237
7.6 Thermodynamics of Biological Reactions 240
7.7 Summary 242
Suggestions for Further Reading 242
Problems 243
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Chapter 8: How Cellular Information Is Altered 247
8.1 Evolving Desirable Biochemical Activities Through Mutation and Selection 247
8.2 Natural Mechanisms for Gene Transfer and Rearrangement 252
8.3 Genetically Engineering Cells 257
8.4 Genomics 267
8.5 Summary 272
Suggestions for Further Reading 272
Problems 273
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Part 2: Engineering Principles for Bioprocesses 275
Chapter 9: Operating Considerations for Bioreactors for Suspension and Immobilized Cultures 275
9.1 Choosing the Cultivation Method 276
9.2 Modifying Batch and Continuous Reactors 278
9.3 Immobilized Cell Systems 298
9.4 Hybrid Bioreactors: Attached and Suspended Cells 311
9.5 Solid-State Fermentations 313
9.6 Summary 316
Suggestions for Further Reading 317
Problems 318
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Chapter 10: Selection, Scale-Up, Operation, and Control of Bioreactors 323
10.1 Scale-Up and its Difficulties 323
10.2 Bioreactor Instrumentation and Control 349
10.3 Sterilization of Process Fluids 356
10.4 Summary 364
Suggestions for Further Reading 365
Problems 366
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Chapter 11: Recovery and Purification of Products 371
11.1 Strategies to Recover and Purify Products 371
11.2 Separation of Insoluble Products 374
11.3 Cell Disruption 382
11.4 Separation of Soluble Products 385
11.5 Finishing Steps for Purification 422
11.6 Integration of Reaction and Separation 424
11.7 Summary 426
Suggestions for Further Reading 426
Problems 427
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Chapter 12: Bioprocess Considerations in Using Animal Cell Cultures 431
12.1 Structure and Biochemistry of Animal Cells 431
12.2 Methods Used for the Cultivation of Animal Cells 434
12.3 Bioreactor Considerations for Animal Cell Culture 443
12.4 Bioreactor Systems for Animal Cell Culture 444
12.5 Products of Animal Cell Cultures 447
12.6 Summary 448
Suggestions for Further Reading 449
Problems 450
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Chapter 13: Bioprocess Considerations in Using Plant Cell Cultures 451
13.1 Why Plant Cell Cultures? 451
13.2 Plant Cells in Culture Compared to Microbes 457
13.3 Bioreactor Considerations 461
13.4 Economics of Plant Cell Tissue Cultures 467
13.5 Summary 468
Suggestions for Further Reading 468
Problems 469
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Chapter 14: Utilizing Genetically Engineered Organisms 471
14.1 How the Product Influences Process Decisions 471
14.2 Guidelines for Choosing Host—Vector Systems 474
14.3 Process Constraints: Genetic Instability 485
14.4 Avoiding Process Problems in Plasmid Design 490
14.5 Predicting Host—Vector Interactions and Genetic Instability 493
14.6 Regulatory Constraints on Genetic Processes 503
14.7 Metabolic Engineering 506
14.8 Synthetic and Systems Biology 509
14.9 Protein Engineering 511
14.10 Summary 513
Suggestions for Further Reading 514
Problems 516
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Chapter 15: Medical Applications of Bioprocess Engineering 519
15.1 Tissue Engineering 519
15.2 Gene Therapy Using Viral Vectors 523
15.3 Bioreactors 528
15.4 Summary 531
Suggestions for Further Reading 532
Problems 532
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Chapter 16: Bioprocesses Utilizing Mixed Cultures 535
16.1 Major Classes of Interactions in Mixed Cultures 536
16.2 Simple Models Describing Mixed-Culture Interactions 539
16.3 Mixed Cultures in Nature 545
16.4 Industrial Utilization of Mixed Cultures 546
16.5 Biological Waste Treatment 549
16.6 Summary 572
Suggestions for Further Reading 572
Problems 573
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Appendix: Traditional Industrial Bioprocesses 577
A.1 Anaerobic Bioprocesses 577
A.2 Aerobic Processes 586
A.3 Bioprocess Technologies: Biofuel and Bioenergy Production from Biomass 596
Suggestions for Further Reading 600
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Index 601