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Bioprocess Engineering

Bioprocess Engineering

Basic Concepts
3rd Edition

Michael Shuler, Fikret Kargi, Matthew DeLisa

Apr 2017, Hardback, 640 pages
ISBN13: 9780137062706
ISBN10: 0137062702
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The Leading Introduction to Biochemical and Bioprocess Engineering, Updated with Key Advances in Productivity, Innovation, and Safety

Bioprocess Engineering, Third Edition, is an extensive update of the world’s leading introductory textbook on biochemical and bioprocess engineering and reflects key advances in productivity, innovation, and safety.

The authors review relevant fundamentals of biochemistry, microbiology, and molecular biology, including enzymes, cell functions and growth, major metabolic pathways, alteration of cellular information, and other key topics. They then introduce evolving biological tools for manipulating cell biology more effectively and to reduce costs of bioprocesses.

This edition presents major advances in the production of biologicals; highly productive techniques for making heterologous proteins; new commercial applications for both animal and plant cell cultures; key improvements in recombinant DNA microbe engineering; techniques for more consistent authentic post-translational processing of proteins; and other advanced topics. It includes new, improved, or expanded coverage of

  • The role of small RNAs as regulators
  • Transcription, translation, regulation, and differences between prokaryotes and eukaryotes
  • Cell-free processes, metabolic engineering, and protein engineering
  • Biofuels and energy, including coordinated enzyme systems, mixed-inhibition and enzyme-activation kinetics, and two-phase enzymatic reactions
  • Synthetic biology
  • The growing role of genomics and epigenomics Population balances and the Gompetz equation for batch growth and product formation
  • Microreactors for scale-up/scale-down, including rapid scale-up of vaccine production
  • The development of single-use technology in bioprocesses
  • Stem cell technology and utilization
  • Use of microfabrication, nanobiotechnology, and 3D printing techniques
  • Advances in animal and plant cell biotechnology

The text makes extensive use of illustrations, examples, and problems, and contains references for further reading as well as a detailed appendix describing traditional bioprocesses.

Preface xvii

About the Authors xxi

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Index 601

  • The field's best-seller, now fully revised
  • Offers greater emphasis on biofuels / bioenergy
  • Includes new coverage of coordinated enzyme systems, disposable bioreactors, cell-free systems, nanobiotechnology, and drug discovery
  • Contains expanded discussions of metabolic engineering, protein engineering, and stem cells New and updated homework and example problems throughout
  • Dr. Michael L. Shuler is Samuel B. Eckert Professor of Engineering at Cornell University. He directed the School of Chemical Engineering (1998-2002) and was founding James and Marsha McCormick Chair for Biomedical Engineering (2004-2014). He also directs the Center on the Microenvironment and Metastasis (CMM), funded by the National Cancer Institute as a Physical Sciences - Oncology Center. He has received numerous teaching, advising, and research related awards, and has been elected to the National Academy of Engineering and the American Academy of Arts and Sciences.

    Fikret Kargi is Professor in the Department of Environmental Engineering at Dokuz Eylul University. His interests include bioprocess engineering, environmental biotechnology, wastewater treatment, biotechnology-bioengineering, and waste bioprocessing. He holds a Ph.D. in Chemical/Biochemical Engineering from Cornell.

    Matthew DeLisa is William L. Lewis Professor of Engineering in Cornell's Department of Chemical and Biomolecular Engineering. His research focuses on understanding and controlling the molecular mechanisms underlying protein biogenesis in the complex environment of a living cell. He has invented numerous commercially important technologies for facilitating the discovery, design and manufacturing of human drugs, and has made seminal discoveries about cellular protein folding and protein translocation. DeLisa has received several awards including an NSF CAREER award, and was named one of the top 35 young innovators by MIT's Technology Review. He was elected as a fellow of the American Institute for Medical and Biological Engineering in 2014.

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