9780130819086

Bioprocess Engineering, Second Editionthoroughly updates the leading introductory textbook on biochemical and bioprocess engineering to reflect advances that are transforming the field -- from genomics to cellular engineering, modeling to nonconventional biological systems. It introduces techniques with wide applicability in pharmaceuticals, biologics, medicine, environmental engineering, and beyond.

Dr. Michael L. Shuler is Professor in the School of Chemical Engineering, Cornell University. His areas of research include structured models, heterologous protein expression systems, cell culture analogs for pharmacokinetic models, in-vitro toxicology, plant-cell tissue culture, microbial functional genomics, and bioremediation. Dr. Fikret Kargi is Professor of Environmental Engineering at Dokuz Eylul University in Ismir, Turkey. His current research includes bioprocessing of wastes for production of commercial products, development of novel technologies for biological treatment of problematic wastewaters, nutrient removal, and novel biofilm reactor development

Preface to the Second Edition

xvii

Preface to the First Edition

xix

Part 1 Introduction

1

(10)

What Is A Bioprocess Engineer?

1

(10)

Introductory Remarks

1

(1)

Biotechnology and Bioprocess Engineering

2

(1)

Biologists and Engineers Differ in Their Approach to Research

3

(1)

The Story of Penicillin: How Biologists and Engineers Work Together

3

(5)

Bioprocesses: Regulatory Constraints

8

(3)

Suggestions for Further Reading

10

(1)

Problems

10

(1)

Part 2 The Basics of Biology: An Engineer's Perspective

11

(234)

An Overview of Biological Basics

11

(46)

Are All Cells the Same?

11

(14)

Microbial Diversity

11

(1)

Naming Cells

12

(2)

Viruses

14

(1)

Procaryotes

15

(4)

Eucaryotes

19

(6)

Cell Construction

25

(21)

Introduction

25

(1)

Amino Acids and Proteins

26

(8)

Carbohydrates: Mono- and Polysaccharides

34

(4)

Lipids, Fats, and Steroids

38

(2)

Nucleic Acids, RNA, and DNA

40

(6)

Cell Nutrients

46

(7)

Introduction

46

(3)

Macronutrients

49

(1)

Micronutrients

50

(2)

Growth Media

52

(1)

Summary

53

(4)

Suggestions for Further Reading

54

(1)

Problems

54

(3)

Enzymes

57

(48)

Introduction

57

(1)

How Enzymes Work

58

(2)

Enzyme Kinetics

60

(19)

Introduction

60

(1)

Mechanistic Models for Simple Enzyme Kinetics

61

(3)

Experimentally Determining Rate Parameters for Michaelis-Menten Type Kinetics

64

(3)

Models for More Complex Enzyme Kinetics

67

(8)

Effects of pH and Temperature

75

(3)

Insoluble Substrates

78

(1)

Immobilized Enzyme Systems

79

(12)

Methods of Immobilization

79

(5)

Diffusional Limitations in Immobilized Enzyme Systems

84

(7)

Electrostatic and Steric Effects in Immobilized Enzyme Systems

91

(1)

Large-scale Production of Enzymes

91

(1)

Medical and Industrial Utilization of Enzymes

92

(4)

Summary

96

(9)

Suggestions for Further Reading

97

(1)

Problems

97

(8)

How Cells Work

105

(28)

Introduction

105

(1)

The Central Dogma

105

(2)

DNA Replication: Preserving and Propagating the Cellular Message

107

(3)

Transcription: Sending the Message

110

(3)

Translation: Message to Product

113

(6)

Genetic Code: Universal Message

113

(1)

Translation: How the Machinery Works

113

(2)

Posttranslational Processing: Making the Product Useful

115

(4)

Metabolic Regulation

119

(5)

Genetic-level Control Which Proteins Are Synthesized?

119

(4)

Metabolic Pathway Control

123

(1)

How the Cell Senses Its Extracellular Environment

124

(4)

Mechanisms to Transport Small Molecules across Cellular Membranes

124

(3)

Role of Cell Receptors in Metabolism and Cellular Differentiation

127

(1)

Summary

128

(1)

Appendix: Examples of Regulation of Complex Pathways

129

(4)

Suggestions for Further Reading

131

(1)

Problems

131

(2)

Major Metabolic Pathways

133

(22)

Introduction

133

(1)

Bioenergetics

134

(3)

Glucose Metabolism: Glycolysis and the TCA Cycle

137

(4)

Respiration

141

(1)

Control Sites in Aerobic Glucose Metabolism

142

(1)

Metabolism of Nitrogenous Compounds

143

(1)

Nitrogen Fixation

144

(1)

Metabolism of Hydrocarbons

144

(1)

Overview of Biosynthesis

145

(3)

Overview of Anaerobic Metabolism

148

(2)

Overview of Autotrophic Metabolism

150

(2)

Summary

152

(3)

Suggestions for Further Reading

154

(1)

Problems

154

(1)

How Cells Grow

155

(52)

Introduction

155

(1)

Batch Growth

156

(19)

Quantifying Cell Concentration

156

(4)

Growth Patterns and Kinetics in Batch Culture

160

(9)

How Environmental Conditions Affect Growth Kinetics

169

(4)

Heat Generation by Microbial Growth

173

(2)

Quantifying Growth Kinetics

175

(14)

Introduction

175

(1)

Using Unstructured Nonsegregated Models to Predict Specific Growth Rate

176

(7)

Models for Transient Behavior

183

(6)

Cybernetic Models

189

(1)

How Cells Grow in Continuous Culture

189

(10)

Introduction

189

(1)

Some Specific Devices for Continuous Culture

190

(1)

The Ideal Chemostat

191

(7)

The Chemostat as a Tool

198

(1)

Deviations from Ideality

198

(1)

Summary

199

(8)

Suggestions for Further Reading

200

(1)

Problems

200

(7)

Stoichiometry of Microbial Growth and Product Formation

207

(12)

Introduction

207

(1)

Some Other Definitions

207

(2)

Stoichiometric Calculations

209

(6)

Elemental Balances

209

(2)

Degree of Reduction

211

(4)

Theoretical Predictions of Yield Coefficients

215

(1)

Summary

216

(3)

Suggestions for Further Reading

216

(1)

Problems

216

(3)

How Cellular Information Is Altered

219

(26)

Introduction

219

(1)

Evolving Desirable Biochemical Activities through Mutation and Selection

219

(6)

How Mutations Occur

220

(1)

Selecting for Desirable Mutants

221

(4)

Natural Mechanisms for Gene Transfer and Rearrangement

225

(5)

Genetic Recombination

225

(2)

Transformation

227

(1)

Transduction

227

(1)

Episomes and Conjugation

228

(2)

Transposons: Internal Gene Transfer

230

(1)

Genetically Engineering Cells

230

(6)

Basic Elements of Genetic Engineering

230

(5)

Genetic Engineering of Higher Organisms

235

(1)

Genomics

236

(5)

Experimental Techniques

237

(3)

Computational Techniques

240

(1)

Summary

241

(4)

Suggestions for Further Reading

241

(1)

Problems

242

(3)

Part 3 Engineering Principles for Bioprocesses

245

(140)

Operating Considerations for Bioreactors for Suspension and Immobilized Cultures

245

(40)

Introduction

245

(1)

Choosing the Cultivation Method

246

(2)

Modifying Batch and Continuous Reactors

248

(15)

Chemostat with Recycle

248

(2)

Multistage Chemostat Systems

250

(6)

Fed-batch Operation

256

(6)

Perfusion Systems

262

(1)

Immobolized Cell Systems

263

(13)

Introduction

263

(1)

Active Immobilization of Cells

263

(3)

Passive Immobilization: Biological Films

266

(2)

Diffusional Limitations in Immobilized Cell Systems

268

(5)

Bioreactor Considerations in Immobilized Cell Systems

273

(3)

Solid-state Fermentations

276

(2)

Summary

278

(7)

Suggestions for Further Reading

280

(1)

Problems

280

(5)

Selection, Scale-Up Operation, and Control of Bioreactors

285

(44)

Introduction

285

(1)

Scale-up and Its Difficulties

286

(21)

Introduction

286

(1)

Overview of Reactor Types

286

(6)

Some Considerations on Aeration, Agitation, and Heat Transfer

292

(5)

Scale-up

297

(4)

Scale-down

301

(6)

Bioreactor Instrumentation and Control

307

(7)

Introduction

307

(1)

Instrumentation for Measurements of Active Fermentation

307

(4)

Using the Information Obtained

311

(3)

Sterilization of Process Fluids

314

(9)

Introduction and the Kinetics of Death

314

(1)

Sterilization of Liquids

315

(5)

Sterilization of Gases

320

(3)

Summary

323

(6)

Suggestions for Further Reading

324

(1)

Problems

325

(4)

Recovery and Purification of Products

329

(56)

Strategies to Recover and Purify Products

329

(2)

Separation of Insoluble Products

331

(10)

Filtration

332

(4)

Centrifugation

336

(4)

Coagulation and Flocculation

340

(1)

Cell Disruption

341

(2)

Mechanical Methods

341

(1)

Nonmechanical Methods

342

(1)

Separation of Soluble Products

343

(35)

Liquid-Liquid Extraction

343

(5)

Aqueous Two-phase Extraction

348

(1)

Precipitation

349

(2)

Adsorption

351

(4)

Dialysis

355

(1)

Reverse Osmosis

356

(2)

Ultrafiltration and Microfiltration

358

(2)

Cross flow Ultrafiltration and Microfiltration

360

(5)

Chromatography

365

(10)

Electrophoresis

375

(1)

Electrodialysis

376

(2)

Finishing Steps for Purification

378

(1)

Crystallization

378

(1)

Drying

378

(1)

Integration of Reaction and Separation

379

(1)

Summary

380

(5)

Suggestions for Further Reading

381

(1)

Problems

382

(3)

Part 4 Applications to Nonconventional Biological Systems

385

(130)

Bioprocess Considerations in Using Animal Cell Cultures

385

(20)

Structure and Biochemistry of Animal Cells

385

(2)

Methods Used for the Cultivation of Animal Cells

387

(9)

Bioreactor Considerations for Animal Cell Culture

396

(4)

Products of Animal Cell Cultures

400

(2)

Monoclonal Antibodies

400

(1)

Immunobiological Regulators

401

(1)

Virus Vaccines

401

(1)

Hormones

401

(1)

Enzymes

401

(1)

Insecticides

402

(1)

Whole Cells and Tissue Culture

402

(1)

Summary

402

(3)

Suggestions for Further Reading

403

(1)

Problems

403

(2)

Bioprocess Considerations in Using Plant Cell Cultures

405

(16)

Why Plant Cell Cultures?

405

(2)

Plant Cells in Culture Compared to Microbes

407

(4)

Bioreactor Considerations

411

(6)

Bioreactors for Suspension Cultures

411

(2)

Reactors Using Cell Immobilization

413

(1)

Bioreactors for Organized Tissues

414

(3)

Economics of Plant Cell Tissue Cultures

417

(1)

Summary

417

(4)

Suggestions for Further Reading

418

(1)

Problems

418

(3)

Utilizing Genetically Engineered Organisms

421

(42)

Introduction

421

(1)

How the Product Influences Process Decisions

421

(3)

Guidelines for Choosing Host-Vector Systems

424

(9)

Overview

424

(1)

Escherichia coli

424

(2)

Gram-positive Bacteria

426

(1)

Lower Eucaryotic Cells

427

(1)

Mammalian Cells

428

(1)

Insect Cell-Baculovirus System

429

(1)

Transgenic Animals

430

(2)

Transgenic Plants and Plant Cell Culture

432

(1)

Comparison of Strategies

432

(1)

Process Constraints: Genetic Instability

433

(5)

Segregational Loss

434

(2)

Plasmid Structural Instability

436

(1)

Host Cell Mutations

436

(1)

Growth-rate-dominated Instability

437

(1)

Considerations in Plasmid Design to Avoid Process Problems

438

(3)

Predicting Host-Vector Interactions and Genetic Instability

441

(10)

Regulatory Constraints on Genetic Processes

451

(1)

Metabolic Engineering

452

(4)

Protein Engineering

456

(1)

Summary

457

(6)

Suggestions for Further Reading

458

(2)

Problems

460

(3)

Medical Applications of Bioprocess Engineering

463

(12)

Introduction

463

(1)

Tissue Engineering

463

(4)

What Is Tissue Engineering?

463

(2)

Commercial Tissue Culture Processes

465

(2)

Gene Therapy Using Viral Vectors

467

(4)

Models of Viral Infection

467

(3)

Mass Production of Retrovirus

470

(1)

Bioreactors

471

(2)

Stem Cells and Hematopoiesis

471

(1)

Extracorporeal Artificial Liver

472

(1)

Summary

473

(2)

Suggestions for Further Reading

473

(1)

Problems

473

(2)

Mixed Cultures

475

(38)

Introduction

475

(1)

Major Classes of Interactions in Mixed Cultures

476

(3)

Simple Models Describing Mixed-culture Interactions

479

(6)

Mixed Cultures in Nature

485

(2)

Industrial Utilization of Mixed Cultures

487

(1)

Biological Waste Treatment: An Example of the Industrial Utilization of Mixed Cultures

488

(20)

Overview

488

(3)

Biological Waste Treatment Processes

491

(10)

Advanced Waste-water Treatment Systems

501

(5)

Conversion of Waste Water to Useful Products

506

(2)

Summary

508

(5)

Suggestions for Further Reading

508

(1)

Problems

509

(4)

Epilogue

513

(2)

APPENDIX TRADITIONAL INDUSTRIAL BIOPROCESSES

515

(20)

A.1. Anaerobic Bioprocesses

515

(9)

A.1.1. Ethanol Production

515

(4)

A.1.2. Lactic Acid Production

519

(2)

A.1.3. Acetone-Butanol Production

521

(3)

A.2. Aerobic Processes

524

(11)

A.2.1. Citric Acid Production

524

(2)

A.2.2. Production of Bakers' Yeast

526

(1)

A.2.3. Production of Penicillins

527

(3)

A.2.4. Production of High-Fructose Corn Syrup (HFCS)

530

(3)

Suggestions for Further Reading

533

(2)

Index

535

What is included with this book?

The New copy of this book will include any supplemental materials advertised. Please check the title of the book to determine if it should include any access cards, study guides, lab manuals, CDs, etc.

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Preface to the Second Edition In the decade since the first edition of Bioprocess Engineering: Basic Concepts, biotechnology has undergone several revolutions. Currently, the ability to sequence the genome of whole organisms presents opportunities that could be hardly envisioned ten years ago. Many other technological advances have occurred that provide bioprocess engineers with new tools to serve society better. However, the principles of bioprocess engineering stated in the first edition remain sound. The goals of this revision are threefold. We want to capture for students the excitement created by these advances in biology and biotechnology. We want to inform students about these tools. Most importantly, we want to demonstrate how the principles of bioprocess engineering can be applied in concert with these advances. This edition contains a new section in the first chapter alerting students to the regulatory issues that constrain bioprocess design and modification. We believe students need to be aware of these industrially critical issues. Part 2, "An Overview of Biological Basics," has been updated throughout and expanded. Greater emphasis is given now to posttranslational processing of proteins, as this is a key issue in choice of bioprocessing strategies to make therapeutic proteins. Basic processes in animal cells are more completely described, since animal cell culture is now an established commercial bioprocess technology. Chapter 5 is made more complete by introduction of a section on noncarbohydrate metabolism. Key concepts in functional genomics have been added to prepare students to understand the impact of these emerging ideas and technologies on bioprocesses. In Part 3, "Engineering Principles for Bioprocesses," greater attention is given to issues associated with animal cell bioreactors. The discussion of chromatographic processes is expanded. In Part 4, "Applications to Nonconventional Biological Systems," the material has been rearranged and updated and a new chapter added. These changes are evident in the chapters on animal and plant cell culture. Particularly important is the expanded discussion on choice of host-vector systems for production of proteins from recombinant DNA technology. Coverage of two areas of increasing importance to bioprocess engineers, metabolic and protein engineering, has been expanded. A new chapter on biomedical applications illustrates how approaches to bioprocess engineering are relevant to problems typically considered to be biomedical engineering. The chapter on mixed cultures has been extended to cover advanced waste-water treatment processes. An appendix providing descriptive overviews of some traditional bioprocesses is now included. The suggestions for further reading at the end of each chapter have been updated. We are unable in this book to provide in-depth treatment of many vital topics. These readings give students an easy way to begin to learn more about these topics. Teaching a subject as broad as bioprocess engineering in the typical one-semester, three-credit class has never been easy. Although some material in the first edition has been removed or condensed, the second edition is longer than the first. For students with no formal background in biology, coverage of all of the material in this book would require a four-credit class. In a three-credit class we suggest that the instructor cover Chapters 1 to 11 (with 7 being optional) and then decide on subsequent chapters based on course goals. A course oriented toward biopharmaceuticals will want to include careful coverage of Chapters 12 and 14 and some coverage of 13 and 15. A course oriented toward utilization of bioresources would emphasize Chapter 16 and the Appendix and selected coverage of topics in Chapters 13 and 14. Many students now enter a bioprocess engineering course with formal, college-level instruction in biology and biochemistry. For such students Chapters 2, 4, 5, 7, and 8 can be given as reading assignments to refresh their memories and to insure a uniform, minimal level of biological knowledge. Lecture time can be reserved for material in other chapters or for supplementary material. For these five chapters study questions are provided for self-testing. Under these circumstances the instructor should be able to cover the rest of the material in the book.

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Bioprocess Engineering Basic Concepts

Bioprocess Engineering Basic Concepts

0130819085

Summary

Author Biography

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