Bioprocess Engineering Basic Concepts

by Shuler, Michael L.; Kargi, Fikret

• ISBN13: 9780130819086
• ISBN10: 0130819085
• Edition: 2nd
• Format: Hardcover
• Copyright: 2001-10-31
• Publisher: Prentice Hall

Summary

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.

Author Biography

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

Table of Contents

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

Excerpts

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.