9780130819086

Bioprocess Engineering Basic Concepts

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  • ISBN13:

    9780130819086

  • ISBN10:

    0130819085

  • Edition: 2nd
  • Format: Hardcover
  • Copyright: 10/31/2001
  • Publisher: Prentice Hall
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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.

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