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by Matthew DeLisa, Fikret Kargi, Michael L. Shuler
Bioprocess Engineering: Basic Concepts, 3rd Edition
About This E-Book
Title Page
Copyright Page
Dedication Page
Contents
Preface
Acknowledgments
About the Authors
Part 1: The Basics of Biology: An Engineer’s Perspective
1. What Is a Bioprocess Engineer?
1.1. Biotechnology and Bioprocess Engineering
1.2. Differing Approaches to Research for Biologists and Engineers
1.3. The Story of Penicillin: How Biologists and Engineers work Together
1.4. Bioprocesses: Regulatory Constraints
Suggestions for Further Reading
Questions
2. An Overview of Biological Basics
2.1. Microbial Diversity
2.1.1. Naming Cells
2.1.2. Viruses
2.1.3. Procaryotes
2.1.4. Eucaryotes
2.2. Cell Construction
2.2.1. Amino Acids and Proteins
2.2.2. Carbohydrates: Mono-and Polysaccharides
2.2.3. Lipids, Fats, and Steroids
2.2.4. Nucleic Acids, RNA, and DNA
2.3. Cell Nutrients
2.3.1. Macronutrients
2.3.2. Micronutrients
2.3.3. Growth Media
2.4. Summary
Suggestions for Further Reading
Questions
3. Enzymes
3.1. How Enzymes Work
3.2. Enzyme Kinetics
3.2.1. Mechanistic Models for Simple Enzyme Kinetics
3.2.2. Determining Rate Parameters for Michaelis–Menten Kinetics
3.2.3. Models for More Complex Enzyme Kinetics
3.2.4. Effects of pH and Temperature
3.2.5. Insoluble Substrates
3.2.6. Multiphase Enzymatic Reactions
3.3. Immobilized Enzyme Systems
3.3.1. Methods of Immobilization
3.3.2. Diffusional Limitations in Immobilized Enzyme Systems
3.3.3. Electrostatic and Steric Effects in Immobilized Enzyme Systems
3.4. Large-Scale Production of Enzymes
3.5. Medical and Industrial Utilization of Enzymes
3.6. Summary
Suggestions for Further Reading
Problems
4. How Cells Work
4.1. The Central Dogma
4.2. DNA Replication: Preserving and Propagating the Message
4.3. Transcription: Sending the Message
4.4. Translation: Going from Message to Product
4.4.1. Genetic Code: Universal Message
4.4.2. Translation: How the Machinery Works
4.4.3. Posttranslational Processing: Making the Product Useful
4.5. Metabolic Regulation
4.5.1. Genetic-Level Control: Which Proteins Are Synthesized?
4.5.2. Metabolic Pathway Control
4.6. How the Cell Senses its Extracellular Environment
4.6.1. Transporting Small Molecules across Cellular Membranes
4.6.2. Role of Cell Receptors in Metabolism and Cellular Differentiation
4.7. Summary
4.8. Appendix: Example Regulation of Complex Pathways†
Suggestions for Further Reading
Problems
5. Major Metabolic Pathways
5.1. Bioenergetics
5.2. Glucose Metabolism: Glycolysis and the TCA Cycle
5.3. Respiration
5.4. Control Sites in Aerobic Glucose Metabolism
5.5. Metabolism of Nitrogenous Compounds
5.6. Nitrogen Fixation
5.7. Metabolism of Hydrocarbons
5.8. Biodegradation of Xenobiotics
5.9. Overview of Biosynthesis
5.10. Overview of Anaerobic Metabolism
5.11. Overview of Autotrophic Metabolism
5.12. Summary
Suggestions for Further Reading
Questions
6. How Cells Grow
6.1. Batch Growth
6.1.1. Quantifying Cell Concentration
6.1.2. Growth Patterns and Kinetics in Batch Culture
6.1.3. How Environmental Conditions Affect Growth Kinetics
6.1.4. Heat Generation by Microbial Growth
6.2. Quantifying Growth Kinetics
6.2.1. Unstructured Nonsegregated Models
6.2.2. Models for Transient Behavior
6.2.3. Cybernetic Models
6.3. Cell Growth In Continuous Culture
6.3.1. Specific Devices for Continuous Culture
6.3.2. The Ideal Chemostat
6.3.3. The Chemostat as a Tool
6.3.4. Deviations from Ideality
6.4. Summary
Suggestions for Further Reading
Problems
7. Stoichiometry of Microbial Growth and Product Formation
7.1. Coefficients for ATP Consumption and Oxygen
7.2. Stoichiometric Calculations
7.2.1. Elemental Balances
7.2.2. Degree of Reduction
7.3. Theoretical Predictions of Yield Coefficients
7.4. Estimation of Elemental cell Composition
7.5. Stoichiometry by Oxidation-Reduction Half-Reactions
7.6. Thermodynamics of Biological Reactions
7.7. Summary
Suggestions for Further Reading
Problems
8. How Cellular Information Is Altered
8.1. Evolving Desirable Biochemical Activities Through Mutation and Selection
8.1.1. How Mutations Occur
8.1.2. Selecting for Desirable Mutants
8.2. Natural Mechanisms for Gene Transfer and Rearrangement
8.2.1. Genetic Recombination
8.2.2. Transformation
8.2.3. Transduction
8.2.4. Episomes and Conjugation
8.2.5. Transposons: Internal Gene Transfer
8.3. Genetically Engineering Cells
8.3.1. Basic Elements of Genetic Engineering
8.3.2. Genetic Engineering of Higher Organisms
8.3.3. Genome Engineering
8.4. Genomics
8.4.1. Experimental Techniques
8.4.2. Computational Techniques
8.5. Summary
Suggestions For Further Reading
Problems
Part 2: Engineering Principles for Bioprocesses
9. Operating Considerations for Bioreactors for Suspension and Immobilized Cultures
9.1. Choosing the Cultivation Method
9.2. Modifying Batch and Continuous Reactors
9.2.1. Chemostat with Recycle
9.2.2. Multistage Chemostat Systems
9.2.3. Fed-Batch Operation
9.2.4. Perfusion Systems
9.2.5. Membrane Bioreactors
9.3. Immobilized cell Systems
9.3.1. Active Immobilization of Cells
9.3.2. Passive Immobilization: Biological Films
9.3.3. Diffusional Limitations in Immobilized Cell Systems
9.3.4. Bioreactor Considerations in Immobilized Cell Systems
9.4. Hybrid Bioreactors: Attached and Suspended Cells
9.5. Solid-State Fermentations
9.6. Summary
Suggestions for Further Reading
Problems
10. Selection, Scale-Up, Operation, and Control of Bioreactors
10.1. Scale-Up and its Difficulties
10.1.1. Overview of Traditional Reactor Types
10.1.2. Reactors with Internal Mechanical Agitation
10.1.3. Bubble Column and Loop Reactor
10.1.4. Single-Use Bioreactors
10.1.5. Considerations in Aeration, Agitation, and Heat Transfer
10.1.6. Approaches to Scale-Up
10.1.7. Scale-Down and Microbioreactors
10.2. Bioreactor Instrumentation and Control
10.2.1. Instrumentation for Measurements of Active Fermentation
10.2.2. Using the Information Obtained
10.3. Sterilization of Process Fluids
10.3.1. The Kinetics of Death
10.3.2. Sterilization of Liquids
10.3.3. Sterilization of Gases
10.4. Summary
Suggestions for Further Reading
Problems
11. Recovery and Purification of Products
11.1. Strategies to Recover and Purify Products
11.2. Separation of Insoluble Products
11.2.1. Filtration
11.2.2. Centrifugation
11.2.3. Coagulation and Flocculation
11.3. Cell Disruption
11.3.1. Mechanical Methods
11.3.2. Nonmechanical Methods
11.4. Separation of Soluble Products
11.4.1. Liquid–Liquid Extraction
11.4.2. Aqueous Two-Phase Extraction
11.4.3. Precipitation
11.4.4. Dialysis
11.4.5. Reverse Osmosis
11.4.6. Ultrafiltration and Microfiltration
11.4.7. Cross-Flow Ultrafiltration and Microfiltration
11.4.8. Adsorption
11.4.9. Chromatography
11.4.10. Electrophoresis
11.4.11. Electrodialysis
11.5. Finishing Steps for Purification
11.5.1. Crystallization
11.5.2. Drying
11.6. Integration of Reaction and Separation
11.7. Summary
Suggestions for Further Reading
Problems
12. Bioprocess Considerations in Using Animal Cell Cultures
12.1. Structure and Biochemistry of Animal Cells
12.2. Methods used for the Cultivation of Animal Cells
12.2.1. Basic Techniques for Animal Cell Culture
12.2.2. Growth Media
12.2.3. Growth Dynamics for Animal Cells
12.3. Bioreactor Considerations for Animal cell Culture
12.4. Bioreactor Systems for Animal Cell Culture
12.4.1. Nonstirred Reactor Systems
12.4.2. Systems for Entrapped Cells in Stirred Reactors
12.4.3. Suspended Cultures
12.5. Products of Animal Cell Cultures
12.6. Summary
Suggestions for Further Reading
Problems
13. Bioprocess Considerations in Using Plant Cell Cultures
13.1. Why Plant Cell Cultures?
13.2. Plant cells in Culture Compared to Microbes
13.3. Bioreactor Considerations
13.3.1. Bioreactors for Suspension Cultures
13.3.2. Reactors Using Cell Immobilization
13.3.3. Bioreactors for Organized Tissues
13.4. Economics of Plant Cell Tissue Cultures
13.5. Summary
Suggestions for Further Reading
Problems
14. Utilizing Genetically Engineered Organisms
14.1. How the Product Influences Process Decisions
14.2. Guidelines for Choosing Host–Vector Systems
14.2.1. Escherichia Coli
14.2.2. Gram-Positive Bacteria
14.2.3. Lower Eucaryotic Cells
14.2.4. Mammalian Cells
14.2.5. Insect Cell–Baculovirus System
14.2.6. Transgenic Animals
14.2.7. Transgenic Plants and Plant Cell Culture
14.2.8. Cell-Free Protein Synthesis
14.2.9. Comparison of Strategies
14.3. Process Constraints: Genetic Instability
14.3.1. Segregational Loss
14.3.2. Plasmid Structural Instability
14.3.3. Host Cell Mutations
14.3.4. Growth-Rate-Dominated Instability
14.4. Avoiding Process Problems in Plasmid Design
14.5. Predicting Host–Vector Interactions and Genetic Instability
14.6. Regulatory Constraints on Genetic Processes
14.7. Metabolic Engineering
14.8. Synthetic and Systems Biology
14.9. Protein Engineering
14.10. Summary
Suggestions for Further Reading
Problems
15. Medical Applications of Bioprocess Engineering
15.1. Tissue Engineering
15.1.1. What Is Tissue Engineering?
15.1.2. Tissue-Engineered Skin Replacements
15.1.3. Chondrocyte Culture for Cartilage Replacement
15.2. Gene Therapy Using Viral Vectors
15.2.1. Models of Viral Infection
15.2.2. Mass Production of Retrovirus
15.3. Bioreactors
15.3.1. Stem Cells and Hematopoiesis
15.3.2. Extracorporeal Artificial Liver
15.3.3. Body-on-a-Chip Systems
15.4. Summary
Suggestions for Further Reading
Problems
16. Bioprocesses Utilizing Mixed Cultures
16.1. Major Classes of Interactions in Mixed Cultures
16.2. Simple Models Describing Mixed-Culture Interactions
16.3. Mixed Cultures in Nature
16.4. Industrial Utilization of Mixed Cultures
16.5. Biological Waste Treatment
16.5.1. Biological Waste-Treatment Processes
16.5.2. Advanced Wastewater Treatment Systems
16.5.3. Conversion of Wastewater to Useful Products
16.6. Summary
Suggestions for Further Reading
Problems
Appendix: Traditional Industrial Bioprocesses
A.1. Anaerobic Bioprocesses
A.1.1. Ethanol Production
A.1.2. Lactic Acid Production
A.1.3. Acetone–Butanol Production
A.2. Aerobic Processes
A.2.1. Citric Acid Production
A.2.2. Production of Baker’s Yeast
A.2.3. Production of Penicillins
A.2.4. Production of High-Fructose Corn Syrup
A.3. Bioprocess Technologies: Biofuel and Bioenergy Production from Biomass
A.3.1. Production of Liquid Fuels
A.3.2. Production of Gaseous Fuels from Biomass
A.3.3. Bioelectricity Generation from Wastes Using Microbial Fuel Cells
Suggestions for Further Reading
Index
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