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
2 AN OVERVIEW OF BIOLOGICAL BASICS
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,
Suggestions for Further Reading
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,
3.2.6. 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
Suggestions for Further Reading
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,
4.5.1. 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,
4.8. Appendix: Example Regulation of Complex Pathways
Suggestions for Further Reading
5.2. Glucose Metabolism: Glycolysis and the TCA Cycle
5.4. Control Sites in Aerobic Glucose Metabolism
5.5. Metabolism of Nitrogenous Compounds
5.7. Metabolism of Hydrocarbons
5.8. Biodegradation of Xenobiotics
5.10. Overview of Anaerobic Metabolism
5.11. Overview of Autotrophic Metabolism
Suggestions for Further Reading
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,
6.3. Cell Growth in Continuous Culture
6.3.1. Specific Devices for Continuous Culture,
6.3.3. The Chemostat as a Tool,
6.3.4. Deviations from Ideality,
Suggestions for Further Reading
7 STOICHIOMETRY OF MICROBIAL GROWTH AND PRODUCT FORMATION
7.1. Coefficients for Atp Consumption and Oxygen
7.2. Stoichiometric Calculations
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
Suggestions for Further Reading
8 HOW CELLULAR INFORMATION IS ALTERED
8.1. Evolving Desirable Biochemical Activities Through Mutation and Selection
8.1.2. Selecting for Desirable Mutants,
8.2. Natural Mechanisms for Gene Transfer and Rearrangement
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,
8.4.1. Experimental Techniques,
8.4.2. Computational Techniques,
Suggestions for Further Reading
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,
9.3.1. 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
Suggestions for Further Reading
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,
Suggestions for Further Reading
11 RECOVERY AND PURIFICATION OF PRODUCTS
11.1. Strategies to Recover and Purify Products
11.2. Separation of Insoluble Products
11.2.3. Coagulation and Flocculation,
11.3.2. Nonmechanical Methods,
11.4. Separation of Soluble Products
11.4.1. Liquid–Liquid Extraction,
11.4.2. Aqueous Two-Phase Extraction,
11.4.6. Ultrafiltration and Microfiltration,
11.4.7. Cross-Flow Ultrafiltration and Microfiltration,
11.5. Finishing Steps for Purification
11.6. Integration of Reaction and Separation
Suggestions for Further Reading
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,
12.2.3. 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,
12.5. Products of Animal Cell Cultures
Suggestions for Further Reading
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
Suggestions for Further Reading
14 UTILIZING GENETICALLY ENGINEERED ORGANISMS
14.1. How the Product Influences Process Decisions
14.2. Guidelines for Choosing Host–Vector Systems
14.2.2. Gram-Positive Bacteria,
14.2.3. Lower Eucaryotic Cells,
14.2.5. Insect Cell–Baculovirus System,
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
14.3.2. Plasmid Structural Instability,
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
14.8. Synthetic and Systems Biology
Suggestions for Further Reading
15 MEDICAL APPLICATIONS OF BIOPROCESS 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,
15.3.1. Stem Cells and Hematopoiesis,
15.3.2. Extracorporeal Artificial Liver,
15.3.3. Body-on-a-Chip Systems,
Suggestions for Further Reading
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,
Suggestions for Further Reading
APPENDIX TRADITIONAL INDUSTRIAL BIOPROCESSES
A.1.2. Lactic Acid Production,
A.1.3. Acetone–Butanol Production,
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,
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