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Bioprocess Engineering: Basic Concepts, Third Edition

Book Description

The Leading Introduction to Biochemical and Bioprocess Engineering, Updated with Key Advances in Productivity, Innovation, and Safety

Bioprocess Engineering, Third Edition, is an extensive update of the world’s leading introductory textbook on biochemical and bioprocess engineering and reflects key advances in productivity, innovation, and safety.

The authors review relevant fundamentals of biochemistry, microbiology, and molecular biology, including enzymes, cell functions and growth, major metabolic pathways, alteration of cellular information, and other key topics. They then introduce evolving biological tools for manipulating cell biology more effectively and to reduce costs of bioprocesses.

This edition presents major advances in the production of biologicals; highly productive techniques for making heterologous proteins; new commercial applications for both animal and plant cell cultures; key improvements in recombinant DNA microbe engineering; techniques for more consistent authentic post-translational processing of proteins; and other advanced topics. It includes new, improved, or expanded coverage of

  • The role of small RNAs as regulators

  • Transcription, translation, regulation, and differences between prokaryotes and eukaryotes

  • Cell-free processes, metabolic engineering, and protein engineering

  • Biofuels and energy, including coordinated enzyme systems, mixed-inhibition and enzyme-activation kinetics, and two-phase enzymatic reactions

  • Synthetic biology

  • The growing role of genomics and epigenomics Population balances and the Gompetz equation for batch growth and product formation

  • Microreactors for scale-up/scale-down, including rapid scale-up of vaccine production

  • The development of single-use technology in bioprocesses

  • Stem cell technology and utilization

  • Use of microfabrication, nanobiotechnology, and 3D printing techniques

  • Advances in animal and plant cell biotechnology

  • The text makes extensive use of illustrations, examples, and problems, and contains references for further reading as well as a detailed appendix describing traditional bioprocesses.

    Table of Contents

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