Comprehensive Biotechnology

Editor-in-Chief

Volume Editors

Section Editors

General Preface

Nomenclature Guidelines

Permission Acknowledgments

1.01. Introduction

1.02. Amino Acid Metabolism

Glossary

1.02.1. Introduction

1.02.2. General Properties, Classification, and Structure of Amino Acids

1.02.3. Biosynthesis of Amino Acids

1.02.4. Catabolism of Amino Acids

1.02.5. Important Biomolecules Synthesized from Amino Acids

1.03. Enzyme Biocatalysis

Glossary

1.03.1. Introduction to Enzymes

1.03.2. Enzyme Kinetics

1.03.3. Enzyme Engineering

1.03.4. Enzyme Production

1.03.5. Immobilized Enzymes

1.03.6. Enzyme Applications

1.03.7. Conclusions

1.04. Immobilized Biocatalysts

1.04.1. Introduction: Definitions and Scope

1.04.2. Applications of Immobilized Enzymes

1.04.3. Methods of Enzyme Immobilization

1.04.4. Properties of Immobilized Enzymes

1.04.5. Evaluation of Enzyme Immobilization

1.04.6. Heterogeneous Biocatalysis

1.04.7. Future Prospects for Immobilized Biocatalysts

1.05. Lipids, Fatty Acids

Glossary

1.05.1. Introduction

1.05.2. Structure of Fatty Acids

1.05.3. Nomenclature

1.05.4. Form in the Cell

1.05.5. What Do Lipids Do?

1.05.6. Biosynthesis of Fatty Acids and Lipids

1.05.7. Biochemistry of Lipid Accumulation

1.06. DNA Cloning in Plasmid Vectors

Glossary

1.06.1. Introduction

1.06.2. Cloning Vectors: Replication Origins and Partition Regions

1.06.3. Cloning Vectors: Selection Markers

1.06.4. Preparing DNA Fragments for Ligation

1.06.5. Ligation Systems

1.06.6. Methods of Bacterial and Yeast Transformation

1.06.7. Exploitation of Bacteriophage Packaging for DNA Cloning in Plasmid Vectors

1.06.8. Screening of Plasmid Clones in Bacteria for the Desired Recombinant Plasmids

1.06.9. Vector-Implemented Systems for the Direct Selection of Recombinant Plasmids

1.06.10. Direct Selection of Recombinant Plasmids Involving Restriction Enzyme Digestion of the Ligation Mixture

1.06.11. Particular Features of Oligonucleotides’ Cloning

1.06.12. Particular Features of Cloning of PCR Amplicons

1.06.13. Introduction of Deletions into Plasmids

1.06.14. Instability of Recombinant Plasmids

1.06.15. DNA Cloning Using Site-Specific Recombination

1.06.16. DNA Cloning Using Homologous (General) Recombination

1.06.17. Employment of Transposons for In Vivo Cloning and Manipulation of Large Plasmids

1.06.18. Conclusion

1.07. Structure and Biosynthesis of Glycoprotein Carbohydrates

Glossary

Acknowledgments

1.07.1. Introduction

1.07.2. Monosaccharide Structure

1.07.3. Oligosaccharide Structure

1.07.4. Biosynthesis of Glycoproteins

1.07.5. Glycosylation of Therapeutic Glycoproteins

1.08. Nucleotide Metabolism

Glossary

1.08.1. Introduction

1.08.2. Synthesis of Phosphoribosyl Diphosphate (PRPP)

1.08.3. Purine Biosynthesis

1.08.4. Pyrimidine Biosynthesis

1.08.5. Nucleoside Triphosphate Formation

1.08.6. Deoxyribonucleotide Biosynthesis

1.08.7. Nucleotide Salvage

1.08.8. Purine and Pyrimidine Catabolism

1.08.9. Regulation of Gene Expression in Bacterial Nucleotide Synthesis

1.08.10. Exploitation of the Knowledge of Nucleotide Metabolism in Biotechnology

1.09. Organic Acids

Glossary

1.09.1. Introduction

1.09.2. Citric Acid

1.09.3. Gluconic Acid

1.09.4. Lactic Acid

1.09.5. Itaconic Acid

1.09.6. Other Acids

1.10. Peptides and Glycopeptides

Glossary

1.10.1. Introduction

1.10.2. Peptide Hormones

1.10.3. Neuropeptides

1.10.4. Antibacterial Peptides

1.10.5. Glycosylation Is a Common and Important Post-Translational Modification of Peptides

1.10.6. Common Glycosidic Linkages

1.10.7. Peptide Synthesis

1.10.8. Glycopeptide Synthesis

1.10.9. Peptides and Glycopeptides as Models of Proteins and Glycoproteins

1.10.10. Application of Synthetic Peptides and Glycopeptides for the Treatment of Disease

1.10.11. Summary

1.11. Protein Structural Analysis

Glossary

1.11.1. Introduction

1.11.2. Protein X-ray Crystallography

1.11.3. NMR Spectroscopy

1.11.4. Structure Analysis Using Intrinsic Protein Fluorescence

1.11.5. Conclusions

1.12. Secondary Metabolites

Glossary

1.12.1. Introduction

1.12.2. Antibiotics

1.12.3. Other Applications of Secondary Metabolites

1.13. Cell Line Isolation and Design

Glossary

1.13.1. Introduction

1.13.2. Clone Selection and Isolation

1.13.3. Automating Clone Screening

1.13.4. Designer Cell Lines for Bioproduction

1.13.5. Future Perspectives and Conclusions

1.14. Cell Preservation Technology

Glossary

1.14.1. Introduction

1.14.2. Hypothermic Storage

1.14.3. Hypothermic Continuum

1.14.4. Cryopreservation

1.14.5. Modes of Cell Death

1.14.6. Cell Death Continuum

1.14.7. Preservation-Induced Cell Death

1.14.8. Targeted Control of Molecular-Based Death

1.14.9. Concluding Thoughts

1.15. Cytoskeleton and Cell Motility

Glossary

1.15.1. Introduction

1.15.2. Myosins

1.15.3. Cell Migration

1.15.4. Involvement of Unconventional Myosins in Cell Migration and Trafficking

1.16. Design of Culture Media

Glossary

1.16.1. Introduction

1.16.2. Universal Requirements

1.16.3. Specific Requirements

1.16.4. Methods for Media Design

1.16.5. Manufacturing of the Designed Medium

1.16.6. Regulatory Considerations

1.16.7. Quality Control Testing

1.16.8. Security of Supply

1.16.9. Summary

1.17. Protein Folding in the Endoplasmic Reticulum

Glossary

Acknowledgments

1.17.1. Introduction: Protein Folding

1.17.2. The Endoplasmic Reticulum as a Folding, Assembly, and Trafficking Vehicle

1.17.3. Key Chaperones Assisting Folding in the ER

1.17.4. Calnexin and Calreticulin: Glycosylation and Glycoprotein Quality Control

1.17.5. PDI: Redox-Dependent Folding and Disulfide Bond Formation

1.17.6. Glycosylation Glycosylphosphatidylinositol Anchor Addition

1.17.7. Quality Control and ER-Associated Degradation

1.17.8. From the ER to the Golgi

1.17.9. Protein-Folding Status Is Communicated to the Cytosol and Nucleus via the UPR

1.17.10. Transduction of the ER Stress/UPR Signal by Three Proximal Sensors

1.17.11. UPR and Apoptosis

1.17.12. Protein Misfolding, ER Dyshomeostasis, and Human Diseases

1.17.13. Concluding Remarks

1.18. Extremophiles

Glossary

1.18.1. Introduction

1.18.2. The Diversity

1.18.3. High Temperature

1.18.4. Low Temperatures

1.18.5. Low pH

1.18.6. Alkaline pH

1.18.7. Conclusion

1.19. Metabolic Design and Control for Production in Prokaryotes

Glossary

1.19.1. Introduction

1.19.2. Classical Mutagenesis

1.19.3. Protoplast Fusion and Genome Shuffling

1.19.4. Recombinant DNA Technology and First-Generation Metabolic Engineering

1.19.5. Quantitative Approaches for Metabolic Design

1.19.6. Targeted Combinatorial Engineering

1.19.7. Synthetic Biology: Parts, Devices, and Circuits

1.20. Microbial Growth Dynamics

Glossary

1.20.1. Introduction

1.20.2. Kinetic Models of Microbial Growth

1.20.3. Growth Dynamic Variation as Dependent on Internal and External Factors

1.21. Modes of Culture/Animal Cells

Glossary

1.21.1. Introduction

1.21.2. Batch Culture: The Basis for All Cell Culture Systems

1.21.3. Fed-Batch Culture: Dominator of Industrial-Scale Processes

1.21.4. Perfusion Culture: The Most Sophisticated Process

1.21.5. Concluding Remarks on the Selection of Culture Mode

1.22. Modes of Culture/Microbial

Glossary

1.22.1. Introduction

1.22.2. Modes of Microbial Culture

1.22.3. When the Microbe Itself Is the End Product

1.22.4. Algal Biodiesel: A Case Study in Contemporary Challenges for Microbial Culture

1.22.5. Concluding Remarks

1.23. Photosynthesis and Photoautotrophy

Glossary

1.23.1. Introduction

1.23.2. Energy Absorption, Trapping, Conversion, and Storage

1.23.3. Photostasis and Cellular Energy Imbalance

1.23.4. Photoacclimation Tailors the Photosynthetic Apparatus

1.23.5. Acclimation to Low Temperature Mimics Photoacclimation

1.23.6. Conclusions

1.24. Protein Expression in Insect Cells

Glossary

1.24.1. Historical Background and General Introduction

1.24.2. Baculovirus Biology

1.24.3. The Origins of the BEVS

1.24.4. Baculovirus Recombination in Bacteria: the Development of Bacmids

1.24.5. Hybrid Systems: Bacmid Recombination in Insect Cells

1.24.6. Baculovirus Recombination In Vitro

1.24.7. Nonlytic Systems for Protein Expression in Insect Cells

1.24.8. Insect Cells

1.24.9. Insect Cell Culture

1.24.10. Removing Bottlenecks in the BEVS

1.24.11. Concluding Summary

1.25. Stem Cells

Glossary

1.25.1. Introduction

1.25.2. Human Embryonic Stem Cells

1.25.3. Human-Induced Pluripotent Stem Cells

1.25.4. Neural Stem Cells

1.25.5. Mesenchymal Stem Cells

1.25.6. Hematopoietic Stem Cells

1.26. Structural Organization of Cells – The Cytoskeleton

Glossary

Acknowledgments

1.26.1. Introduction

1.26.2. Molecular and Supramolecular Components

1.26.3. Cytoskeletal Arrays and Their Structural Functions

1.26.4. Motility

1.26.5. Diseases and the Cytoskeleton

1.27. Viruses Produced from Cells

Glossary

1.27.1. Introduction

1.27.2. Cell Culture

1.27.3. Types of Growth Flasks

1.27.4. Parameters of Virus Growth

1.27.5. Virus Purification

1.27.6. Future Perspectives

1.28. Cell Transfection

Glossary

1.28.1. Introduction

1.28.2. Methods of Transfection

1.28.3. Advances in Large-Scale Transfection Technology

1.29. mRNA Translation and Recombinant Gene Expression from Mammalian Cell Expression Systems

1.29.1. Introduction

1.29.2. Translational Machinery

1.29.3. Manipulation of mRNA for Optimal Translational Efficiency

1.29.4. Importance of 5′-UTR and Secondary Structure in 5′-UTR Region of mRNA

1.29.5. mRNA Translation Shutdown

1.29.6. MicroRNAs and Translational Control

1.29.7. In Vitro mRNA Translation Systems

1.29.8. Conclusions and Future Prospects

1.30. Posttranslation Modifications Other Than Glycosylation

Glossary

Acknowledgments

1.30.1. Introduction

1.30.2. Cell Influences on Protein Expression

1.30.3. Induction of Protein Expression

1.30.4. Improving the Protein Folding and Secretory Pathways

1.30.5. Role of Chaperones

1.30.6. Multiple Gene Activators

1.30.7. Cell Clearance of Misfolded Proteins

1.30.8. Protein Aggregation

1.30.9. Analytical Techniques for Protein Aggregate Detection

1.30.10. Asparagine Deamidation

1.30.11. Methionine Oxidation

1.30.12. Surface-Plasmon Resonance

1.30.13. Conclusions

1.31. Engineering Protein Folding and Secretion in Eukaryotic Cell Factories

Glossary

1.31.1. Introduction

1.31.2. Direct Engineering of Recombinant Protein Folding and Assembly

1.31.3. Engineering the Regulation of Protein Folding and Assembly: The Unfolded Protein Response

1.31.4. Glycosylation Engineering for Improved Protein Processing

1.31.5. Engineering of the Secretory Apparatus

1.31.6. Mathematical Modeling of Recombinant Protein Synthesis and Secretion

1.32. Glycomics

Glossary

1.32.1. Introduction

1.32.2. Methods for the Structural Analysis of Glycans

1.32.3. Glycomics in Bioproduction

1.32.4. The Changing Landscape of Regulatory Agencies toward Glycosylation of Biopharmaceuticals

1.32.5. Summary

1.33. Metabolomics – The Combination of Analytical Biochemistry, Biology, and Informatics

Glossary

Acknowledgments

1.33.1. Introduction

1.33.2. Technologies Used to Measure Metabolites

1.33.3. Metabolomics Approaches

1.33.4. Bioinformatics: What Can It Do

1.33.5. What Does the Informatician Need to Analyze the High-Density Data?

1.33.6. Data Preprocessing: From Raw to Sense

1.33.7. Requirements and Problems of Statistical and Multivariant Analysis of Metabolomics Data

1.33.8. Conclusions

1.34. Theory and Applications of Proteomics

Glossary

1.34.1. Introduction

1.34.2. Proteomics Technologies

1.34.3. Separation Technologies

1.34.4. Quantitative Proteomics

1.34.5. Data Processing

1.34.6. Applications in Biotechnology

1.35. Systems Metabolic Engineering for the Production of Non-innate Chemical Compounds

Glossary

1.35.1. Introduction and Scope

1.35.2. Systems Metabolic Engineering

1.35.3. Summary

1.36. Apoptosis

Glossary

1.36.1. Introduction

1.36.2. Apoptosis Regulators and Executioners

1.36.3. Apoptotic Pathways

1.36.4. Apoptosis and Autophagy

1.36.5. Inhibition of Apoptosis

1.36.6. Apoptosis affects Metabolic Pathways

1.36.7. Conclusion

1.37. Design Principles of Self-assembling Peptides and Their Potential Applications

Glossary

1.37.1. Introduction

1.37.2. Design Principles of Self-Assembling Peptides

1.37.3. Applications of Self-Assembling Peptides

1.38. Rational Design of Strategies Based on Metabolic Control Analysis

Glossary

Acknowledgments

1.38.1. Introduction

1.38.2. Fundamentals of Metabolic Control Analysis

1.38.3. Modulation of Clinically and Biotechnologically Relevant Metabolism

1.38.4. Concluding Remarks

1.39. Unfolded Protein Response

Glossary

Acknowledgments

1.39.1. Introduction

1.39.2. Molecular Mechanism of the UPR

1.39.3. Stress Responses in Other Organelles

1.39.4. Concluding Remarks

1.40. Cell Migration

Glossary

Acknowledgments

1.40.1. Introduction

1.40.2. Biological Mechanisms for Cell Migration

1.40.3. Cell Migration in Selected Physiological Systems

1.40.4. Approaches for Measuring Cell Migration

1.40.5. Summary and Outlook

1.41. Biofilms

Glossary

1.41.1. Introduction

1.41.2. Model Systems for Growing and Analyzing Biofilms

1.41.3. Heterogeneity in Biofilms

1.41.4. Stages of Biofilm Development

1.41.5. Regulation of Biofilm Development

1.41.6. Biofilm Infections

1.41.7. Pathogenicity and Antibiotic Resistance of Biofilms

1.41.8. Antibiotics Act as Signals that Stimulate Biofilm Formation

1.41.9. Concluding Remarks

1.42. Flow Cytometry

Glossary

1.42.1. Introduction

1.42.2. Principles and Instrumentation

1.42.3. Data Representation

1.42.4. Common Applications

1.43. Biological Imaging by Superresolution Light Microscopy

Glossary

Acknowledgments

1.43.1. Introduction

1.43.2. The Case for Superresolution Microscopy Techniques

1.43.3. Near-Field Scanning Optical Microscopy

1.43.4. Stimulated Emission Depletion

1.43.5. Superresolution Structured Illumination Microscopy

1.43.6. Photoactivation Localization Microscopy, Fluorescence Photoactivation Localization Microscopy, and Stochastic Optical Reconstruction Microscopy

1.43.7. Conclusions

1.44. Cell Isolation from Tissue

Glossary

1.44.1. Introduction

1.44.2. Tissue/Organ Procurement

1.44.3. Tissue/Organ Preservation

1.44.4. Tissue/Organ Rinsing

1.44.5. Tissue/Organ Fragmentation

1.44.6. Cell Dissociation

1.44.7. Purification

1.44.8. Cell Yield, Viability, and Purity Assessment

1.44.9. Conclusions

1.45. Nanobiotechnology

1.45.1. Introduction

1.45.2. Nanoparticles

1.45.3. Role of Nanobiotechnology in Molecular Diagnostics

1.45.4. Pharmaceutical Applications of Nanobiotechnology

1.45.5. Role of Nanobiotechnology in Biological Therapies

1.45.6. Clinical Nanomedicine

1.45.7. Nanooncology

1.45.8. Nanoneurology

1.45.9. Nanocardiology

1.45.10. Nanosurgery

1.45.11. Nanorobotics

1.45.12. Role of Nanobiotechnology for the Development of Personalized Medicine

1.45.13. Safety Issues of Nanoparticles

1.45.14. Future Prospects of Nanobiotechnology

1.46. Effects of Shear Stress on Cells

Glossary

1.46.1. Introduction

1.46.2. Shear Stress

1.46.3. Mechanisms of Mechanosignaling

1.46.4. Role of Shear Stress on ECs

1.46.5. Shear Stress Plays a Role in Stem Cell Fate

1.47. Viruses and Virus-Like Particles in Biotechnology

Glossary

Acknowledgments

1.47.1. Introduction

1.47.2. Types of Viruses

1.47.3. Types of VLPs

1.47.4. Production Platforms: A Focus on Animal Cell Technology

1.47.5. Applications: Prevention and Treatment

1.47.6. Bioengineering Challenges

1.47.7. Concluding Remarks and Future Trends

1.48. Mathematical Models in Biotechnology

Glossary

1.48.1. Introduction

1.48.2. Metabolic Network Models and Flux Balance Analysis

1.48.3. Reverse Engineering of Gene Regulatory Networks

1.48.4. Continuous Ordinary Differential Equation-Based Dynamic Models

1.48.5. Single-Cell Models and Stochastic Simulations

1.48.6. Qualitative Models: Fuzzy Logic and Petri Nets

1.48.7. Conclusion

1.49. Immunoassays in Biotechnology

Glosssary

Acknowledgments

1.49.1. Introduction

1.49.2. Immunoassay Formats

1.49.3. Applications

1.49.4. Conclusions

1.50. Mass Spectrometry

Glossary

Acknowledgments

1.50.1. Introduction

1.50.2. Recent Ionization Techniques

1.50.3. Commonly Used Mass (m/z) Analyzers

1.50.4. Online and Offline Coupling of MS with Liquid Chromatography and Electrophoresis

1.50.5. Quantitative Analysis (i-tag, i-traq, etc.)

1.50.6. Concluding Remarks

1.51. Bioprocessing Techniques

Glossary

1.51.1. Introduction

1.51.2. Production Strain Development

1.51.3. Fermentation Process

1.51.4. Product Recovery and Purification

1.51.5. Process Validation

1.51.6. Process Documentation

1.51.7. Conclusion

2.01. Introduction

2.02. Bioengineering at the Interface between Science and Society

Glossary

2.02.1. Introduction

2.02.2. The Impact of Science and Technology on Society

2.02.3. Roots and Development of Evolutionary Biology and of Genetics

2.02.4. Genetic Engineering as a Source of Genetic Variants

2.02.5. Molecular Mechanisms and Natural Strategies of Spontaneous Genetic Variation

2.02.6. High Similarity between Natural Biological Evolution and the Contribution of Genetic Engineering to Biological Evolution

2.02.7. Risk Evaluation of Evolutionary Processes

2.02.8. Prospects of Bioengineering

2.02.9. Public Perception of Genetics, Biological Evolution, and Bioengineering

2.02.10. Call for Sustainability of Cultural Developments

2.03. Cellular Systems

Glossary

2.03.1. Introduction

2.03.2. Bacteria

2.03.3. Fungi

2.03.4. Plant Cells

2.03.5. Animal Cells

2.03.6. Human Stem Cells

2.03.7. Artificial Cells

2.04. Cell Growth Dynamics

Glossary

2.04.1. Introduction

2.04.2. Models of Cells in Submerged Culture

2.04.3. Models of Cells in Multiphase Fermentor

2.05. Reaction Kinetics and Stoichiometry

Glossary

2.05.1. Introduction

2.05.2. Enzyme Kinetics

2.05.3. Factors Affecting Reaction Kinetics

2.05.4. Biochemical Reaction Rate Related to Cellular Systems

2.05.5. Stoichiometry

2.06. Bioreactor Fluid Dynamics

Glossary

2.06.1. Introduction

2.06.2. Mixing

2.06.3. Residence Time Measurements of the Gas Flow

2.06.4. Flow around Single Bubbles

2.06.5. Flow around Impeller Blades

2.06.6. Oxygen Mass Transfer

2.06.7. Flow Patterns in Stirred Tanks

2.06.8. Flow Patterns in Bubble Columns

2.06.9. Take-Home Messages

2.07. Mixing in Bioreactor Vessels

Glossary

2.07.1. Introduction

2.07.2. Characterization of Mixing

2.07.3. Mixing Models

2.07.4. Experimental Verification

2.07.5. The Airlift

2.07.6. Comparison of the Reactor Types

2.07.7. Gas-Phase Mixing

2.07.8. The Meaning of Mixing

2.07.9. Conclusions

2.08. Genetic Engineering

Glossary

2.08.1. Introduction to Genetic Engineering

2.08.2. Molecular Cloning and Recombinant DNA Technology

2.08.3. Molecular Manipulations

2.08.4. Cellular Manipulations

2.09. Bio-Feedstocks

Glossary

2.09.1. Common Feedstocks

2.09.2. Lignocellulose

2.09.3. Use of Perennial Grasses

2.10. Substrate Hydrolysis

Glossary

2.10.1. Introduction

2.10.2. Substrate for Hydrolysis

2.10.3. Physical Methods for Hydrolysis

2.10.4. Chemical Methods for Hydrolysis

2.10.5. Enzymatic Hydrolysis

2.10.6. Concluding Remarks

2.11. Medium Formulation and Development

Glossary

2.11.1. Introduction

2.11.2. Medium Formulation

2.11.3. Medium Optimization

2.11.4. Genetic Algorithms

2.11.5. Platforms for Medium Development

2.12. Sterilization in Biotechnology

Nomenclature

2.12.1. Introduction

2.12.2. Sterilization of Gases

2.12.3. Sterilization of Liquids

2.12.4. Sterilization of Small Equipment

2.12.5. Sterilization of Large Equipment

2.12.6. Validation of Sterilization

2.12.7. Conclusions

2.13. Inoculum Preparation

Glossary

Acknowledgments

2.13.1. Introduction

2.13.2. Criteria for Inoculum Preparation for Fermentation Process

2.13.3. Inoculum Development Process for Fermentation

2.13.4. Monitoring Inoculum Development

2.13.5. Transfer of Inoculum to the Fermentor Vessel or Scale-Up Process

2.13.6. Inoculum Preparation for Antimicrobial Susceptibility Testing

2.13.7. Measurement of Bacteria and Inoculum Preparation

2.13.8. Inoculum Preparation for Viral Cultures

2.13.9. Inoculum Preparation for Mammalian Cell Culture

2.13.10. Inoculum for Immunization

2.13.11. Conclusion

2.14. Bioreactor Engineering

Glossary

Acknowledgment

2.14.1. Introduction

2.14.2. Design and Types of Bioreactors

2.14.3. Effects of Process Parameters on Biological Performances

2.14.4. Bioreactor Operation Strategy

2.14.5. Industrial Applications of Bioreactors

2.14.6. Trends in Bioreactor Engineering

2.15. Stirred Tank Bioreactors

Glossary

2.15.1. Introduction

2.15.2. Mass and Energy Balances

2.15.3. Kinetic Models

2.15.4. Case in Study: Xanthan Gum Production

2.16. Airlift Bioreactors

Glossary

2.16.1. Introduction

2.16.2. Reactor Configurations

2.16.3. Power Input

2.16.4. Gas–Liquid Hydrodynamics

2.16.5. Mass Transfer

2.16.6. Heat Transfer

2.16.7. Mixing

2.16.8. Applications

2.16.9. Conclusions

2.17. Shake-Flask Bioreactors

Glossary

2.17.1. Introduction

2.17.2. Specific Power Input in Shake Flasks

2.17.3. Out-of-Phase Phenomena in Shake Flasks

2.17.4. Maximum Energy Dissipation Rate in Shake Flasks

2.17.5. Gas/Liquid Mass Transfer in Shake Flasks

2.17.6. Baffled Shake Flasks

2.17.7. Use of Engineering Parameters for Scale-Up from Shake Flask to Stirred-Tank Reactor

2.17.8. Fed-Batch and Continuous Cultures in Shake Flasks

2.17.9. Online Measuring Techniques in Shake Flasks

2.18. Photobioreactors – Models of Photosynthesis and Related Effects

Glossary

2.18.1. Introduction

2.18.2. The P–I Curve

2.18.3. Mathematical Representation of Photosynthesis

2.18.4. Modeling and Interpretation of Irradiance

2.18.5. The Kinetic Model

2.18.6. Modeling Photoacclimation

2.18.7. Photosynthesis in the Bioreactor

2.18.8. Simulated Illumination–Darkness Cycles

2.18.9. Experimental Evaluation of Illumination–Darkness Cycles

2.18.10. Conclusions

2.19. Disposable Bioreactors

Glossary

2.19.1. Introduction

2.19.2. Types of Single-Use Bioreactors with Disposable Bags

2.19.3. Conclusions

2.20. Membrane Bioreactors

Glossary

2.20.1. Introduction

2.20.2. Basic Concepts in Membrane Bioreactors

2.20.3. Membrane Bioreactors for Production and Separation of Bioactive Molecules

2.20.4. Membrane Bioreactors for Bioartificial Organs and Engineered-Tissue Culture

2.20.5. Conclusions

2.21. Microbioreactors

Glossary

2.21.1. Introduction

2.21.2. Microfluidic Devices

2.21.3. Microbioreactors for Cell Culturing

2.21.4. Enzymatic Microreactors

2.21.5. Future Perspectives of Bioreactor Miniaturization

2.22. Biofilters

Glossary

2.22.1. Introduction

2.22.2. Types of Biofilters

2.22.3. Filter Media

2.22.4. Microorganisms

2.22.5. Factors Affecting BF Performance

2.22.6. Design

2.23. Enzyme Bioreactors

Glossary

2.23.1. Introduction

2.23.2. Forms of Enzymes Used in Enzyme Reactors

2.23.3. Enzyme Reactors

2.23.4. Design and Choice of Enzyme Reactors

2.23.5. Novel Enzyme Reactors

2.24. Immobilized Cell Bioreactors

Glossary

2.24.1. Introduction

2.24.2. Immobilization of Microbial Cells

2.24.3. Immobilized Cell Bioreactors: Configuration and Design Characteristics

2.24.4. Mass Transfer and Biokinetics in Immobilized Cell Bioreactors

2.24.5. Merits of Immobilized Cell Bioreactors

2.24.6. Potential Drawbacks

2.24.7. Concluding Remarks

2.25. Bioreactors for Solid-State Fermentation

Glossary

2.25.1. Introduction

2.25.2. Classification of SSF Bioreactors and Basic Principles of Operation

2.25.3. Tray Bioreactors

2.25.4. Packed-Bed Bioreactors

2.25.5. Rotating-Drum and Stirred-Drum Bioreactors

2.25.6. Forcefully Aerated Agitated Bioreactors

2.25.7. Challenges Related to Changes Provoked by Microbial Growth

2.25.8. Other Considerations

2.25.9. Conclusion

2.26. Bioreactors for Plant Cell Culture

Glossary

2.26.1. Introduction

2.26.2. General Aspects of Plant Cells

2.26.3. Various Types of Reactors for Plant Cell Culture

2.26.4. Operation of Plant Cell Reactors

2.26.5. Industrial Applications and Outlook for the Future

2.26.6. Summary

2.27. Bioreactors for Animal Cell Cultures

Glossary

2.27.1. Introduction

2.27.2. Bioreactor Design

2.27.3. Bioreactors for High Cell Density Cultures

2.27.4. Automation of Cell Processing toward Clinical Application

2.27.5. Concluding Remarks

2.28. Bioreactors for Tissue Engineering

Glossary

Acknowledgments

2.28.1. Introduction

2.28.2. Engineering Concepts in Tissue Mass Growth

2.28.3. Reactor Designs for Tissue Engineering

2.28.4. Noninvasive and Nondestructive Imaging Techniques to Monitor Bioreactor Tissue Cultures

2.28.5. Conclusions

2.29. Recombinant Technology

Glossary

2.29.1. Introduction

2.29.2. Mammalian Expression Vectors

2.29.3. Nonviral Gene Delivery

2.29.4. Cells

2.29.5. Host Cell Engineering

2.29.6. Generation of Recombinant Cell Lines

2.29.7. Transient Gene Expression

2.29.8. Regulatory Issues

2.30. Metabolic Regulation Analysis and Metabolic Engineering

Glossary

2.30.1. Introduction

2.30.2. Metabolic Engineering Practice

2.30.3. The Effect of Single-Gene Knockouts on the Metabolism

2.30.4. Global Regulators in Relation to the Cultural Environment

2.30.5. The Systems Biology Approach

2.30.6. Conclusion

2.31. Proteomics, Protein Engineering

Glossary

2.31.1. Introduction

2.31.2. Mass Spectrometry-Based Proteome Profiling Techniques

2.31.3. Current Advances in Protein Identification: Online and Microfluidic Proteomic Systems

2.31.4. Current Challenges in Proteomics

2.32. Heterologous Protein Expression

Glossary

2.32.1. Introduction

2.32.2. Heterologous Protein Expression in Bacterial Cultures

2.32.3. Heterologous Protein Expression in Yeast Culture

2.32.4. Heterologous Protein Expression in Insect Cell Culture

2.32.5. Heterologous Protein Expression in Mammalian Cell culture

2.32.6. Heterologous Protein Expression in Plant Cell Culture

2.32.7. Heterologous Protein Expression in Algal Cell Culture

2.32.8. Heterologous Protein Expression in Moss Culture

2.32.9. Heterologous Protein Expression in Cell-Free Systems

2.32.10. Summary and Future Directions

2.33. Biotransformations

Glossary

2.33.1. Introduction

2.33.2. Enzymes versus Whole Cells

2.33.3. Extremophiles as a Source of New Enzymes

2.33.4. Biotransformations as a Source of Chiral Compounds

2.33.5. Types of Reaction Systems

2.33.6. Industrial Processes – Overview on Present and Prospective Trends

2.34. Immobilized Enzymes

Glossary

2.34.1. Introduction

2.34.2. What Are Immobilized Enzymes?

2.34.3. Classification of Immobilized Enzymes

2.34.4. Approaches toward Robust Immobilized Enzymes

2.34.5. Engineering the Immobilized Enzymes

2.34.6. Prospectives and Future Developments

2.35. Immobilization Technology

Glossary

2.35.1. Introduction

2.35.2. Strategies for Cell Immobilization

2.35.3. Products Suitable for Immobilized Cells

2.35.4. Immobilized-Cell Bioreactors

2.35.5. Conclusions

2.36. Immobilized Viable Cell Biocatalysts

Glossary

2.36.1. Introduction: Development and Main Application Fields of Immobilized Cell Cultures

2.36.2. Original Motivation of Viable IC Technology

2.36.3. Current Data on IC Physiology

2.36.4. Proteomic Approach and Biofilm Phenotype

2.36.5. Conclusion

2.37. Fermentation Processes

Glossary

2.37.1. Introduction

2.37.2. Microbial Growth and Stoichiometry

2.37.3. Autocatalytic Nature of Microbial Growth

2.37.4. Cell Yields

2.37.5. Product Yields

2.38. Fed-Batch Fermentation – Design Strategies

Glossary

2.38.1. Introduction

2.38.2. Different Types of Fed-Batch Cultivations

2.38.3. Applications of Fed-Batch Cultivation

2.38.4. Control Techniques for Fed-Batch Fermentation

2.38.5. Design of Specific Fed-Batch Cultivation Strategies Using the Mathematical Model of the System

2.38.6. Model-Based Fed-Batch Cultivation Strategies

2.38.7. Parameters Used to Control the Fed-Batch Fermentations

2.38.8. Conclusion

2.39. Continuous Operation

Glossary

2.39.1. Introduction

2.39.2. Homogeneous System

2.39.3. Heterogeneous Systems

2.40. Multistage Continuous High Cell Density Culture

Glossary

2.40.1. Introduction

2.40.2. Historical Background

2.40.3. High Cell Density Culture

2.40.4. Multistage Continuous HCDC

2.40.5. Summary

2.41. Integrated Production and Separation

Glossary

2.41.1. Introduction

2.41.2. Integration Methodology for Reducing Process Step

2.41.3. Cross-Sectional Technologies through Integration Methodology

2.41.4. Separation Techniques for the Integration in Terms of Product Characteristics

2.41.5. Bioreactor Configuration for the Integration of Production and Separation

2.41.6. Techniques for ISPR

2.41.7. Process Integration by Biotechnology

2.41.8. Perspective for the Process Integration

2.42. Product Recovery

Glossary

2.42.1. Introduction

2.42.2. Historical Background

2.42.3. Modular Unit Operations in Downstream Processing

2.42.4. Integrated Unit Operations in Downstream Processing

2.42.5. Product Purification

2.42.6. Product Formulation and Stabilization

2.42.7. Conclusion

2.43. Membrane Systems and Technology

Glossary

2.43.1. Introduction

2.43.2. Membrane Materials

2.43.3. Membrane Configurations

2.43.4. Characterization of Membranes

2.43.5. Solute and Particle Deposition

2.43.6. Membrane Cleaning

2.43.7. Ultrafiltration and Microfiltration

2.43.8. Membrane Bioreactors

2.43.9. Membrane Chromatography

2.43.10. Membrane Contactors

2.43.11. Conclusion

2.44. Cell Disruption

Glossary

2.44.1. Introduction

2.44.2. Characteristics of the Microbial Cell Influencing Resistance to Disruption

2.44.3. Approaches to Microbial Cell Disruption

2.44.4. Large-Scale Cell Disruption Technologies

2.44.5. Laboratory-Scale, and Developing, Cell Disruption Technologies

2.44.6. Selective Product Release

2.44.7. Pretreatment to Augment Product Release

2.44.8. Integration of Biomass Formation and Product Release

2.44.9. Integration of Product Release and Product Recovery and Purification

2.44.10. Closing Remarks

2.45. Autolysis of Yeasts

Glossary

2.45.1. Introduction

2.45.2. Yeast Autolysis Mechanism

2.45.3. Yeast Autolysis Compounds

2.45.4. Conclusion

2.46. Precipitation and Crystallization

Glossary

Acknowledgments

2.46.1. Introduction

2.46.2. Solid–Liquid Equilibrium: Phase Diagrams

2.46.3. Modeling of Solid–Liquid Equilibrium

2.46.4. Crystallization of Proteins

2.46.5. Developing a Protein Crystallization Process

2.47. Adsorption and Chromatography

Glossary

2.47.1. Introduction

2.47.2. Molecular Interactions in Adsorption

2.47.3. Chromatographic Methods

2.47.4. Theoretical Aspects of Adsorption and Chromatography

2.47.5. Development of Adsorption and Chromatography

2.47.6. Conclusions

2.48. Modeling Chromatographic Separation

Glossary

2.48.1. Introduction

2.48.2. Theoretical Background

2.48.3. Models for Chromatography

2.48.4. Case Studies

2.48.5. Summary

2.49. Aqueous Two-Phase Systems

Glossary

2.49.1. Introduction

2.49.2. Theoretical Background

2.49.3. Application of ATPSs for the Recovery of Biological Products

2.49.4. Conclusions

2.50. Foam Separations

Glossary

2.50.1. Introduction

2.50.2. Applications of Foam Fractionation

2.50.3. Mechanism of Foam Fractionation

2.50.4. Design

2.50.5. Process Intensification

2.51. Drying

Glossary

2.51.1. Introduction

2.51.2. Applications

2.51.3. Traditional Drying Processes

2.51.4. Other Drying Technologies

2.51.5. Summary

2.52. Chiral Separations

Glossary

2.52.1. General Introduction

2.52.2. Crystallization

2.52.3. Chromatography

2.52.4. Capillary Electrophoresis

2.52.5. Liquid–Liquid Extraction

2.52.6. Membrane-Assisted Separations

2.52.7. Inclusion Distillation and Precipitation

2.53. Lab on a Chip – Future Technology for Characterizing Biotechnology Products

Glossary

Acknowledgments

2.53.1. Introduction

2.53.2. Technology

2.53.3. Components

2.53.4. Applications

2.53.5. Concluding Remarks

2.54. Protein Refolding/Renaturation

Glossary

2.54.1. Introduction

2.54.2. Inclusion Bodies

2.54.3. Isolation and Purification of Inclusion Bodies

2.54.4. Solubilization of Inclusion Bodies

2.54.5. Mechanism of Protein Aggregation

2.54.6. Renaturation of Denatured Protein

2.54.7. Concluding Remarks

2.55. Biogas Production

Glossary

2.55.1. Introduction

2.55.2. Advantages of the AD Processes

2.55.3. Microbiology of AD

2.55.4. Factors Affecting the AD Process

2.55.5. Types of Anaerobic Reactors

2.55.6. Effect of Operational and Environmental Variations on AD

2.55.7. Biogas Utilization

2.55.8. Biogas Upgrading Methods

2.55.9. Applications of AD Technology

2.56. Purification Process Design and the Influence of Product and Technology Platforms

Glossary

2.56.1. Introduction

2.56.2. Impurities

2.56.3. Purification Unit Operations

2.56.4. Purification Process Flow-Sheet Organization and Design

2.56.5. Processing Platforms – Examples and Characteristics

2.56.6. Conclusions

2.57. The Proportion of Downstream Costs in Fermentative Production Processes

Glossary

2.57.1. Introduction

2.57.2. Overview of literature data

2.57.3. Conclusions

2.58. Biorefinery Engineering

Glossary

Acknowledgments

2.58.1. Introduction

2.58.2. Feedstock Availability

2.58.3. Platform of Bioprocess Technologies

2.58.4. Examples of Current Improvements of Key Biorefinery Processes

2.58.5. Prospect

2.59. Instrumentation and Analytical Methods

2.59.1. Introduction

2.59.2. Physical Process Parameters

2.59.3. Cell Mass Measurements

2.59.4. Analysis of Substrates and Products

2.59.5. Miscellaneous Techniques

2.59.6. Conclusions and Remarks

2.60. Life Cycle Assessment in Biotechnology

Glossary

2.60.1. Introduction

2.60.2. The Methodology of LCA

2.60.3. LCA: Utility and Limitations

2.60.4. Application of LCA in Food Biotechnology

2.60.5. Application of LCA in Pharmaceutical Biotechnology

2.60.6. Application of LCA in Biopolymers

2.60.7. Application of LCA in Biofuels

2.60.8. Application of LCA in Biodegradable Waste Management

2.60.9. Some New Tendencies

2.61. Metabolic Control

Glossary

Acknowledgments

2.61.1. Introduction

2.61.2. Regulation of Biological Systems

2.61.3. Control of Biological Systems

2.61.4. Network Rigidity

2.61.5. Biochemical Systems Theory

2.61.6. Metabolic Control Analysis

2.61.7. Determination of the Flux Control Coefficients

2.61.8. In Vivo Applications

2.61.9. Conclusion

2.62. Fuzzy Control of Bioprocess

Glossary

2.62.1. Direct Inference of Process Variables

2.62.2. Determination of Process Variables Based on Identification of Culture Phase

2.62.3. Combination of Fuzzy Inference with Other Methods

2.62.4. Conclusion

2.63. Online Control Strategies

Glossary

Acknowledgment

2.63.1. Introduction

2.63.2. Current Practice of Bioprocess Control

2.63.3. Advanced Process Control Strategies

2.63.4. Concluding Remarks

2.64. Process Optimization

Glossary

2.64.1. Introduction

2.64.2. Review of the Most Relevant Optimization Techniques

2.64.3. Case Studies

2.64.4. Conclusions

2.65. Micro-Biochemical Engineering

Glossary

Acknowledgments

2.65.1. Introduction

2.65.2. Overview of Micro-Biochemical Engineering

2.65.3. Examples of Micro-Biochemical Engineering

2.65.4. Future Challenges in Applying Micro-Biochemical Engineering

2.65.5. Conclusions

2.66. Sustainability

Glossary

2.66.1. Introduction

2.66.2. About Sustainability

2.66.3. Spatial and Temporal Dimensions of Sustainability

2.66.4. Challenges of Sustainability

2.66.5. Indicators of Sustainability

2.66.6. Keys to Sustainable Development in Practice

2.66.7. Biotechnology and Sustainability

2.66.8. Renewable Resources and Energy

2.66.9. Concluding Remarks

2.67. Nanostructured Biocatalysts

Glossary

2.67.1. Introduction

2.67.2. Nonaqueous Enzymatic Catalysis

2.67.3. Enzymes in Nanostructures

2.67.4. Preparation of Enzyme Nanogels

2.67.5. Molecular Fundamentals of Enzyme Nanogels

2.67.6. Potential Applications of Enzyme Nanogels as Biocatalysts

2.67.7. Summary

2.68. Aseptic Operations

Glossary

2.68.1. Introduction

2.68.2. Design and Procedural Approaches to Minimizing Contamination

2.68.3. Fermentation/Cell Culture Considerations

2.68.4. Considerations for Purification and Formulation/Fill

2.68.5. Validation and Verification

2.68.6. Sterility Analysis and Culture Purity

2.68.7. Summary

2.69. Oxygen Mass Transfer in Bioreactors

Glossary

2.69.1. Introduction

2.69.2. Effect of Various Parameters on Oxygen Mass Transfer

2.69.3. Conclusions

2.70. Cavitation in Biotechnology

Glossary

2.70.1. Introduction

2.70.2. Reactor Designs

2.70.3. Different Applications of Cavitation

2.70.3.7. Concluding Remarks

2.71. Flow Cytometry

Glossary

2.71.1. Introduction

2.71.2. Description of the FC Technique

2.71.3. Cell Viability and Functionality

2.71.4. Applications to Industrial Bioprocesses

2.71.5. Monitoring and Control of Biotransformations

2.71.6. Theoretical Applications: Kinetic Modeling

2.71.7. Devices of Practical Use and Automation of FC Equipments

2.71.8. Conclusions

2.72. Cleaning in Place

Glossary

2.72.1. Introduction

2.72.2. Hygiene Agents

2.72.3. Overview of CIP Systems

2.72.4. Cleaning Principles

2.72.5. Other Technological Aspects

2.73. Ionic Liquids

Glossary

2.73.1. Introduction

2.73.2. Applications of Enzymes in Ionic Liquids

2.73.3. Environmental Impact of Ionic Liquids

2.73.4. Conclusions

2.74. Supercritical Fluids

Glossary

2.74.1. Introduction

2.74.2. Pure Substances as Supercritical Fluids

2.74.3. Properties of Supercritical Fluids

2.74.4. Modifiers

2.74.5. Solubility in a Supercritical Fluid

2.74.6. Calculations to Predict Whether a Modifier Is Required

2.74.7. Supercritical Fluid Extraction

2.74.8. Supercritical Fluid Chromatography

2.74.9. Supercritical Fluid Particle Engineering

2.74.10. Supercritical Fluid Tissue Engineering and Regenerative Medicine

2.74.11. Supercritical Fluids as Alternative Enzymatic Reaction Solvents

2.74.12. Sterilization Using SF-CO2

2.74.13. Critical Point Drying of Biological Samples

2.74.14. Summary

2.75. Computational Fluid Dynamics

Glossary

Acknowledgment

2.75.1. Introduction

2.75.2. Fundamentals

2.75.3. Single-Phase Flow Simulations

2.75.4. Multiphase Flow Simulations

2.75.5. CFD in Biochemical Engineering

2.75.6. Conclusions and Future Perspectives

3.01. Introduction

Acknowledgments

3.02. Industrial Enzymes

Glossary

3.02.1. Introduction

3.02.2. Protease

3.02.3. Lipase

3.02.4. Amylase

3.02.5. Pullulanases

3.02.6. Pectinases

3.02.7. Xylanase

3.02.8. Laccases

3.02.9. Transglutaminases

3.02.10. Phytase

3.02.11. Perspective

3.03. Multifunctional Enzyme Systems for Plant Cell Wall Degradation

Glossary

Acknowledgments

3.03.1. Introduction

3.03.2. Diversity of Multifunctional Enzymes

3.03.3. Inter- and Intra Molecular Synergism

3.03.4. Intra Molecular Synergism: Clues from Three-Dimensional Structures

3.03.5. Artificial Chimeras

3.03.6. Future Perspective

3.04. Ethanol Production from Sugar-Based Feedstocks

Glossary

3.04.1. Introduction

3.04.2. Feedstocks

3.04.3. Land Availability Scenarios

3.04.4. Feedstock Processing for Ethanol

3.04.5. Conclusions

3.05. Ethanol from Starch-Based Feedstocks

Glossary

3.05.1. Introduction

3.05.2. Biochemistry of the Ethanol Process

3.05.3. Yeasts Used in the Process

3.05.4. Unit Operations Relevant to Ethanol Production

3.05.5. Environmental Requirements in Fermentation

3.05.6. Yield Coefficient and Net Rate Expression

3.05.7. Metabolic Flux Analysis

3.05.8. Summary

3.06. Biofuels from Cellulosic Feedstocks

Glossary

3.06.1. Introduction

3.06.2. Cellulosic Biomass

3.06.3. Conversion of Cellulosic Biomass into Ethanol

3.06.4. Development of Microorganisms for Fermenting Cellulosic Biomass Hydrolyzates to Ethanol

3.06.5. Conclusions

3.07. Biodiesel

Glossary

3.07.1. Introduction

3.07.2. Pyrolysis or Thermal Cracking

3.07.3. Microemulsions

3.07.4. Transesterification – Conventional Methods

3.07.5. Transesterification – Supercritical Fluids

3.07.6. Transesterification – Enzymatic

3.07.7. Nonedible Oils as Potential Substrates

3.07.8. Packed-Bed Reactors Containing Whole-Cell Biocatalysts

3.07.9. Conclusion and Future Prospects

3.08. Biofuels and Bioenergy

Glossary

3.08.1. Introduction

3.08.2. History

3.08.3. Microorganisms

3.08.4. Metabolic Pathway of Acetone and Butanol Formation

3.08.5. Genetic Engineering

3.08.6. Systems Biology

3.08.7. Fermentation

3.08.8. Development of Fermentation Technology

3.09. Microbial Production of 2,3-Butanediol

Glossary

3.09.1. Introduction

3.09.2. Properties and Applications of 2,3-Butanediol

3.09.3. Microorganisms Producing 2,3-Butanediol

3.09.4. Metabolic Pathway and Pathway Engineering

3.09.5. Fermentation of 2,3-Butanediol

3.09.6. Recovery of 2,3-Butanediol

3.09.7. Summary and Future Prospects

3.10. Biogas

Glossary

3.10.1. Introduction

3.10.2. Fundamentals

3.10.3. AD Process

3.10.4. Application of Biogas Technology

3.10.5. Utilization of Biogas

3.10.6. Perspectives

3.11. Biohydrogen

Glossary

3.11.1. Introduction

3.11.2. Biophotolysis of Water

3.11.3. Photofermentation by Photosynthetic Bacteria

3.11.4. Dark Fermentation

3.11.5. CO Gas Fermentation

3.11.6. Closing Remarks

3.12. Biofuel from Microalgae

Glossary

3.12.1. Introduction and Scope

3.12.2. Major Algal Composition

3.12.3. Different Types of Biofuels from Microalgae

3.12.4. Algal Biodiesel Production Pipeline

3.12.5. Conclusion and Perspectives

3.13. Citric Acid

Glossary

3.13.1. Introduction and Scope

3.13.2. Properties and Applications of Citric Acid

3.13.3. Historical Background of Citric Acid Production

3.13.4. Microorganisms and Biosynthesis of Citric Acid

3.13.5. Factors Affecting Citric Acid Production by A. niger

3.13.6. Fermentation Processes for Citric Acid Production

3.13.7. Product Recovery

3.13.8. Perspectives for the Future

3.14. Gluconic and Itaconic Acids

Glossary

3.14.1. Introduction and Scope

3.14.2. d-Gluconic Acid

3.14.3. Itaconic Acid

3.14.4. Perspectives for Future

3.15. Organic Acids

Glossary

Acknowledgments

3.15.1. Introduction

3.15.2. Succinic Acid Production

3.15.3. Use of Succinic Acid and Its Derivatives

3.15.4. Malic Acid Production

3.15.5. Malic Acid and Its Applications

3.15.6. Conclusion

3.16. Fumaric Acid

Glossary

Acknowledgments

3.16.1. Introduction

3.16.2. Properties and Applications

3.16.3. Industrial Production Methods

3.16.4. Fumaric Acid Fermentation Microbiology

3.16.5. Fermentation Process Development and Optimization

3.16.6. Conclusion and Future Prospects

3.17. Industrial Production of Lactic Acid

Glossary

3.17.1. Introduction

3.17.2. General Characteristics of Lactic Acid

3.17.3. Biological Production of Lactic Acid

3.17.4. The Cargill Yeast

3.17.5. Fermentation Carbon Sources

3.17.6. Purification of Lactic Acid from Fermentation Broth

3.17.7. An Emergent Commercial Application of Lactic Acid: PLA

3.18. Acetic and Propionic Acids

Glossary

Acknowledgments

3.18.1. Introduction

3.18.2. Properties and Applications of Acetic and Propionic Acids

3.18.3. Microbiology of Acetic Acid Fermentation

3.18.4. Product Recovery and Purification

3.18.5. Summary

3.19. Acrylic Acid

Glossary

Acknowledgments

3.19.1. Introduction

3.19.2. Process Development

3.19.3. Proposed Novel Biosynthetic Pathways and Industrial Production Process

3.19.4. Summary

3.20. Butyric Acid

Glossary

Acknowledgments

3.20.1. Introduction

3.20.2. Properties and Uses of Butyric Acid

3.20.3. Fermentation of Butyric Acid

3.20.4. Fundamentals and Molecular Manipulation

3.20.5. Product Recovery

3.20.6. Summary

3.21. PHA/PHB

Glossary

3.21.1. Introduction

3.21.2. Production of PHA/PHB by Wild-Type Microorganisms

3.21.3. PHA Production by Metabolically Engineered Microorganisms

3.21.4. Applications of PHA/PHB

3.22. 1,3-Propanediol and Polytrimethyleneterephthalate

Glossary

3.22.1. Introduction

3.22.2. Polytrimethyleneterephthalate

3.22.3. Properties and Uses of PDO

3.22.4. Metabolic Pathways and Engineering of PDO Formation

3.22.5. Fermentation Conditions and Operation Modes

3.22.6. Recovery and Purification of PDO

3.22.7. Production Costs and Biorefinery Concept

3.22.8. Conclusion and Perspectives

3.23. Antibiotics

Glossary

3.23.1. Introduction

3.23.2. The Miracle of Antibiotics

3.23.3. The Golden Era of Antibiotic Discovery

3.23.4. Microbial Genomics and the Failure of Antibiotic Discovery Research

3.23.5. Medical Need, Antimicrobial Resistance, and the Anti-Infective Marketplace

3.23.6. The Regulatory Environment for Antibacterials

3.23.7. Large Pharmaceutical Companies Exit and Biotechnology Enters

3.23.8. Conclusions

3.24. Penicillins and Cephalosporins

Glossary

3.24.1. Introduction to Penicillins and Cephalosporins

3.24.2. Structure and Mechanism of Action of Penicillins and Cephalosporins

3.24.3. Penicillin and Cephalosporin Biosynthesis

3.24.4. Biotechnological Implications in the Biosynthesis of Penicillins and Cephalosporins

3.24.5. Future Outlook

3.25. Tetracyclines and Tetracycline Derivatives

Glossary

3.25.1. Introduction and Scope

3.25.2. Tetracycline Generations and Origins

3.25.3. First-Generation Tetracyclines

3.25.4. Antibacterial Uses of the Tetracyclines

3.25.5. First- and Second-Generation Tetracyclines and Their Semisynthetic Modifications

3.25.6. Semisynthesis of Third-Generation Tetracyclines: Derivatives of Minocycline, Sancycline, and Doxycycline

3.25.7. Tetracycline Antibacterial Quantitative Structure-Activity Relationships (QSAR)

3.25.8. Antibacterial and General Chemical Properties of the Tetracyclines: Uptake and Membrane Activity

3.25.9. Mechanism of Action and Antibacterial Activity

3.25.10. Conclusions

3.26. Microbial Secondary Metabolites

Glossary

3.26.1. Introduction

3.26.2. Source of Bioactive Microbial Secondary Metabolites

3.26.3. Overview of Bioactivities

3.26.4. Microbial Product Screening

3.26.5. Production Processes

3.26.6. Examples of Successful Secondary Metabolites

3.26.7. Conclusions

3.27. Plant Secondary Metabolites

Glossary

Acknowledgments

3.27.1. Plants and Secondary Metabolites

3.27.2. Heterogeneity of Plant Secondary Metabolites

3.27.3. Secondary Metabolite Production by Plant Cell Culture

3.27.4. Signal Transduction Engineering for Enhancing Secondary Metabolite Production

3.27.5. Modulation of Secondary Metabolic Pathway

3.27.6. Conclusions and Perspectives

3.28. Biocatalyzed Production of Fine Chemicals

Glossary

3.28.1. Introduction

3.28.2. Preparation of Fine Chemicals from Renewable Raw Materials

3.28.3. Whole Cell-Catalyzed Synthesis of Fine Chemicals

3.28.4. Enzyme-Catalyzed Production of Fine Chemicals

3.29. Production of Recombinant Proteins by Microbes and Higher Organisms

Glossary

3.29.1. Introduction

3.29.2. Enzyme Production

3.29.3. Systems for Producing Recombinant Proteins

3.29.4. Conclusions

3.30. Vaccines

Glossary

3.30.1. Introduction

3.30.2. Smallpox Vaccine and Other Vaccines of the Nineteenth Century

3.30.3. The Importance of Vaccines

3.30.4. Milestones in Vaccine Technology

3.31. Manufacturing Recombinant Proteins in kg-ton Quantities Using Animal Cells in Bioreactors

Glossary

3.31.1. Introduction

3.31.2. Generation of CHO-Derived Cell Lines

3.31.3. Improved Recovery of High-Producing Cell Lines

3.31.4. High-Throughput Bioprocess Development

3.31.5. Disposable Bioreactors

3.31.6. Transient Gene Expression

3.31.7. Conclusions

3.32. Recent and Emerging Trends and Concerns Related to the Manufacturing and Testing of Monoclonal Antibodies Intended for Clinical Use

Glossary

3.32.1. Introduction

3.32.2. Characterization of mAb Quality Attributes

3.32.3. QbD/Design Space

3.32.4. New and Emerging Antibody-Related Products

3.32.5. Engineering Enhanced mAb Domain Functionality

3.32.6. Emerging Product Quality Concerns

3.32.7. Comparability Considerations

3.32.8. New Analytics

3.32.9. Platform Technologies

3.32.10. Emerging Chemistry, Manufacturing and Controls Technology

3.32.11. Conclusion

3.33. Therapeutic Enzymes and Biomimetic Substrates

Glossary

3.33.1. Introduction

3.33.2. Nomenclature

3.33.3. Enzyme Kinetics

3.33.4. Substrate Considerations

3.33.5. Complex Heterodisperse Natural Substrates

3.33.6. Application of Cell-Based Activity Assays to Qualification of Non-Biomimetic Substrates

3.33.7. Conclusions

3.34. Cell-Free Production of Pharmaceutical Proteins

Glossary

3.34.1. Introduction

3.34.2. Types of Cell-Free Systems

3.34.3. Advantages of Cell-Free Protein Production

3.34.4. Challenges with Cell-Free Protein Production

3.34.5. Small-Scale Applications

3.34.6. Novel Pharmaceutical Product Opportunities

3.34.7. Large-Scale Considerations

3.34.8. Summary

3.35. Combination Products Are Not Solely Biological Products, Drugs, or Devices

Glossary

Acknowledgment

3.35.1. Introduction and Definitions

3.35.2. FDA’s Organization and the Office of Combination Products

3.35.3. Request for Designation, Primary Mode of Action, and Assignment of Jurisdiction

3.35.4. How Things Work – Differences in Processes between Centers

3.35.5. How Things Work – Similarities in Processes between Centers

3.35.6. The Future

3.35.7. Conclusions

3.36. Cellular Therapies

Glossary

3.36.1. Introduction

3.36.2. Sources of Cells and Clinical Applications of Cell Therapy

3.36.3. Cell-Based Products for Reconstructive or Structural Repair

3.36.4. Cellular Vaccines

3.36.5. Adoptive Cell Therapies

3.36.6. Stem Cell-Derived Therapies

3.36.7. Cell Isolation and Processing Methods

3.36.8. Summary

3.37. Gene Therapies

Glossary

3.37.1. Introduction and Scope

3.37.2. Current Status of Gene Therapy Products in Commerce and Clinical Development

3.37.3. Challenges Pertinent to the Development of Gene Therapy Products

3.37.4. Regulatory Issues and Standardization Activities Pertinent to Gene Therapy Products

3.37.5. Manufacturing of Gene Therapy Products

3.37.6. Vectors Employed in Gene Therapy Products

3.37.7. Manufacturing and Purification Strategies

3.37.8. Product Characterization

3.37.9. Process Validation

3.37.10. Product Administration of Gene Therapy Products

3.37.11. Conclusion

3.38. Regulatory Aspects of Chemistry Manufacturing and Controls for Investigational New Drug Applications and Biologic License Applications to the United States Food and Drug Administration

Glossary

3.38.1. Introduction

3.38.2. IND Applications

3.38.3. Biologic License Application

3.38.4. Comparability Testing

3.38.5. Communication with the FDA from Pre-IND through Licensure

3.38.6. Conclusions

3.39. Raw Materials in the Manufacture of Biotechnology Products

Glossary

3.39.1. Introduction: Raw Materials in the Biotechnology Industry

3.39.2. Regulations on Raw Materials

3.39.3. Considerations on Raw Materials

3.39.4. Impact of the Quality of the Raw Material on the Quality of the Final Biotechnology Product

3.39.5. Control of the Quality of Raw Materials

3.39.6. Life Cycle of a Raw Material in Biotechnology Products

3.39.7. Management of Raw Materials in the Context of ICH Guidelines

3.39.8. Controlling the Risk of Introducing Raw Materials

3.39.9. Future Directions

3.40. Characterization of Biotechnological/Biological/Biosimilar Products

Glossary

3.40.1. Assessment of Product Characteristics

3.40.2. Biotechnology Product Characterization, Comparability, Release, and Stability Tool Kits

3.40.3. Selection of Analytical Methods

3.40.4. Analytical Method Lifecycle Issues

3.40.5. Conclusions

3.41. Protein Glycosylation

Glossary

3.41.1. Introduction

3.41.2. Analysis of Intact Glycoproteins and Glycopeptides

3.41.3. Analysis of Free Glycans

3.41.4. Analysis of Monosaccharides

3.41.5. Glycan Analysis Design for Therapeutic Glycoproteins

3.42. Immunogenicity Assay Development and Validation

Glossary

3.42.1. Introduction

3.42.2. Development of Binding Antibody Methods

3.42.3. Validation of Binding Antibody Methods

3.42.4. Development of NAb Methods

3.42.5. Validation of NAb Methods

3.42.6. Practical Considerations and Recommendations

3.42.7. Concluding Remarks

3.43. Process Analytical Technology in Bioprocess Development and Manufacturing

Glossary

3.43.1. Introduction and Scope

3.43.2. PAT Tools

3.43.3. Concluding Remarks

3.44. Process Validation

Glossary

3.44.1. Introduction and Scope

3.44.2. General Requirements and Considerations

3.44.3. Process Knowledge

3.44.4. Validation of the Commercial Process

3.45. Follow-On Protein Products

Glossary

3.45.1. Introduction

3.45.2. Unique challenges associated with protein products

3.45.3. Impact of the manufacturing process on product quality

3.45.4. Impact of product quality on clinical performance

3.45.5. Conclusions

3.46. Amino Acid Production

Glossary

3.46.1. Introduction

3.46.2. Microbial Production

3.46.3. Enzymatic Production

3.46.4. Future Prospects

3.47. Lysine

Glossary

Acknowledgment

3.47.1. Introduction

3.47.2. Biological Properties and Applications of d-Lysine, ε-Poly-l-Lysine, and l-Lysine

3.47.3. History of Industrial l-Lysine Production

3.47.4. Different Commercial Production Methods for l-Amino Acids

3.47.5. Fermentation Is the Dominant Method for Industrial l-Lysine Production

3.47.6. The l-Lysine Biosynthetic Pathway from Aspartate

3.47.7. Metabolic Engineering of C. glutamicum for l-Lysine Overproduction

3.47.8. Alternative Raw Materials and Production Strains for l-Lysine Production

3.47.9. Conclusions and Perspectives

3.48. Food-Grade Enzymes

Glossary

Acknowledgments

3.48.1. Introduction

3.48.2. Sources of Food-Grade Enzymes

3.48.3. Food-Grade Enzymes Targeted at Processing

3.48.4. Food-Grade Enzymes Targeted at Preservation

3.48.5. Production of Food-Grade Enzymes

3.48.6. Recovery of Food-Grade Enzymes

3.48.7. Polishing of Food-Grade Enzymes

3.48.8. Safety Concerns with Food-Grade Enzymes

3.49. Proteases

Glossary

3.49.1. Introduction

3.49.2. Protease Types

3.49.3. Principal Industrial Sources/Production Processes

3.49.4. Principal Applications of Proteases

3.49.5. Protease Inhibitors

3.50. Application of Enzymes and Microbes for the Industrial Production of Vitamins and Vitamin-Like Compounds

Glossary

3.50.1. Introduction and Scope

3.50.2. Riboflavin – Vitamin B2

3.50.3. Niacin – Vitamin B3

3.50.4. R-Pantothenic Acid and R-Panthenol – Vitamin B5 and Provitamin B5

3.50.5. Biotin – Vitamin B7

3.50.6. Cobalamin – Vitamin B12

3.50.7. l-Ascorbic Acid – Vitamin C

3.50.8. Phylloquinones and Menaquinones – Vitamin K

3.50.9. Coenzyme Q10

3.50.10. Pyrroloquinoline Quinone

3.50.11. l-Carnitine

3.50.12. Outlook

3.51. Fungal Biotechnology in Food and Feed Processing

Glossary

3.51.1. Introduction

3.51.2. Use of Fungi in Dietary Food

3.51.3. Use of Fruiting Body

3.51.4. Fungi as and in Processed Food

3.51.5. Processed Fungal Food as an Alternative to SCPs

3.51.6. Use of Enzymes in Food and Feed Bioprocessing

3.51.7. Fungal Enzymes Used in Feed

3.51.8. Commercial Recombinant Enzymes from Fungi

3.51.9. Secondary Metabolites from Fungi used in Food and Feed

3.51.10. Pharmaceutical and Nutraceutical Byproducts from Fungi

3.51.11. Symbiotic Fungus Termitomyces: A Filamentous Basidiomycota

3.51.12. Termitomyces clypeatus: An Edible Fungus and Producer of Enzymes

3.51.13. Bioprocessing of Food by T. clypeatus

3.51.14. Concluding Remarks and Future Prospects

3.52. Metabolic Engineering

Glossary

3.52.1. Introduction: Evolution of Metabolic Engineering

3.52.2. Biological Systems

3.52.3. Desired Products

3.52.4. Engineering Strategies

3.52.5. Future Perspectives

3.53. Synthetic Biology

Glossary

3.53.1. Introduction

3.53.2. Historical Foundation

3.53.3. Foundational Research and Development

3.53.4. Enabling Technologies

3.53.5. Research and Education

3.53.6. Applications of Synthetic Biology

3.53.7. Regulatory Debate

3.53.8. Synbioethics

3.53.9. Intellectual Property

3.53.10. Looking Ahead

3.54. Industrial Biotechnology and Commodity Products

Glossary

3.54.1. Introduction

3.54.2. Upstream Activities

3.54.3. Downstream Activities

3.54.4. General Components

3.54.5. Future Designs and Facility Layouts

3.55. Bioreactors for Commodity Products

Glossary

3.55.1. Introduction

3.55.2. Classifications of Bioreactors

3.55.3. Types of Bioreactors

3.55.4. Bioreactors and Sustainability

3.56. Integrating Process Scouting Devices (PSDs) With Bench-Scale Devices

Glossary

3.56.1. Introduction

3.56.2. Process Scouting Devices Challenges

3.56.3. Integrating PSDs with Bench-Scale Devices by Developing a Scale-Up Strategy

3.56.4. Types of Process Scouting Devices

3.56.5. Future Developments

3.56.6. Conclusion

3.57. Overview of Downstream Processing in the Biomanufacturing Industry

Glossary

3.57.1. Introduction and Scope

3.57.2. Principles of DSP

3.57.3. Clarification Methods in DSP

3.57.4. Chromatography for Product Capture and Polishing

3.57.5. Filtration Methods Used in Product Purification and Formulation

3.57.6. Crystallization as a Low-Technology Polishing Method

3.57.7. Current Trends in the Biomanufacturing Industry

3.58. Nanotechnology

Glossary

3.58.1. Introduction

3.58.2. Types of Nanotechnology

3.58.3. Bionanotechnology and Nanobiotechnology

3.58.4. Nanotechnology at the Biological Interface

3.59. Biosurfactants

Glossary

3.59.1. Introduction

3.59.2. General Aspects

3.59.3. Applications

3.59.4. Perspectives and Future Development

3.59.5. Perspectives for Future Development

3.60. Bioleaching and Biomining for the Industrial Recovery of Metals

Glossary

3.60.1. Introduction

3.60.2. Microorganisms Involved in Biomining

3.60.3. Industrial Biomining of Ores

3.60.4. Environmental Impact of Biomining Activities

3.60.5. Microbial Metal Solubilization Mechanisms

3.60.6. Importance of Molecular Biology Studies in Metal Extraction

3.60.7. Perspectives

3.61. Biological Control

Glossary

3.61.1. Introduction

3.61.2. Biological Control

3.61.3. Biopesticides Classification

3.61.4. Biopesticide Categories

3.61.5. Biological Control of Aflatoxin Contamination of Crops

3.61.6. Use of Genetic-Engineering Technology

3.61.7. Engineering Biological Control Agents

3.61.8. Integrated Pest Management

3.61.9. Market

3.61.10. Conclusion

4.01. Introduction

4.02. Plant Biotechnology and GMOs

Glossary

4.02.1. Introduction

4.02.2. The Need for New Agricultural Crops

4.02.3. The Answer to Twentieth-Century Food Production Problems

4.02.4. The Adoption of GM Crops

4.02.5. The Second Generation of GM Crops

4.02.6. The Future of Agricultural Biotechnology

4.03. Bioactivity of Herbicides

Glossary

4.03.1. Introduction

4.03.2. Biochemical Pathways and Physiological Processes Involved with Photosynthesis

4.03.3. Formation of Biological Building Blocks and Their Assembly into Biopolymers

4.03.4. Other Modes of Action

4.03.5. Parting Comments

4.04. Starch Biosynthesis in Higher Plants

Glossary

4.04.1. Introduction

4.04.2. Overview of Starch Structure

4.04.3. Granule Initiation

4.04.4. Control of Starch Granule Size

4.04.5. Starches with Improved Functionalities

4.04.6. Amylose-Free Starches

4.04.7. High-Amylose Starches

4.04.8. Prospects for Altering Amylopectin Structure

4.04.9. Other Functional Properties

4.05. Starch Biosynthesis in Higher Plants

Glossary

4.05.1. Introduction

4.05.2. Origins

4.05.3. The Pathway of Starch Biosynthesis

4.05.4. The Formation of ADP-glucose by ADP-glucose Pyrophosphorylase

4.05.5. Glucan Chain Formation by Starch Synthases

4.05.6. Amylose Biosynthesis

4.05.7. Amylopectin Biosynthesis

4.05.8. Starch Synthase I

4.05.9. Starch Synthase II

4.05.10. Starch Synthase III

4.05.11. Starch Synthase IV

4.05.12. Branching of the Glucan Chain

4.05.13. The Role of Debranching Enzymes in Amylopectin Synthesis

4.05.14. Other Enzymes Implicated in the Pathway of Starch Biosynthesis

4.05.15. Coordination of Enzyme Activities during Starch Granule Synthesis

4.05.16. Starch Granule Proteins

4.05.17. Summary and Future Prospects

4.06. Metabolic Engineering of Higher Plants to Produce Bio-Industrial Oils

Glossary

Acknowledgments

4.06.1. Introduction

4.06.2. Plant Storage Lipids

4.06.3. Industrial Uses of Plant Oils

4.06.4. Seed Oil Biosynthesis

4.06.5. Oils for Biodiesel Production

4.06.6. High-Oleic Acid Oils

4.06.7. Oils Enriched in VLCFAs

4.06.8. Oils for the Detergent Industry

4.06.9. Increasing Functionality: FA Modification in Membrane Lipids

4.06.10. Increasing Seed Oil Content and Producing Oil in Vegetative Tissue

4.06.11. Platform Crops for Industrial Oil Production

4.06.12. Potential for Wax-Based Industrial Lipids

4.06.13. Closing Comments

4.07. Biodiesel – An Integrated Approach for a Highly Efficient Biofuel

Glossary

4.07.1. Overview of the Need and Potential

4.07.2. Biodiesel Feedstocks

4.07.3. Genetic Improvement of Feedstock Crop Plants

4.07.4. Low-Input Production Systems for Feedstock Crops

4.07.5. Conversion of Oils to Biodiesel

4.07.6. Pyrolysis – An Alternative

4.07.7. Fuel Quality and Use in Engines

4.07.8. Conclusions

4.08. Matching Crops for Selected Bioproducts

Glossary

4.08.1. Introduction

4.08.2. Biopolymers and Biofiber Composites

4.08.3. Manufacturing Bioproducts

4.08.4. Applications of Bioproducts

4.08.5. Recent Developments and Concluding Remarks

4.08.6. Acknowledgments

4.09. Nanotechnologies for Agricultural Bioproducts

Glossary

4.09.1. Introduction

4.09.2. Agricultural Bioproducts

4.09.3. Nanotechnologies for Agricultural Bioproducts

4.09.4. Potential Applications and Future Prospects

4.09.5. Conclusions

4.10. Transgenic Crops with Producer-Oriented Traits

Glossary

4.10.1. Introduction

4.10.2. Case Study 1 – Herbicide-Tolerant Crops: Roundup Ready Soybean

4.10.3. Case Study 2 – Insect-Tolerant Crops: Bt Maize

4.10.4. Case Study 3 – Virus-Tolerant Crops: Papaya

4.10.5. Case Study 4 – Hybridization Systems: Canola

4.10.6. The Role of Biotechnology in Future Crop Improvement: The Next Wave

4.11. Plant Genetic Techniques

Glossary

4.11.1. Introduction

4.11.2. Doubled Haploids

4.11.3. Molecular Markers

4.11.4. Quantitative Trait Loci

4.11.5. Strengths and Weaknesses of LD Mapping

4.11.6. Marker-Assisted Breeding

4.11.7. Conclusions and Perspectives on Using DH and Molecular Markers in Plant Breeding

4.12. Plant Bioinformatics and Microarray Technologies

Glossary

4.12.1. Introduction

4.12.2. Transcriptional Profiling with a Focus on Microarrays

4.12.3. Identifying Differentially Expressed Genes across Treatments

4.12.4. Identifying Shared Patterns among Genes and Samples

4.12.5. Conclusion and Future Directions

4.13. Increasing Photosynthesis/RuBisCO and CO2-Concentrating Mechanisms

Glossary

Acknowledgments

4.13.1. Introduction

4.13.2. Improvement of RuBisCO’s Enzymatic Properties

4.13.3. Engineering Regulation of RuBisCO Activation

4.13.4. Increasing CO2 Concentration in the Vicinity of RuBisCO

4.13.5. Conclusions

4.14. Photosynthesis and Productivity of Vascular Plants in Controlled and Field Environments

Glossary

4.14.1. Introduction

4.14.2. Leaf Source Strength

4.14.3. Whole-Plant Traits Relating to Source and Sink Strength

4.14.4. Optimizing Photosynthesis and Productivity in Controlled and Field Environments

4.14.5. Conclusions

4.15. Roles of Dark Respiration in Plant Growth and Productivity

Glossary

4.15.1. Introduction

4.15.2. Genetic Modification of Glycolytic Enzymes

4.15.3. Genetic Modification of OPPP Enzymes

4.15.4. Genetic Modification of TCA Cycle Enzymes

4.15.5. Genetic Modification of Aerobic Respiratory Pathway Enzymes

4.15.6. Genetic Modification of Anaerobic Respiratory Enzymes

4.15.7. Conclusion

4.16. Improving Plant Nitrogen-Use Efficiency

Glossary

4.16.1. Introduction

4.16.2. What Is NUE?

4.16.3. Agronomic Approaches for Improving NUE

4.16.4. Transgenic Efforts to Improve NUE

4.16.5. Quantitative Trait Loci Mapping to Find New Targets for Manipulation

4.16.6. Improving NUE: A Systems Biology Approach

4.16.7. Global Status of NUE

4.17. Circadian Clocks/Photoperiodism and Crop Quality

Glossary

4.17.1. Introduction and Scope

4.17.2. Introduction to Biological Rhythms and the Plant Circadian Clock

4.17.3. The Genetic and Molecular Nature of the Plant Circadian Clock in the Model Plant Species A. thaliana

4.17.4. Plant Processes Regulated by the Circadian Clock

4.17.5. Adaptive Significance of Plant Circadian Rhythms

4.17.6. Photoperiodism and the Plant Circadian Clock

4.17.7. Manipulation of Photoperiod-Sensitive Reproductive and Vegetative Organ Initiation in Crop Plants

4.17.8. Abiotic and Biotic Stress Tolerance and the Plant Circadian Clock

4.17.9. Photosynthetic Carbon Metabolism

4.17.10. Nitrogen Acquisition and Assimilation

4.17.11. Conclusions

4.18. Breadfruit

Glossary

4.18.1. Introduction: Breadfruit (Artocarpus altilis)

4.18.2. Traditional Propagation of Breadfruit

4.18.3. Advantages of Micropropagation of Breadfruit

4.18.4. Micropropagation and Bioreactor Production of Breadfruit

4.18.5. Conclusions

4.19. Wines

Glossary

4.19.1. Introduction

4.19.2. Grape Cultivars

4.19.3. Grape-Growing Regions of the World

4.19.4. Grape and Wine Genomics

4.19.5. Genetically Modified Yeasts for Wine Production

4.19.6. GMO Grapevines and Fermentation Organisms in Grape and Wine Production

4.20. Sulfur Metabolism in Plants and Related Biotechnologies

Glossary

4.20.1. Introduction

4.20.2. Sulfur Metabolism

4.20.3. Sulfur-Containing Secondary Metabolite in Plants/Microbes and Their Importance/Role

4.20.4. Biotechnology Based on Sulfur Metabolism

4.20.5. Conclusion and Future Challenges

4.21. Emerging Roles for Plant Terpenoids

Glossary

4.21.1. Introduction to Plant Terpenoids and Scope

4.21.2. Carotenoids and Apocarotenoid Products

4.21.3. Isoprene Emission

4.21.4. Menthol

4.21.5. Taxol

4.21.6. Iridoid Glycosides

4.21.7. Conclusions

4.22. Antibody Production in planta

Glossary

4.22.1. Introduction

4.22.2. Antibody Expression in planta

4.22.3. Purification of Plant-Derived Antibodies

4.22.4. Applications of Plant-Derived Antibodies

4.22.5. Conclusion

4.23. Microalgae as Bioreactors for Production of Pharmaceutical Proteins

Glossary

Acknowledgment

4.23.1. Introduction

4.23.2. C. reinhardtii as Protein Expression Platforms

4.23.3. Pharmaceutically Relevant Proteins Produced in Transplastomic C. reinhardtii

4.23.4. Chlamydomonas Chloroplast Expression Systems and Strategies to Increase Recombinant Protein Expression

4.23.5. Conclusions

4.24. Algal Chemostats

Glossary

4.24.1. Introduction

4.24.2. Chemostat Design

4.24.3. Limiting Nutrients

4.24.4. Multiple-Organism Studies

4.24.5. Product Technology Using Chemostats

4.24.6. Toxin Studies Using Chemostats

4.24.7. Chemostats in Algal Symbiont Studies

4.24.8. Ecostats

4.25. Improvement of Ginseng by In Vitro Culture

Glossary

Acknowledgment

4.25.1. Introduction

4.25.2. Plant Growth Characteristics

4.25.3. Micropropagation

4.25.4. In Vitro Growth Requirements of Panax Species

4.25.5. Summary and Conclusions

4.26. Can Plants Really Improve Indoor Air Quality?

Glossary

4.26.1. Introduction

4.26.2. Phytoremediation in the Indoor Environment

4.26.3. Gas Exchange between the PPM and Its Surroundings

4.26.4. Effluent Quality

4.26.5. Conclusions

4.27. Regulating the Ripening Process

Glossary

4.27.1. Introduction

4.27.2. Model Systems for Fruit Development

4.27.3. Ethylene Synthesis and Fruit Ripening

4.27.4. Ethylene Perception and Fruit Ripening

4.27.5. Cell-Wall Metabolism and Fruit Ripening

4.27.6. The Role of Light in Fruit Ripening

4.27.7. Insights into Developmental Control from Ripening Mutants

4.27.8. Future Directions

4.28. Pre- and Postharvest Treatments Affecting Nutritional Quality

Glossary

4.28.1. Introduction

4.28.2. Inhibition of Ethylene Biosynthesis

4.28.3. Inhibition of Ethylene Action

4.28.4. Phospholipase D Inhibition Technologies

4.28.5. Effects of Pre- and Postharvest Treatments on Firmness

4.28.6. Effects of Pre- and Postharvest Treatments on Color and Phenolics

4.28.7. Effects of Pre- and Postharvest Treatments on Antioxidant Levels

4.28.8. Effects of Pre- and Postharvest Treatments on Aroma

4.29. Embryo Genomics State of the Art

Glossary

4.29.1. Introduction

4.29.2. Decoding the Genome of Livestock

4.29.3. The Rise of Omics

4.29.4. The Single Gene Phenotypes

4.29.5. Applications in Animal Biotechnology

4.29.6. The Necessary Link between Reproductive Biology and the Exploitation of the Genetic Information

4.29.7. The Emerging Role of Epigenetics

4.29.8. The DNA-Based Tools for the Study of Gene Expression

4.29.9. Microarray versus Deep Sequencing

4.29.10. Conclusion

4.30. Aquaculture Genomics

Glossary

4.30.1. Introduction

4.30.2. Required Resources for the Whole Genome Sequence Assembly

4.30.3. Required Resources for the Whole Genome Sequence Annotation

4.30.4. Whole Genome Sequencing

4.30.5. Aquaculture Genomics and Performance Traits

4.31. Epigenetics and Animal Health

Glossary

4.31.1. Introduction and Scope

4.31.2. Epigenetic Mechanisms Regulating Gene Activity

4.31.3. Epigenetic Regulation of the NEI

4.31.4. Environmental Quos That Contribute to the Epigenetic Programming of Genes Associated with Disease

4.31.5. Molecular Approaches to Studying Epigenetics

4.31.6. Conclusion

4.32. Quest for Novel Muscle Pathway Biomarkers by Proteomics in Beef Production

Glossary

4.32.1. Introduction and Scope

4.32.2. New Insights in to Muscle Biology

4.32.3. Identification of Markers of Beef Tenderness

4.32.4. Conclusion

4.33. From Stem Cell to Gamete

Glossary

4.33.1. Introduction

4.33.2. Oogenesis In Vivo

4.33.3. In Vitro Germ Cell Development from Stem Cells

4.33.4. Potential Applications of In Vitro-Generated Female Gametes

4.34. Stem Cells and Animal Therapies

Glossary

4.34.1. Introduction

4.34.2. Stem Cell Therapies in Domestic Species

4.34.3. Summary and Perspectives

4.34.4. Conclusion

4.35. Flow Cytometric Sorting of Mammalian Sperm for Predetermination of Sex

Glossary

4.35.1. Introduction

4.35.2. Sex Preselection

4.35.3. Flow Cytometric Sorting of Sperm

4.35.4. Delivery of Sexed Sperm

4.35.5. Sorting of Frozen–Thawed Sperm

4.35.6. Concluding Remarks

4.36. Animal Cloning

Glossary

4.36.1. Introduction

4.36.2. Technical Aspects of Animal Cloning by NT

4.36.3. Cloning Applications

4.36.4. Problems of SCNT Cloning

4.36.5. Nuclear Reprogramming in SCNT Embryos

4.36.6. Gene Expression in SCNT Cloned Embryos

4.36.7. Effects of Cell Cycle Coordination on SCNT Cloning

4.36.8. Effect of Cell Differentiation on SCNT Cloning

4.36.9. Alternatives to Facilitate Nuclear Reprogramming in SCNT Embryos

4.36.10. Concluding Remarks

4.37. Transgenesis

Glossary

4.37.1. Introduction

4.37.2. SCNT: Current Methodology for Transgenic Animal Production

4.37.3. Emerging Transgenic Technologies

4.37.4. Applications of Transgenic Domestic Animals

4.37.5. Health and Welfare of Transgenic Farm Animals

4.37.6. Safety Aspects and Outlook

4.38. Arrest or Survive

Glossary

4.38.1. Introduction

4.38.2. Survival of the Early Embryo

4.38.3. Factors Involved in Embryo Loss

4.38.4. Why Does an Embryo Arrest?

4.38.5. Metabolomic Signatures: Markers for Embryo Health

4.39. Heat Stress and Climate Change

Glossary

4.39.1. Introduction – the Impact of Heat Stress on Animal Production

4.39.2. Homeothermy

4.39.3. Use of Biotechnology to Enhance Genetic Thermotolerance

4.39.4. Uses of Biotechnology to Facilitate Physiological Manipulation to Counteract Effects of Heat Stress

4.39.5. Final Perspective

4.40. Analytical Methods – Functional Foods and Dietary Supplements

Glossary

4.40.1. Introduction

4.40.2. Bioactive Compounds Used in Functional Foods and Dietary Supplements

4.40.3. Phenolic Compounds

4.40.4. Omega-3 Fatty Acids and Conjugated Linoleic Acid (CLA)

4.40.5. Carotenoids

4.40.6. Phytosterols

4.40.7. Coenzyme Q10

4.40.8. Vitamins

4.40.9. Glucosamine

4.40.10. Chondroitin Sulfate

4.40.11. Dietary Fiber

4.40.12. Selected Botanicals

4.40.13. Conclusions

4.41. Plant Derived Bioactives

Glossary

4.41.1. Introduction

4.41.2. Indigestible Carbohydrates

4.41.3. Essential Fatty Acids

4.41.4. Proteins and Peptides

4.41.5. Polyphenolic Compounds

4.41.6. Carotenoids

4.41.7. Conclusions

4.42. Functional Properties of Dietary Fiber

Glossary

4.42.1. Introduction

4.42.2. Sources and Chemistry of Dietary Fiber

4.42.3. Physiological Properties of Dietary Fiber

4.42.4. Functional Properties of Dietary Fiber

4.42.5. Applications of Dietary Fibers in Food Products

4.42.6. Conclusions

4.43. Resistant Starches in Foods

Glossary

4.43.1. Introduction

4.43.2. Definition and Classification of RS

4.43.3. Strategies for the Enhancement of RS

4.43.4. Determination of RS

4.43.5. Future Directions

4.44. Plant Sterols

Glossary

4.44.1. Introduction

4.44.2. Occurrence and Structure

4.44.3. Metabolism of Plant Sterols

4.44.4. Physiological Aspects of Plant Sterols in Human Health

4.44.5. Plant Sterols and Coronary Heart Disease Risk

4.44.6. Factors Affecting Efficacy of Plant Sterols

4.44.7. Combination Therapies of Plant Sterols

4.44.8. Safety of Plant Sterols

4.44.9. Conclusion

4.45. Soy Protein Functionality

Glossary

4.45.1. Introduction

4.45.2. Soy Storage Proteins: Glycinin and β-Conglycinin

4.45.3. Adsorption of Soy Proteins at Interfaces: Emulsifying Properties

4.45.4. Gelling Properties of Soy Protein

4.45.5. Conclusions

4.46. Egg Components for Heart Health

Glossary

4.46.1. Introduction

4.46.2. Composition of Egg

4.46.3. Pathogenesis of Cardiovascular Diseases

4.46.4. Cholesterol Content and Level of Cardiovascular Risk

4.46.5. PUFA-Enriched Egg Improves Heart Health

4.46.6. Antihypertensive Bioactive Peptides from Eggs

4.46.7. Egg Antioxidants Improve Cardiovascular Health

4.46.8. Other Beneficial Effects Improve CVD Risk

4.46.9. Conclusion and Notes

4.47. Enzyme Technology – Dairy Industry Applications

Glossary

4.47.1. Introduction

4.47.2. Industrially Important Enzymes Indigenous to Milk

4.47.3. Exogenous Enzymes Employed in the Manufacture of Dairy Products [15]

4.48. Gut Microbiology – A Relatively Unexplored Domain

Glossary

4.48.1. Introduction

4.48.2. Diversity of the Gut Microbiota

4.48.3. Immunomodulatory Effects of Gut Microbes

4.48.4. Complementation of the Gut Microbiota

4.48.5. Use of Animal Models to Study the Microbiota–Host Interaction

4.49. Probiotics

Glossary

4.49.1. Introduction

4.49.2. Microorganisms

4.49.3. Probiogenomics

4.49.4. Selection of Probiotic Strains

4.49.5. Technology

4.49.6. Probiotic Food Products

4.49.7. The Probiotic Concept

4.49.8. Safety Considerations

4.49.9. Conclusions

4.50. Novel Lipid Substitutes

Glossary

4.50.1. Introduction

4.50.2. Traditional Fat Crystal Networks

4.50.3. Novel Lipid Substitutes

4.50.4. Modifying the Crystal Structure of Novel Lipid Substitutes

4.50.5. Summary and Future Directions

4.51. Microwave Dehydration of Food and Food Ingredients

Glossary

4.51.1. Introduction

4.51.2. Background Information on Microwave Energy and Microwave Dehydration

4.51.3. Microwave-Applicator Designs

4.51.4. Microwave Dehydration

4.51.5. Microwave-Assisted Fluidized-Bed Drying

4.51.6. Microwave-Assisted Freeze-Drying

4.51.7. Food Culture and Probiotics

4.51.8. Conclusions

4.52. Active and Intelligent Packaging Materials

Glossary

4.52.1. Introduction

4.52.2. Antimicrobial AFP

4.52.3. Vapor and Gas Scavengers

4.52.4. Intelligent Packaging

4.52.5. Conclusion: Acceptance and Safety issues of AFP and IFP

4.53. Antimicrobials from Plants – Food Preservation and Shelf-Life Extension

Glossary

4.53.1. Introduction

4.53.2. Major Groups of Antimicrobial Compounds from Plants

4.53.3. Antimicrobial Activities

4.53.4. Mechanisms

4.53.5. Applications

4.53.6. Conclusion

4.54. Biosensors for Foodborne Pathogen Detection

Glossary

4.54.1. Introduction

4.54.2. Target Microbes

4.54.3. Conventional Microbiological Detection and Enumeration

4.54.4. Diagnostics for Pathogen Detection

4.54.5. Microbial Capture and Concentration

4.54.6. Transduction Strategies

4.54.7. Conclusions and Future Directions

4.55. Microemulsions as Nanoscale Delivery Systems

Glossary

4.55.1. Literature Review

4.55.2. Controlled Release of Food-Based Ingredients

4.55.3. Conclusion

4.56. Origins and Compositional Analysis of Novel Foods

Glossary

4.56.1. Introduction

4.56.2. Unique Animal Bio-Processed Foods

4.56.3. Conclusions

4.57. Nutrigenomics

Glossary

4.57.1. Introduction

4.57.2. Alcohol

4.57.3. Caffeine

4.57.4. Dietary Fat

4.57.5. Fruits and Vegetables

4.57.6. Micronutrients

4.57.7. Conclusions

4.58. Plant and Endophyte Relationships

Glossary

4.58.1. Introduction: Plant Nutrient Management and Agricultural Productivity

4.58.2. Endophyte Nutrient Uptake

4.58.3. Enhancing Root Growth

4.58.4. Nitrogen Fixation

4.58.5. Other Endophytic Mechanisms Affecting Plant Nutrient Status

4.58.6. Application of Endophytes to Agriculture

4.58.7. Conclusions

4.59. Disease Resistance/Pathology/Fusarium

Glossary

4.59.1. Introduction

4.59.2. Fusarium Life Cycles

4.59.3. Economic Impacts of Fusarium Infections and Their Toxins

4.59.4. Plant–Pathogen Interactions and Plant Resistance Mechanisms

4.59.5. Biotechnological Approaches to Resistance in Plants

4.59.6. F. graminearum

4.59.7. F. culmorum

4.59.8. F. verticillioides

4.59.9. F. oxysporum

4.60. Plant Biochemistry

Glossary

4.60.1. Introduction

4.60.2. Leguminous Antifungal Proteins

4.60.3. Nonleguminous Antifungal Proteins

4.60.4. Conclusion and Future Perspectives

4.61. Biological Control and Biotechnological Amelioration in Managed Ecosystems

Glossary

4.61.1. Introduction

4.61.2. Biocontrol of Weeds

4.61.3. Biocontrol of Plant Pathogens

4.61.4. Biocontrol of Plant Pathogens and Insect Pests by Pollinator Vectors

4.61.5. Biocontrol of Insect, Mite, and Nematode Pests

4.61.6. Biocontrol of Vertebrate Pests

4.61.7. Biocontrol in Veterinary and Medical Applications

4.61.8. Production, Deployment, and Establishment of Biocontrol Agents

4.61.9. Genetic Engineering and Biological Control

4.61.10. Ecological Considerations

4.62. Genetic Basis of Disease Resistance in the Honey Bee (Apis mellifera L.)

Glossary

4.62.1. Introduction

4.62.2. Colony Collapse Disorder and Parasites

4.62.3. Genetic Basis of Disease Resistance

4.62.4. Conclusion

4.63. Food Safety, Genetically Engineered Foods and Perception

Glossary

4.63.1. Introduction

4.63.2. Use New Media

4.64. Socio-Environmental Factors Influencing Food Behavior

Glossary

4.64.1. Introduction

4.64.2. The Economic Environment

4.64.3. Social Determinants of Healthy Eating

4.64.4. Influences of the Physical Environment on Healthy Eating

4.64.5. The Interaction of Determinants – The Obesogenic Environment

4.64.6. Policy

4.64.7. Conclusion

4.65. Policy and Novel Foods from Animal Sources

Acknowledgement

4.65.1. Introduction

4.65.2. Background

4.65.3. Food Derived from Animal Clones and Their Progeny: A Case Study

4.65.4. Specific Legislations Governing Food Products Derived from Biotechnology-Derived Animals

4.65.5. Conclusion

5.01. Introduction

5.02. Functional Biomaterials

Glossary

5.02.1. Introduction

5.02.2. Current Use of Materials in Medicine

5.02.3. Functionality in Biomaterials

5.02.4. Conclusions

5.03. Biomaterials/Cryogels

Glossary

5.03.1. Introduction

5.03.2. Production of Cryogels in Semi-Frozen Systems

5.03.3. Cryogel Characterization

5.03.4. Cryogel Properties

5.03.5. Composite Cryogel Materials: Inherent Features and Applications

5.03.6. Cryogels in Biomedicine and Biotechnology

5.04. Biomaterials

Glossary

5.04.1. Introduction

5.04.2. Principle of Electrospinning

5.04.3. Electrospun Biomaterials: A Wide Range of Possibilities

5.04.4. Applications of Electrospun Biomaterials

5.04.5. Biocompatibility of Electrospun Biomaterials

5.04.6. Electrospun Biomaterials for 3D Tissue Regeneration

5.04.7. Current Challenges with Electrospun Biomaterials

5.04.8. Conclusion

5.05. Mesoscale Engineering of Collagen as a Functional Biomaterial

Glossary

Acknowledgment

5.05.1. Introduction

5.05.2. Two Application Streams for Engineered Tissues

5.05.3. Which Cell Support Materials to Use: Indirect and Direct TE?

5.05.4. Interstitial Cell Seeding: Cell-Matrix Embedding from the Start

5.05.5. Structure of Collagen – A Raw Material for Weavers?

5.05.6. Collagen Materials: Engineering the Basics

5.05.7. Building Blocks

5.05.8. Antigenicity

5.05.9. Collagen Purity (and Antigenicity)

5.05.10. Bottom-Up Collagen Engineering, Where Is the Bottom – Amino Acids or Tropocollagen?

5.05.11. Conclusion

5.06. Biomaterials

Glossary

5.06.1. Introduction

5.06.2. Temperature-Responsive Intelligent Surfaces for Chromatographic Separation

5.06.3. Temperature-Responsive Intelligent Surfaces for Cell Culture

5.07. Surface Modification to Improve Biocompatibility

Glossary

5.07.1. Introduction

5.07.2. Surface Events, Interactions, and Material Characteristics

5.07.3. Surface Modification

5.07.4. Future

5.07.5. Conclusions

5.08. Cryopreservation

Glossary

Acknowledgments

5.08.1. Introduction

5.08.2. Cryopreservation Methodology

5.08.3. Natural Tissue Cryopreservation

5.08.4. Engineered Tissue Cryopreservation

5.08.5. Future Challenges

5.09. The Artificial Organ

Glossary

Acknowledgments

5.09.1. Introduction

5.09.2. Materials of Encapsulation

5.09.3. Properties of the Microcapsules

5.09.4. Applications of Encapsulated Cells

5.09.5. Conclusions and Future Considerations

5.10. Isolation of Mesenchymal Stem Cells from Bone Marrow Aspirate

Glossary

5.10.1. The Cellular Composition of Bone Marrow

5.10.2. Why Isolate MSC Populations?

5.10.3. Separation Techniques

5.10.4. Conclusions

5.11. Nanoimprint Lithography and Its Application in Tissue Engineering and Biosensing

Glossary

5.11.1. Introduction

5.11.2. Biosensing Applications of NIL

5.11.3. Application of NIL in Tissue Engineering

5.11.4. Appendix: Additional References

5.12. Microfluidic Technology and Its Biological Applications

Glossary

5.12.1. Introduction

5.12.2. Microfluidic Technology

5.12.3. Basic Components in Microfluidic Systems

5.12.4. Biological Applications

5.12.5. Concluding Remarks

5.13. Multifunctional Biosensor Development and Manufacture

Glossary

5.13.1. Introduction

5.13.2. Biomolecule Immobilization

5.13.3. Transduction Technologies

5.13.4. Potentiometric Transduction

5.13.5. Optical Transduction

5.13.6. Nanowire Arrays

5.13.7. Micromechanical

5.13.8. Recent Developments

5.13.9. Conclusions

5.14. Treating Intracranial Aneurysms – A Review of Existing and Emerging Methods

Glossary

5.14.1. Introduction

5.14.2. Existing Options for Treating Intracranial Aneurysms

5.14.3. Cerebral Stents for Direct Treatment of Intracranial Aneurysms

5.14.4. Conclusions

5.15. RNA Interference (RNAi) Technology

Glossary

5.15.1. Introduction

5.15.2. The Discovery of the Phenomena

5.15.3. The Mechanism of RNAi

5.15.4. The Discovery of miRNA Pathway and Functions of miRNA

5.15.5. The Generation of siRNA

5.15.6. The Assessment of siRNA Specificity and Off-Target Effects

5.15.7. The Progress of siRNA Drug Development

5.15.8. Conclusion Remarks

5.16. Rheology and Its Applications in Biotechnology

Glossary

5.16.1. Introduction

5.16.2. Shear Rheometry

5.16.3. Material Rheology

5.16.4. Other Rheological Considerations

5.16.5. Applications

5.16.6. Conclusion

5.17. Biological Fluid Mechanics

Glossary

Acknowledgment

5.17.1. Introduction

5.17.2. Vascular Diseases

5.17.3. Computational Biofluid Techniques

5.17.4. Evolving to Multiscale, Multiphysics Models

5.17.5. Epilogue

5.18. Mechanobiology of Bone

Glossary

5.18.1. Introduction

5.18.2. Fundamental Cell Mechanics

5.18.3. A Case Study of Mechanobiology: Bone

5.18.4. Bone Anatomy

5.18.5. The Osteocyte

5.18.6. Basic Mechanics of Solid Materials

5.18.7. A Top-Down Approach to Bone Mechanosensation: What Happens to a Bone When You Take a Step?

5.18.8. The Effect of Fluid Flow on the Osteocyte

5.18.9. Nonmechanical Fluid Flow Effects on the Osteocyte

5.18.10. Intracellular Signaling Downstream of Mechanical Deformation

5.18.11. Osteocyte Mechanotransduction Guides Bone Remodeling

5.18.12. How BMUs Remodel Bone

5.18.13. Outcome of Bone Remodeling

5.18.14. Biomedical Applications

5.18.15. Summary

5.19. Biofluids