Comprehensive biotechnology Vol. 3/ principles and practices in industry agriculture medicine and the environment Moo-Young,Murray

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