Written for industrial and academic researchers and development scientists in the life sciences industry, Bioprocessing Technology for Production of Biopharmaceuticals and Bioproducts is a guide to the tools, approaches, and useful developments in bioprocessing. This important guide:
* Summarizes state-of-the-art bioprocessing methods and reviews applications in life science industries
* Includes illustrative case studies that review six milestone bio-products
* Discuses a wide selection of host strain types and disruptive bioprocess technologies
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978-1-119-37828-0 (9781119378280)
Schweitzer Klassifikation
1 - Cover [Seite 1]
2 - Title Page [Seite 5]
3 - Copyright [Seite 6]
4 - Contents [Seite 7]
5 - List of Contributors [Seite 13]
6 - Part I Case Study [Seite 17]
6.1 - Chapter 1 Bacillus and the Story of Protein Secretion and Production [Seite 19]
6.1.1 - 1.1 Bacillus as a Production Host: Introduction and Historical Account [Seite 19]
6.1.2 - 1.2 The Building of a Production Strain: Genetic Tools for B. subtilis Manipulation [Seite 21]
6.1.2.1 - 1.2.1 Promoters [Seite 21]
6.1.2.2 - 1.2.2 Vectors for Building a Production Strain [Seite 22]
6.1.2.3 - 1.2.3 B. subtilis Competent Cell Transformation [Seite 23]
6.1.2.4 - 1.2.4 Protoplasts?Mediated Manipulations [Seite 25]
6.1.2.5 - 1.2.5 Genetics by Electroporation [Seite 25]
6.1.3 - 1.3 B. subtilis Secretion System and Heterologous Protein Production [Seite 25]
6.1.3.1 - 1.3.1 Bacillus Fermentation and Recovery of Industrial Enzyme [Seite 27]
6.1.3.2 - 1.3.2 Fermentation Stoichiometry [Seite 28]
6.1.3.3 - 1.3.3 Fermentor Kinetics and Outputs [Seite 30]
6.1.3.4 - 1.3.4 Downstream Processing [Seite 33]
6.1.4 - 1.4 Summary [Seite 37]
6.1.5 - References [Seite 37]
6.2 - Chapter 2 New Expression Systems for GPCRs [Seite 45]
6.2.1 - 2.1 Introduction [Seite 45]
6.2.2 - 2.2 Recombinant GPCR Production - Traditional Approaches for Achieving High?Level Production [Seite 55]
6.2.3 - 2.3 Engineered Expression Systems for GPCR Production [Seite 58]
6.2.3.1 - 2.3.1 Bacteria [Seite 58]
6.2.3.2 - 2.3.2 Yeasts [Seite 64]
6.2.3.3 - 2.3.3 Insect Cells [Seite 67]
6.2.3.4 - 2.3.4 Mammalian Cells [Seite 70]
6.2.3.5 - 2.3.5 Transgenic Animals [Seite 70]
6.2.3.6 - 2.3.6 Cell?Free Systems [Seite 72]
6.2.4 - 2.4 Conclusion [Seite 73]
6.2.5 - References [Seite 74]
6.3 - Chapter 3 Glycosylation [Seite 87]
6.3.1 - 3.1 Introduction [Seite 87]
6.3.2 - 3.2 Types of Glycosylation [Seite 88]
6.3.2.1 - 3.2.1 N?linked Glycans [Seite 88]
6.3.2.2 - 3.2.2 O?linked Glycans [Seite 90]
6.3.3 - 3.3 Factors Affecting Glycosylation [Seite 92]
6.3.3.1 - 3.3.1 Nutrient Depletion [Seite 92]
6.3.3.2 - 3.3.2 Fed?batch Cultures and Supplements [Seite 95]
6.3.3.3 - 3.3.3 Specific Culture Supplements [Seite 96]
6.3.3.4 - 3.3.4 Ammonia [Seite 98]
6.3.3.5 - 3.3.5 pH [Seite 98]
6.3.3.6 - 3.3.6 Oxygen [Seite 99]
6.3.3.7 - 3.3.7 Host Cell Systems [Seite 99]
6.3.3.8 - 3.3.8 Other Factors [Seite 101]
6.3.4 - 3.4 Modification of Glycosylation [Seite 102]
6.3.4.1 - 3.4.1 siRNA and Gene Knockout/Knockin [Seite 102]
6.3.4.2 - 3.4.2 Glycoprotein Processing Inhibitors and In Vitro Modification of Glycans [Seite 104]
6.3.5 - 3.5 Glycosylation Analysis [Seite 105]
6.3.5.1 - 3.5.1 Release of Glycans from Glycoproteins [Seite 106]
6.3.5.2 - 3.5.2 Derivatization of Glycans [Seite 107]
6.3.6 - 3.6 Methods of Analysis [Seite 107]
6.3.6.1 - 3.6.1 Lectin Arrays [Seite 107]
6.3.6.2 - 3.6.2 Liquid Chromatography [Seite 109]
6.3.6.2.1 - 3.6.2.1 HILIC Analysis [Seite 109]
6.3.6.2.2 - 3.6.2.2 Reversed Phase (RP) and Porous Graphitic Carbon (PGC) Chromatography [Seite 111]
6.3.6.2.3 - 3.6.2.3 Weak Anion Exchange (WAX) HPLC Analysis [Seite 112]
6.3.6.2.4 - 3.6.2.4 High pH Anion Exchange Chromatography with Pulsed Amperometric Detection (HPAEC?PAD) [Seite 112]
6.3.6.3 - 3.6.3 Capillary Electrophoresis (CE) [Seite 113]
6.3.6.4 - 3.6.4 Fluorophore?assisted Carbohydrate Electrophoresis (FACE) and CGE?LIF [Seite 115]
6.3.6.5 - 3.6.5 Mass Spectrometry (MS) [Seite 116]
6.3.6.5.1 - 3.6.5.1 Ionization [Seite 116]
6.3.6.5.2 - 3.6.5.2 Derivatization Techniques Used for MS Analysis of Glycans [Seite 118]
6.3.6.5.3 - 3.6.5.3 Fragmentation of Carbohydrates [Seite 119]
6.3.7 - 3.7 Conclusion [Seite 125]
6.3.8 - References [Seite 125]
7 - Part II Bioreactors [Seite 147]
7.1 - Chapter 4 Bioreactors for Stem Cell and Mammalian Cell Cultivation [Seite 149]
7.1.1 - 4.1 Overview of (Mammalian and Stem) Cell Culture Engineering [Seite 149]
7.1.1.1 - 4.1.1 Cell Products for Therapeutics [Seite 150]
7.1.1.2 - 4.1.2 Cell as a Product: Stem Cells [Seite 152]
7.1.2 - 4.2 Bioprocess Characterization [Seite 156]
7.1.2.1 - 4.2.1 Cell Cultivation Methods [Seite 156]
7.1.2.2 - 4.2.2 Cell Metabolism [Seite 157]
7.1.2.3 - 4.2.3 Culture Medium Design [Seite 159]
7.1.2.4 - 4.2.4 Culture Parameters [Seite 160]
7.1.2.5 - 4.2.5 Culture Modes [Seite 161]
7.1.3 - 4.3 Cell Culture Systems [Seite 163]
7.1.3.1 - 4.3.1 Static Culture Systems [Seite 163]
7.1.3.2 - 4.3.2 Roller Bottles [Seite 166]
7.1.3.3 - 4.3.3 Spinner Flask [Seite 166]
7.1.3.4 - 4.3.4 Airlift Bioreactor [Seite 167]
7.1.3.5 - 4.3.5 Fixed/Fluidized?Bed Bioreactor [Seite 168]
7.1.3.6 - 4.3.6 Wave Bioreactor [Seite 168]
7.1.3.7 - 4.3.7 Rotating?Wall Vessel Bioreactor [Seite 170]
7.1.3.8 - 4.3.8 Stirred Tank Bioreactor [Seite 171]
7.1.3.8.1 - 4.3.8.1 Agitation/Shear Stress [Seite 172]
7.1.4 - 4.4 Cell Culture Modeling [Seite 173]
7.1.5 - 4.5 Case Studies [Seite 175]
7.1.5.1 - 4.5.1 Antibody Production in Bioreactor Systems [Seite 175]
7.1.5.2 - 4.5.2 mESC Expansion on Microcarriers in a Stirred Tank Bioreactor [Seite 177]
7.1.6 - 4.6 Concluding Remarks [Seite 178]
7.1.7 - List of Symbols [Seite 179]
7.1.8 - References [Seite 180]
7.2 - Chapter 5 Model?Based Technologies Enabling Optimal Bioreactor Performance [Seite 191]
7.2.1 - 5.1 Introduction [Seite 191]
7.2.2 - 5.2 Basics [Seite 192]
7.2.2.1 - 5.2.1 Balances [Seite 192]
7.2.2.2 - 5.2.2 Model Identification [Seite 193]
7.2.2.3 - 5.2.3 Model?Based Process Optimization [Seite 194]
7.2.3 - 5.3 Examples [Seite 196]
7.2.3.1 - 5.3.1 Model?Based State Estimation [Seite 196]
7.2.3.1.1 - 5.3.1.1 Static Model Approach [Seite 196]
7.2.3.1.2 - 5.3.1.2 Dynamic Alternatives [Seite 199]
7.2.3.2 - 5.3.2 Optimizing Open Loop?Controlled Cultivations [Seite 200]
7.2.3.2.1 - 5.3.2.1 Robust Cultivation Profiles [Seite 200]
7.2.3.2.2 - 5.3.2.2 Evolutionary Modeling Approach [Seite 204]
7.2.3.3 - 5.3.3 Optimization by Model?Aided Feedback Control [Seite 206]
7.2.3.3.1 - 5.3.3.1 Improving the Basic Control [Seite 206]
7.2.3.3.2 - 5.3.3.2 Optimizing the Amount of Soluble Product [Seite 206]
7.2.3.4 - 5.3.4 CO2?Removal in Large?Scale Cell Cultures [Seite 210]
7.2.4 - 5.4 Conclusion [Seite 213]
7.2.5 - References [Seite 214]
7.3 - Chapter 6 Monitoring and Control of Bioreactor: Basic Concepts and Recent Advances [Seite 217]
7.3.1 - 6.1 Introduction [Seite 217]
7.3.2 - 6.2 Challenges in Bioprocess Control [Seite 218]
7.3.2.1 - 6.2.1 Process Dynamics and Modeling [Seite 218]
7.3.2.2 - 6.2.2 Limits of Hardware and Software and Their Integration [Seite 219]
7.3.2.3 - 6.2.3 Regulatory Aspects [Seite 220]
7.3.3 - 6.3 Basic Elements of Bioprocess Control [Seite 221]
7.3.3.1 - 6.3.1 Bioprocess Monitoring [Seite 221]
7.3.3.2 - 6.3.2 Parameter Estimators [Seite 221]
7.3.3.3 - 6.3.3 Bioprocess Modeling [Seite 222]
7.3.4 - 6.4 Current Practices in Bioprocess Control [Seite 224]
7.3.4.1 - 6.4.1 PID Control [Seite 224]
7.3.4.2 - 6.4.2 Model?Based Control [Seite 225]
7.3.4.3 - 6.4.3 Adaptive Control [Seite 227]
7.3.4.4 - 6.4.4 Nonlinear Control [Seite 230]
7.3.5 - 6.5 Intelligent Control Systems [Seite 233]
7.3.5.1 - 6.5.1 Fuzzy Control [Seite 233]
7.3.5.2 - 6.5.2 Neural Control [Seite 235]
7.3.5.3 - 6.5.3 Statistical Process Control [Seite 238]
7.3.5.4 - 6.5.4 Integrated and Plant?Wide Bioprocess Control [Seite 240]
7.3.5.5 - 6.5.5 Metabolic Control [Seite 241]
7.3.6 - 6.6 Summary [Seite 242]
7.3.7 - 6.7 Future Perspectives [Seite 243]
7.3.8 - Acknowledgments [Seite 243]
7.3.9 - References [Seite 243]
8 - Part III Host Strain Technologies [Seite 255]
8.1 - Chapter 7 Metabolic Engineering for Biocatalyst Robustness to Organic Inhibitors [Seite 257]
8.1.1 - 7.1 Introduction [Seite 257]
8.1.2 - 7.2 Mechanisms of Inhibition [Seite 259]
8.1.3 - 7.3 Mechanisms of Tolerance [Seite 261]
8.1.4 - 7.4 Membrane Engineering [Seite 262]
8.1.5 - 7.5 Evolutionary and Metagenomic Strategies for Increasing Tolerance [Seite 267]
8.1.6 - 7.6 Reverse Engineering of Improved Strains [Seite 270]
8.1.7 - 7.7 Concluding Remarks [Seite 271]
8.1.8 - Acknowledgments [Seite 271]
8.1.9 - References [Seite 271]
9 - Index [Seite 283]
10 - EULA [Seite 290]
