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E-grāmata: Bioprocessing Technology for Production of Biopharmaceuticals and Bioproducts [Wiley Online]

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Bioprocessing Technology for Production of Biopharmaceuticals and BioproductsPalielināt
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In the wake of rapid advances in genetic technologies, new products continue to be developed to help improve human health and quality of life. Summarizing state-of-the art bioprocessing methods, Novel Bioprocessing Technology for Production of Biopharmaceuticals and Bioproducts presents a concise exploration of the latest developments in bioprocessing for applications in both the biopharmaceutical and biochemical industries. Including case study reviews of six milestone byproducts, the authors provide industrial and academic researchers and development scientists and students with a wide selection of host strain types and a review disruptive bioprocess technologies.
List of Contributors
xi
Part I Case Study
1(130)
1 Bacillus and the Story of Protein Secretion and Production
3(1)
Giulia Barbieri
Anthony Calabria
Gopal Chotani
Eugenlo Ferrari
1.1 Bacillus as a Production Host: Introduction and Historical Account
3(2)
1.2 The Building of a Production Strain: Genetic Tools for B. subtilis Manipulation
5(4)
1.2.1 Promoters
5(1)
1.2.2 Vectors for Building a Production Strain
6(1)
1.2.3 B. subtilis Competent Cell Transformation
7(2)
1.2.4 Protoplasts-Mediated Manipulations
9(1)
1.2.5 Genetics by Electroporation
9(1)
1.3 B. subtilis Secretion System and Heterologous Protein Production
9(12)
1.3.1 Bacillus Fermentation and Recovery of Industrial Enzyme
11(1)
1.3.2 Fermentation Stoichiometry
12(2)
1.3.3 Fermentor Kinetics and Outputs
14(3)
1.3.4 Downstream Processing
17(4)
1.4 Summary
21(8)
References
21(8)
2 New Expression Systems for GPCRs
29(1)
Dimitra Gialama
Fragiskos N. Kolisis
Georgios Skretas
2.1 Introduction
29(10)
2.2 Recombinant GPCR Production -- Traditional Approaches for Achieving High-Level Production
39(3)
2.3 Engineered Expression Systems for GPCR Production
42(15)
2.3.1 Bacteria
42(6)
2.3.2 Yeasts
48(3)
2.3.3 Insect Cells
51(3)
2.3.4 Mammalian Cells
54(1)
2.3.5 Transgenic Animals
54(2)
2.3.6 Cell-Free Systems
56(1)
2.4 Conclusion
57(14)
References
58(13)
3 Glycosylation
71(1)
Maureen Spearman
Erika Lattovd
Hilene Perreault
Michael Butler
3.1 Introduction
71(1)
3.2 Types of Glycosylation
72(4)
3.2.1 N-linked Glycans
72(2)
3.2.2 O-linked Glycans
74(2)
3.3 Factors Affecting Glycosylation
76(10)
3.3.1 Nutrient Depletion
76(3)
3.3.2 Fed-batch Cultures and Supplements
79(1)
3.3.3 Specific Culture Supplements
80(2)
3.3.4 Ammonia
82(1)
3.3.5 pH
82(1)
3.3.6 Oxygen
83(1)
3.3.7 Host Cell Systems
83(2)
3.3.8 Other Factors
85(1)
3.4 Modification of Glycosylation
86(3)
3.4.1 siRNA and Gene Knockout/Knockin
86(2)
3.4.2 Glycoprotein Processing Inhibitors and In Vitro Modification of Glycans
88(1)
3.5 Glycosylation Analysis
89(2)
3.5.1 Release of Glycans from Glycoproteins
90(1)
3.5.2 Derivatization of Glycans
91(1)
3.6 Methods of Analysis
91(18)
3.6.1 Lectin Arrays
91(2)
3.6.2 Liquid Chromatography
93(1)
3.6.2.1 HILIC Analysis
93(2)
3.6.2.2 Reversed Phase (RP) and Porous Graphitic Carbon (PGC) Chromatography
95(1)
3.6.2.3 Weak Anion Exchange (WAX) HPLC Analysis
96(1)
3.6.2.4 High pH Anion Exchange Chromatography with Pulsed Amperometric Detection (HPAEC-PAD)
96(1)
3.6.3 Capillary Electrophoresis (CE)
97(2)
3.6.4 Fluorophore-assisted Carbohydrate Electrophoresis (FACE) and CGE-LIF
99(1)
3.6.5 Mass Spectrometry (MS)
100(1)
3.6.5.1 Ionization
100(2)
3.6.5.2 Derivatization Techniques Used for MS Analysis of Glycans
102(1)
3.6.5.3 Fragmentation of Carbohydrates
103(6)
3.7 Conclusion
109(22)
References
109(22)
Part II Bioreactors
131(108)
4 Bioreactors for Stem Cell and Mammalian Cell Cultivation
133(1)
Ana Femandes-Platzgummer
Sara M. Badenes
Cldudia L. da Silva
Joaquim M. S. Cabral
4.1 Overview of (Mammalian and Stem) Cell Culture Engineering
133(7)
4.1.1 Cell Products for Therapeutics
134(2)
4.1.2 Cell as a Product: Stem Cells
136(4)
4.2 Bioprocess Characterization
140(7)
4.2.1 Cell Cultivation Methods
140(1)
4.2.2 Cell Metabolism
141(2)
4.2.3 Culture Medium Design
143(1)
4.2.4 Culture Parameters
144(1)
4.2.5 Culture Modes
145(2)
4.3 Cell Culture Systems
147(10)
4.3.1 Static Culture Systems
147(3)
4.3.2 Roller Botdes
150(1)
4.3.3 Spinner Flask
150(1)
4.3.4 Airlift Bioreactor
151(1)
4.3.5 Fixed/Fluidized-Bed Bioreactor
152(1)
4.3.6 Wave Bioreactor
152(2)
4.3.7 Rotating-Wall Vessel Bioreactor
154(1)
4.3.8 Stirred Tank Bioreactor
155(2)
4.3.8.1 Agitation/Shear Stress
156(1)
4.4 Cell Culture Modeling
157(2)
4.5 Case Studies
159(3)
4.5.1 Antibody Production in Bioreactor Systems
159(2)
4.5.2 mESC Expansion on Microcarriers in a Stirred Tank Bioreactor
161(1)
4.6 Concluding Remarks
162(1)
List of Symbols
163(1)
References
164(11)
5 Model-Based Technologies Enabling Optimal Bioreactor Performance
175(1)
Rimvydas Simutis
Marco Jenzsch
Andreas Lubbert
5.1 Introduction
175(1)
5.2 Basics
176(4)
5.2.1 Balances
176(1)
5.2.2 Model Identification
177(1)
5.2.3 Model-Based Process Optimization
178(2)
5.3 Examples
180(17)
5.3.1 Model-Based State Estimation
180(1)
5.3.1.1 Static Model Approach
180(3)
5.3.1.2 Dynamic Alternatives
183(1)
5.3.2 Optimizing Open Loop-Controlled Cultivations
184(1)
5.3.2.1 Robust Cultivation Profiles
184(4)
5.3.2.2 Evolutionary Modeling Approach
188(2)
5.3.3 Optimization by Model-Aided Feedback Control
190(1)
5.3.3.1 Improving the Basic Control
190(1)
5.3.3.2 Optimizing the Amount of Soluble Product
190(4)
5.3.4 COrRemoval in Large-Scale Cell Cultures
194(3)
5.4 Conclusion
197(4)
References
198(3)
6 Monitoring and Control of Bioreactor: Basic Concepts and Recent Advances
201(1)
James Gomes
Viki Chopda
Anurag S. Rathore
6.1 Introduction
201(1)
6.2 Challenges in Bioprocess Control
202(3)
6.2.1 Process Dynamics and Modeling
202(1)
6.2.2 Limits of Hardware and Software and Their Integration
203(1)
6.2.3 Regulatory Aspects
204(1)
6.3 Basic Elements of Bioprocess Control
205(3)
6.3.1 Bioprocess Monitoring
205(1)
6.3.2 Parameter Estimators
205(1)
6.3.3 Bioprocess Modeling
206(2)
6.4 Current Practices in Bioprocess Control
208(9)
6.4.1 PID Control
208(1)
6.4.2 Model-Based Control
209(2)
6.4.3 Adaptive Control
211(3)
6.4.4 Nonlinear Control
214(3)
6.5 Intelligent Control Systems
217(9)
6.5.1 Fuzzy Control
217(2)
6.5.2 Neural Control
219(3)
6.5.3 Statistical Process Control
222(2)
6.5.4 Integrated and Plant-Wide Bioprocess Control
224(1)
6.5.5 Metabolic Control
225(1)
6.6 Summary
226(1)
6.7 Future Perspectives
227(12)
Acknowledgments
227(1)
References
227(12)
Part III Host Strain Technologies
239(28)
7 Metabolic Engineering for Biocatalyst Robustness to Organic Inhibitors
241(1)
Liam Royce
Laura R. Jarboe
7.1 Introduction
241(2)
7.2 Mechanisms of Inhibition
243(2)
7.3 Mechanisms of Tolerance
245(1)
7.4 Membrane Engineering
246(5)
7.5 Evolutionary and Metagenomic Strategies for Increasing Tolerance
251(3)
7.6 Reverse Engineering of Improved Strains
254(1)
7.7 Concluding Remarks
255(12)
Acknowledgments
255(1)
References
255(12)
Index 267
CLAIRE KOMIVES, PHD, is a Professor in the Chemical and Materials Engineering Department at San Jose State University. Her research interests focus on the development of low cost snake antivenom compounds.

WEICHANG ZHOU, PHD, is Chief Technology Officer, Biologics Development & Manufacturing at WuXi Biologics. He has previously worked at Genzyme Corporation and Merck Research Laboratories.
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