Fundamental Bioengineering

; Jens Nielsen ; Gregory Stephanopoulos ; John Villadsen (Redaktør)

A thorough introduction to the basics of bioengineering, with a focus on applications in the emerging "white" biotechnology industry. As such, this latest volume in the "Advanced Biotechnology" series covers the principles for the design and analysis of industrial bioprocesses as well as the design of bioremediation systems, and several biomedical applications. Les mer
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A thorough introduction to the basics of bioengineering, with a focus on applications in the emerging "white" biotechnology industry. As such, this latest volume in the "Advanced Biotechnology" series covers the principles for the design and analysis of industrial bioprocesses as well as the design of bioremediation systems, and several biomedical applications. No fewer than seven chapters introduce stoichiometry, kinetics, thermodynamics and the design of ideal and real bioreactors, illustrated by more than 50 practical examples. Further chapters deal with the tools that enable an understanding of the behavior of cell cultures and enzymatically catalyzed reactions, while others discuss the analysis of cultures at the level of the cell, as well as structural frameworks for the successful scale-up of bioreactions. In addition, a short survey of downstream processing options and the control of bioreactions is given. With contributions from leading experts in industry and academia, this is a comprehensive source of information peer-reviewed by experts in the field.

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Innholdsfortegnelse

List of Contributors xiii About the Series Editors xv 1 Introduction and Overview 1 John Villadsen Part One Fundamentals of Bioengineering 3 2 Experimentally Determined Rates of Bio-Reactions 5 John Villadsen Summary 5 2.0 Introduction 5 2.1 Mass Balances for a CSTR Operating at Steady State 7 2.2 Operation of the Steady-State CSTR 13 References 16 3 Redox Balances and Consistency Check of Experiments 17 John Villadsen Summary 17 3.1 Black-Box Stoichiometry Obtained in a CSTR Operated at Steady State 17 3.2 Calculation of Stoichiometric Coefficients by Means of a Redox Balance 20 3.3 Applications of the Redox Balance 23 3.4 Composition of the BiomassX 28 3.5 Combination of Black-Box Models 30 3.6 Application of Carbon and Redox Balances in Bio-Remediation Processes 34 References 38 4 Primary Metabolic Pathways and Metabolic Flux Analysis 39 John Villadsen Summary 39 4.0 Introduction 39 4.1 Glycolysis 43 4.2 Fermentative Metabolism: Regenerating the NAD+ Lost in Glycolysis 47 4.3 The TCA Cycle: Conversion of Pyruvate to NADH + FADH2, to Precursors or Metabolic Products 50 4.4 NADPH and Biomass Precursors Produced in the PP Pathway 56 4.5 Oxidative Phosphorylation: Production of ATP from NADH (FADH2) in Aerobic Fermentation 57 4.6 Summary of the Biochemistry of Primary Metabolic Pathways 59 4.7 Metabolic Flux Analysis Discussed in Terms of Substrate to Product Pathways 61 4.8 Metabolic Flux Analysis Discussed in Terms of Individual Pathway Rates in the Network 88 4.9 Propagation of Experimental Errors in MFA 94 4.10 Conclusions 96 References 96 5 A Primer to 13C Metabolic Flux Analysis 97 Wolfgang Wiechert, Sebastian Niedenfuhr, and Katharina Noh Summary 97 5.1 Introduction 97 5.2 Input and Output Data of 13C MFA 99 5.3 A Brief History of 13C MFA 101 5.4 An Illustrative Toy Example 102 5.5 The Atom Transition Network 104 5.6 Isotopomers and Isotopomer Fractions 104 5.7 The Isotopomer Transition Network 105 5.8 Isotopomer Labeling Balances 107 5.9 Simulating an Isotope Labeling Experiment 109 5.10 Isotopic Steady State 110 5.11 Flux Identifiability 112 5.12 Measurement Models 113 5.13 Statistical Considerations 114 5.14 Experimental Design 115 5.15 Exchange Fluxes 116 5.16 Multidimensional Flux Identifiability 118 5.17 Multidimensional Flux Estimation 120 5.18 The General Parameter Fitting Procedure 121 5.19 Multidimensional Statistics 123 5.20 Multidimensional Experimental Design 124 5.21 The Isotopically Nonstationary Case 127 5.22 Some Final Remarks on Network Specification 130 5.23 Algorithms and Software Frameworks for 13C MFA 132 Glossary 135 References 137 6 Genome-Scale Models 143 Basti Bergdahl, Nikolaus Sonnensc

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