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An introduction to metabolic and cellular engineering / S. Cortassa ... [et al.]. — 2nd ed. — Singapore : World Scientific, c2012. – (59.10582/I61a/2nd ed.) |
Contents
Contents
Chapter 1. Introduction 1
Metabolic and Cellular Engineering in the Context of Bioprocess Engineering 4
Tools for Metabolic and Cellular Engineering 17
Engineering Cells for Specific Biotransformations 20
Current Trends: Biofuels and Biomass Interconversion Processes 23
Metabolic Areas that have been Subjected to MCE 27
Genome Sequencing， Comparative Genomics， and Biological Complexity 30
From DNA Sequence to Biological Function 32
Systems Biology 35
Systems Biology and the Complex Systems Approach 38
Networks in Systems Biology 40
Temporal and Spatial Scaling in Cellular Processes 44
Scaling in microbial and biochemical systems 47
Views of the Cell 49
Black and gray boxes: Levels of description of metabolic behavior in microorganisms 49
Transduction and Intracellular Signaling 55
Self-Organized Emergent Phenomena 57
Homeodynamics and Coherence 62
Functions of Rhythms and Clocks 66
Chapter 2. Matter and Energy Balances 69
Mass Balance 69
General formulation of mass balance 70
Integral and differential mass balances 72
Growth stoichiometry and product formation 72
Biomass and product yields 77
Electron balance 78
Theoretical oxygen demand 81
Opening the "Black Box": Mass balance as the basis of metabolic flux analysis 82
Anabolic fluxes 82
Catabolic fluxes 89
Energy Balance 93
Forms of energy and enthalpy 94
Calorimetric studies of energy metabolism 97
Heat of combustion 99
An energetic view of microbial metabolism 102
Chapter 3. Cell Growth and Metabolite Production: Basic Concepts 107
Microbial Growth under Steady and "Balanced" Conditions 107
Microbial Energetics under Steady-State Conditions 113
Growth Kinetics under Steady-State Conditions 115
The dilution rate 115
The dilution rate and biomass concentration 116
The Dilution Rate and the Growth-limiting Substrate Concentration 117
Biomass and Growth-limiting Substrate Concentration at Steady State 118
Metabolic Fluxes during Balanced and Steady-State Growth 121
Growth as a Balance of Fluxes 123
The Flux Coordination Hypothesis 126
Flux imbalance and cell cycle arrest 129
Redirecting Central Metabolic Pathways under Kinetic or Thermodynamic Control 131
Thermodynamic or Kinetic Control of Flux under Steady-State Conditions 132
Kinetic and Thermodynamic Limitations in Microbial Systems: Case Studies 134
Saccharomyces cerevisiae 134
Catabolite repression and cell cycle regulation in yeast 137
Escherichia coli 142
Metabolic Design of Cells as Catalysts 143
Increasing carbon flow to aromatic biosynthesis in Escherichia coli 143
Multipurpose engineered microbes 146
Chapter 4. Engineering of Process Performance 149
Biochemical Rationale of Growth and Product Formation 149
A General Formalism for MFA 153
MFA Applications 154
MFA applied to prokaryotic organisms 155
MFA applied to lower eukaryotic organisms 158
Amphibolic pathways flux in different carbon sources 159
Interaction between carbon and nitrogen regulatory pathways in S. cerevisiae 160
MFA as applied to studying the performance of mammalian cells in culture 162
Bioenergetic and Physiological Studies in Batch and Continuous Cultures: Genetic or Epigenetic Redirection of Metabolic Fluxes 163
Introduction of heterologous metabolic pathways 163
Metabolic engineering of lactic acid bacteria for optimizing essential flavor compounds production 166
High throughput Bioenergetic and Physiological Studies of H2 Production by Algae 169
A metabolic switch elicited by the limitation of sulfur... 169
MFA under different growth conditions and high throughput metabolomics in plant cells 171
Flux analysis during H2 production using data from plant metabolomics 174
Metabolic engineering of microalgae 176
The engineered metabolome of C. reinhardtii 178
Rational Design of Microorganisms: Two Case Studies 179
Increase of Ethanol Production in Yeast 180
Phase I: Physiological， metabolic， and bioenergetic studies of different strains of S. cerevisiae 180
Phase II: Metabolic control analysis and metabolic flux analysis of the strain under the conditions defined in phase I 181
Yields and flux analysis 181
Metabolic control analysis 183
Phases III and IV: To obtain a recombinant yeast strain with an increased dose of PFK， and to assay the engineered strain in chemostat cultures under the conditions specified in phase I 186
Increase of L-threonine Production in E. coli 187
Appendix 189
Conditions for parameter optimization and simulation of a mathematical model of glycolysis 189
Chapter 5. Modeling Networks: Concepts and Tools
Cells as Networks of Processes
From "-Omics" to Functional Impact in Integrated Metabolic Networks
Networks Analyzed with Stoichiometric Models
Topological Analysis of Networks
Basic concepts on networks and graphs
Usefulness of the Analysis of Metabolic Networks in the Context of MCE 208
Kinetic Modeling in Microbial Physiology and Energetics 209
Modular building of kinetic models 209
Mathematical models behavior and tools: Reliability criteria
Model building process
Assembling the modules
Running simulations with the model: A combined experimental-computational approach
Metabolic Control Analysis of Networks
General concepts of MCA
MCA: Summation and connectivity theorems
Control and Regulation
Control of Metabolite Concentrations
Control of metabolites in relation to catabolite repression mutants of S. cerevisiae
MCA of Metabolic and Transport Networks
Analysis and Detection of Complex Nonlinear Behavior in Networks
Methods of Time Series Analysis
Relative Dispersional Analysis
Power Spectral Analysis
Applications to Time Series Analysis from Cardiomyocytes and Spontaneously Synchronized Continuous Yeast Cell Cultures
Cardiomyocytes
Yeast cultures
Complex Qualitative Behavior in Networks
Stability and Bifurcation Analyses
Emergent Spatiotemporal Behavior in Networks
Appendix
A simplified mathematical model to illustrate the Sauro-Westerhoff method of MCA
Chapter 6. Dynamic Aspects of Bioprocess Behavior
Transient and Oscillatory States of Continuous Culture
Mathematical model building
Transfer-function analysis and transient-response techniques
Theoretical transient response and approach to steady state
Substrate-inhibition model
Phase plane analysis
Transient Responses of Microbial Cultures to Perturbations of the Steady State
Dilution rate
Feed substrate concentration
Contents
Growth with two substrates
Temperature
Dissolved Oxygen
The meaning of steady-state performance in chemostat culture
Oscillatory Phenomena in Continuous Cultures
Oscillations as a consequence of equipment artifacts .
Oscillations derived from feedback between cells and environmental parameters
Oscillations derived from intracellular feedback regulation
Glycolytic oscillations
Respiratory oscillations
Growth rate oscillations
Oscillations derived from interactions between different species in continuous culture
Oscillations due to synchronous growth and division
Self-synchronized continuous cultures of yeast
Chapter 7. Bioprocess Development with Plant Cells 281
MCE in Plants: Realities and Potentialities 282
Plant transformation for studies on metabolism and physiology 283
Emerging scenarios from -omics projects and systems biology 283
Improving Plants through Genetic Engineering 286
Improving plant resistance to chemicals， pathogens， and stress 287
Improving quality and quantity of plant products 289
Using genetic engineering to produce heterologous proteins in plants 294
Tools for the Manipulation and Transformation of Plants 295
Plant Metabolism: Matter and Energy Flows and the Prospect of MCA 299
Metabolic Compartmentation in Plant Cells 300
Carbon Assimilation， Partitioning， and Allocation 303
Carbon Fixation in Higher Plants 303
Carbon Partitioning within One Cell and between Source and Sink Tissues 310
Plants as a source of soluble and storage carbohydrates and sugar-alcohols 311
Plants as producers of lignocellulosic biomass 315
Plants as a source for oils 316
Distinctive characteristics of metabolic reactions in the cytoplasm of plant cells with relevance for carbon and energy partitioning
MCA and MFA Studies in Plants
Regulation and Control: Starch Synthesis: A Case Study
The Relevance of Unicellular Algae: Auto-， Hetero-， and Mixo-Trophy
Concluding Remarks
Chapter 8. Animal Cell Culture Techniques
General Remarks: Cells Cultured as Organisms
Mammalian Stem Cell Culture
Fish Cell Lines
Amphibian Cell Lines
Insect Cell Lines
Mammalian Cells
Chapter 9. Metabolic and Cellular Engineering
and Bioprocess Engineering in the Industrial Production of Therapeutic Proteins 343
Bioprocess Engineering in the Industrial Production of Therapeutic Proteins
Bioprocess Design and Product Development
Stage 1: Molecule design
Stages 2 and 3: Host strain selection and process development
Stage 4: Risk assessment
Stage 5: Process characterization.
Chapter 10. Systems Biology of Metabolic and Cellular Engineering 359
Biological Complexity and Systems Bioengineering 359
Cellular Systems Biology 360
An In Silico Cell: Multiple Temporal and Spatial Scales of Interacting Dynamic Systems in the Heart 361
Signaling Networks: Connecting and Modulating the Mass-Energy-Information Networks 366
Adaptation to Ischemic Conditions in the Heart 368
Components and mechanisms 368
Targets 369
Conditions for signaling activation 369
Physiological response 369
Adaptation to a glucose pulse in S. cerevisiae 370
Control and Regulation in Complex Networks 371
Systems Bioengineering 374
The Challenges Ahead 376
The Next Generation of Biofuels 377
Systems Bioengineering as Applied to Biomedicine 380
Bibliography
Index
