目錄
Preface
List of Abbreviations
Introduction
Introductory Outlines
Metabolic and Cellular Engineering in the Context of Bioprocess Engineering
Tools for Metabolic and Cellular Engineering
Engineering Cells for Specific Biotransformations
Metabolic Areas that Have Been Subjected to MCE
From DNA Sequence to Biological Function
Temporal and Spatial Scaling in Cellular Processes
Scaling in Microbial and Biochemical Systems
Views of the Cell
Black and Grey Boxes: Levels of Description of Metabolic Behavior in Microorganisms
Transduction and Intracellular Signalling
Self-organized Emergent Phenomena
Homeodynamics and Coherence
Matter and Energy Balances
Mass Balance
General Formulation of Mass Balance
Integral and Differential Mass Balances
Growth Stoichiometry and Product Formation
Biomass and Product Yields
Electron Balance
Theoretical Oxygen Demand
Opening the Black Box Mass Balance as the Basis of Metabolic Flux Analysis
Energy Balance
Forms of Energy and Enthalpy
An Introduction to Metabolic and Cellular Engineering Calorimetric Studies of Energy Metabolism
Heat of Combustion
An Energetic View of Microbial Metabolism
Cell Growth and Metabolite Production.Basic Concepts
Microbial Growth under Steady and Balanced Conditions
Microbial Energetics under Steady State Conditions
Growth Kinetics under Steady State Conditions
The Dilution Rate
The Dilution Rate and Biomass Concentration
The Dilution Rate and the Growth-limiting Substrate Concentration 87 Biomass and Growth-limiting Substrate Concentration at
the Steady State
Growth as a Balance of Fluxes
The Flux Coordination Hypothesis
Toward a Rational Design of Cells
Redirecting Central Metabolic Pathways under Kinetic or Thermodynamic Control
Thermodynamic or Kinetic Control of Flux under Steady State Conditions
Kinetic and Thermodynamic Limitations in Microbial Systems Case Studies
Saccharomyces cerevisiae
Escherichia coli
Increasing Carbon Flow to Aromatic Biosynthesis in Escherichia coli
Methods of Quantitation of Cellular Processes Performance
Stoichiometry of Growth: The Equivalence between Biochemical Stoichiometries and Physiological Parameters
A General Formalism for Metabolic Flux Analysis
A Comparison between Different Methods of MFA
MFA Applied to Prokaryotic and Lower Eukaryotic Organisms
MFA as Applied to Studying the Performance of Mammalian Cells in Culture
Metabolic Fluxes during Balanced and Steady State Growth
Bioenergetic and Physiological Studies in Batch and Continuous Cultures.Genetic or Epigenetic Redirection of Metabolic Flux
Introduction of Heterologous Metabolic Pathways
Metabolic Engineering of Lactic Acid Bacteria for Optimising Essential Flavour Compounds Production
Metabolic Control Analysis
Summation and connectivity theorems
Control and Regulation
The Control of Metabolites Concentration
A Numerical Approach for Control Analysis of Metabolic Networks and Nonlinear Dynamics
The TDA Approach as Applied to the Rational Design of Microorganisms: Increase of Ethanol Production in Yeast
Phase I: Physiological， Metabolic and Bioenergetic Studies of Different Strains of S.cerevisiae
Phase II: Metabolic Control Analysis and Metabolic Flux Analysis of the Strain under the Conditions Defined in Phase Ⅰ
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
Appendix A
A Simplified Mathematical Model to Illustrate the Matrix Method of MCA
Appendix B
Conditions for Parameter Optimisation and Simulation of the Mathematical Model of Glycolysis
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
Transient Responses of Microbial Cultures to Perturbations of the Steady State
Dilution Rate
Feed Substrate Concentration
Growth with Two Substrates
Temperature
Dissolved Oxygen
The Meaning of Steady State Performance in Chemostat Culture
Oscillatory Phenomena in Continuous Cultures
1.Oscillations as a Consequence of Equipment Artifacts
2.Oscillations Derived from Feedback Between Cells and Environmental Parameters
3.Oscillations Derived from Intracellular Feedback Regulation
4.Oscillations Derived from Interactions between Different Species in Continuous Culture
5.Oscillations Due to Synchronous Growth and Division
Bioprocess Development with Plant Cells
MCE in Plants：Realities and Potentialities
Plant Transformation for Studies on Metabolism and Physiology
Improving Plants through Genetic Engineering
Improving Plant Resistance to Chemicals，Pathogens and Stresses
Improving Quality and Quantity of Plant Products
Using Plant Genetic Engineering to Produce Heterologous Proteins
Tools for the Manipulation and Transfolrmation of Plants
Plant Metabolism：Matter and Energy Flows and the Prospects of MCA
Metabolic Compartmentation in Plant Cells
Carbon Assimilation.Partitioning and Allocation
Carbon fixation in higher plants
MCA Studies in Plants
Regulation and Control：Starch Synthesi s.a Case Study
Concluding Remarks
Cellular Engineering
Outline
The Global Functioning of Metabolic Networks
The Nature of the Carbon Source Determines the Activation of
Whole Blocks of Metabolic Pathways with Global Impact on
Cellular Energetics
Carbon Sources that Share Most Enzymes Required to TransfclITn
the Substrates into Key Intermediary Metabolites under Similar
Growth Rates.Bring About Similar Fluxes through the Main
Amphibolic Pathways
Interaction between Carbon and Nitrogen Regulatory Pathways
in Scerevisiae
Flux Redirection toward Catabolic(Fermenti
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