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(Fermention)or Anabolic (Carbohydrates)Products Mav Be Generated as a Result of AIteration in Redox and Phosphorylation Potentials Temperature—Dependent Expression of Certain Mutations Depend upon the Carbon Source There Seems to Exist a General PaRem of Control of the Intracellular Concen~ion of Metabolites Dependence of the Control of Giycolysis on the Genetic Background and the Physiological Status of Yeast in Chemostat Cultures Cellular Engineering Growth Rate.G1 Phase ofthe Cell Cycle.Production of Metabolites and Macromolecules as Targets for Cellular Engineering Catabolite Repression and Cell Cycle Regulation in Yeast Protein Production as a Function of Growth Rate The Selective Functioning of Whole Metabolic Pathways is Permissive for Differentiation Bibliography Index