Contents -- 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 -- 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 -- 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 Flavor 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 Optimization 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 Transformation 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 Synthesis 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 Transform 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 S. cerevisiae -- Flux Redirection toward Catabolic (Fermentation) or Anabolic (Carbohydrates) Products May Be Generated as a Result of Alteration in Redox and Phosphorylation Potentials -- Temperature-Dependent Expression of Certain Mutations Depend upon the Carbon Source -- There Seems to Exist a General Pattern of Control of the Intracellular Concentration of Metabolites -- Dependence of the Control of Glycolysis on the Genetic Background and the Physiological Status of Yeast in Chemostat Cultures -- Cellular Engineering -- Growth Rate Gl Phase of the 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.