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[null,null,"Titolo",null,"Metabolic engineering : concepts and applications / / edited by Sang Yup Lee, Jens Nielsen, Gregory Stephanopoulos"]
[null,null,"Pubbl/distr/stampa",null,"Weinheim, Germany : , : WILEY-VCH, , [2021]"]
[{"$nulls":4},"©2021"]
[null,null,"ISBN",null,"3-527-82345-X"]
[{"$nulls":4},"3-527-82344-1"]
[{"$nulls":4},"3-527-82346-8"]
[null,null,"Descrizione fisica",null,"1 online resource (962 pages)"]
[null,null,"Collana",null,"Advanced Biotechnology ; ; Volume 13b"]
[null,null,"Disciplina",null,"660.62"]
[null,null,"Soggetti",null,"Microbial biotechnology"]
[{"$nulls":4},"Microbial genetic engineering"]
[null,null,"Lingua di pubblicazione",null,"Inglese"]
[null,null,"Formato",null,"Materiale a stampa"]
[null,null,null,"Livello bibliografico","Monografia"]
[null,null,"Nota di contenuto",null,"Cover -- Title Page -- Copyright -- Contents -- Preface -- Part 1 Concepts -- Chapter 1 Metabolic Engineering Perspectives -- 1.1 History and Overview of Metabolic Engineering -- 1.2 Understanding Cellular Metabolism and Physiology -- 1.2.1 Computational Methods in Understanding Metabolism -- 1.2.2 Experimental Methods in Understanding Metabolism -- 1.3 General Approaches to Metabolic Engineering -- 1.3.1 Rational Metabolic Engineering -- 1.3.2 Combinatorial Metabolic Engineering -- 1.3.3 Systems Metabolic Engineering -- 1.4 Host Organism Selection -- 1.5 Substrate Considerations -- 1.6 Metabolic Engineering and Synthetic Biology -- 1.7 The Future of Metabolic Engineering -- References -- Chapter 2 Genome‐Scale Models: Two Decades of Progress and a 2020 Vision -- 2.1 Introduction -- 2.2 Flux Balance Analysis -- 2.2.1 Dynamic Mass Balances -- 2.2.2 Analogy to Deriving Enzymatic Rate Equations -- 2.2.3 Formulating Flux Balances at the Genome‐Scale -- 2.2.4 Constrained Optimization -- 2.2.5 Principles -- 2.2.6 Additional Constraints -- 2.2.7 Flux-Concentration Duality -- 2.2.8 Recap -- 2.3 Network Reconstruction -- 2.3.1 Assembling the Reactome -- 2.3.2 Basic Principles of Network Reconstruction -- 2.3.3 Curation -- 2.3.4 GEMs Have a Genomic Basis -- 2.3.5 Computational Queries -- 2.3.6 Scope Expansion -- 2.3.7 Knowledge Bases -- 2.3.8 Availability of GEMs -- 2.3.9 Recap -- 2.4 Brief History of the GEM for E. coli -- 2.4.1 "]
[{"$nulls":4},"Origin -- 2.4.2 Model Organism -- 2.4.3 Key Predictions -- 2.4.4 Design Algorithms -- 2.4.5 Scope Expansions -- 2.4.6 Recap -- 2.5 From Metabolism to the Proteome -- 2.5.1 ME Models -- 2.5.2 Capabilities of ME Models -- 2.5.2.1 Growth‐Coupled Metabolic Designs Can Be Reproduced in GEMs -- 2.5.2.2 ME Models Can Reflect Properties of the Metalloproteome -- 2.5.2.3 ME Models Can Compute the Biomass Objective Function."]
[{"$nulls":4},"2.5.2.4 Computing Stresses -- 2.5.3 Recapitulation -- 2.6 Current Developments -- 2.6.1 Kinetics -- 2.6.2 Transcriptional Regulation -- 2.6.2.1 iModulons -- 2.6.2.2 Activities -- 2.6.3 Protein Structures -- 2.7 Broader Perspectives -- 2.7.1 Distal Causation -- 2.7.2 Contextualization of GEMs Within Workflows -- 2.8 What Does the Future Look Like for GEMs? -- Disclaimer -- Acknowledgments -- References -- Chapter 3 Quantitative Metabolic Flux Analysis Based on Isotope Labeling -- 3.1 Introduction -- 3.1.1 What Metabolic Flux Analysis Is About -- 3.1.2 The Variants of 13C‐MFA -- 3.2 A Toy Example Illustrates the Basic Principles -- 3.2.1 Fluxomics: More Than Just a Branch of Metabolomics -- 3.2.2 Isotope Labeling: The Key to Metabolic Fluxes -- 3.2.3 From the Data to the Intracellular Fluxes -- 3.2.4 INST‐13C‐MFA: Metabolic Stationary, but Isotopically Nonstationary -- 3.2.5 From Measurements to Flux Estimates: Parameter Fitting -- 3.2.6 Flux Estimates Have Confidence Bounds: Statistical Analysis -- 3.2.7 The Classical Approach at Metabolic and Isotopic Stationary State -- 3.2.8 An Additional Source of Information: Carbon Atom Transitions -- 3.2.9 Input Labeling Design: How Informative Can an Experiment Be Made? -- 3.2.10 The Isotopomers of a Single Metabolite can be a Rich Source of Information -- 3.2.11 Bidirectional Reaction Steps: More Than Just Nuisance Factors -- 3.2.12 Isotopomer Fractions Cannot Be Measured Comprehensively -- 3.3 Lessons Learned from the Example -- 3.3.1 Definition of 13C‐MFA Revisited -- 3.3.2 Statistical Evaluation and Optimal Experimental Design -- 3.4 How to Configure an Isotope Labeling Experiment -- 3.4.1 Modeling and Simulation of Isotope Labeling Experiments -- 3.4.2 Metabolic Network Specification -- 3.4.3 Atom Transition Network Specification -- 3.4.4 Input Labeling Composition -- 3.4.5 Measurement Specification."]
[{"$nulls":4},"3.4.6 Flux Constraints -- 3.4.7 In Silico Experimental ILE Design -- 3.5 Putting Theory into Practice -- 3.5.1 A Recipe How to Start -- 3.5.2 Metabolic and Isotopic Stationarity -- 3.5.3 Measuring Extracellular Fluxes -- 3.5.4 Administering Labeled Substrate(s) -- 3.5.5 Metabolomics: Sampling, Sample Preparation, and Analytical Procedures -- 3.5.6 Adjusting Labeling Enrichments for Isotopic Steady State Approximation -- 3.5.7 Correcting Labeling Enrichments for Natural Isotope Abundance -- 3.5.8 Simulation of Labeling Data and Flux Estimation -- 3.5.9 Delicacies of INST‐13C‐MFA -- 3.6 Future Challenges of 13C‐MFA -- Acknowledgments -- Abbreviations -- References -- Chapter 4 Proteome Constraints in Genome‐Scale Models -- 4.1 Introduction -- 4.2 Cellular Constraints -- 4.3 Formulation of Proteome Constraints -- 4.3.1 Coarse‐Grained Integration of Proteome Constraints -- 4.3.2 Fine‐Tuned Integration of Proteome Constraints -- 4.4 Perspectives -- References -- Chapter 5 Kinetic Models of Metabolism -- 5.1 Introduction -- 5.2 Definition of Enzyme Kinetics -- 5.2.1 Michaelis-Menten Formula -- 5.3 Factors Affecting Intracellular Enzyme Kinetics -- 5.4 Kinetic Model: Definition and Scope -- 5.4.1 What Is a Kinetic Model? -- 5.4.2 Scope of Kinetic Models -- 5.4.3 How to Build a Functional Kinetic Model? -- 5.5 Main Mathematical Expressions in Description of Reaction Rates -- 5.5.1 Mechanistic Rate Expressions -- 5.6 Approximative Rate Expressions -- 5.7 Approaches "]
[{"$nulls":4},"to Assign Parameters in the Rate Expressions -- 5.7.1 Direct Measurements of Kinetic Parameters in Enzyme Assays -- 5.7.2 Querying Databases -- 5.7.3 Inferring from Measured Fluxes -- 5.7.4 Parameters Inference Using the Statistical Analysis -- 5.8 Applications -- 5.9 Perspectives -- References -- Chapter 6 Metabolic Control Analysis."]
[{"$nulls":4},"6.1 The Metabolic Engineering Context of Metabolic Control Analysis -- 6.2 MCA Theory -- 6.2.1 Metabolic Steady State -- 6.2.2 Flux Control Coefficients -- 6.2.3 Examples of the Flux-Enzyme Relationship -- 6.2.4 Flux Summation Theorem -- 6.2.5 Concentration Control Coefficients -- 6.2.6 Linking Control Coefficients to Enzyme Properties -- 6.2.6.1 Enzyme Rate Equations and Elasticity Coefficients -- 6.2.6.2 Elasticities and Control Coefficients -- 6.2.6.3 Block Coefficients and Top‐Down Analysis -- 6.2.7 Feedback Inhibition -- 6.2.8 Large Alterations of Enzyme Activity -- 6.3 Implications of MCA for Metabolic Engineering Strategies -- 6.3.1 Abolishing Feedback Inhibition -- 6.3.2 Increasing Demand for Product -- 6.3.3 Inhibition of Competing Pathways -- 6.3.4 Designing Large Changes in Metabolic Flux -- 6.3.4.1 Yeast Tryptophan Synthesis -- 6.3.4.2 The Universal Method -- 6.3.4.3 Bacterial Production of Aromatic Amino Acids -- 6.3.4.4 Penicillin and Other Instances -- 6.3.5 Impacts on Yield from a Growing System -- 6.4 Conclusion -- Appendix 6.A: Feedback Inhibition Simulation -- References -- Chapter 7 Thermodynamics of Metabolic Pathways -- 7.1 Bioenergetics in Life and in Metabolic Engineering -- 7.2 Thermodynamics‐Based Flux Analysis Workflow -- 7.2.1 Thermodynamic Model Curation -- 7.2.1.1 Estimation of the Standard Free Energies of Formation -- 7.2.1.2 Compensating for Compartment‐Specific Ionic Strength and pH -- 7.2.1.3 Compensating the Free Energy of Formation for Isomer Distributions -- 7.2.1.4 Computing the Transformed Free Energies of Reaction -- 7.2.2 Mathematical Formulation -- 7.3 Thermodynamics‐Based Flux Analysis Applications -- 7.3.1 Constraining the Flux Space with Metabolomics Data -- 7.3.2 Characterizing the Feasible Concentration Space -- 7.4 Conclusion and Future Perspectives -- References -- Chapter 8 Pathway Design."]
[{"$nulls":4},"Definition -- 8.1 De Novo Design of Metabolic Pathways -- 8.1.1 Manual Versus Computational Design -- 8.2 Pathway Design Workflow -- 8.2.1 Biochemical Search Space -- 8.2.1.1 Reaction Prediction -- 8.2.1.2 Retrobiosynthesis -- 8.2.1.3 Network Data Representation -- 8.2.2 Pathway Search -- 8.2.2.1 Stoichiometric Matrix‐Based Search -- 8.2.2.2 Graph‐Based Search -- 8.2.2.3 Pathway Ranking -- 8.2.3 Enzyme Assignment -- 8.2.3.1 Enzyme Prediction for Orphan and Novel Reactions -- 8.2.3.2 Choice of Protein Sequence -- 8.2.4 Pathway Feasibility -- 8.2.4.1 Chassis Metabolic Model -- 8.2.4.2 Stoichiometric Feasibility -- 8.2.4.3 Thermodynamic Feasibility -- 8.2.4.4 Kinetic Feasibility -- 8.2.4.5 Toxicity of Intermediates -- 8.3 Applications -- 8.3.1 Available Tools for Pathway Design -- 8.3.2 Successful Applications of Pathway Design Tools -- 8.3.3 Practical Example of Pathway Design -- 8.3.3.1 Creating a Biochemical Network Around BDO -- 8.3.3.2 Search for Biosynthetic Pathways -- 8.3.3.3 Finding Enzymes for Novel Reactions -- 8.3.3.4 Stoichiometric and Thermodynamic Pathway Evaluation -- 8.3.3.5 Overall Ranking of Pathways -- 8.4 Conclusions and Future Perspectives -- References -- Chapter 9 Metabolomics -- 9.1 Introduction -- 9.2 Fundamentals -- 9.2.1 Experimental Design -- 9.2.2 Targeted and Untargeted Metabolomics -- 9.2.3 Sequences and Standards -- 9.3 Analytical Techniques -- 9.3.1 Sample Preparation -- 9.3.2 Separation Techniques -- 9.3.2.1 Liquid Chromatography -- 9.3.2.2 Gas Chromatography -- 9.3.2.3 Alternative Separation Techniques -- 9.3.3 "]
[{"$nulls":4},"Mass Spectrometry -- 9.3.3.1 Ionization Techniques -- 9.3.3.2 Low‐Resolution MS -- 9.3.3.3 High‐Resolution MS -- 9.3.3.4 Acquisition Modes for Targeted MS -- 9.3.3.5 Acquisition Modes for Untargeted Metabolomics -- 9.4 Data Analysis -- 9.4.1 Data Processing in Untargeted Metabolomics."]
[{"$nulls":4},"9.4.1.1 Preprocessing of Individual MS Runs."]