Note: Intro -- Title page -- Copyright page -- Contents -- Foreword -- Preface -- Contributors -- 1: Classical Strain Improvement -- 1.0 Introduction -- 1.1 The Approach Defined -- 1.2 Mutagenesis -- 1.2.1 Numerical Considerations in Screen Design -- 1.2.2 Random Genetic Drift -- 1.2.3 Forced Mutagenesis -- 1.2.4 Strain Mating -- 1.3 Genotypic Landscapes -- 1.4 Screening -- 1.4.1 Rational Screens -- 1.4.2 Random Screens -- 1.4.3 Screening Platforms -- 1.5 Conclusions -- References -- 2: Tracer-Based Analysis of Metabolic Flux Networks -- 2.0 Introduction -- 2.1 Setting Up a Stoichiometric Network Model -- 2.2 Small-Scale Models versus Genome Scale Models -- 2.3 Network Analysis: Maximum Theoretical Yield -- 2.4 (Stoichiometric) Metabolic Flux Analysis -- 2.5 Carrying Out a Labeling Experiment -- 2.6 MEASURING ISOTOPE LABELING PATTERNS -- 2.7 Tracer-Based MFA -- 2.8 Validating Metabolic Flux Networks -- 2.9 Conclusions -- Acknowledgments -- References -- 3: Integration of "Omics" Data with Genome-Scale Metabolic Models -- 3.0 Introduction -- 3.1 Genome-Scale Metabolic Networks -- 3.2 Constraint-Based Modeling Theory -- 3.3 Current Analysis of Omics Data -- 3.4 New Approaches to Developing Model Constraints -- 3.5 Use of Gene Expression Data in Metabolic Models -- 3.6 Use of Metabolomics Data in Metabolic Models: TMFA Example -- 3.7 Integration of Multiple Omics Data Sets -- 3.8 Future Directions and Applications to Strain Engineering -- References -- 4: Strain Improvement via Evolutionary Engineering -- 4.0 Introduction -- 4.1 Methodologies for Evolutionary Engineering -- 4.1.1 Adaptive Evolution -- 4.1.2 Genome Shuffling -- 4.1.3 Global Transcriptional Machinery Engineering -- 4.1.4 Transposon Insertion Mutagenesis -- 4.1.5 Multiplex Automated Genome Engineering -- 4.1.6 Tractable Multiplex Recombineering. , 4.1.7 Chemically Induced Chromosomal Evolution -- 4.1.8 Multiscale Analysis of Library Enrichment (SCALE) -- 4.1.9 Screening and Selection -- 4.2 Examples of Evolutionary Engineering -- 4.2.1 Enhancement of Product Yield and Productivity -- 4.2.2 Extension of Substrate Range -- 4.2.3 Improvement of Cellular Properties -- 4.3 Conclusions and Future Prospects -- Acknowledgments -- References -- 5: Rapid Fermentation Process Development and Optimization -- 5.0 Introduction -- 5.1 Overview of Classical Fermentation Process Development Methodology -- 5.1.1 Noninvasive Sensor Technologies -- 5.2 Fermentation Process Development and Optimization -- 5.2.1 Medium Design and Optimization -- 5.2.2 Optimization of Growth Conditions -- 5.3 Rapid Process Development and Optimization Using Conventional Fermentation System -- 5.3.1 Dynamic DO Control to Determine Optimal Feed Rate for Carbon Source-Limited Fermentation -- 5.3.2 Feed Forward Control for Carbon Source Excess Fermentation -- 5.4 Strain Evaluation and Process Optimization under Scale-Down Conditions -- 5.4.1 Identify Scale-Down Parameters -- 5.4.2 Scale-Down of Mixing Related Parameters -- 5.4.3 Oxygen Uptake Rate (OUR) Clipping -- 5.4.4 Dissolved CO2 -- 5.5 Control and Sensor Technologies for Minibioreactor -- 5.5.1 Temperature Sensing and Control -- 5.5.2 Mixing -- 5.5.3 DO -- 5.5.4 pH -- 5.5.5 Cell Concentration -- 5.5.6 Feeding -- 5.6 Commercial High-Throughput Fermentation Systems -- 5.6.1 Shaken Minibioreactors -- 5.6.2 Stirred Minibioreactor -- 5.6.3 Parallel Benchtop Fermentation System -- 5.7 Trends in Development of High the greata-Throughput Minibioreactor System -- 5.8 Case Studies of Fermentation Process Development and Optimization Using High-Throughput Minibioreactors -- 5.8.1 Case Study 1: Protein Production -- 5.8.2 Case Study 2: Antibody Fragment Expression. , 5.9 Conclusions and THE Path Forward -- References -- 6: The Clavulanic Acid Strain Improvement Program at DSM Anti-Infectives -- 6.0 Introduction -- 6.1 The Biosynthetic Pathway to Clavulanic Acid -- 6.2 The Strategy for Improvement of Multiple Complex Phenotypes -- 6.3 Results and Discussion -- 6.3.1 The Panlabs Years-Results from 1991 to 1999 -- 6.3.2 The DSM Years-Results from 1999 to 2006 -- 6.4 Future Perspectives -- Acknowledgments -- References -- 7: Metabolic Engineering of Recombinant E. coli for the Production of 3-Hydroxypropionate -- 7.0 Introduction to Biosynthesis of 3-Hydroxypropionic Acid -- 7.1 Organic Acid Toxicity -- 7.2 Understanding 3-HP Toxicity -- 7.2.1 Choosing an Approach for Evolving Tolerance -- 7.2.2 Selection Design for Evolving 3-HP Tolerance -- 7.2.3 Taking a Closer Look at Selection Design -- 7.2.4 Constructing the 3-HP Toleragenic Complex -- 7.3 Strain Design -- 7.3.1 Evaluation of the 3-HP-TGC -- 7.3.2 Complex Tolerant Phenotype: Metabolism of 3-HP to a Toxic Intermediate -- 7.4 Combining 3-HP Tolerance and 3-HP Production -- 7.5 Summary -- References -- 8: Complex System Engineering: A Case Study for an Unsequenced Microalga -- 8.0 Historical Perspective -- 8.1 Analysis of Algal Biomass Composition -- 8.1.1 Defining the Parameters of an "Ideal" Strain -- 8.1.2 Tool Development for the Analysis of Growth and Lipid Production -- 8.1.3 Selection and Characterization of a Promising C. vulgaris Strain -- 8.2 Development of Hypothesis-Driven Strain Improvement Strategies -- 8.2.1 Systems Biology Analysis in an Unsequenced Microalga -- 8.2.2 Transcriptome-to-Proteome Pipelining -- 8.2.3 Identification of Strain Engineering Targets -- 8.3 Implementation of Biological Tools I-Development of a Transformation System -- 8.3.1 Vector Construction -- 8.3.2 Protoplast Preparation and Transformation of C. vulgaris UTEX395. , 8.3.3 Stability Evaluation of Transformants -- 8.3.4 C. vulgaris Endogenous Promoter Identification and Characterization -- 8.4 Implementation of Biological Tools II-Development of a Self-Lysing, Oil-Producing Alga for Biofuels Production -- 8.4.1 Algal Lipid Extraction -- 8.4.2 Algal Cell Wall Complexity and Enzymatic Treatment Effects -- 8.4.3 High-Resolution Imaging of Enzymatic Treatment Effects -- 8.4.4 Production Strain Development -- 8.5 Concluding Remarks -- Acknowledgments -- References -- 9: Meiotic Recombination-Based Genome Shuffling of Saccharomyces cerevisiae and Schefferomyces stiptis for Increased Inhibitor Tolerance to Lignocellulosic Substrate Toxicity -- 9.0 Introduction -- 9.1 Methodology -- 9.1.1 Meiotic Recombination-Mediated Genome Shuffling -- 9.1.2 Inducing Genome Shuffling through Meiosis versus Protoplast Fusion -- 9.2 Results and Discussion of Strain Development -- 9.2.1 Generation of Mutant Pools -- 9.2.2 Screening and Selection of Mutant and Evolved Populations -- 9.2.3 Increasing HWSSL Tolerance through Genome Shuffling -- 9.2.4 Tolerance to HWSSL Leads to Increased Ethanol Production -- 9.2.5 Tolerance to HWSSL Leads to Cross-Tolerance to Multiple Inhibitors -- 9.2.6 Comparison between the S. stipitis and S. cerevisiae Genome Shuffling Studies -- 9.3 Conclusions and Future Directions -- References -- Index -- Supplemental Images.

Note: Cover -- Half Title -- Title Page -- Copyright Page -- Dedication -- Contents -- Preface -- Authors -- Chapter 1: Introduction to Environmental Measurements -- 1.1 Role of Measurement in Environmental Studies -- 1.1.1 Units of Measurement -- 1.1.2 Conversions between Units -- 1.1.3 Significant Figures -- 1.2 Pollutants: Sources and Measurements -- 1.2.1 Classes of Environmental Contaminants -- 1.2.1.1 Products of Combustion -- 1.2.1.2 Industrial Emissions -- 1.2.1.3 Other Sources of Environmental Contamination -- 1.2.2 Regulating the Environment -- 1.3 Design of Environmental Studies -- 1.3.1 Sampling and Analysis -- 1.4 Basic Statistical Data Handling -- 1.4.1 Errors in Quantitative Analysis -- 1.4.2 Statistics of Repeated Measurements: Precision -- 1.4.2.1 Precision and Standard Deviation -- 1.4.3 Distribution of Error -- 1.4.4 Confidence Interval and the t-Distribution -- 1.4.4.1 Estimation of Mean from Several Sets of Measurements -- 1.4.4.2 Estimation of Standard Deviation from Several Sets of Measurements -- 1.5 Significance Tests -- 1.5.1 Hypothesis Testing -- 1.5.1.1 Comparison between a Measured and a Known Value -- 1.5.1.2 Comparison of the Mean of Two Samples -- 1.5.1.3 Comparison of Standard Deviations Using the F-Test -- 1.5.2 Outliers -- 1.5.2.1 Rule of the Huge Error -- 1.5.2.2 Dixon Test for Rejection of Outliers -- 1.5.3 Reporting Data -- 1.6 Standards and Calibration -- 1.6.1 Calibration Methods -- 1.6.2 Standard Addition Method -- 1.7 Performance of Analytical Methods: Figures of Merit -- 1.7.1 Sensitivity -- 1.7.2 Detection Limit -- 1.7.3 Range of Quantitation -- 1.7.4 Validation of New Methods -- Study Questions -- Chapter 2: Environmental Sampling -- 2.1 The Sampling Plan -- 2.1.1 Spatial and Temporal Variability -- 2.1.2 Development of the Plan -- 2.1.3 Sampling Strategies -- 2.1.3.1 Systematic Sampling. , 2.1.3.2 Random Sampling -- 2.1.3.3 Judgmental Sampling -- 2.1.3.4 Stratified Sampling -- 2.1.3.5 Haphazard Sampling -- 2.1.3.6 Continuous Monitoring -- 2.2 Types of Samples -- 2.3 Sampling and Analysis -- 2.3.1 Samples in the Laboratory -- 2.4 Statistical Aspects of Sampling -- 2.5 Water Sampling -- 2.5.1 Surface Water Sampling -- 2.5.2 Ground Water Well Sampling -- 2.6 Biological Tissue Sampling -- 2.7 Soil Sampling -- 2.8 Sampling Stratified Levels in Containers -- 2.9 Preservation of Samples -- 2.9.1 Volatilization -- 2.9.2 Choice of Proper Containers -- 2.9.3 Absorption of Gases from the Atmosphere -- 2.9.4 Chemical Changes -- 2.9.5 Sample Preservation for Soil, Sludges, and Hazardous Wastes -- Study Questions -- Chapter 3: Spectroscopic Methods -- 3.1 Spectroscopic Methods for Environmental Analysis -- 3.1.1 Properties of Electromagnetic Radiation -- 3.1.2 The Electromagnetic Spectrum -- 3.1.3 Radiation and Matter -- 3.2 Absorption Spectroscopy -- 3.2.1 Beer's Law -- 3.3 Emission Spectroscopy -- 3.3.1 Fluorescence -- 3.3.2 Atomic Emission -- 3.4 Spectroscopic Apparatus -- 3.4.1 Light Sources -- 3.4.2 Wavelength Selection -- 3.4.2.1 Filters -- 3.4.2.2 Monochromators -- 3.4.3 Detectors -- 3.5 Ultraviolet and Visible Absorption Spectroscopy -- 3.5.1 UV and Visible Instrumentation -- 3.5.1.1 Light Sources -- 3.5.1.2 UV-Vis Detectors -- 3.5.1.3 Ultraviolet: Visible Spectroscopy Samples -- 3.5.2 Colorimetry -- 3.6 Infrared Spectroscopy -- 3.6.1 Scanning Infrared Instrumentation -- 3.6.1.1 IR Sources -- 3.6.1.2 Infrared Monochromators -- 3.6.2 Fourier Transform Infrared Spectrometry -- 3.6.2.1 Advantages of FTIR -- 3.6.2.2 Samples for Infrared Spectroscopy -- 3.7 Atomic Absorption Spectroscopy -- 3.7.1 Flame Atomic Absorbance Spectroscopy -- 3.7.2 Graphite Furnace Atomic Absorption Spectrometry -- 3.7.3 Interferences in Atomic Absorption. , 3.7.3.1 Spectral Interference -- 3.7.3.2 Chemical Interference -- 3.7.3.3 Ionization Interference -- 3.7.3.4 Background Correction in Atomic Absorption Spectrometry -- 3.8 Inductively Coupled Plasma Emission Spectroscopy -- 3.8.1 Comparison of Atomic Spectroscopic Methods -- 3.9 X-Ray Fluorescence -- 3.9.1 Wavelength-Dispersive XRF versus Energy-Dispersive XRF -- 3.9.2 X-Ray Instrumentation -- 3.9.2.1 Sources -- 3.9.2.2 X-Ray Detectors -- 3.9.2.3 X-Ray Fluorescence Samples -- 3.10 Hyphenated Spectroscopic Methods -- Study Questions -- Chapter 4: Chromatographic Methods -- 4.1 Principles of Chromatography -- 4.1.1 Column Efficiency -- 4.1.2 The General Elution Problem -- 4.2 Quantitation in Chromatography -- 4.2.1 External Standard Method -- 4.2.2 The Internal Standard Method -- 4.3 Gas Chromatography -- 4.3.1 Injection Devices -- 4.3.2 Columns -- 4.3.2.1 Packed Columns -- 4.3.2.2 Open Tubular Columns -- 4.3.2.3 Column Temperature -- 4.4 GC Detectors -- 4.4.1 Thermal Conductivity Detector -- 4.4.2 Flame Ionization Detector -- 4.4.3 Electron Capture Detector -- 4.4.4 Photoionization Detector -- 4.4.5 Flame Photometric Detector -- 4.4.6 Pulsed Flame Photometric Detector -- 4.4.7 Thermionic or Nitrogen-Phosphorous Detector -- 4.4.8 Pulsed Discharge Detector -- 4.4.9 Mass Selective Detector -- 4.4.10 Comparison of Detectors -- 4.5 High-Performance Liquid Chromatography -- 4.5.1 Reverse Phase Liquid Chromatography -- 4.5.2 Normal Phase Liquid Chromatography -- 4.6 HPLC Instrumentation -- 4.6.1 Solvent Delivery Systems -- 4.6.2 Solvent Gradient Systems -- 4.6.3 Sample Injectors -- 4.6.4 HPLC Columns -- 4.6.4.1 Precolumns and Guard Columns -- 4.6.4.2 Analytical Columns -- 4.6.4.3 Eluents -- 4.7 HPLC Detectors -- 4.7.1 UV Absorption Detectors -- 4.7.2 Fluorescence Detectors -- 4.7.3 Evaporative Light Scattering Detector -- 4.7.4 Mass Spectrometric Detection. , 4.8 Ion Chromatography -- 4.9 Supercritical Fluid Chromatography -- 4.9.1 SFC Instrumentation -- 4.10 Applications of Chromatography in Environmental Analysis -- Study Questions -- Chapter 5: Mass Spectrometry -- 5.1 Interpretation of Spectra -- 5.2 Basic Instrumentation -- 5.2.1 Vacuum System -- 5.2.2 Inlet -- 5.3 Ion Sources -- 5.3.1 Electron Impact Ionization -- 5.3.2 Chemical Ionization -- 5.3.3 Atmospheric Pressure Ionization Sources -- 5.3.4 Proton Transfer Reaction MS -- 5.4 Mass Analyzers -- 5.4.1 Quadrupole Mass Analyzer -- 5.4.2 Magnetic Sector Mass Analyzer -- 5.4.3 The Ion Trap Mass Analyzer -- 5.5 Ion Detectors -- 5.6 Gas Chromatography MS -- 5.7 Liquid Chromatography MS -- 5.8 Inductively Coupled Plasma MS -- 5.9 Data Collection -- 5.10 Library Searching Techniques -- Study Questions -- Chapter 6: Sample Preparation Techniques -- 6.1 Extraction of Organic Analytes from Liquid Samples -- 6.1.1 Liquid-Liquid Extraction -- 6.1.1.1 Successive Extractions -- 6.1.1.2 Instrumentation for LLE -- 6.1.1.3 Continuous LLE -- 6.1.2 Solid-Phase Extraction -- 6.1.2.1 The SPE Process -- 6.1.2.2 Advantages of SPE -- 6.1.3 Solid-Phase Microextraction -- 6.2 Extraction of Organic Analytes from Solid Samples -- 6.2.1 Soxhlet Extraction -- 6.2.2 Accelerated Solvent Extraction -- 6.2.3 Ultrasonic Extraction of Organics -- 6.2.4 Supercritical Fluid Extraction -- 6.2.4.1 Instrumentation -- 6.2.4.2 Choosing SFE Conditions -- 6.2.4.3 Advantages of SFE -- 6.3 Post-Extraction Procedures -- 6.3.1 Concentration of Sample Extracts -- 6.3.2 Sample Cleanup -- 6.4 Extraction of Metals from Sample Matrices -- 6.4.1 Acid Digestion of Samples for Determination of Metals -- 6.4.2 Extraction Procedures -- 6.4.3 Microwave Digestion -- 6.4.4 Ultrasonic Extraction -- 6.4.5 Organic Extraction of Metals -- 6.4.5.1 Formation of Metal Chelates. , 6.5 Speciation of Metals in Environmental Samples -- Study Questions -- Chapter 7: Chemical Methods -- 7.1 Types of Chemical Reactions -- 7.1.1 Precipitation -- 7.1.2 Complexation and Chelation Reactions -- 7.1.3 Oxidation/Reduction Reactions -- 7.1.4 Derivatization Reactions -- 7.1.4.1 Alkylation and Acylation -- 7.1.4.2 Sylilation -- 7.1.4.3 Diazotization -- 7.1.4.4 Selection of Derivatizing Reagent -- 7.2 Wet Methods -- 7.2.1 Titrations -- 7.2.2 Titration Calculations -- 7.2.3 Types of Titrations -- 7.3 Colorimetric Methods -- 7.3.1 Colorimetric Indicating Tubes for Air Pollutants -- Study Questions -- Suggested Reading -- Chapter 8: Electrochemical Methods -- 8.1 Potentiometric Measurements -- 8.1.1 pH Measurement -- 8.1.2 Other Specific Ion Electrodes -- 8.2 Determination of Metals by Voltammetry -- Study Questions -- Chapter 9: Radiochemical Methods -- 9.1 Units of Measurement -- 9.2 Instruments for Measuring Radioactivity -- 9.2.1 Gas: Flow Proportional Counters -- 9.2.2 Alpha Scintillation Counter -- 9.2.3 Liquid Scintillation Counters -- 9.2.4 Alpha Spectrometers -- 9.2.5 Gamma Spectrometers -- 9.3 Determination of Gross Alpha and Gross Beta Radioactivity -- 9.3.1 Evaporation Method -- 9.3.1.1 Gross Activity of the Sample -- 9.3.1.2 Activity of Dissolved and Suspended Matter -- 9.3.1.3 Activity of Semisolid Samples -- 9.3.2 Coprecipitation Method for Gross Alpha Activity -- 9.4 Measurement of Specific Radionuclides -- 9.4.1 Radium -- 9.4.1.1 Precipitation Method and Alpha Counting -- 9.4.1.2 Precipitation and Emanation Method to Measure Radium as Radon-222 -- 9.4.1.3 Sequential Precipitation Method -- 9.4.1.4 Measurement of Radium-224 by Gamma Spectroscopy -- 9.4.2 Radon -- 9.4.3 Uranium -- 9.4.3.1 Determination of Total Alpha Activity -- 9.4.3.2 Determination of Isotopic Content of Uranium Alpha Activity -- 9.4.4 Radioactive Strontium. , 9.4.5 Tritium.