MODERN BIOTECHNOLOGY -- CONTENTS -- Preface -- Acknowledgments -- List of Illustrations -- 1 Biotechnology -- Introduction -- The Directed Manipulation of Genes Distinguishes the New Biotechnology from Prior Biotechnology -- Growth of the New Biotechnology Industry Depends on Venture Capital -- Submerged Fermentations Are the Industry's Bioprocessing Cornerstone -- Oil Prices Affect Parts of the Fermentation Industry -- Growth of the Antibiotic/Pharmaceutical Industry -- The Existence of Antibiotics Was Recognized in 1877 -- Penicillin Was the First Antibiotic Suitable for Human Systemic Use -- Genesis of the Antibiotic Industry -- Other Antibiotics Were Quickly Discovered after the Introduction of Penicillin -- Discovery and Scaleup Are Synergistic in the Development of Pharmaceutical Products -- Success of the Pharmaceutical Industry in Research, Development, and Engineering Contributed to Rapid Growth but Also Resulted in Challenges -- Growth of the Amino Acid/Acidulant Fermentation Industry -- Production of Monosodium Glutamate (MSG) via Fermentation -- The Impact of Glutamic Acid Bacteria on Monosodium Glutamate Cost Was Dramatic -- Auxotrophic and Regulatory Mutants Enabled Production of Other Amino Acids -- Prices and Volumes Are Inversely Related -- Biochemical Engineers Have a Key Function in All Aspects of the Development Process for Microbial Fermentation -- References -- Homework Problems -- 2 New Biotechnology -- Introduction -- Growth of the Biopharmaceutical Industry -- The Biopharmaceutical Industry Is in the Early Part of Its Life Cycle -- Discovery of Type II Restriction Endonucleases Opened a New Era in Biotechnology -- The Polymerase Chain Reaction (PCR) Is an Enzyme-Mediated, In Vitro Amplification of DNA -- Impacts of the New Biotechnology on Biopharmaceuticals, Genomics, Plant Biotechnology, and Bioproducts.

Biotechnology Developments Have Accelerated Biological Research -- Drug Discovery Has Benefited from Biotechnology Research Tools -- The Fusing of Mouse Spleen Cells with T Cells Facilitated Production of Antibodies -- Regulatory Issues Add to the Time Required to Bring a New Product to Market -- New Biotechnology Methods Enable Rapid Identification of Genes and Their Protein Products -- Genomics Is the Scientific Discipline of Mapping, Sequencing, and Analyzing Genomes -- Products from the New Plant Biotechnology Are Changing the Structure of Large Companies that Sell Agricultural Chemicals -- Bioproducts from Genetically Engineered Microorganisms Will Become Economically Important to the Fermentation Industry -- References -- Homework Problems -- 3 Bioproducts and Biofuels -- Introduction -- Biocatalysis and the Growth of Industrial Enzymes -- Glucose Isomerase Catalyzed the Birth of a New Process for Sugar Production from Corn -- Identification of a Thermally Stable Glucose Isomerase and an Inexpensive Inducer Was Needed for an Industrial Process -- The Demand for High-Fructose Corn Syrup (HFCS) Resulted in Large-Scale Use of Immobilized Enzymes and Liquid Chromatography -- Rapid Growth of HFCS Market Share Was Enabled by Large-Scale Liquid Chromatography and Propelled by Record-High Sugar Prices -- Biocatalysts Are Used in Fine-Chemical Manufacture -- Growth of Renewable Resources as a Source of Specialty Products and Industrial Chemicals -- A Wide Range of Technologies Are Needed to Reduce Costs for Converting Cellulosic Substrates to Value-Added Bioproducts and Biofuels -- Renewable Resources Are a Source of Natural Plant Chemicals -- Bioseparations Are Important to the Extraction, Recovery, and Purification of Plant-Derived Products -- Bioprocess Engineering and Economics -- Bioseparations and Bioprocess Engineering -- References.

Homework Problems -- 4 Microbial Fermentations -- Introduction -- Fermentation Methods -- Fermentations Are Carried Out in Flasks, Glass Vessels, and Specially Designed Stainless-Steel Tanks -- Microbial Culture Composition and Classification -- Microbial Cells: Prokaryotes versus Eukaryotes -- Classification of Microorganisms Are Based on Kingdoms -- Prokaryotes Are Important Industrial Microorganisms -- Eukaryotes Are Used Industrially to Produce Ethanol, Antibiotics, and Biotherapeutic Proteins -- Wild-Type Organisms and Growth Requirements in Microbial Culture -- Wild-Type Organisms Find Broad Industrial Use -- Microbial Culture Requires that Energy and All Components Needed for Cell Growth Be Provided -- Media Components and Their Functions (Complex and Defined Media) -- Carbon Sources Provide Energy, and Sometimes Provide Oxygen -- Complex Media Have a Known Basic Composition but a Chemical Composition that Is Not Completely Defined -- Industrial Fermentation Broths May Have a High Initial Carbon (Sugar) Content (Ethanol Fermentation Example) -- The Accumulation of Fermentation Products Is Proportional to Cell Mass in the Bioreactor -- A Microbial Fermentation Is Characterized by Distinct Phases of Growth -- Expressions for Cell Growth Rate Are Based on Doubling Time -- Products of Microbial Culture Are Classified According to Their Energy Metabolism (Types I, II, and III Fermentations) -- Product Yields Are Calculated from the Stoichiometry of Biological Reactions (Yield Coefficients) -- The Embden-Meyerhof Glycolysis and Citric Acid Cycles Are Regulated by the Relative Balance of ATP, ADP, and AMP in the Cell -- References -- Homework Problems -- 5 Modeling and Simulation -- Introduction -- The Runge-Kutta Method -- Simpson's Rule -- Fourth-Order Runge-Kutta Method -- Ordinary Differential Equations (ODEs).

Runge-Kutta Technique Requires that Higher-Order Equations Be Reduced to First-Order ODEs to Obtain Their Solution -- Systems of First-Order ODEs Are Represented in Vector Form -- Kinetics of Cell Growth -- K(s) Represents Substrate Concentration at Which the Specific Growth Rate Is Half Its Maximum -- Simulation of a Batch Ethanol Fermentation -- Ethanol Case Study -- Luedeking-Piret Model -- Continuous Stirred-Tank Bioreactor -- Batch Fermentor versus Chemostat -- References -- Homework Problems -- 6 Aerobic Bioreactors -- Introduction -- Fermentation Process -- Fermentation of Xylose to 2,3-Butanediol by Klebsiella oxytoca Is Aerated but Oxygen-Limited -- Oxygen Transfer from Air Bubble to Liquid Is Controlled by Liquid-Side Mass Transfer -- Chapter 6 Appendix: Excel Program for Integration of Simultaneous Differential Equations -- References -- Homework Problems -- 7 Enzymes -- Introduction -- Enzymes and Systems Biology -- Industrial Enzymes -- Enzymes: In Vivo and In Vitro -- Fundamental Properties of Enzymes -- Classification of Enzymes -- Sales and Applications of Immobilized Enzymes -- Assaying Enzymatic Activity -- Enzyme Assays -- Batch Reactions -- Thermal Enzyme Deactivation -- References -- Homework Problems -- 8 Enzyme Kinetics -- Introduction -- Initial Rate versus Integrated Rate Equations -- Obtaining Constants from Initial Rate Data Is an Iterative Process -- Batch Enzyme Reactions: Irreversible Product Formation (No Inhibition) -- Rapid Equilibrium Approach Enables Rapid Formulation of an Enzyme Kinetic Equation -- The Pseudo-Steady-State Method Requires More Effort to Obtain the Hart Equation but Is Necessary for Reversible Reactions -- Irreversible Product Formation in the Presence of Inhibitors and Activators -- Inhibition -- Competitive Inhibition -- Uncompetitive Inhibition -- (Classical) Noncompetitive Inhibition.

Substrate Inhibition -- Example of Reversible Reactions -- Coenzymes and Cofactors Interact in a Reversible Manner -- King-Altman Method -- Immobilized Enzyme -- Online Databases of Enzyme Kinetic Constants -- References -- Homework Problems -- 9 Metabolism -- Introduction -- Aerobic and Anaerobic Metabolism -- Glycolysis Is the Oxidation of Glucose in the Absence of Oxygen -- Oxidation Is Catalyzed by Oxidases in the Presence of O(2), and by Dehydrogenases in the Absence of O(2) -- A Membrane Bioreactor Couples Reduction and Oxidation Reactions (R-Mandelic Acid Example) -- Three Stages of Catabolism Generate Energy, Intermediate Molecules, and Waste Products -- The Glycolysis Pathway Utilizes Glucose in Both Presence (Aerobic) and Absence (Anaerobic) of O(2) to Produce Pyruvate -- Glycolysis Is Initiated by Transfer of a High-Energy Phosphate Group to Glucose -- Products of Anaerobic Metabolism Are Secreted or Processed by Cells to Allow Continuous Metabolism of Glucose by Glycolysis -- Other Metabolic Pathways Utilize Glucose Under Anaerobic Conditions (Pentose Phosphate, Entner-Doudoroff, and Hexose Monophosphate Shunt Pathways) -- Knowledge of Anaerobic Metabolism Enables Calculation of Theoretical Yields of Products Derived from Glucose -- Economics Favor the Glycolytic Pathway for Obtaining Oxygenated Chemicals from Renewable Resources -- Citric Acid Cycle and Aerobic Metabolism -- Respiration Is the Aerobic Oxidation of Glucose and Other Carbon-Based Food Sources (Citric Acid Cycle) -- The Availability of Oxygen, under Aerobic Conditions, Enables Microorganisms to Utilize Pyruvate via the Citric Acid Cycle -- The Citric Acid Cycle Generates Precursors for Biosynthesis of Amino Acids and Commercially Important Fermentation Products -- Glucose Is Transformed to Commercially Valuable Products via Fermentation Processes: A Summary.

Essential Amino Acids Not Synthesized by Microorganisms Must Be Provided as Nutrients (Auxotrophs).