Modern Biotechnology - Connecting Innovations in Microbiology and Biochemistry to Engineering Fundamentals

A unique resource for the next generation of biotech innovators Enabling everything from the deciphering of the human genome to environmentally friendly biofuels to lifesaving new pharmaceuticals, biotechnology has blossomed as an area of discovery and opportunity. Modern Biotechnology provides a much-needed introduction connecting the latest innovations in this area to key engineering fundamentals. With an unmatched level of coverage, this unique resource prepares a wide range of readers for the practical application of biotechnology in biopharmaceuticals, biofuels, and other bioproducts. Organized into fourteen sections, reflecting a typical semester course, Modern Biotechnology covers such key topics as: Metabolic engineering Enzymes and enzyme kinetics Biocatalysts and other new bioproducts Cell fusion Genetic engineering, DNA, RNA, and genes Genomes and genomics Production of biopharmaceuticals Fermentation modeling and process analysis Taking a practical, applications-based approach, the text presents discussions of important fundamentals in biology, biochemistry, and engineering with relevant case studies showing technology applications and manufacturing scale-up. Written for today's wider, more interdisciplinary readership, Modern Biotechnology offers a solid intellectual foundation for students and professionals entering the modern biotechnology industry.Table of Content1. 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 Scale-up Are Synergistic in the Development of Pharmaceutical Products. The 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. Bibliography. 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 Bringing 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. Bibliography. 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. 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. Bibliography. Homework Problems. 4. MICROBIAL FERMENTATIONS. Introduction. Fermentations Are Carried Out In Flasks, Glass Vessels, and Specially Designed Stainless Steel Tanks. Microbial Cells Are Either Prokaryotes or Eucaryotes. 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 Find Broad Industrial Use. Microbial Culture Requires That Energy and All Components Needed for Cell Growth Be Provided. Media Components and Their Function (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 In Relation To Their Energy Metabolism (Type 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. Bibliography. Homework Problems. 5. MODELING AND SIMULATION. Introduction. Simpson’s Rule. Fourth-Order Runge-Kutta Method. Runge-Kutta Technique Requires that Higher Order Equations be reduced to 1st Order ODEs to Obtain Their Solution. Systems of First Order ODE’s Are Represented in Vector Form. Kinetics of Cell Growth. Ks Represents Substrate Concentration at Which the Specific Growth Rate is Half of its Maximum. Simulation of a Batch Ethanol Fermentation. Ethanol Case Study. Luedeking-Piret Model. Continuous Stirred Tank Bioreactor. Batch Fermentor vs. Chemostat. Bibliography. Homework Problems. 6. AEROBIC BIOREACTORS. Introduction. Fermentation of Xylose to 2,3 Butanediol by Klebsiella oxytoca is Aerated but Oxygen Limited. Phase I. Oxygen sufficient growth occurs early in the fermentation. Phase II. A transition to oxygen limitation occurs at low cell concentration (1 g/L). Phase III. Butanediol is produced under oxygen limiting conditions. Oxygen Transfer from Air Bubble to Liquid is Controlled by Liquid-side Mass Transfer. Bibliography. Homework Problems. Appendix for Chapter 6. Excel Program for Integration of Simultaneous Differential Equations. 7. ENZYMES. Introduction. Enzymes and Systems Biology. Industrial Enzymes. Enzymes: In vivo and In vitro. Fundamental Properties of Enzymes. Classification of Enzymes. Industrial Enzymes. Assaying Enzyme Activity. Enzyme Assays. Batch Reactions. Thermal Enzyme Deactivation. Bibliography. Homework Problems. 8. ENZYME KINETICS. Introduction. Initial Rate vs. 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 Non-competitive Inhibition. Substrate Inhibition. Example of Reversible Reactions. Coenzymes and Co-factors Interact in a Reversible Manner. King-Altman Method. Immobilized Enzyme. Bibliography. 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 O2, and by Dehydrogenases in the Absence of O2. 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 Both In the Presence (Aerobic and Absence of O2 (Anaerobic to Produce Pyruvate. Glycolysis Is Initiated By the 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 That 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 Favors 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-Food-Sources (Citric Acid Cycle). The Availability of Oxygen, Under Aerobic Conditions, Enables Microorganisms t