Chm Eng 170A Biochemical Engineering

Last Updated: Fall 2008 Description Introduction of chemical engineers to the basic concepts of biochemical engineering; application of chemical engineering skills to the analysis and design of biologically based processes; kinetics, heat and mass transfer, and thermodynamics as they apply to enzyme catalysis, microbial growth, bioreactor design, and product recovery. Prerequisite knowledge and/or skills Introductory biochemistry and general chemistry General understanding of chemical engineering fundamentals and processes Heat and mass transfer

Course Prerequisite(s) Survey of the Principles of Biochemistry and Molecular Biology (MCellBi 102) Transport and Separation Processes (Chm Eng 150B)

Course Objectives and Outcomes Objectives the students learn: the fundamental properties of amino acids and proteins; DNA structure, transcription, and translation; the terminology of biochemical engineering; mechanisms of enzymatic reactions; how to derive rate equations for single-substrate enzymatic reactions; transition-state theory and enzyme inhibition; design principles for enzyme inhibitors; kinetics and thermodynamics of protein unfolding; applications of protein engineering and strategies for enzyme stabilization; theory of external and internal mass transfer effects on immobilized enzyme and cell kinetics; determination of external and internal effectiveness factors for immobilized biocatalysts; stoichiometry and energetics of cellular growth; unstructured growth models; kinetics of substrate consumption and bioproduct formation; design and analysis of batch and continuous stirred tank bioreactors (chemostats); packed bed bioreactors formulation of two-phase (gas-liquid) mass balances for continuous bioreactors; estimation of the mass transfer coefficient kLa; the Power number and how to determine the power requirements for mixing bioreactors basic principles of sterilization and how to design batch and continuous sterilizers; general methods of downstream processing for bioproduct purification theory of centrifugation and filtration (ordinary and tangential flow); sizing of centrifuges and filtration modules; principles of chromatography and fixed-bed adsorption; isotherms; plate theory and differential mass balance equations; biopharmaceutical product economics.

Chm Eng 170A Biochemical Engineering (cont.)

Last Updated: Fall 2008 Outcomes Students must be able to: Derive rate equations from the mechanisms of enzymatic reactions and determine the primary kinetic and inhibition parameters; Determine whether an immobilized enzyme reaction is limited by mass transfer and estimate the corresponding effectiveness factor(s); Apply mass and energy conservation criteria to balance stoichiometric equations for microbial growth and product formation, and calculate relevant yield coefficients; Analyze microbial growth, substrate consumption, and product formation in batch reactors and chemostats; calculate steady-state concentrations in a chemostat; calculate steady-state conversions for enzymatic reactions in a packed bed reactor Derive material balances for two-phase bioreactors and estimate kLa values; determine power requirements for mixing multi-phase bioreactors Analyze and design batch and continuous sterilization processes; Set-up and solve conservation equations for centrifugation, filtration, and chromatography; solve for relevant process parameters in each case; estimate retention times and resolutions in chromatographic processes; formulate and critically assess product recovery schemes.

Topics Covered 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. Biocatalysis and principles of enzyme catalysis; transition-state theory. Enzyme kinetics and inhibition. Enzyme denaturation and inactivation. Enzyme immobilization and heterogeneous biocatalysis. Stoichiometry/energetics of microbial growth. Unstructured models of microbial growth. Batch and continuous stirred tank bioreactors. Plug-flow and packed bed bioreactors. Gas-liquid mass transfer in bioreactors. Power requirements for bioreactors. Sterilization. Bioproduct recovery: cell removal by centrifugation or filtration. Plate theory and chromatographic resolution. Fixed-bed adsorption and affinity chromatography. Integrated purification process design and scale-up. Biopharmaceutical product economics.

Contribution of course to meeting the professional component This course provides education in an area of considerable and growing importance to chemical engineering. It contributes to the students' knowledge of biochemical engineering topics, as required for bioprocess analysis and design. The course introduces students to concepts and principles necessary to apply chemical engineering analysis to biotechnological systems and processes over a wide range of scales.

Chm Eng 170A Biochemical Engineering (cont.)

Last Updated: Fall 2008 Relationship of course to undergraduate degree program objectives and outcomes This course introduces basic concepts needed to analyze and design biological products and biochemical processes on vastly different scales with an understanding of the biochemical and biophysical properties of biological systems. It does not provide direct design experience, but includes substantial discussion and illustration of design issues with respect to the unique challenges presented by the physicochemical properties of biological products and the economics of biotechnology. Textbook(s) and/or other required material (at the ASUC store) Blanch, H. W.; Clark, D. S. Biochemical Engineering; Marcel Dekker: New York, NY, 1996. In addition to the required text, many supplemental handouts are provided.

Reference Texts (on reserve in the Chemistry Library) Voet, D.; Voet, J. G. Biochemistry, 2nd ed.; Wiley: New York, 1995. Creighton, T. E. Proteins: Structures and Molecular Properties, 2nd ed.; W. H. Freeman & Co.: New York, 1993. Alberts, B., et al. Molecular Biology of the Cell, 4th ed.; Garland Publishing, Inc.: New York, 2002. Nester, E. W., et al. Microbiology, 3rd ed.; Saunder College Publishing: New York, 1983.

Class/laboratory schedule Three 50-minute lectures/week One 50-minute discussion session

Assessment of student progress toward course objectives Weekly homework-problem assignments Participation in class and discussion sections Two one-hour mid-term examinations A final examination.

Students Evaluation of Course Outcome Indicate the number (1 to 5) that best describes your ability to do the following, where 5 is for strong ability and 1 is for weak (or no) ability: 1. Derive a rate equations from the mechanism of an enzymatic reactions and determine the primary kinetic parameters. 2. Estimate the effectiveness factor for an immobilized enzyme reaction . 3. Balance stoichiometric equations for microbial growth and product formation, and calculate relevant yield coefficients.

Chm Eng 170A Biochemical Engineering (cont.)

Last Updated: Fall 2008 4. Determine the steady-state operating parameters (i.e., substrate, product, biomass concentrations, dilution rate) for a chemostat. 5. Formulate material balances for a two-phase bioreactor and estimate the corresponding kLa value. 6. Predict the performance of a continuous sterilizer. 7. Design a hypothetical recovery and purification scheme for a high-value intracellular biotherapeutic; evaluate the advantages and disadvantages of the different techniques available for each step. 8. Estimate the retention times and resolution for two proteins separated by elution chromatography.