CBE10L-4

CBE10L-4 - Bioproduction: Opportunities & Challenges...

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Harold G. Monbouquette, Chemical Engineering Department, University of California, Los Angeles, Box 951592, Los Angeles, CA 90095-1592, harold@seas.ucla.edu The broad universe of metabolic processes and enzyme activities for exploitation Specialty chemical bioprocessing: “Cheap stuff in, expensive stuff out” The promising biorefinery concept Integration of enzymes into chemical synthesis processes
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Diverse Lifeforms and Metabolic Pathways Huber & Stetter, J. Biotechnol., 64 (1998) 39-52 Most Genetic Diversity Among Microbes M. Madigan et al ., Brock Biology of Microorganisms , 10th Ed., Prentice-Hall, 2003
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Diverse Enzyme Toolkit of Industrial Utility K. Faber, Biotransformations in Organic Chemistry , Springer, 1997 ~3000 enzymes known, ~25,000 existing, ~300 commercially available
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“Cheap stuff in, Expensive stuff out”: The Penicillin Story 1939: Penicillin culture concentration ~0.001 g/L 1940: Unproven fermentation process chosen over chemical synthesis Microbiologists engage in mutation/selection; Engineers designed large-scale submerged culture process 1945: Sufficient penicillin produced for ~100,000 patients Current yields: ~50 g/L; Chemical synthesis approach still cannot compete!
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Can we engineer life for the economical, environmentally friendly production of chemicals?
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Isoprenoid Biosynthesis Pathways Lead to Important Natural Products Mevalonic Acid Pathway G3P/Pyruvate Pathway Limonene, Geraniol, Citranellol Periplanone B, Artemisinin Casbene, Taxol (Tetraterpenoid pigments) C. Khosla, J.D. Keasling, Nature Rev. Drug Discov ., 2 , 1019-1025 (2003) R. Barkovich, J.C. Liao, Metab. Engin ., 3 , 27-39 (2001)
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Metabolic Engineering: Genes from Three Microbes Give E.coli Pathway for Production of the Carotenoid, Astaxanthin C.-W. Wang, M.-K. Oh, J.C. Liao, Biotechnol. Bioeng. (1999) 62 , 235-241 Archaeoglobus fulgidus Agrobacterium aurantiacum
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D. Umeno and F.H. Arnold, J. Bacteriol ., 186 , 1531-1536 (2004) Protein Engineering of a S. aureus C 30 Carotenoid Synthase for Biosynthesis of Novel C 45 and C 50 Carotenoids in E. coli Powerful combination of metabolic and protein engineering
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Using Biosynthetic Tools Khosla & Keasling, Nature Rev. Drug Discov ., 2 , 1019-1025 (2003)
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This note was uploaded on 04/03/2008 for the course CHE 10 taught by Professor Monbouquette during the Fall '07 term at UCLA.

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CBE10L-4 - Bioproduction: Opportunities & Challenges...

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