1、Bioprocess Technology: Fundamentals and Applications1 Introduction2 Reactor Design and Instrumentation3 Metabolic Basis of Product Formation4 Kinetic models5 Mass Transport in Bioreactors6 Modes of Process Operation7 Scale-up of Aerobic Processes8 Immobilization of Biocatalysts9 Sterilization Part 1

2、 Fundamentals Part 2 Applications10 Fermented Food 11 Microbial Energy Conversion Processes12 Antibiotics13 Industrial Use of Enzymes14 Biology of Waste Water Treatment enzymesChapter 1Introduction1.1. History of Industrial BiotechnologyProducts of fermentation processes Products typeExampleProducts

3、 typeExampleAlcoholsEthanol Butanol (+acetone)Organic acidsCitric acid Acetic acidAmino acidsGlutamic acid LysinePolysaccharidesDectran XanthanAntibioticPenicillins TetracyclinesPurified waste waterBOD-removal SenitrificationEnzymesProteases AmylasesSingle-cell proteinFodder yeastHormonesInsulin Hum

4、an growth hormoneStarter culturesBakers yeast Lactic startersInsecticidesThuringiensinSteroid transformationCortisoneMethaneBiogasfrom sewage/waterVaccinesTetanusNucleotidesIMP GMPVitaminsRiboflavin 1.1.1 Era of mioorganisium(19 century 1944）1857. France Pasteur microorganism1897. Germany Buchner en

5、zyme A： primary metabolism product: ethanol, citric acid B: anaerobic fermentation1.1.2 Biochemical EngineeringPenicillin productionlab: 1000mL; 40u/ml, recovery35%, purity20%, 80000 flask produce 1kg penicillin, 16000 $/kg1941年 US and English 1943年 化學工程師和生物學家合作 A: 通氣發酵罐，效價提高到200u/ml B: 離心最取齊萃取器，萃取過

6、程連續化，純度為60%，收率75% 解決：通氣、培養基滅菌和分離提取1944年 鏈霉素1947年 美國麥克爾公司被授予“生物化學工程的專題研究”的麥可老希爾化 學工程成就獎Tiselius 開創生物色譜和電泳Arne Tiselius的貢獻1925年 23歲作為Svedberg研究生 外力場： 離心場+電場1930年 一個電泳：移動界面電泳方法 （Moving boundary method)，畢業論文1934年 兩個學生Phipot&Svensson 紫外光光學照像系統：最早的監測器 1935年-1936年投稿 3次，都被拒稿 Professor Arne Tiselius in his c

7、hromatography laboratory in the early 1950s. In some experiments he used quartz columns and UV-light to follow the migration of protein zones using a television monitor. Photo: Uppsala Bild / Upplandsmuseet.1.2. Enzyme Engineering1894 Japan amylase（first commercial enzyme ）1953 Grubhofer and Schleit

8、h immobilization of enzyme 1969 immobilized enzyme in industry to produce amino acid(Japan ) The system of enzyme and viable cell immobiliton was coupled amino acid, organic acid, ribonucleotide and antibioticsNovel biotechnologies were applied in enzyme engineering cell fusion and DNArecombination

9、used to improve the strain of enzyme1.3. Genetic Engineering 1974. US Boyer and Cohen recombinant DNA1976. Genentech first biotechnology company was established1977. Boyer hGH1977. W.Gilbert（1978年獲諾貝爾化學獎） insulinProductOriginProducting organismhGHHumanEscherichia coliIGF-IHumanEscherichia coliIFN-2a

10、HumanEscherichia coliProtein GStreptococcusEscherichia coliInsulinHumanSaccharomyces cerevisiaeHepatitis B vaccineHepatitis virusSaccharomyces cerevisiaeChymosinCalfKluyveromyces lactisLipaseHumicola lanuginosaAspergillus oryzaetPaHumanAnimal cellsSuperoxide dismutaseHumanAnimal cellsSome recombinan

11、t products that became available by the introduction of the genetic engineering technique代謝工程策略碳水化合物原料丙酮丁醇C2酸C2醇C2CoAC3酮酸C2醛C2PC3酮酸PC3酸PC4CoAC3酮C4醇C6糖PC3醛PC6糖PC6糖P 利用系統生物學手段，發現了新的支路途徑和調控位點酸PC3二醇C3羥酮PC4酸C5酮酸C4CoAC6酸 設計新的代謝工程策略C3烯酰CoAC3羥酸C3烯酸代謝工程策略碳水化合物原料C2酸C2醇C2CoAC3酮酸C2醛C2PC3酮酸PC3酸PC4CoAC3酮C4醇C6糖PC3醛PC6糖PC6糖P酸PC3二醇C3羥酮PC4酸C5酮酸C4CoAC6酸C3烯酰CoAC3羥酸C3烯酸丙烯酸實現代謝途徑重構丙酮丁醇Penicillin production1.4. The Biotechnical Process Mutation random mutation rays （UV ） NTG Cell fusion protoplast fusion hybridoma technique monoclonal anitibody Genetic engineering Extremphilic organisms pH、tempera