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【正文】 ion The Mechanism example BaeyerVilliger oxidation using Whole Cell Catalysis BaeyerVilliger monooxygenase or BVMO cofactors such as NADPH Drug Manufacture and Discovery by Microbial Bioconversion The industrial conversion and biosynthesis of Penicillin Penicillin 青黴素 Fleming, at his laboratory in St. Mary39。s Hospital (now one of Imperial College teaching hospitals) in London, noticed a halo of inhibition of bacterial growth around a contaminant bluegreen mold on a Staphylococcus plate culture. 佛來明發(fā)現(xiàn)青黴素 牛頓 (1985) no. 25 p. 122 Fleming Chain Florey (1945) 佛來明（ Alexander Fleming）於 1928年發(fā)現(xiàn)黴菌（青黴菌 Penicillium）抑制細(xì)菌（金黃葡萄球菌Staphylococcus）的現(xiàn)象；佛羅瑞（ Howard Florey）和芡恩（ Ernst Chain）則於 1939年從青黴菌分離青黴素（ penicillin）證明其治療細(xì)菌感染的功效。其後（ 1940到 1945年）在美國發(fā)展出大量生產(chǎn)青黴素的技術(shù)，這是結(jié)合微生物學(xué)家、生化學(xué)家、和遺傳學(xué)家篩選並改造出能在沉浸液體培養(yǎng)（ submerged liquid culture）中大量累積與菌體生長沒有直接關(guān)聯(lián)的二級代謝產(chǎn)物（ secondary metabolites）且進(jìn)行好氧（ aerobic）生長的絲狀真菌，並透過工程師的努力以通氣攪拌醱酵槽大量生產(chǎn)的結(jié)果。佛來明、佛羅瑞、芡恩於 1945年獲得諾貝爾獎。 This antibiotic is manufactured mercially using Penicillium chrysogenum. The penicillin is produced in large stainless steel fermenters, which have a capacity of around 10000 dm3. Fermentation of Penicillin ? The fermenter is sterilised by steam and then loaded with a sterilised growth medium for the Penicillium chrysogenum to feed on, containing lactose, amino acids and mineral salts amongst other things. The temperature and pH are monitored constantly to ensure that the conditions in the fermenter are optimum for the bacteria. The fermenter is also continuously stirred and sterile air fed in. ? The penicillin in the resultant broth after 160 – 200 hours of fermenting is obtained by solvent extraction. The Biosynthetic Pathway of blactam Analogs RNA DNA Protein 轉(zhuǎn) 錄 轉(zhuǎn) 譯 Transcription Translation Replication 複 製 逆轉(zhuǎn)錄 Reverse Transcription Central Dogma Juang RH (2022) BCbasics 挑出所要群落 得到純系轉(zhuǎn)殖菌株 大量培養(yǎng)生產(chǎn) 人類胰島素 Human Insulin 探針 Probe 互補(bǔ) DNA 專一性抗體 送入宿主細(xì)菌 基因接入載體 目標(biāo)基因剪接 Stryer (1995) Biochemistry, p. 119 Kleismith amp。 Kish (1995) Cell and Molecular Biology, p. 115 The Gene Clusters of Penicillin Biosynthesis
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