第九章：抗生素的生產(chǎn)-文庫(kù)吧資料
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【正文】 ocess of enzyme engineering ? Conversion of Pen G to 6APA Used in penicillin recovery process Action of 6APA PGA（青霉素?；福? is the natural substrate for Pen. G Penicillin G is hydrolysed in a reversible reaction to 6APA and phenylacetic acid. Vital intermediate for the production of semisyntheic penicillins Acyl Group Nature of acyl group confers certain properties on the penicllin analogue Selective hydrolysis occurs by hydrolysis by lactamaseproducing culture ? lactamase ? These are the most mon cause of bacterial resistance to beta lactam antibiotics ? Most important ? lactamase was produced by S. aureus. This was responsible for rise in resistance to penicillin in the 1950’s ? Beta Lactam ring is crucial for penicillin to remain active Action of ? lactamase ? ? lactamase destroys penicillin by hydrolyzing a bond in this ring Some Statistics 10,985 tonnes of 6APA were produced in 1998 Of the 10,985, 48% was used for ampicilllin production, and 27% for amoxicillin. Resistance Linked to overuse of a specific agent or to the introductiob of a new class of ? lactam By the late 1970’s fewer than 10% of Staphlococcus infections could be cured by penicillin，到 1999年， WHO報(bào)道 95%的金黃色葡萄球菌抗青霉素， 100%大腸桿菌抗鏈霉素 Conclusion Semisynthetic variants are now the favoured choice of antibitic for bating bacterial resistance Can be orally administered They have a broadened range of specifity More chemically stable than their native counterpart. 抗生素的生產(chǎn)和提取工藝 菌種 孢子制備 發(fā)酵 種子制備 發(fā)酵液的預(yù)處理 提取和精制 成品包裝 現(xiàn)代抗生素工業(yè)生產(chǎn)工藝 Configuration amp。 除了用效價(jià)單位之外，當(dāng)物質(zhì)被制成純凈的化學(xué)物質(zhì)時(shí)，就可以用質(zhì)量表示，而且與效價(jià)單位之間有一定的換算關(guān)系 如 1mg青霉素鈉鹽相當(dāng)于 1667個(gè)單位 1 mg鏈霉菌素堿相當(dāng)于 1000個(gè)單位 Industrial evolution of penicillin production Date Yield (units/mL) Development 1929 220 Wildtype (P. notatum) 1941 4080 WT 1943 80100 New WT (P. chrysogenum) 1944 100200 Colony selection 1944 300500 Xirradiation 1945 8001000 UVirradiation 1949 15002020 Chemical mutagenesis 1951 2400 Chemical mutagenesis 1953 2700 Strain selection 1960 5000 Strain selection 1970 10000 Strain selection Common antibiotics and their sources Bacitracin Cephalospor
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