第九章：抗生素的生产

第九章：抗生素的生产内容摘要：

菌素） Chloramphenicol（氯霉素） Cycloheximide（放线菌酮） Hygromycin Penicillin Streptomycin Tetracycline(s) Vanycin Bacillus subtilis Cephalosporium sp. S. venezuelae S. griseus S. hygromyces P. chrysogenum S. griseus S. aurofaciens S. orientalis BetaLactam Structure 半合成抗生素 用化学或生物化学的方法改变一直抗生素的化学结构或引入特定的功能基团而获得的新抗生素品种或其衍生物的总称。 其目的：减低毒副作用，增强抗菌力，扩大抗菌谱，对耐药菌有效 ，便于口服，改善药理性质，提高生物有效性。 STRUTURE OF PENICILLIN What is a semisynthetic variant of penicillin??? • Discovered that natural penicillins can be chemically modified by removing the R group and adding a new one that confers new properties • It is the variation in the R group that leads to the semisynthetic forms of penicillin. • Over 20,000 semisynthetic variants • 3 main variants of industrial importance Main Variants  Ampicillin（氨卡青霉素）  Methicillin  Amoxycillin Methicillin(甲氧霉素 ) 1986（ 13%， 1998， 26%） Originally introduced to bat S. Aureus BLactamase resistant 1960’s a semisynthetic broad spectrum pound produced Over production of betalactamase enzyme has been shown to contribute to methicillin resistance. Ampicillin（氨卡青霉素） Discovered in 1963 One of only few penicillins that can be administered orally Has improved acid stability Broad spectrum. Amoxycillin（羟氨卡青霉素） The preffered choice of drug for oral use. The highest absorbance levels in the body First marketed in 1998 by Smitkline Beechams™ Benefits of semisynthetic variants Can be administered orally as they are resistant to stomach acid They have a broader spectrum of activity The semisynthetic variant of penicillin is chemically more stable than the volatility of the BLactam ring, in the penicillin G 6APA（ 6氨基青霉烷酸） • First discovered in 1959 • First industrial process of enzyme engineering • Conversion of Pen G to 6APA Used in penicillin recovery process Action of 6APA PGA（青霉素酰化酶） 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 a。