Yoshida M, Konomi T, Kohsaka M, Baldwin J E, Herchen S, Singh P, Hunt N A, Demain A L
Proc Natl Acad Sci U S A. 1978 Dec;75(12):6253-7. doi: 10.1073/pnas.75.12.6253.
To examine microbiological ring expansion of penicillin N to a cephalosporin, we obtained five mutants of Cephalosporium acremonium blocked in beta-lactam antibiotic biosynthesis from 2500 survivors of mutagenesis. In submerged fermentation, mutants M-0198, M-0199, and M-2351 produced no beta-lactam antibiotic (type A), whereas mutants M-1443 and M-1836 formed penicillin N but not cephalosporin C (type B). Cell-free extracts of type A mutants converted penicillin N to a cephalosporin; those of type B mutants did not. The product of the cell-free reaction was identified as deacetoxycephalosporin C by thin-layer chromatography, paper chromatography, paper electrophoresis, and enzyme tests. These data strongly support our hypothesis that penicillin N is an intermediate of cephalosporin biosynthesis.
为了研究青霉素N向头孢菌素的微生物环扩展，我们从2500个诱变存活菌株中获得了5株阻断β-内酰胺抗生素生物合成的顶头孢霉突变体。在深层发酵中，突变体M-0198、M-0199和M-2351不产生β-内酰胺抗生素（A型），而突变体M-1443和M-1836产生青霉素N但不产生头孢菌素C（B型）。A型突变体的无细胞提取物可将青霉素N转化为头孢菌素；B型突变体的无细胞提取物则不能。通过薄层色谱、纸色谱、纸电泳和酶测试，将无细胞反应的产物鉴定为去乙酰氧头孢菌素C。这些数据有力地支持了我们的假设，即青霉素N是头孢菌素生物合成的中间体。
