Microbiological ring expansion of penicillin N

A mutant of Cephalosporium acremonium producing high amounts of penicillin N was isolated. This antibiotic was purified and characterized. It was possible to convert this penicillin N to deacetoxycephalosporin C enzymatically. The reaction could be carried out with enzyme systems prepared from C. acremonium mutants producing either no beta-lactam antibiotics or excreting only penicillin N. It was surprising that a high level of transformation capacity was just found in a cephem negative mutant which overproduces penicillin N. For that reason the inability of the latter mutant to produce cephem compounds cannot be explained by a functional block of the ring expanding enzyme complex. The enzyme preparations used to carry out this reaction were made by ether-treatment or sonication of C. acraemonium cells, or by submitting them to osmotic shock. The ring expanding enzyme system is strongly dependent on ATP and behaves as a 2-oxoglutarate dependent dioxygenase.