G. N. Rolinson

Abstract: In submerged culture, Emericellopsis minima (Stolk) I.M.I. 69015 produced a substance resembling 6-aminopenicillanic acid in its behaviour on paper chromatograms and in its properties after reaction with phenylacetyl chloride. The substance was destroyed by penicillinase but was acid-stable. The culture also produced cephalosporin N and two unidentified antibiotics which have been named emericellopsin A and B. When other fungi of the genera Emericellopsis and Cephalosporium were examined in a similar manner, C. salmosynnematum and Cephalosporium I.M.I. 49137 were also found to produce small amounts of a substance resembling 6-aminopenicillanic acid. Examination of Emericellopsis minima (Stolk) also showed the presence of penicillin amidase activity in this culture.

Abstract: Candida lipolytica synthetisiert das Antibioticum Tryptanthrin aus 1 Mol Tryptophan und 1 Mol Anthranilsaure. Bei Verfutterung von Tryptophan und substituierter Anthranilsaure, bzw. substituiertem Tryptophan und Anthranilsaure, konnten die zu erwartenden Tryptanthrinderivate isoliert und identifiziert werden. Die Enzyme der Tryptanthrinbiosynthese wiesen in bezug auf diese Substrate, mit Ausnahme von Bromtryptophan, keine Spezifitat auf. Parallel zu diesen Versuchen wurden durch chemische Synthese substituierte Tryptanthrine hergestellt. Die Dierivate wurden auf ihre antibiotische Wirksamkeit gepruft; als besonders wirksam erwiesen sich die halogenierten Verbindungen.

Abstract: Publisher Summary This chapter describes the process of microbial transformation of antibiotics into useful compounds, which is mostly concentrated upon the production of 6-aminopenicillanic acid (6-APA) by enzymatic hydrolysis of biosynthetic penicillins. The chapter describes biotransformation processes of penicillins into 6-APA that use, as a source of acylase, intact bacterial cells, fungal mycelium, fungal spores, crude cell extracts, purified enzyme preparations, stabilized enzymes, and supernatant liquid of extracellular acylase-producing microorganisms. The chapter examines methods to isolate and purify penicillin acylases and to stabilize these enzyme preparations. It reviews the physicochemical properties and the degradation reactions in relation to the structure of penicillins and describes the reaction of cysteine and related compounds with penicillins, resulting in a loss of antibacterial activity. 6-APA was originally produced by fermentation synthesized in a purely chemical way. Enzymatic transformation of biosynthetic penicillins into 6-APA is an industrial process of economic importance as the main source of 6-APA used in the preparation of semisynthetic penicillins.

Abstract: Several penicillin-producing fungi were examined for ability to produce 6-aminopenicillanic acid (6-APA) and penicillin acylase. 6-APA was found in corn steep liquor fermentations of Trichophyton mentagrophytes, Aspergillus ochraceous, and three strains of Penicillium sp. 6-APA was not detected in fermentations of Epidermophyton floccosum although penicillins were produced. 6-APA formed a large part of the total antibiotic production of T. mentagrophytes. The types of penicillins produced by various fungi were identified by paper chromatography, and it was found that all cultures produced benzylpenicillin. T. mentagrophytes and A. ochraceous showed increased yields of benzylpenicillin and the formation of phenoxymethylpenicillin in response to the addition to the fermentation medium of phenylacetic acid and phenoxyacetic acid, respectively. Washed mycelia of the three Penicillium spp. and two high penicillin-yielding strains of P. chrysogenum possessed penicillin acylase activity against phenoxymethylpenicillin. A. ochraceous, T. mentagrophytes, E. floccosum, and Cephalosporium sp. also had penicillin acylase activity against phenoxymethylpenicillin. Only two of the above fungi, T. mentagrophytes and E. floccosum, showed significant penicillin acylase activity against benzylpenicillin; in both cases it was very low. The acylase activity of A. ochraceous was considerably increased by culturing in the presence of phenoxyacetic acid. It is concluded that 6-APA frequently but not invariably accompanies the formation of penicillin, and that penicillin acylase activity against phenoxymethylpenicillin is present in all penicillin-producing fungi.

Abstract: The discovery of penicillin by Fleming (1929) and its development by the Oxford group (Florey et al. 1949) began the antibiotic era. The success of this β-lactam antibiotic led the way for the development of all other antibiotics. As will be described later in this chapter, new and more effective β-lactam antibiotics are being discovered now, over 50 years after Fleming’s initial discovery.