Fungi Cephalosporium acremonium

Fermentation. The commercial P-lactam antibiotics which act as starting material for all of the cephalosporins ate produced by submerged fermentation. The organisms used for the commercial production of the penicillins and cephalosporins ate mutants of PenicU/in chTysogenum and Cephalosporium acremonium respectively (3,153,154). Both ate tme fungi (eucaryotes). In contrast, the cephamycins ate produced by certain species of procaryotic Streptomyces including Streptomyces clavuligerus and Streptomyces lipmanii (21,103). 

The filament thickness can be another interesting feature. Production of cephalosporin by Cephalosporium acremonium has been observed in conjunction with some swelling of the hyphae [152]. It has been often reported that, when cultivated on solid substrate, apical parts of filamentous species tend to become thinner, apparently due to substrate limitation, which induces the cell to increase its surface to volume ratio. Similar behavior has been observed in suspended media on fungi (Trichoderma reesei [151] and S. ambofaciens [153, 154]) (Fig. 24). Hyphae are often regarded as solid cylinders, and, in order to... 

The anti-bacterial activity of the penicillins stimulated a major search for other antibiotics. Many compounds were isolated from amongst the metabolites of Streptomycetes obtained from soil. These included therapeutically useful antibiotics such as chloramphenicol, the tetracyclines, erythromycin and streptomycin. Several fungi yielded useful compounds. One of these was Cephalosporium acremonium. A biologically-active strain was obtained by Brotzu from a sewage outfall near Cagliari in Sardinia in 1945 and described in 1946. The p-lactam cephalosporin C (1.23) was isolated from this organism in 1954 and its structure determined in 1961 by Abraham and Newton. 

The peptidic nature of penicillin was not recognized immediately after its isolation. In its jS-lactam bicyclic ring structure the tripeptide -(L-a-aminoadipoyl)-L-cysteinyl-D-valine is hidden but in 1960 it was discovered in extracts of Penicillium by Arnstein et al. [11]. Experiments on biosynthesis of penicillins in the intact mycelium of the producing fungi did not lead to unequivocal results, due to the poor permeability of the cell wall. Protoplasts, naked cells obtained after enzymatic removal of the outer wall, however, were able to serve in studies with radioactively labeled potential precursors, and in cell-free systems from Cephalosporium acremonium, the route to isopenicillin N was finally revealed [12]. The tripeptide L-a-aminoadipoyl-L-cysteinyl-D-valine first forms the j -lactam moiety and a second, oxidative step closes the thiazolidine ring between the -carbon of valine and the thiol of cysteine (Fig. 9). 

Cephalosporins Alfatil, Cefaloject, Cefaxyl, Ceporin, Cephalosporium acremonium Semi-marine fungi Antibiotic Lactam Since 1964 (the most recent fourth-generation cephalosporins... 

---