Mitomycin from Streptomyces caespitosus

Mitomycin is an antibiotic isolated from Streptomyces caespitosus. It is intracellularly activated to a reduced quinone and then becomes an alkylating agent. It cross-links DNA and inhibits DNA synthesis. Part of the resistance to mitomycin can be ascribed to inactivation of the reduced quinone. Mitomycin is used in combination regimens against carcinomas of the cervix, colon, recmm, breast, bladder, head and neck, and lung. 

The production, isolation from Streptomyces caespitosus, and properties of the first two component members of the mitomycin antibiotic complex, namely mitomycins A and mitomycin B, were described in 1956 (Figure 3.19) [32], The third component, mitomycin C, was described in 1958 [33]. The fourth mitomycin, named porfiromycin, was reported in 1960 [34], One year later, the fifth component of the... 

The mitomycins are potent antibiotics that belong to the family of antitumor quinones. In 1956, mitomycin A (28) and B (34) were isolated from Streptomyces caespitosus, and shortly thereafter, mitomycin C (30) was discovered within the same strain [61, 62]. The A-methyl derivative of (31), porfiromycin, was isolated in 1960 from Streptomyces ardus, which was followed by the discovery of mitiromycin from Streptomyces verticillatus [63, 64]. Among all these different mitomycins, (31) enjoyed early widespread clinical use as a consequence of its uniquely superior activity against solid tumors. Secondly, it possessed reduced toxicity when compared to the natural counterparts (28) and (34). Mitomycin A,... 

The commercial production of mitomycin involves the preparation of mitomycin-containing broths by culturing a mitomycin-producing organism, e.g. Streptomyces caespitosus, in suitable media as described at length In the literature. At the end of the fermentation cycle the whole broth is usually centrifuged, filtered or otherwise treated to separate the solids (mycelia) from the supernatant which contains substantially all of the antibiotic activity. 

Mitomycin C (3.37) is an antitumor antibiotic isolated from the growth of Streptomyces caespitosus. Its unique feature is an aziridine ring fused onto a pyrrolidine ring. Other related aziridines are also present in the fermentation broth. 

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