Streptomyces caespitosus Mitomycins

Microorganisms, by fermentation (cont d) Streptomyces caespitosus Mitomycin... 

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 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. 

Mitomycin C, 1, is a potent antitumor antibiotic discovered by Japanese scientists in fermentation cultures of Streptomyces caespitosus. It has been described as "small, fast and deadly (but very selective)" and has an extraordinary ability to crosslink the complementary strands of the DNA double helix with high efficiency and absolute specificity. It is so lethal that one crosslink per genome is sufficient to cause death of a bacterial cell. Mitomycin C, which is widely used clinically as an antitumor drug, does not react with DNA, but enzymatic reduction of the quinone induces a cascade of transformations which results, ultimately, in formation of the DNA crosslink 2. 

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. 

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,... 

Streptomyces caespitosus produces several mitomycins, antibiotics that show an excellent antitumor activity but of limited utility because of their toxicity. The only substance acceptable for human use is mitomycin C, approved by FDA in 1974. Mitomycin C acts by forming covalent bridges across two opposite DNA strands, causing a rapid cell death (Tomasz 1995). In contrast to most antitumor agents, it is also active against the hypoxic cells in the core of solid tumors and therefore is indicated for the treatment of specific type of neoplasms such as gastric, colorectal, and lung cancer. 

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