We have isolated and studied the organization of Streptomyces hygroscopicus genes responsible for the biosynthesis of the antibiotic herbicide bialaphos. Bialaphos production genes were cloned from genomic DNA using a plasmid vector (pIJ702). Three plasmids were isolated which restored productivity to S. hygroscopicus mutants blocked at different steps of the biosynthetic pathway. Subcloning experiments using other nonproducing mutants showed that four additional bialaphos production genes were also contained on these plasmids. A gene conferring resistance to bialaphos, which was independently cloned using the plasmid vector plJ61, and an antibiotic-sensitive host (S. lividans), was also linked to the production genes. Cosmids were isolated which defined the location of these genes in a 16 kb cluster.
Azinomycins A and B, isolated from the culture broth of Streptomyces griseofuscus S 42227, were examined for antitumor activities against P388 leukemia, P815 mastocytoma, B-16 melanoma, Ehrlich carcinoma, Lewis lung carcinoma and Meth A fibrosarcoma. Azinomycin B was markedly effective against the intraperitoneally inoculated tumors such as P388 leukemia, B-16 melanoma and Ehrlich carcinoma. The intraperitoneal administration of azinomycin B showed 57% survivors for 45 days and 193 % ILS against P388 leukemia. For Ehrlich carcinoma, azinomycin B gave 161 % ILS and 63% survivors for 45 days, but solid tumors such as Lewis lung carcinoma and Meth A fibrosarcoma were not susceptible to repeated injection of this substance. AzinomycinA was somewhatless effective than azinomycin B for the tumor systems tested.
A strain of Streptomyces griseofuscus S42227 (FERM P-8443) was found to produce new antitumor antibiotics, called azinomycins A and B. The molecular formulas of azinomycins A and B were determined as C30H33N3O10 and C31H33N3O11, respectively. They were active against Gram-positive bacteria, Gram-negative bacteria and L5178Y cells in tissue culture.
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