PH()l)r("'ri()\ OK ANTJIUO'IMCS 



231 



7. (Irisciii ;iii(l oilier ii'oii-coiil , •lining iiiiti- 

 hiotics. 



8. Sult'ui-coiitaiuiiiii; aiitihiodcs. 

 !). 'riic polyenes. 



10. Hie iioiiiiit r()i>;eiH)Us substances. 



11. Antitumor and aiiti\'ii'al at>;(Mits. 



12. \'arious unidentilied antibiotics. 

 Sonic of tlu'sc j>;r()ups, because of their 



historical si^iiificancc, may now be discussed 

 in iireater detail. 



The Actiiioiiiyt'iiis 



The first representati\'e of tlu^ actinomy- 

 cins was isolated and crystallized in 1U40 by 

 Waksman and Woodruff. It was produced by 

 an organism described as S. antibioticus. Its 

 chemical nature was studied by Waksman 

 and Tishler, and it was designated as actino- 

 mycin A. Although highly effective against 

 different microorganisms, it proved to be too 

 toxic to experimental animals (Robinson and 

 Waksman). Another representative of this 

 group was isolated by Lehr and Berger; it 

 was studied by Dalgliesh and Todd (1949- 

 1952), who designated it as actinomycin B. 

 In 1949, Brockmann and Grubhofer (1949- 

 1953) isolated a third form of actinomycin 

 (C) from a cultiu-e of *S. chrysomallus. (See 

 also Brockmann, 1954; Brockmann and 

 Grone, 1954; Brockmann and Aluxfeldt, 

 1954-1956). Still other actinomycins were 

 isolated later, in varions parts of the world, 

 notably actinomycin D by Waksman and 

 Gregory from a culture of S. parvullus (see 

 Vining ct al., 1954; Johnson, ]95(); Bullock 

 and Johnson, 1957), actinomycin I and X 

 (Brockmann d al.), J (Hirata and Xaka- 

 nishi), M, and others. Some related com- 

 pounds, like actinoleucin, have also been iso- 

 lated (Ueda et al.). It appeared that in every 

 new screening progi'am of actinomycetes, 

 actinomycin was the first antibiotic obtained 

 (Waksman ct al., 194(i; Welsch c( al., 1946). 



Although nearly all actinomycins are pro- 

 duced by streptomyces, some are also formed 

 by certain niicromonosporas (Fisher ct al.). 



'I'ahi.k ()1 

 Ejfcri of carhoh 1/(1 rales as carbon sources on actino- 

 mycin production hi/ S. uiitibioticu.s 

 (Katz, Pienta, and Sivak) 



Carbohydrate, 1.0 per cent 



Maximum actinomycin 

 assay, jxg/ml 



The composition of the medium was found 

 to exert a marked effect upon the composi- 

 tion of the actinomycin molecule (Schmidt - 

 Karsten, Goss and Katz). Sevcik (1957) has 

 shown that the production of actinomycin by 

 S. antibioticus depends on the amount of 

 phenol oxidase (laccase type) present in the 

 mycelium and decreases with the pH of the 

 medium, the optimum being pH 5.0. Certain 

 soil bacteria are capable of producing an en- 

 zyme which has the capacity of inactivating 

 actinomycin preparations (Katz and Pienta, 

 1957). 



Each form of actinomycin, produced b}^ 

 different organisms or under difTerent con- 

 ditions of culture, was found to be a heter- 

 ogeneous compoimd, made up of several in- 

 dividual chemical entities. The molecule 

 consists of a chromophore nucleus to which 

 are attached several amino acids. The nature 

 of these actinomycins and their indi\'idual 

 components depend on the makeup of the 

 polypeptide part of the molecule. Waksman, 



