170 



DESCRIPTIONS OF ANTIBIOTICS 



Table 39 



Amino acid composition of various (ictinoiii ijnns 

 Data given as moles of amino acid per mole of actiiiomyein (molecular weight, 1200). 



Amino acids 



L-Thieonine 



D-Valine 



L-Proline 



Sarcosine 



N-CH3-L-valine. . . 

 D-AUoisoleucine. . . 

 4-Hydroxyproline. . 



4-Ketoproline 



N-Methylisoleiicine 

 N-Methylalanine . . 



Actinomycins 



IV 



VI 



VII 



El 



F= 



F4 



+ 

 + 

 + 

 + 

 + 





 

 



2104L 



" Designates presence of amino acid. 



Streptoniyces sp. was shown to produce, in earlj^ 

 stages of growth, an actinomyci" similar in the 

 proportions of its components to the "B mixture," 

 whereas at later stages of growth, the proportion 

 of components was changed to that of an "A mix- 

 ture." This was demonstrated by circular paper 

 chromatography in 5 per cent Na-o-cresotinate 

 and ethyl acetate-n-butyl ether (2:1). Under dif- 

 ferent nutritional conditions, this culture could 

 produce only A-, or only B-tj'pe "mixtures" (61, 

 66). A "C-mixture'"-producing culture formed 

 VII (C3) as the major component actinomycin in 

 early growth stages, whereas later, VI (C2) became 

 the major component (28). Addition of sarcosine 

 to an L-glutamic acid-containing synthetic 

 medium in which an "A mixture "-producer was 

 grown changed the proportions of the actinomy- 

 cins normally formad. Amounts of actinomycins 

 IV and V were decreased, and II and III increased 

 (100). 



It has also been possible to produce new actin- 

 omycins when different amino acids or amino acid 

 derivatives (such as oligopeptides) were added to 

 the culture media in which "C" or "A mixture"- 

 producers were grown (58, 86). These new actin- 

 omycins are referred to below as "biosynthetic" 

 actinomycin mixtures. 



In the descriptions which follow, no data have 

 been included from reports in which the complex 

 was tested as though it were a single entity instead 

 of a mixture; only references to such publications 

 will be given. The heterogeneity of the complexes 

 makes such data invalid. 



Actinomycin Mixtures (A, B, D, J, X) Containiny 

 Actinomycins I, II , III , /T', and V 



Produced by: Streptoniyces antibiuticus (2, 82) 

 (A, B mixtures) ; S. parvus and others (8, 31, 35, 80) 

 (A mixture); S. kitasawaensis (103) (A mixture); 

 Streptoniyces sp. (10, 13) (B mixture); S. parvullus 

 (31) (D mixture); S.flavus (6, 17) (J mixture); S. 

 flaveolus (17) (J mixture); <S. griseus (S. parvus) 

 (71) (X mixture); *S. michiganensis (72, 99) (X 

 mixture) ; S. galbiis (99) (X mixture) ; S galbus var. 

 achromogen.es (99) (X mixture); S. murinus (99) 

 (X mixture); S. lanatus (99) (X mixture); and 

 Streptoniyces sp. (18, 22, 23, 28). 



Synonyms: Antibiotic X 45 (B mixture) (13). 

 Actinoflavin (J mixture) (9). 



Method of extraction: I. Broth and/or mycelium 

 extracted with ether, n-butanol, benzene, or butyl 

 acetate. Extract concentrated to dryness. Residue 

 treated with petroleum ether and extracted into 

 acetone, benzene, or cold chloroform, filtered and 

 evaporated to dryness. Recrystallized from cold 

 ethanol on addition of successive aliquots of 

 petroleum ether, or from acetone, ether, warm 

 ethanol, or other solvents. Purified by chromatog- 

 raph}' on alumiiui from benzene and elution with 

 30 per cent acetone in benzene or with ethyl ace- 

 tate (4, 10, 23, 32). Actinomycins I, II, III, IV, 

 and V are partially separated by chromatography 

 of the crude mixture on acid-washed alumina from 

 benzene-chloroform (3:1) and elvition with the 

 same mixture, gradually changing the proportion 

 to 1:3. Particular fractions are further separated 

 by rechromatographing as before, but gradually 



