PRODUCTION OF ANTIBIOTICS 



39 



The effect of the medium upon tlie nature 

 of the antibiotic can best be ilhistrated by 

 an analysis of the production of different 

 actinomycins. Schmidt-Kastner first demon- 

 strated (195()) that by increasing the amino 

 acid content of the medium or by the addi- 

 tion of special amino acids, notably sarcosine, 

 new actinomycins can be produced. These 

 results were fully confirmed in subsecjuent 

 studies carried out in our laboratories, as 

 shown in Tables 14 and 15. 



An examination of the chemical nature of 

 the actinomycins produced by different 

 organisms revealed certain pertinent differ- 

 ences in the concentrations of the various 

 components of the actinomycin molecule. »S. 

 antibioticus (the original producer of actino- 

 mycin A) gives, in certain media, the follow- 

 ing actinomycins: I, 10 per cent; IV, 60 per 

 cent; V, 30 per cent. Streptomyces 3723 (the 

 original producer of actinomycin B) gives, in 

 certain media: I, 10 per cent; IV, 30 per 

 cent; V, 60 per cent. S. chrysomaUus (the 

 original producer of actinomycin C) gives: 

 IV, 10 per cent; V, 50 per cent; VII, 40 per 

 cent. S. parvuUus (the original producer of 

 actinomycin D) gives: IV, nearly 100 per 

 cent. 



Katz and Goss (1958) have demonstrated 

 that it is possible to change to a limited 

 extent the proportion of any particular com- 

 ponent in a natural mixture of actinomycins. 

 Certain components normally produced in 

 small amounts may be increased until they 

 represent the major constituents of an 



actinomycin complex. Actinomycin \, for 

 example, was the major component in the 

 actinomycin mixture produced by *S. anti- 

 bioticus when L-threonine was the sole 

 nitrogen source, whereas actinomycin IV 

 represented the main constituent when L- 

 glutamic acid was used. Schmidt-Kastner 

 (1960) demonstrated that actinomycin IV 

 increased from 10 to 83 per cent of the ac- 

 tinomycin mixture formed by S. chrysomaUus 

 when 0.5 per cent i)L-valine was added to a 

 glycerol-nitrate medium. 



Various amino acids, notably hydroxy-L- 

 proline, sarcosine, N-acetylglycine, and l- 

 isoleucine, bring about marked (juantitative 

 changes in the actinomycin complex pro- 

 duced. Components normally formed in 

 small amounts were found, in certain specific 

 conditions, to represent major constituents 

 of such mixtures. 



Among the many other factors influencing 

 the (luantitative yield of an antibiotic, the 

 mineral constituents occupy a prominent 

 place. In this connection, the importance of 

 the effect of phosphorus starvation upon the 

 yield of streptomycin must be emphasized. 

 The presence of iron in the mediiun will favor 

 the accumulation of mannosidostrepto- 

 mycin, whereas the addition of calcimn will 

 lead to the transformation of the latter to 

 streptomycin. Detailed studies of the role of 

 trace elements in the profluction of strepto- 

 mycin have been made by Chesters and 

 Rolinson (1951) and numerous others. 



