BIOGENESIS OF ANTIBIOTICS 



73 



Table 26 

 Neutralization by DL-threonine of DL-isoIeucine 

 inhibition of aciinotnycin production (Kawamata 



of proline into certain actinomycin peptides. 

 The results obtained support the view that 

 sarcosine competes with and replaces pro- 

 line in the peptide of certain actinomycins 

 (Katz and Goss, UJoS). 



Kawamata et al. (1960) found that addi- 

 tion of DL-isoleucine to the medium (starch- 

 glutamate-salts) represses the formation of 

 actinomycin, whereas growth of the organ- 

 ism is not adversely affected and is exen 

 stimulated. The addition of 1 mg per ml of 

 isoleucine l)rought about complete inhibition 

 of antibiotic production. The addition of 

 DL-threonine to the mediiun completely 

 reversed this repressive effect, as shown in 

 Table 26. 



Antibiotics Dcrirahh from Acetate 



ERYTHUOMYCIX 



Erythromycin has two sugar-like groups 

 attached to a large lactone nucleus. The 

 lactone nucleus is made up of seven pro- 

 pionic acid units (Woodward, 11)")7). Acetic, 

 propionic, and valeric acids may be incor- 

 porated into the lactone ring. This is true 

 especially of propionic acid, a fact which 

 suggests that this acid is an important pre- 



cursor, and that the other two acids are 

 converted into it before incorporation. 



Gerzon et al. (1956) suggested that the 

 macrolide ring arises, at least in the erythro- 

 mycins, by a process analogous to that by 

 which many long-chain molecules are built 

 from acetate, but utilizing propionate in- 

 stead. The long carbon chains of such anti- 

 biotics as the methymycins, picromycin, and 

 narbomycin would be deri\'ed in essentially 

 the same way except for incorporation of one 

 acetate moiety. 



Alusilek and Sevcik (1958a) demonstrated 

 that the addition of sodium arsenite (final 

 concentration of 4 X 10~^ M) to the fermen- 

 tation medium reduced the biosynthesis of 

 erythromycin by S. erijthreus bj- 87 per cent, 

 whereas it increased the accumulation of 

 pyruvic acid (Figs. 1 and 2). The addition 



Eryfhro- . 

 mycin 



4 00- 



300- 



200- 



100- 



C)^"^~0 Conrrol 



(§)- © AceTaTe 



0— —0 As" 



(g) (g) As^acerare 



13 



Days 



FuiCRE 1. Inhil)itioii l)y arsenite of erythro- 

 mycin biosynthesis in submerged cultivation of 

 S. erythreus. (Reproduced from Mu.silek, V. and 

 Sevcik, V. Folia Biol. 4: 319-327. 1958b.) 



