ri{()i)L("rioN oi' im(;.mi;nts 



203 



tyrosinase. The majority of the "cliromo- 

 jrenic" actiiioniyc'ctcs |)i-o(iuco such pi^incnls 

 on ori;aiii(' nuHlia. ("crtaiii spo('i(\s produce 

 thcst' pi^nu'Uts also on syntlictic nictiia. 

 Sonu> of tlic lirown to l)lack i)i«>;inents re- 

 main in tiu> mycelium ("melanin"); others 

 (lissol\(> in the mediuni. 'I'he nature of the 

 nunlium greatly influences the nature and 

 intensity of the piii;ment produced. 



Pereivai and Stewart made a detailed 

 study of the mechanism of melanin foi'ina- 

 tion. They found that in the presence of 

 tyrosinase, the formation of melanin from 

 tyrosine is apparently due to the oxidati\'e 

 formation of the red indok' ([uinone through 

 the action of the enzyme. The suhseciuent 

 reactions, the formation of o,4-hydroxyin- 

 dole and its further oxidation to melanin, are 

 able to take place merely in the presence of 

 molecular ox\^gen, and without the interven- 

 tion of any enzyme. 



Environmental conditions, notably the 

 degree of oxidation and the temperature of 

 incubation, influence the formation of pig- 

 ments. Aerobic conditions and lower tem- 

 peratures (7-1 5°C) fa^'or pigment formation 

 in the culture. At 37°C pigment formation 

 is greatly diminished. 



Role of Pigments in the Life and Me- 

 tabolism of Actinomycetes 



Various hypotheses have been proposed to 

 explain the role of pigments in the growth 

 of the microbial cell. Their function in the 

 respirator}' mechanisms of the cell has been 

 suggested. Some have claimed for them a 

 role in the defense mechanism of the cell 

 against the action of foreign cells or against 

 the effect of sun raj^s. The recent interest 

 in the subject of antibiotics has tended to 

 concentrate attention upon these substances 

 that are pigmented in nature. 



Benedict and Lindenfelder (1951) ha\e 

 shown that the different varieties of *S. (jri- 

 seus possess characteristic pigment-produc- 

 ing capacities on special media. Some of the 



streptomycin-pioducing strains are able to 

 form yellow [)igments on syntiieti(^ calcium 

 nialate nunlia and green pigments on calcium 

 succinate media. (Jrisein-pi'oducing sti'ains 

 are unable to produce such pigments (Table 

 49). 



Antibiotic Pigments 



A large numbei' of actinomycetes jjroduce 

 pigmented antilnotics, which I'ecently have 

 recei\-ed much consideration. Benedict pro- 

 posed a system of classificat ion of pigmented 

 antibiotics produced by actinomycetes 

 ('liable 50). Some of these groups deserve 

 more detailed consideration. 



Actinomycins 



Actinomj'cin was the first antibiotic iso- 

 lated in a pure state from a cultvn-e of a 

 streptomyces. It crystallizes from ethyl ace- 

 tate or from acetone-ether mixtures as red 

 platelets, m.p. 250°, [a]f (C = 0.25 per cent 

 in ethanol) —320 dz 5°. It is soluble in 

 chloroform, acetone, ethanol, hot ethyl ace- 

 tate, carbon disulfide, and benzene, but only 

 slightly soluble in water or ether. It is stable 

 in acjueous alcohol when boiled for 30 min- 

 utes, but unstable in dilute acid or alkali. An 

 alcoholic solution of actinonwcin gives no 

 coloration with ferric chloride; it shows char- 

 acteristic light absorption in the visible re- 

 gion (E\'^j^ = 200 at -450 /x) and in the uhra- 

 violet region (EW, = 216 at 215 m/z). It 

 is highly active against certain gram-posi- 

 tive bacteria. Waksman and Tishler found 

 that 10 (Jig given intraperitoneally or sub- 

 cutaneously, killed 20-gm mice in 2-4 to 48 

 hours. 



Various forms of actinomycin ha\'e since 

 been isolated. Interest in this group of anti- 

 biotics has grown especially since it has been 

 demonstrated that they exert a marked effect 

 in the treatment of certain forms of cancer. 

 The chemical studies of Dalgleish ct al., of 

 Brockmann and Grubhofer, and of many 

 others added greatly to our understanding 



