SERIES AND SPECIES OF GEMS STh'l-l'Ti >\l ) I ES 



139 



a maximum al 24 to •">() hours, followed by 

 a decrease up to about 96 hours; a gradual 

 Leveling of growth then took place. 



Growth of S. griseus in stationary cultures 

 teaches a maximum iu 10 days, whereas 

 maximum growth in submerged cultures is 

 usually attained in 3 to 5 days. This is fol- 

 lowed by lysis of the mycelium. Growth of 

 the organism is accompanied by a gradual 

 rise in pll value of the culture and in the 

 ammonia and amino nitrogen content; the 

 total nitrogen in the mycelium tends to be 

 higher during the active stages of growth. 

 The production and accumulation of strep- 

 tomycin parallel the growth of the organism, 

 reaching a maximum when lysis just sets in; 

 this is followed by a decrease when the rate 

 of lysis readies a maximum. 



Metabolism 



The metabolic changes of S. griseus in a 

 glucose-peptone-meat extract medium have 

 been found by Dulaney and Perlman (1947) 

 to fall into two phases. During the first 

 phase, the organism grows rapidly and forms 

 extensive mycelium; this is accompanied by 

 a reduction in the quantity of soluble con- 

 stituents in the medium, namely, the nitro- 

 gen, the inorganic phosphate, and the avail- 

 able carbohydrate; the quantity of lactic 

 acid present is first increased and then uti- 

 lized to some extent ; the oxygen demand is 

 high, and the Q02 values may reach L50; 

 little streptomycin is produced; the soluble 

 carbon content of the medium during the 

 growth phase rapidly falls as the glucose is 

 utilized; about 50 per cent of the carbon 

 appears to be unavailable to the organism 

 during the first stage; the nitrogen content 

 of the mycelium varies with age. During the 

 second or autolytic phase of growth con- 

 siderable lysis sets in; streptomycin is pro- 

 duced actively, and the pll of the medium 

 rises; the quantity of mycelium is decreased 

 as a resull of lysis; the lactic acid content 

 remains more or less constant, as does the 



soluble carbon content of the medium; the 

 oxygen demand slowly decreases; the am- 

 monia nitrogen, soluble nitrogen, and inor- 

 ganic phosphate contents of the medium 

 rise rather markedly, paralleling die autoly- 

 sis of the cells. 



Ammonium compounds, bu1 not nitrates 

 are favorable sources of nitrogen for growth 

 and streptomycin production. S. griseus 

 rapidly assimilates phosphate in a phos- 

 phorus-poor medium. An excess of phos- 

 phorus lias a depressive elTeel both upon 

 growth of the organism and upon strepto- 

 mycin production. 



The supplementary addition of amino ac- 

 ids or of more complex organic compounds 

 has been found to stimulate production of 

 streptomycin. Eiser and McFarlane (1948) 

 found that, of the amino acids, histidine is 

 essential for both mycelial growth and strep- 

 tomycin production; inositol also increased 

 the yield of both; valine favored the latter. 

 and aspartic or glutamic acid the former. 

 If the salt concentration is low, most of the 

 streptomycin will be found in the mycelium, 

 thus suggesting that streptomycin is a prod- 

 uct of intracellular synthesis. Woodruff and 



linger ( 1948) reported that yields as high as 

 1 g of streptomycin per liter are produced 

 by S. griseus in media containing proline 

 as the only source of nil rogen. 



The ability of S. griseus to form an en- 

 zyme (mannosidostreptomycinase) which de- 

 composes mannosidostreptomycin into strep- 

 tomycin and mannose has been recently 

 demonstrated. This enzyme is not produced 

 by other actinomycetes or fungi (Volume I. 

 p. 1ST). 



On a dry basis, the mycelium of S. griseus 

 contains about 16 per cent ether-soluble 

 material and about 37 per cent cold water- 

 soluble substances. Little study has been 

 made of the specific chemical composition 

 of these and other tract ions. 



Stokes and Gunness < L946) grew S. griseus 

 in stationary cultures in a nutrienl medium 



