176 CHEMICAL NATURE OF ANTIBIOTIC SUBSTANCES 



The strain of the organism used, the composition of the medium, and 

 the conditions of growth greatly influence the yield of penicillin. Com- 

 plex organic media containing glucose or brown sugar as a source of 

 carbon are essential. Nitrate is used as a source of nitrogen j the medium 

 also must contain a phosphate and certain other minerals. The supple- 

 mentary addition of a stimulating substance in the form of yeast extract, 

 corn steep, or certain vegetable juices is essential for the maximum pro- 

 duction of penicillin. Since the organism produces an acid, probably glu- 

 conic, in the medium, some CaCOg must also be added. The metabolism 

 of P. notatum in relation to penicillin production is illustrated in Fig- 

 ure 13 (page 129). 



Four methods have been proposed for the growth of the fungus and 

 production of penicillin. These are: 



Surface growth in shallow liquid media; usually flasks, bottles, and other 

 containers are employed, the depth of the medium being 1.5 to 

 2.0 cm. 



Submerged growth in liquid media; the vessels must be provided with 

 proper stirrers and aeration 



Surface growth upon semi-solid media, including grain and bran (730) 



Circulation of medium through a column, the supporting material being 

 made up of wood shavings or pebbles; the rate of flow of the me- 

 dium is very important 



Since the various strains of penicillin-producing organisms vary 

 greatly in their optimum conditions for the production of this antibiotic 

 substance, different strains must be used for different conditions of cul- 

 tivation. 



Penicillin is produced in the medium when active growth begins but 

 reaches a maximum soon after the growth maximum, which occurs in 

 7 to 14 days in stationary cultures and in 3 to 7 days in submerged cul- 

 tures, at 20° to 25° C. 



Penicillin is soluble in ether, acetone, esters, and dioxanej it is mod- 

 erately soluble in chloroform, slightly soluble in benzene and in carbon 

 tetrachloride. It is soluble in water to the extent of 5 mg./ml. 



It is inactivated by oxidation and by evaporation at 40° to 45° C. in 

 acid and in alkaline solutions, although it is fairly stable at /»H 5 to 6. 



