SUBSTANCES PRODUCED BY FUNGI 201 



inactivation by penicillinase and by copper ionsj inactivation by methyl 

 alcohol J characteristic antibiotic spectrum, such as activity against S. 

 aureus and not against E. coU (270). 



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

 the conditions of growth greatly influence not only the yield of penicil- 

 lin but also its chemical nature. Complex organic media containing glu- 

 cose 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 supplementary addition of a stimulating 

 substance in the form of yeast extract, corn steep, or certain vegetable 

 juices is essential for the maximum production of penicillin. Since the 

 organism produces an acid, probably gluconic, in the medium, some 

 CaCOg must also be added. The metabolism of P. notatum in relation 

 to penicillin production is illustrated in Figure 13 (p. 135). 



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

 the 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 (762) 



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 formed in the medium when active growth begins and 

 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- 



