ANTIBACTERIAL EFFECTS 139 



mutant strains. This freeing of mutants must be carried out continu- 

 ously, in order to avoid the degeneration of the culture. By strain se- 

 lection and improvement of medium (addition of corn steep liquor, use 

 of lactose), the penicillin yield of such cultures has been increased from 

 ■2 to 6 to more than 200 O.U./ml. (662). For submerged cultures, how- 

 ever, strains of P. notatum and P. chrysogenum are used which are not 

 related to the Fleming strain. The best medium for tank production is 

 about half the concentration of the nutrients used for surface culture. 

 Pregerminated inocula are used {66'^). 



In a study of the metabolism of the penicillin-producing fungi 

 (308a) it was established that the most important factors for high 

 yields of penicillin are the nature of the culture, aeration, temperature, 

 and proper balance among the nutrients of the medium, especially the 

 relation between the carbon and nitrogen sources (591 )• Specific amino 

 acids have an influence on the yield of penicillin, especially in sub- 

 merged culture (375). Yields ranging from 90 to 900 units of peni- 

 cillin were obtained under submerged conditions of growth. 



The rate of utilization of different sugars and oxygen consumption 

 by penicillin-producing strains of a submerged culture is brought out 

 in the following summary (519) : 



The lactose is more slowly utilized than the glucose, and less oxygen 

 is required for penicillin production. The addition of boron to the me- 

 dium favors lactose utilization and results in a higher rate of respiration 

 and nitrogen utilization, with a less abundant mycelium, lower am- 

 monia levels, and higher penicillin yields (520). 



At least four different penicillins have been isolated, namely, F, G, 

 X, and K, two or more being found in the same culture broth. These 

 penicillins differ in their chemical characteristics, in their antibacterial 

 spectra, and also in their chemotherapeutic utilization. For example, 

 penicillin X is more effective in the treatment of gonorrhea than G. 



