PENICILLIN 



185 



process with penicillin formation. It is possible to specify fairly 

 exactly the optimal conditions for penicillin formation by a given 

 strain, but not possible to define the way in which these conditions act. 



The metabolic changes which take place during penicillin produc- 

 tion are conveniently divided into three phases: an initial phase of 

 rapid growth and metabolic activity, with assimilation of the more 

 available nutrients, a second phase of slower growth with carbohydrate 

 utilization, and a third phase of autolysis and low metabolic activity. 

 These are illustrated in Figure 9. Penicillin formation begins late in 

 the first phase and is most vigorous during the second. Rates differ, 

 but in broad outline this pattern is followed by different strains in 

 both complex and synthetic media, with various carbon sources, and 

 under diverse conditions of aeration (31, 209, 217, 239, 300, 324). 

 Lactose or other slowly utilizable carbohydrates yield both a favorable 

 rate of growth and a favorable pH for penicillin formation (385, 484). 



Penicillin production is also directly affected by aeration (483). The 

 metal requirement for maximal penicillin formation by a strain of 



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E 



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4 6 



Time, days 



10 



Figure 9. Metabolic changes accompanying penicillin formation by Penicillium 

 notatum in shaken flasks in a corn steep liquor-lactose medium. Redrawn from 

 Koffler, Emerson, Perlman, and Burris (323), by permission of the Williams and 

 Wilkins Company. 



