92 A MANUAL OF THE PENICILLIA 



tion at the Northern Laboratory and elsewhere. The successful results of 

 studies conducted here were reported by Moyer and Coghill (1946b), while 

 more or less similar investigations were reported by Foster, Woodruff, and 

 McDaniel (1946). In the former studies it was found that the same type 

 of nutrient solution used for surface production of penicillin, could be 

 employed, but that the concentrations of lactose and of corn steep liquor 

 should be reduced approximately one-half. The formulas of media de- 

 veloped by Moyer for surface and submerged production of penicillin, and 

 reported in papers by Moyer and Coghill (1946a and 1946b), follow: 



Surface production Submerged production 



Corn steep liquor 100.0 g. 40.0 g. 



Lactose 44.0 g. 27.5 g. 



NaNOs 3.0 g. 3.0 g. 



KH2PO4 0.500 g. 0.500 g. 



MgS04-7H20 0.250 g. 0.250 g. 



ZnS04-7H20 0.044 g. 0.020 g. 



Glucose 2.75 g. 3.00 g. 



Water to make 1 liter 1 liter 



Sterilize in autoclave for 20 minutes at 15 lb. pressure and 120°C. 

 To the solution for submerged culture, sterile calcium carbonate was usually 

 added in the amount of approximately 1 per cent just prior to inoculation. 



Starting with the basic information developed at the Northern Labora- 

 tory, Professors Peterson and Johnson and their associates at the University 

 of Wisconsin have investigated in great detail the various factors affecting 

 the production of penicillin in submerged culture, both in the laboratory 

 and on a ssmi-plant scale (fig. 25). While a detailed analysis of their con- 

 tent is not necessary in this connection, the following papers should be 

 cited: Knight and Frazier, 1945 a and b; Koffler et al., 1945, 1946, 1947; 

 Johnson, 1946; Gailey, et al., 1946; Stefaniak, ct al., 1946a and 1946b; and 

 Peterson, 1947. In general, the levels of nutrients, aeration, pH, etc., 

 cited in these papers are believed to approximate those employed for large 

 scale production by industry. 



In laboratory experiments, cultures are usually seeded with conidia, 

 or a suspension of conidia, derived directly from heavily sporing cultures 

 as reported by Moyer and Coghill (1946a), and others. Under some condi- 

 tions the production of seed material in submerged culture has marked 

 advantages. Foster, et al, (1945) reported methods of obtaining heavy 

 conidium production under these conditions and reported a high concen- 

 tration of the calcium ion to be the most important factor involved. Gil- 

 bert and Hickey (1946) found the addition of iron in fairly high concentra- 

 tions to stimulate submerged sporulation. Savage and Vanderbrook (1946) 

 demonstrated that mycelium fragmented in a high speed blender provided 

 suitable seed for setting penicillin fermentations. 



