90 A MANUAL or THE PENICILLIA 



been used by Fleming and by the Oxford group. Particular attention was 

 given to the development of an optimum medium for penicillin production, 

 and the successful and highly significant results of this work have been 

 published by Moyer and Coghill (1946a). The most important constituent 

 of the optimal medium was corn steep liquor, which, at levels below actual 

 toxicity, was found to produce yields of penicillin more or less proportional 

 to the amount of steep liquor contained in the medium. Of various carbon 

 sources tested, lactose was found to give the highest penicillin yields, and 

 afterward was regularly included in the production medium. The lactose- 

 steep liquor medium, thus evolved, was generally adopted for the com- 

 mercial production of penicillin by surface culture methods (see p. 000). 

 Studies of a similar but less productive nature were reported by Foster, 

 et al. (1943). 



Much attention has been given to the use of other ingredients without 

 finding, up to this time, any substitute equal to the lactose-steep liquor 

 combination. Foster, ei al. (1946) have recommended the use of cotton- 

 seed meal as a substitute for corn steep liquor. Mohan, et al. (1946) re- 

 ported bran extract to favorably influence penicillin production. Cook, 

 et al. (1945) reported the successful use of extracts of ground peas (Pisum 

 sativum). Taylor (1943) used "amigen," a partially hydrolyzed starch 

 preparation, as a carbon source. Lochhead and Chase (1945) used sulphite 

 waste liquor as a basal substrate, obtaining increased yields when they 

 supplemented this with additional inorganic nitrogen and phosphorus, or 

 corn steep liquor. Shwartzman (1944) claimed enhanced production of 

 penicillin in fluid media containing cellophane. Murkherjee and Sarkhel 

 (1946) reported glycerine to afford a suitable carbon source. 



Bowden and Peterson (1946) investigated a number of natural materials 

 but found no satisfactory substitute for corn steep liquor, although they 

 obtained increased yields of penicillin by supplementing the corn steep 

 liquor with meat-scraps meal and potatoes. They likewise reported that 

 prior fermentation of the corn steep liquor with yeast seemed to increase 

 penicillin production. Knight and Frazier (1945) investigated the effect 

 of corn steep liquor ash on penicillin production and obtained some increase 

 by the addition of such ash to the usual production medium. 



Miscellaneous Production Methods 



Various methods of producing penicillin have been investigated. The 

 production in surface or still cultures was first investigated, and was prac- 

 ticed on a commercial scale for a period of two to three years prior to 1945. 

 Clifton (1943) proposed trickling the culture medium through a column of 

 wood shavings, of the type used in vinegar manufacture, which had been 

 inoculated with a favorable mold strain. Various investigators studied the 



