94 



A MANUAL OF THE PENICILLIA 



corn steep liquor appeared to be largely responsible for its activity. Stone 

 and Farrell (1946) developed a synthetic medium suitable for penicillin 

 production, but it has not been generally adopted since yields do not exceed 

 those obtained in media containing corn steep liquor and the substratum 

 is somewhat more expensive. Cook and Brown (1946) have also proposed 

 a synthetic medium based upon their prior studies of Pisum extracts. 

 Pratt and co-workers (1945 and 1946) investigated the influence of inorganic 

 salts on the penicillin fermentation. 



Fig. 26. Cultures of penicillin-producing molds from which variant substrains 

 may be isolated. A , Three -week-old colony oi Penicilliiun nolatum, NRRL 1249. -B21, 

 on steep agar showing conspicuous sectors; B, Streak culture seeded with my- 

 celia (in pellet form) from a one-week-old submerged culture of P. chrysogenum, 

 NRRL 1951. B25. (After Raper and Alexander, Jour, of The Elisha Mitchell 

 Scientific Society, 61, 1945.) 



Development of More Productive Strains 



Much study has been devoted to the development of improved penicillin 

 producing organisms. All of the early work, both in England and the 

 United States, was conducted with Fleming's original strain of Penicillium 

 notatum. It was early discovered at our Laboratory and elsewhere that 

 this mold was subject to considerable variation in culture (fig. 26A). Sub- 

 cultures showing definite cultural characteristics were isolated and tested 

 for penicillin production, and a limited number of monospore selections 

 were made. One of these, designated NRRL 1249.B21 (fig. 27C), was 

 found to produce greatly increased yields in surface culture and was widely 

 used for the commercial production of penicillin by this method (see Moyer 

 and Coghill, 1946a and Raper and Alexander, 1945b). Attempts to further ' 

 increase yields of penicillin by continued strain selection proved ineffective 

 although a wide range of natural variants (fig. 27) were isolated and tested 

 (Raper and Alexander, 1945b). 



After it was found that penicillin could be produced in submerged cul- 



