96 



A MANUAL OF THE PENICILLIA 



ture, and that this method of production was the most feasible industrially, 

 particular attention was directed toward the development of strains capable 

 of producing greater yields under these conditions. A strain of Penicillium 

 notatum, NRRL 832 (fig. 97E), was the culture first found to produce satis- 

 factory yields when grown submerged. Attempts to develop higher yield- 

 ing substrains from it were unsuccessful (Raper and Alexander, 1945b). 

 A wide search for other and possibly higher yielding strains was, therefore, 

 undertaken. A simple screening technique (fig. 28) was developed which 

 ciuickly and effectively eliminated poor producing strains, whereas more 

 promising strains were tested in flask cultures. Of many cultures isolated 



Fig. 28. Screening test for preliminary evaluation of penicillin producing molds. 

 A, The selected mold is grown upon steep agar at 24°C., and a radial series of agar 

 plugs removed with a cork borer at 4 (upper), 6 (lower), and 8 (center) days. B, The 

 agar plugs are placed upon an agar plate, previously seeded with Staphylococcus, and 

 incubated for 16 hours at 37°C. Resulting zones of inhibition are compared with 

 zones produced by controls representing known good penicillin producing strains 

 grown and tested under identical conditions. 



and examined by Raper, Alexander, and Coghill (1944) a strain of P. chryso- 

 genum, NRRL 1951, (isolated from a cantaloupe in Peoria), proved to be 

 the most productive (Col. PL II and fig. 95). Selective recultivation of 

 naturally occurring variant types from this strain soon yielded a substrain, 

 NRRL 1951. B25 (Col. PI. II and fig. 29), which produced penicillin 

 yields up to 200-250ii/ml. in submerged culture. Attempts to realize 

 further increases in yield by the isolation and testing of natural variants 

 of NRRL 1951. B25 were unsuccessful, although even a wider range of 

 variants was obtained (fig. 30) than had been encountered in NRRL 

 1249.B21 (Raper and Alexander, 1945b). 



Under a program of research sponsored by the Oflfice of Production Re- 

 search and Development, conidia of strain NRRL 1951. B25 were subse- 



