130 FUNGI AS ANTAGONISTS 



An extensive literature soon began to accumulate on the production 

 (5, 117, 118, 164, 282, 332, 422), isolation (113, 469), and identifica- 

 tion (6, 8) of penicillin. The course of its formation in the culture of 

 the organism is illustrated in Figure 13. Conditions of nutrition were 

 found to be particularly important. Preparations having an activity of 

 2,000 Oxford units or 100,000,000 dilution units have been obtained. 

 The importance of the dual nature of P. notatu?n (the culture being 

 composed of two distinct cell constituents) must be recognized for maxi- 

 mum penicillin production (34, 376). The low toxicity of penicillin, its 

 solubility in water, and its in vivo activity make it an ideal agent for 

 combating disease caused by gram-positive bacteria (p. 232). 



In addition to true penicillin, P. notatum was found to produce an- 

 other substance, which in glucose-containing media is active against not 

 only gram-positive but also gram-negative bacteria. It was designated 

 as the E. colt factor, penatin, notatin, and penicillin B (p. 179). 



P. notatum represents an extremely variable group of organisms, 

 some of the strains producing considerable penicillin, others producing 

 little penicillin but large amounts of notatin. Some strains of a closely 

 related fungus, P. chrysogenum, are also capable of producing peni- 

 cillin that is apparently the same as the penicillin of P. notatum. The 

 P. notatum-chryso genum group of fungi is widely distributed in nature, 

 having been isolated from different soils (919) and from various moldy 

 food products J however, only a few strains produce enough penicillin 

 to justify their use for the commercial production of this substance 

 (732). Members of the A. flavus group of fungi, as well as strains of 

 A. niger, Aspergillus nldulans, A. oryzae, Penicillium citreo-roseum 

 (282), i4. gtganteus (688), yl. parasiticus (142), and others, are also 

 capable of producing penicillin or closely related compounds. 



Among the other fungi that produce antibiotic substances largely ac- 

 tive against gram-positive bacteria may be listed Aspergillus flavifes 

 (976), Chaetomium cochliodeSy and others. 



Certain species of Penicillium are also capable of producing other 

 antibacterial substances, namely, citrinin, penicillic acid, and claviformin 

 (p. 181), the first of which is also produced by certain species of Asper- 

 gillus belonging to the candidus group ( 883) . 



