SUBSTANCES PRODUCED BY FUNGI 175 



many respects to streptothricin, although it differs somewhat in its anti- 

 bacterial spectrum and its lower toxicity for animals. 



Proactinomycin is produced by N. gardneri grown in soft agar 

 media, from which it is extracted by organic solvents, such as ether, amyl 

 acetate, benzene, and carbon tetrachloride. It can be re-extracted in 

 water by adjusting the ^H to 4.0 with HCl or H2SO4. The aqueous 

 extract is concentrated in vacuo and evaporated to dryness from the 

 frozen state. A white powder, very easily soluble in water, is obtained. 

 The yield of the material is 60 mg. from i liter of culture. The sub- 

 stance is fairly stable, though boiling for 10 minutes at fVL 2.0 or fH 

 7.0 results in a small loss of activity. Boiling at />H lo.o destroys the 

 greater part of the antibacterial activity. Proactinomycin has basic prop- 

 erties and is precipitated from aqueous solution by such base precipitants 

 as picric acid, picrolonic acid, and flavianic acid. 



SUBSTANCES PRODUCED BY FUNGI 



The early studies of the phenomenon of staling accompanied by the 

 production of antibacterial and antifungal substances (83), some of 

 which could be removed from the acidified medium by ether or by col- 

 loidal clay (700), have recently been superseded by more exact and 

 detailed chemical studies. Only a few of the many antibiotic substances 

 produced by fungi have so far been identified, however. Some are pro- 

 duced in complex organic media, others in simple synthetic media. Only 

 the more important substances will be discussed here. Among these, 

 penicillin occupies a leading place because of its low toxicity and its ac- 

 tivity in vivo. 



Penicillin is produced by various strains of P. notatum and P. 

 chrysogenum, and probably by a variety of other fungi (272a, 940a). 

 The penicillin-like nature of an antibiotic substance is usually estab- 

 lished by its biological and chemical properties: activity against S. au- 

 reus and not against E. colt; extraction in organic solvents at fH 2 

 and re-extraction in water at fH 7 ; inactivation by acid and alkali j par- 

 tial inactivation by heating at 100° C. and /)H 7 for 15 minutes j com- 

 plete inactivation by penicillinase and by copper ionsj inactivation by 

 methyl alcohol (272a). 



