506 A MANUAL OF THE PENICILLIA 



culture previously studied by Alsberg and Black and found it to produce 

 from glucose two new metabolic products in addition to penicillic acid, 

 which was also formed but in reduced yield. For one of these, having the 

 empirical formula CsHeOe, they proposed the name "puberulic acid," 

 whereas the other was referred to as acid C8H4O6. Penicillium aurantio- 

 virens (Biourge's type strain) also was investigated and found to produce 

 greater quantities of both puberulic acid and acid C8H4O6 than the strain 

 of P. puberulum from which these compounds were first identified. Puber- 

 ulic acid was found to be a practically colorless dibasic acid (M.P. 316- 

 318°C.), and to give a purple-brown color with FeCls. It was thought to 

 possibly form an oxidation-reduction sj^'stem with acid C8H4O6. Barger 

 and Dorrer (1934) investigated further the production of puberulic acid 

 and acid C8H4O6, which they referred to as a "yellow acid." Methods of 

 obtaining increased yields together with additional information regarding 

 the chemical properties of the two acids were reported. O.xford, Raistrick, 

 and Smith (1942b) investigated the antibacterial properties of puberulic 

 acid and the hitherto unnamed yellow acid, C8H4O6, for which they proposed 

 the name puberulonic acid. The latter is characterized by bright yellow 

 prisms, M.P. 298°C., and upon neutralization undergoes a series of curious 

 color changes (also noted by Barger and Dorrer, 1934). Various species of 

 bacteria were inhibited by both acids in fairly low concentration, with 

 puberulic generally the more potent. Both were generally more effective 

 against cocci than against the various Gram -negative forms tested. Strains 

 of P. johannioli Zaleski ( = P. martensii Biourge of this Manual) were most 

 productive of puberulonic acid. 



The biochemistry of Penicillium puberulum was re-examined by Birkin- 

 shaw, Oxford, and Raistrick in 1936, with special reference to the produc- 

 tion, study, and characterization of penicillic acid. A culture of P. cyclo- 

 pium from Baarn (derived from Westling's original strain) was found to 

 produce considerably greater yields than the Alsberg and Black strain of 

 P. puberulum as then maintained in laboratory culture. Penicillic acid was 

 reported to be slightly soluble in cold water and readily soluble in hot 

 water, ether, alcohol, benzene, and chloroform; it crystallized as needles 

 (M.P. 83-84°C.) ; gave no color with FeCls in the cold but turned orange- 

 brown upon warming. It was optically inactive. Whereas the production 

 of penicillic acid is generally considered as characteristic of P. puberulum 

 and related species of the Fasciculata, Karow, et al. (1944) reported its 

 production also by P. suavolens, P. ihomii, and Aspergillus ochraceus. 



Alsberg and Black (1913) demonstrated the toxicity of penicillic acid. 

 Its antibacterial properties were carefully investigated by Oxford, Raistrick, 

 and Smith (1942a), who fomid the pure anhydrous acid to inhibit Staphylo- 

 coccus aureus at a concentration of 1:50,000 to 1:100,000. Professor 



