SUBSTANCES PRODUCED BY FUNGI 181 



in every respect to penicillin, is produced by A. flavus (929) j the same 

 is true of gigantic acid produced by A. giganteus (688). Preparations 

 of flavicin have also been designated as flavatin (716, 717), aspergillin 

 (100), flavacidin (461), and parasiticin. 



AsPERGiLLic Acid is produced by A. -flavus (461, 978) grown on 

 tryptone-glucose media, as shown previously (page 131). The pure 

 acid has an m.p. of 93° C. (84° to 96'^) and has optical activity of 

 [ajo = +14°- The formula CioHoqNoOo has been proposed for this 

 substance. It possesses a hydroxyl group which gives it its acid nature 

 (^K S-S)- It is stable under acid and alkaline conditions and can be dis- 

 tilled with steam or in vacuo without loss of activity. When grown in 

 brown-sugar-containing media, a closely related substance is formed, 

 having the formula CioHooO.-jNo and an m.p, of 149°, with lower bio- 

 logical activity. Aspergillic acid is active against both gram-positive and 

 gram-negative bacteria. 



CiTRiNiN was isolated from Penicillium ckrinum (714). It is pro- 

 duced by growing the organism on a synthetic medium, with inorganic 

 salts of nitrogen and with glucose as a source of carbon. The culture fil- 

 trate is acidified with HCl, and the substance crystallized from boiling 

 alcohol. Citrinin forms a monosodium salt which, at ^H 7.0 to 7.2, gives 

 virtually colorless solutions in water. Its bacteriostatic activity is much 

 lower than that of penicillin (33). It is a yellow crystalline solid, m.p. 

 170-171° (with decomposition). Its formula is C10H14O5. 



Citrinin is a strong acid, changing in color from lemon-yellow at /)H 

 4.6 to orange-pink at fYl S-^ to 5.8 and to cherry-red at /)H 9.9 (352). 

 Addition of FeCla to the culture solution gives a heavy buff-colored 

 precipitate, which dissolves in excess of reagent to give an intense iodine- 

 brown solution (871 ). It has little if any activity against gram-negative 

 bacteria and about 50,000 dilution units against B. subtilis and S. aureus. 



Penicillic Acid was first isolated in 1 9 1 3 by Alsberg and Black (19) 

 as a metabolic product of Penicillium fuberulum. A limited air supply 

 and an acid reaction of the medium favor the production of this acid, to 

 which the chemical formula C8H10O4 was given. This acid is a rather 

 weak antibiotic substance active largely against gram-positive bacteria j 

 however, it is more active against gram-negative bacteria than penicillin, 

 giving complete inhibition of E. coli m concentrations of 1:50,000, 



