Mycoversilin

The structure of a new antifungal antibiotic, mycoversilin, produced by Aspergillus versicolor (N5)17 was determined as I by various spectroscopic and chemical methods. Mycoversilin is a unique polynuclear aromatic compound having two methyl and six hydroxyl groups and two ether linkages. The acetyl derivative prepared was found to have no antifungal property.

Antibiotically active producer mutants derived from the spontaneous degenerate parent Aspergillus versicolor N5 possessed not only mutual but also self-sensitive activity. The producer mutants, like the inactive parent, were only 3.5-fold less sensitive than the most sensitive unrelated organism, Trichophyton rubrum. The germination of spores is generally more sensitive than growth of vegetative cells. The antifungal spectrum of these mutual and self-sensitive mutants was fairly wide, unlike the host range specificity of bacteriocinogenic strains acting on organisms closely related to the producers. The self and mutual growth inhibitory principle was finally identified as the antibiotics mycoversilin and versilin in the case of producer mutants (N5)17 and N5T10(7), respectively, or Vx, an antibiotic of unknown molecular species, in the case of another producer mutant N5T10(8). Thus self-sensitivity, instead of self-resistance, of these antibiotically active mutant derivatives is a unique property among filamentous fungi in having simultaneously expressed two loci of contradictory functions, one for synthesis of, and the other for sensitivity towards, the same or related antibiotics.

Mycoversilin is active against filamentous fungi, being specifically inhibitory to Trichophyton rubrum, minimum inhibitory concentration being 15 micrograms/ml. Mycoversilin inhibits sporulation to the extent of 28.5% even at the growth inhibitory concentration whereas inhibition of spore germination requires higher concentration. It has no effect on radial growth. Further it shows no action either on the release of UV absorbing materials or on the respiration of T. rubrum. However, the antibiotic inhibits in vivo synthesis of protein fairly strongly, DNA moderately and RNA slightly at the minimum inhibitory concentration. Cell-free protein synthesis is also strongly inhibited, the site of action being the inhibition of leucyl-tRNA formation by the antibiotic which has no action on leucine activation.