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. 1973 Mar;3(3):357–363. doi: 10.1128/aac.3.3.357

Mode of Action of Illudin S

J Walser 1, P F Heinstein 1
PMCID: PMC444415  PMID: 4208286

Abstract

The effect of the antitumor antibiotic illudin S on bacterial macromolecular synthesis was investigated. Illudin S was found to be inhibitory to in vivo deoxyribonucleic acid (DNA) synthesis from thymidine. Ribonucleic acid (RNA) synthesis was inhibited only at a concentration of illudin S 10 times that which inhibited DNA synthesis. The rate of protein synthesis remained the same except for a brief initial inhibition. When thymidine triphosphate was used for in vitro DNA synthesis, inhibition by illudin S did not occur, as tested with partially purified DNA polymerase II from Escherichia coli pol A1−, with E. coli DNA-dependent RNA polymerase, with E. coli pol A1− spheroplasts, and with frozen and thawed Bacillus subtilis cells. A protein fraction isolated from B. subtilis capable of forming thymidine mono-, di-, and triphosphates from thymidine was not inhibited by illudin S. Furthermore, 14C-illudin S taken up by B. subtilis cells was reisolated unchanged, making an intracellular activation of illudin S unlikely. Therefore, an attractive hypothesis is that illudin S inhibits DNA synthesis from thymidine which does not proceed through deoxyribonucleoside triphosphates, the generally accepted substrates for DNA synthesis.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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