Walser J, Heinstein P F
Antimicrob Agents Chemother. 1973 Mar;3(3):357-63. doi: 10.1128/AAC.3.3.357.
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 A(1) (-), with E. coli DNA-dependent RNA polymerase, with E. coli pol A(1) (-) 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, (14)C-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.
研究了抗肿瘤抗生素鬼笔环肽S对细菌大分子合成的影响。发现鬼笔环肽S对体内由胸苷合成脱氧核糖核酸（DNA）具有抑制作用。核糖核酸（RNA）合成仅在鬼笔环肽S浓度为抑制DNA合成浓度的10倍时才受到抑制。除了最初有短暂的抑制外，蛋白质合成速率保持不变。当用三磷酸胸苷进行体外DNA合成时，用来自大肠杆菌pol A(1) (-) 的部分纯化的DNA聚合酶II、大肠杆菌DNA依赖性RNA聚合酶、大肠杆菌pol A(1) (-) 原生质球以及冻融的枯草芽孢杆菌细胞进行测试，未发现鬼笔环肽S有抑制作用。从枯草芽孢杆菌中分离出的一种能够由胸苷形成胸苷一磷酸、二磷酸和三磷酸的蛋白质组分不受鬼笔环肽S的抑制。此外，枯草芽孢杆菌细胞摄取的(14)C - 鬼笔环肽S被重新分离出来时未发生变化，这使得鬼笔环肽S在细胞内被激活的可能性不大。因此，一个有吸引力的假说是，鬼笔环肽S抑制不由脱氧核糖核苷三磷酸（DNA合成通常公认的底物）参与的由胸苷合成DNA的过程。
