Topostatin, a novel inhibitor of topoisomerases I and II produced by Thermomonospora alba strain no. 1520 - III. Inhibitory properties

A novel inhibitor of topoisomerases designated as topostatin was isolated f rom the culture filtrate of The, Thermonospora alba strain No. 1520. The in hibitory activity of topostatin was shown to be pH- and temperature-depende nt with a maximum around at pH 6 and 28 degrees C. The stability of toposta tin decreased with decreasing pH and rising temperature. Topostatin inhibit ed topoisomerases I and II in a competitive manner with respect to DNA. The inhibitor also inhibited some restriction endonucleases such as Sca I, Hin dIII and PstI, but not AluI, Bam HI, Eco RI, RNase A, DNase I, DNase II and DNA ligase. Topostatin did not induce the nuclear accumulation of p53 prot ein by DNA damage in the normal human cells.