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DNAtopoisomerases I and II are enzymes that alter DNA conformation through a concerted breaking and rejoining of DNAstrands1*. Recently topoisomerase II has been identified as the primary cellular target for a number of clinically important antitumor agents with diverse and unrelated chemical structures2'3*. These antitumor drugs, termed "topoisomerase II poisons" have the commonproperty of stabilizing the DNA-topoisomerase II complex which upon exposure to denaturing agents results in the induction of DNA cleavage2'3*. Several lines of evidence indicate that the ability to induce topoisomerase II dependent DNAcleavage (TDC) is responsible for the antitumor activity of these drugs2 ~4). In order to identify a specific new topoisomerase II poison, we have screened cultures of actinomycetes and fungi for their ability to induce TDCin vitro. We found that flavonoids such as genistein and orobol are potent inducer of TDC5), and have now isolated a novel compound with TDC activity, saintopin, from the culture broth of Paecilomyces sp. The producing organism was isolated from a soil collected at a vineyard in Yamanashi Prefecture, Japan and was assigned to the genus, Paecilomyces. Fermentation was carried out at 25°C for 5 days under aeration and agitation in 30-liter jar fermenter containing 18 liters of a culture mediumconsisting of sucrose 5%, dry yeast 3%, KH2PO4 0.05%, MgSO4-7H2O 0.05%, Mg3(PO4)2-8H2O 0.05%,

Saintopin, a new antitumor antibiotic with topoisomerase II dependent DNA cleavage activity, from Paecilomyces.