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DNAtopoisomerases are enzymes that alter DNA conformation through a concerted breaking and rejoining of DNAstrands thereby controlling the topological state of DNA1}. Topoisomerase II has been shown to be the primary cellular target for a numberof clinically important antitumor agents with diverse and unrelated chemical structures2'3*. These antitumor drugs, referred as to "topoisomerase II poisons", trap the enzyme in an intermediary reversible complex with DNA,termed "cleavable complex" which prevents the final rejoining step of the reaction and results in increased DNAstrands breaks2?3). It is believed that the ability to form the cleavable complex with topoisomerase II is responsible for antitumor activity of these drugs. In order to identify a specific new topoisomerase II poison, we have screened cultures of actinomycetes and fungi for their ability to induce topoisomerase II mediated DNAcleavage in vitro. Wefound that the diterpeniod antitumor antibiotics terpentecin and clerocidin are potent inducers of DNA cleavage4), and have now isolated a novel compound with DNAcleavage activity, UCT4B, from the culture broth of actinomycetes which produces terpentecin. The producing organism was isolated from a soil collected in Yamaguchi Prefecture, Japan and was assigned to the genus Streptomyces. Fermentation was carried out at 28°C for 3 days under aeration of 400 liters/minute and agitation at lOOrpm in 200-liter tank fermenter containing 100 liters of culture mediumconsisting of sucrose 5%, KNO3 3%, KH2PO4 0.05%, MgSO4-7H2O 0.05%, Mg3(PO4)2 -8H2O 0.05%, pH 7.0. UCT4B accumulated in the culture medium. The culture filtrate was applied to a column of Diaion HP-20 (Mitsubishi Chemical Industries Limited). The column was washed with deionized water-MeOH (1 : 1) and eluted with deionized water-MeOH (3:7). The active eluate was concentrated and applied to a

UCT-4B, a new antitumor antibiotic with topoisomerase II mediated DNA cleavage activity, from streptomyces sp.