HYBRID ANTHRACYCLINE ANTIBIOTICS - PRODUCTION OF NEW ANTHRACYCLINES BY CLONED GENES FROM STREPTOMYCES-PURPURASCENS IN STREPTOMYCES-GALILAEUS

A DNA segment cloned from Streptomyces purpurascens ATCC 25489 close t o a region that hybridized to a probe containing part of the adinorhod in polyketide synthase caused S. galilaeus ATCC 31615 to produce new a nthracyclines. When transformed with certain sub-clones of this segmen t, the host produced glycosides of epsilon-rhodomycinone, beta-rhodomy cinone, 10-demethoxycarbonylaklavinone and 11-deoxy-beta-rhodomycinone in addition to those of aklavinone, the natural anthracyclines of S. galilaeus. The first two compounds are S. purpurascens products and th e other two are novel compounds that conceptually are structural hybri ds between S. galilaeus and S. purpurascens products. Three glycosides of one of the novel aglycones, 11-deoxy-beta-rhodomycinone, were puri fied and found to possess cytotoxic activity against L1210 mouse leuka emia cells. Separate regions of the cloned S. purpurascens DNA are res ponsible for modification of the S. galilaeus host product at the 10- and 11-positions.