Hybrid anthracycline antibiotics: production of new anthracyclines by cloned genes from Streptomyces purpurascens in Streptomyces galilaeus

Leiras OY, PO Box 415, FIN-20101, Turku, Finland Department of Biochemistry and Food Chemistry, University of Turku, Vatselankatu 2, FIN-20500, and Tykistökatu 6, FIN-20520, Turku, Finland * Author for correspondence: Jarmo Niemi. Tel: +358 21 6336856. Fax: +358 21 633 6860. e-mail: janiemi@finabo.abo.fi (Internet;, janiemi@finabo (Bitnet). ABSTRACT A DNA segment cloned from Streptomyces purpurascens ATCC 25489 close to a region that hybridized to a probe containing part of the actinorhodin polyketide synthase caused S. galilaeus ATCC 31615 to produce new anthracyclines. When transformed with certain sub-clones of this segment, the host produced glycosides of β-rhodomycinone,β-rhodomycinone, 10-demethoxycarbonylaklavinone and 11-deoxy-β-rhodomycinone in addition to those of aklavinone, the natural anthracyclines of S. galilaeus. The first two compounds are S. purpurascens products and the other two are novel compounds that conceptually are structural hybrids between S. galilaeus and S. purpurascens products. Three glycosides of one of the novel aglycones, 11-deoxy-β-rhodomycinone, were purified and found to possess cytotoxic activity against L1210 mouse leukaemia cells. Separate regions of the cloned S. purpurascens DNA are responsible for modification of the S. galilaeus host product at the 10- and 11-positions. Keywords: Streptomyces purpurascens , anthracycline antibiotics, hybrid antibiotics, cloning Present address: Centre for Biotechnology, University of Turku, Tykistökatu 6, BioCity, FIN-20520, Turku, Finland. Present address: Department of Biochemistry and Food Chemistry, University of Turku, Arcanum, Vatselankatu 2. FIN-20500, Turku, Finland. Present address: Department of Biochemistry and Food Chemistry, University of Turku, Tykistökatu 6, FIN-20520, Turku, Finland.