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Microbiology 142 (1996), 1965-1972; DOI  10.1099/13500872-142-8-1965
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Production of hybrid anthracycline antibiotics by heterologous expression of Streptomyces nogalater nogalamycin biosynthesis genes

Kristiina Ylihonko1,3, Juha Hakala2, Tero Kunnari2 and Pekka Mäntsälälä1

Department of Biochemistry and Food Chemistry, University of Turku, Arcanum, Vatselantie 2, FIN-20500, Turku, Finland
Galilaeus Oy, Arcanum, Vatselantie 2, FIN-20500, Turku, Finland

3Author for correspondence: Kristiina Ylihonko. Tel: +358 21 3336856. Fax: +358 21 3336860. e-mail: kylihonk@finabo.abo.fi

ABSTRACT

A cluster of anthracycline biosynthetic genes isolated from Streptomyces nogalater was expressed in Streptomyces lividans and in Streptomyces galilaeus. A 12 kb DNA fragment cloned from this cluster in pIJ486 caused the production of a novel compound when introduced into S. lividans. The compound is derived from nogalonic acid methyl ester, an early intermediate in nogalamycin biosynthesis. Complementation with the cloned 12 kb fragment of S. galilaeus mutants blocked in aclacinomycin biosynthesis caused the production of hybrid anthracyclines. Cloning of the nogalamycin gene cluster should make possible a detailed study of the biosynthesis of this interesting antibiotic, as well as the production of novel anthracyclines of potential value as cytostatic drugs.

Keywords: Streptomyces nogalater, anthracycline, nogalamycin, gene cloning




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