PRODUCTION OF HYBRID ANTHRACYCLINE ANTIBIOTICS BY HETEROLOGOUS EXPRESSION OF STREPTOMYCES NOGALATER NOGALAMYCIN BIOSYNTHESIS GENES

A cluster of anthracycline biosynthetic genes isolated from Streptomyc es nogalater was expressed in Streptomyces lividans and in Streptomyce s galilaeus, A 12 kb DNA fragment cloned from this cluster in plJ486 c aused the production of a novel compound when introduced into S. livid ans. The compound is derived from nogalonic acid methyl ester, an earl y intermediate in nogalamycin biosynthesis, Complementation with the c loned 12 kb fragment of S. galilaeus mutants blocked in aclacinomycin biosynthesis caused the production of hybrid anthracyclines. Cloning o f the nogalamycin gene cluster should make possible a detailed study o f the biosynthesis of this interesting antibiotic, as well as the prod uction of novel anthracyclines of potential value as cytostatic drugs.