Molecular genetic analysis of enediyne antibiotic biosynthesis genes

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Dynemicin is an enediyne antitumor antibiotic with unique hybrid structure of anthraquinone and enediyne structures. To elucidate its biosynthesis mechanism, cloning of type-II polyketide biosynthesis gene was carried out from Micromonospora chersina, a dynemicin producing actinomycete. By screening with actI probe, ca.20kb fragment was cloned from M.chersina genomic DNA library. The nucleotide sequence of 14.3 kb region was determined and open reading frame (ORF) analysis was carried out. In this region, 12 ORFs were found. Data base homology search indicated that ORF2,4,5,6 and 8 encode cyclase, beta-ketoacyl synthase, chain length factor, CoA-ligase and acyltransferase, respectively. Thus, the cloned gene consisted of typical type-II polyketide synthase gene cluster with unique ORFs such as oxygenases and addtitional beta-ketoacyl synthase. Further analysis is on the way to identify whether this cloned gene cluster is involved in dynemicin biosynthesis in M.chersina.