Cloning and heterologous expression of a gene cluster for the biosynthesis of tetracenomycin C, the anthracycline antitumor antibiotic of Streptomyces glaucescens.
Through complementation of mutations specifically blocking the biosynthesis of tetracenomycin C by Streptomyces glaucescens and selecting for resistance to tetracenomycin C in Streptomyces lividans, all of the genes for the production of tetracenomycin C were inserted in pIJ702, a high copy-number Streptomyces gene cloning vector. The tcm biosynthetic and resistance genes occur as a single cluster in the S. glaucescens genome and are expressed in heterologous streptomycete hosts like S. lividans, resulting in the overproduction of pigmented intermediates of the tetracenomycin C biosynthetic pathway.
D003001:Cloning, Molecular; D004352:Drug Resistance, Microbial; D005656:Fungal Proteins / Q000235:genetics* / Q000378:metabolism; D005800:Genes, Fungal; D005816:Genetic Complementation Test; D009279:Naphthacenes / Q000096:biosynthesis / Q000494:pharmacology; D013302:Streptomyces / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism
D005656:Fungal Proteins; D009279:Naphthacenes; C020938:tetracenomycin C