Isolation, Characterization, and Heterologous Expression of the Biosynthesis Gene Cluster for the Antitumor Anthracycline Steffimycin

• DOI: 10.1128/aem.00734-06
• Publication Date: 2006-06-02T20:36:26Z
• Authors: Sonia Gullón; Carlos Olano; Mohamed S. Abdelf...; Alfredo F. Braña; Jürgen Rohr; Carmen Méndez; José A. Salas
• Keywords: Streptomyces albus; Gene cluster; Heterologous expression; ORFS

ABSTRACT The biosynthetic gene cluster for the aromatic polyketide steffimycin of anthracycline family has been cloned and characterized from “ Streptomyces steffisburgensis ” NRRL 3193. Sequence analysis a 42.8-kbp DNA region revealed presence 36 open reading frames (ORFs) (one them incomplete), 24 which, spanning 26.5 kb, are probably involved in biosynthesis. They code all activities required biosynthesis, tailoring, regulation, resistance but show no evidence genes l -rhamnose involvement biosynthesis was confirmed by expression about 15 kb containing ORFS, 11 forming part cluster, heterologous host albus , allowing isolation intermediate. In addition, S. entire contained 34.8 combined with plasmid pRHAM, directing -rhamnose, led to production steffimycin. Inactivation stfX gene, coding putative cyclase, that this enzymatic activity participates cyclization fourth ring, making final steps aglycon similar those jadomycin or rabelomycin. stfG glycosyltransferase attachment allowed new compound corresponding also observed upon cluster.