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http://purl.uniprot.org/citations/8807845http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/8807845http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/8807845http://www.w3.org/2000/01/rdf-schema#comment"

Background

Mithramycin, chromomycin, and olivomycin belong to the aureolic acid family of clinically important anti-tumor agents. These natural products share a common aromatic aglycone. Although isotope labeling studies have firmly established the polyketide origin of this aglycone, they do not distinguish between alternative biosynthetic models in which the aglycone is derived from one, two or three distinct polyketide moieties. We set out to determine the biosynthetic origin of this moiety using a recombinant approach in which the ketosynthase and chain-length factor proteins from the antibiotic-producer strain, which determine the chain length of a polyketide, are produced in a heterologous bacterial host.

Results

The ketosynthase and chain-length factor genes from the polyketide synthase gene cluster from the mithramycin producer, Streptomyces argillaceus ATCC 12956, and the acyl carrier protein and ketoreductase genes from the actinorhodin polyketide synthase were expressed in Streptomyces coelicolor CH999. The recombinant strain produced a 20-carbon polyketide, comprising the complete backbone of the aglycone of mithramycin.

Conclusions

The aglycone moieties of mithramycin, chromomycin, and olivomycin are derived from a single polyketide backbone. The nascent polyketide backbone must undergo a series of regiospecific cyclizations to form a tetracenomycin-like tetracyclic intermediate. The final steps in the aglycone biosynthetic pathway presumably involve decarboxylation and oxidative cleavage between C-18 and C-19, followed by additional oxidation, reduction, and methylation reactions."xsd:string
http://purl.uniprot.org/citations/8807845http://purl.org/dc/terms/identifier"doi:10.1016/S1074-5521(96)90262-8"xsd:string
http://purl.uniprot.org/citations/8807845http://purl.org/dc/terms/identifier"doi:10.1016/s1074-5521(96)90262-8"xsd:string
http://purl.uniprot.org/citations/8807845http://purl.uniprot.org/core/author"Fu H."xsd:string
http://purl.uniprot.org/citations/8807845http://purl.uniprot.org/core/author"Fu H."xsd:string
http://purl.uniprot.org/citations/8807845http://purl.uniprot.org/core/author"Khosla C."xsd:string
http://purl.uniprot.org/citations/8807845http://purl.uniprot.org/core/author"Khosla C."xsd:string
http://purl.uniprot.org/citations/8807845http://purl.uniprot.org/core/author"Blanco G."xsd:string
http://purl.uniprot.org/citations/8807845http://purl.uniprot.org/core/author"Blanco G."xsd:string
http://purl.uniprot.org/citations/8807845http://purl.uniprot.org/core/author"Mendez C."xsd:string
http://purl.uniprot.org/citations/8807845http://purl.uniprot.org/core/author"Mendez C."xsd:string
http://purl.uniprot.org/citations/8807845http://purl.uniprot.org/core/author"Salas J.A."xsd:string
http://purl.uniprot.org/citations/8807845http://purl.uniprot.org/core/author"Salas J.A."xsd:string
http://purl.uniprot.org/citations/8807845http://purl.uniprot.org/core/date"1996"xsd:gYear
http://purl.uniprot.org/citations/8807845http://purl.uniprot.org/core/date"1996"xsd:gYear
http://purl.uniprot.org/citations/8807845http://purl.uniprot.org/core/name"Chem. Biol."xsd:string
http://purl.uniprot.org/citations/8807845http://purl.uniprot.org/core/name"Chem Biol"xsd:string
http://purl.uniprot.org/citations/8807845http://purl.uniprot.org/core/pages"193-196"xsd:string
http://purl.uniprot.org/citations/8807845http://purl.uniprot.org/core/pages"193-196"xsd:string
http://purl.uniprot.org/citations/8807845http://purl.uniprot.org/core/title"Deciphering the biosynthetic origin of the aglycone of the aureolic acid group of anti-tumor agents."xsd:string
http://purl.uniprot.org/citations/8807845http://purl.uniprot.org/core/title"Deciphering the biosynthetic origin of the aglycone of the aureolic acid group of anti-tumor agents."xsd:string
http://purl.uniprot.org/citations/8807845http://purl.uniprot.org/core/volume"3"xsd:string
http://purl.uniprot.org/citations/8807845http://purl.uniprot.org/core/volume"3"xsd:string
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