Abstract | 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: 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.
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Authors | G Blanco, H Fu, C Mendez, C Khosla, J A Salas |
Journal | Chemistry & biology
(Chem Biol)
Vol. 3
Issue 3
Pg. 193-6
(Mar 1996)
ISSN: 1074-5521 [Print] United States |
PMID | 8807845
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
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Chemical References |
- Antibiotics, Antineoplastic
- Plicamycin
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Topics |
- Antibiotics, Antineoplastic
(chemistry)
- Magnetic Resonance Spectroscopy
- Plicamycin
(chemistry)
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