Biosynthesis of fredericamycin A, a new antitumor antibiotic

Fredericamycin A (FM A), produced by a strain of Streptomyces griseus, represents a new structural class of antitumor antibiotics containing a spiro ring system. Studies on the producer organism showed that glucose in the fermentation medium is not utilized until late in the growth stage, just prior...

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Bibliographic Details
Published in:Biochemistry (Easton) 1985-01, Vol.24 (2), p.478-486
Main Authors: Byrne, Kevin M, Hilton, Bruce D, White, Richard J, Misra, Renuka, Pandey, Ramesh C
Format: Article
Language:English
Subjects:
Acetates - metabolism
Acetic Acid
Antibiotics, Antineoplastic - biosynthesis
Bioconversions. Hemisynthesis
Biological and medical sciences
Biotechnology
fredericamycin A
Fundamental and applied biological sciences. Psychology
Glucose - metabolism
Malonates - metabolism
Methods. Procedures. Technologies
Streptomyces griseus
Streptomyces griseus - metabolism
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Summary:Fredericamycin A (FM A), produced by a strain of Streptomyces griseus, represents a new structural class of antitumor antibiotics containing a spiro ring system. Studies on the producer organism showed that glucose in the fermentation medium is not utilized until late in the growth stage, just prior to synthesis of FM A. [14C]Glucose tracer experiments demonstrated that glucose is incorporated into FM A by catabolism to acetate. Biosynthetic enrichment of FM A with single- and double-labeled [13C]acetate showed that the entire carbon skeleton of the spiro ring system is derived from acetate. L-Methionine was shown to provide the only nonskeletal carbon in FM A, the methoxy carbon at position C-6. The direction of the polyketide chain and the position of the carbon lost during biosynthesis were established by using stable isotope experiments. A general model for FM A biosynthesis is proposed, and a possible scheme for the formation of the spiro carbon center is presented.
ISSN:0006-2960
1520-4995
DOI:10.1021/bi00323a035