Nucleoside Antibiotics. Biosynthesis of the Maleimide Nucleoside Antibiotic, Showdomycin, by Streptomyces showdoensis

E. F. Elstner, R. J. Suhadolnik

Research output: Contribution to journalArticlepeer-review

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The biosynthesis of showdomycin, the maleimide nucleoside antibiotic, elaborated by Streptomyces showdoensis has been studied. Of the twelve radioactive compounds studied, α-ketoglutarate-5-14C is incorporated into the maleimide ring of showdomycin with the highest efficiency. The data strongly suggest that carbons-2, -3, -4, and -5 of α-keto glutarate contribute to the biosynthesis of the four carbons of the maleimide ring of showdomycin. Carbon-14 from succinate-2,3-14C, fumarate-2,3-14C, and malate-U-14C, but not succinate-1,4-14C or fumarate-1, 4-14C, is uniformly incorporated into the maleimide ring. Similarly, 14C from acetate-7-14C is only incorporated into the carbonyl carbons of the maleimide ring while 14C from acetate-2-14C is incorporated uniformly into all four carbons. The labeling patterns from these 14C acids are in agreement with the notion that carbons-2 and -3 of succinate, fumarate, and malate and both carbons of acetate are incorporated exclusively into the maleimide ring of showdomycin, but only after these mono- and dicarboxylic acids enter the Krebs cycle. Carbons-2, -3, -4, and -5 of glutamate or α-ketoglutarate appear to be direct precursors for the biosynthesis of four carbons of the maleimide ring of showdomycin for the following reason:: (1) all of the 14C in the maleimide ring from the glutamate-2-14C or glutamate-5-14C experiments were shown to reside in the carboxyl carbons; (2) 14C from α-ketoglutarate-7-14C is not incorporated into showdomycin; (3) if glutamate-2-14C or α-ketoglutarate-5-l4C entered the Krebs cycle prior to their incorporation into the maleimide ring, all of the 14C would be lost upon completion of one passage of the Krebs cycle. Carbon-14 from maleic acid-2,3-14C, phenylalanine-U-14C, and fluoro-acetate-2-14C is not incorporated into showdomycin. The possibility that glutamate could be decarboxylated to form 7-aminobutyric acid, which then serves as the four-carbon-nitrogen precursor for the maleimide ring has been eliminated. Ribose appears to be the five-carbon pentose that forms the C-C riboside bond in showdomycin biosynthesis. The intermediate compounds between α-ketoglutarate and showdomycin are not yet known. The findings reported here are the first example of the biosynthesis of a nucleoside antibiotic in which purine or pyrimidine nucleosides and/or nucleotides are not the precursors. These studies also add another role of α-ketoglutaric acid in the biosynthesis of heterocyclic rings and the formation of a carbon-carbon bond with ribose.

Original languageEnglish
Pages (from-to)3608-3614
Number of pages7
Issue number19
StatePublished - 1 Sep 1971


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