Studies on the formation and incorporation of streptolidine in the biosynthesis of the peptidyl nucleoside antibiotic streptothricin F

Michael D. Jackson, Steven J. Gould, Mark Zabriskie

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

Streptothricin F (STF, 1) is a peptidyl nucleoside antibiotic produced by Streptomyces lavendulae. Studies were conducted to address the formation and timing of incorporation of the arginine-derived base streptolidine (4) during the biosynthesis of 1. [guanidino- 13C]Streptolidine (10) was prepared by modification of an established method and used in whole-cell incorporation experiments. Analysis of the purified STF by 13C NMR revealed a 1.9% enrichment of the guanidino carbon, confirming 4 as an advanced precursor to 1 and supporting proposals that 1 is assembled via a convergent biosynthetic pathway. To identify advanced intermediates in the conversion of L-arginine to 4, (2S,3R)-[guanidino- 13C]capreomycidine (32) was prepared from oxazolidine aldehyde (18) via 1,1-dimethylethyl (4R,1′S)-4-(1′,3′ -diaminopropyl)-2,2-dimethyl-3-oxazolidinecarboxylate (30). Treatment of 30 with Br 13CN yielded the corresponding diprotected amino alcohol, which was readily converted to 32. The STF isolated from whole-cell incorporation experiments with 32 showed no significant 13C enrichment at the guanidino carbon. These results suggest that 32 may be an enzyme-bound intermediate, unable to enter the cell, or is not a precursor to STF.

Original languageEnglish (US)
Pages (from-to)2934-2941
Number of pages8
JournalJournal of Organic Chemistry
Volume67
Issue number9
DOIs
StatePublished - May 3 2002
Externally publishedYes

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Biosynthesis
Nucleosides
Arginine
Carbon
Amino Alcohols
Anti-Bacterial Agents
Aldehydes
Experiments
Nuclear magnetic resonance
Enzymes
streptothricin F
streptolidine
Biosynthetic Pathways
capreomycidine
oxazolidine

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Studies on the formation and incorporation of streptolidine in the biosynthesis of the peptidyl nucleoside antibiotic streptothricin F. / Jackson, Michael D.; Gould, Steven J.; Zabriskie, Mark.

In: Journal of Organic Chemistry, Vol. 67, No. 9, 03.05.2002, p. 2934-2941.

Research output: Contribution to journalArticle

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