Biogenesis of the unique 4′,5′-dehydronucleoside of the uridyl peptide antibiotic Pacidamycin

Amany E. Ragab, Sabine Grüschow, Daniel R. Tromans, Rebecca J. M. Goss

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)

Abstract

The pacidamycins belong to a class of antimicrobial nucleoside antibiotics that act by inhibiting the clinically unexploited target translocase I, a key enzyme in peptidoglycan assembly. As with other nucleoside antibiotics, the pacidamycin 4′,5′-dehydronucleoside portion is an essential pharmacophore. Here we show that the biosynthesis of the pacidamycin nucleoside in Streptomyces coeruleorubidus proceeds through three steps from uridine. The transformations involve oxidation of the 5′-alcohol by Pac11, transamination of the resulting aldehyde by Pac5, and dehydration by the Cupin-domain protein Pac13.
Original languageEnglish
Pages (from-to)15288-15291
Number of pages4
JournalJournal of the American Chemical Society
Volume133
Issue number39
DOIs
Publication statusPublished - 23 Aug 2011

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