Identification of genes essential for fluorination and sulfamylation within the nucleocidin gene clusters of Streptomyces calvus and Streptomyces virens

Marta Wojnowska, Xuan Feng, Yawen Chen, Hai Deng, David O'Hagan*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)
5 Downloads (Pure)

Abstract

The gene cluster in Streptomyces calvus associated with the biosynthesis of the fluoro- and sulfamyl-metabolite nucleocidin was interrogated by systematic gene knockouts. Out of the 26 gene deletions most did not affect fluorometabolite production, nine abolished sulfamylation but not fluorination, and three precluded fluorination, having no effect on sulfamylation. In addition to nucI, nucG, nucJ, nucK, nucL, nucN, nucO, nucQ and nucP we identified two genes (nucW, nucA), belonging to a phosphoadenosine phosphosulfate (PAPS) gene cluster, as required for sulfamyl assembly. Three genes (orf(-3), orf2 and orf3) were found to be essential for fluorination, although the activities of their protein products are unknown. These genes as well as nucK, nucN, nucO and nucPNP, whose knockouts produced results differing from those described in a recent report, were also deleted in Streptomyces virens - with confirmatory outcomes. This genetic profile should inform biochemistry aimed at uncovering the enzymology behind nucleocidin biosynthesis.
Original languageEnglish
Article numbere202200684
Number of pages9
JournalChemBioChem
Volume24
Issue number5
Early online date26 Jan 2023
DOIs
Publication statusPublished - 28 Feb 2023

Keywords

  • Gene knockouts
  • Fluorometabolite biosynthesis
  • Nucleocidin
  • Streptomyces
  • Natural products

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