Identification of the biosynthetic gene cluster of A-500359s in streptomyces griseus SANK60196

Masanori Funabashi, Koichi Nonaka, Chieko Yada, Masahiko Hosobuchi, Nobuhisa Masuda, Tomoyuki Shibata, Steven G. Van Lanen

Research output: Contribution to journalArticlepeer-review

34 Scopus citations


A-500359s, produced by Streptomyces griseus SANK60196, are inhibitors of bacterial phospho-N-acetylmuramyl-pentapeptide translocase. They are composed of three distinct moieties: a 5′-carbamoyl uridine, an unsaturated hexuronic acid and an aminocaprolactam. Two contiguous cosmids covering a 65-kb region of DNA and encoding 38 open reading frames (ORFs) putatively involved in the biosynthesis of A-500359s were identified. Reverse transcriptase PCR showed that most of the 38 ORFs are highly expressed during A-500359s production, but mutants that do not produce A-500359s did not express these same ORFs. Furthermore, orf21, encoding a putative aminoglycoside 3′- phosphotransferase, was heterologously expressed in Escherichia coli and Streptomyces albus, yielding strains having selective resistance against A-500359B, suggesting that ORF21 phosphorylates the unsaturated hexuronic acid as a mechanism of self-resistance to A-500359s. In total, the data suggest that the cloned region is involved in the resistance, regulation and biosynthesis of A-500359s.

Original languageEnglish
Pages (from-to)325-332
Number of pages8
JournalJournal of Antibiotics
Issue number6
StatePublished - Jun 2009


  • A-500359s
  • Biosynthetic gene cluster
  • RT-PCR
  • Resistance gene
  • Streptomyces griseus

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery


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