Deciphering the biosynthetic codes for the potent anti-SARS-CoV cyclodepsipeptide valinomycin in Streptomyces tsusimaensis ATCC 15141

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Abstract

Valinomycin was recently reported to be the most potent agent against severe acute respiratory-syndrome coronavirus (SARS-CoV) in infected Vero E6 cells. Aimed at generating analogues by metabolic engineering, the valinomycin biosynthetic gene cluster has been cloned from Streptomyces tsusimaensis ATCC 15141. Targeted disruption of a nonribosomal peptide synthetase (NRPS) gene abolishes valinomycin production, which confirms its predicted nonribosomal-peptide origin. Sequence analysis of the NRPS system reveals four distinctive modules, two of which contain unusual domain organizations that are presumably involved in the generation of biosynthetic precursors D-α-hydroxyisovaleric acid and L-lactic acid. The respective adenylation domains in these two modules contain novel substrate-specificity-conferring codes that might specify for a class of hydroxyl acids for the biosynthesis of the depsipeptide natural products.

Original languageEnglish
Pages (from-to)471-477
Number of pages7
JournalChemBioChem
Volume7
Issue number3
DOIs
StatePublished - Mar 2006

Keywords

  • Antiviral agents
  • Biosynthesis
  • Natural products
  • Nonribosomal peptide synthetase
  • Valinomycin

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