Elucidating the Rimosamide-Detoxin Natural Product Families and Their Biosynthesis Using Metabolite/Gene Cluster Correlations

Ryan A. McClure, Anthony W. Goering, Kou San Ju, Joshua A. Baccile, Frank C. Schroeder, William W. Metcalf, Regan J. Thomson*, Neil L. Kelleher

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

As microbial genome sequencing becomes more widespread, the capacity of microorganisms to produce an immense number of metabolites has come into better view. Utilizing a metabolite/gene cluster correlation platform, the biosynthetic origins of a new family of natural products, the rimosamides, were discovered. The rimosamides were identified in Streptomyces rimosus and associated with their NRPS/PKS-type gene cluster based upon their high frequency of co-occurrence across 179 strains of actinobacteria. This also led to the discovery of the related detoxin gene cluster. The core of each of these families of natural products contains a depsipeptide bond at the point of bifurcation in their unusual branched structures, the origins of which are definitively assigned to nonlinear biosynthetic pathways via heterologous expression in Streptomyces lividans. The rimosamides were found to antagonize the antibiotic activity of blasticidin S against Bacillus cereus.

Original languageEnglish (US)
Pages (from-to)3452-3460
Number of pages9
JournalACS chemical biology
Volume11
Issue number12
DOIs
StatePublished - Dec 16 2016

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine

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