Genome- and Mass Spectrometry-Guided Discovery of Ralstoamides A and B from Ralstonia solanacearum Species Complex

ACS Chem Biol. 2020 Nov 20;15(11):2860-2865. doi: 10.1021/acschembio.0c00605. Epub 2020 Oct 28.


Strains of Ralstonia solanacearum species complex (RSSC) are devastating plant pathogens distributed globally with a wide host range and genetic diversity. Many RSSC strains harbor the polyketide synthase-nonribosomal peptide synthetase (PKS-NRPS) hybrid gene rmyA/rmyB for ralstonin production. We report that ralstoamides A (1) and B (2), which are ralstonin-like but shorter lipopeptides, were discovered from the Japanese strains using accumulated RSSC genome data and LC/MS-based metabolite analysis. Their structures, including absolute configurations, were elucidated by spectroscopic analysis and chemical techniques. ramA, a PKS-NRPS gene for ralstoamide production, was identified from the producer strains by genome sequencing and gene-deletion experiments. Based on the analysis of biosynthetic genes of ralstoamides and ralstonins, we suggest the occurrence of NRPS-module reduction of rmyA/rmyB genes in some RSSC strains. This possible molecular evolution changed not only the structures, but also the biological activity of RSSC lipopeptides.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins / genetics
  • Genome, Bacterial
  • Lipopeptides / chemistry*
  • Lipopeptides / genetics*
  • Mass Spectrometry
  • Nicotiana / microbiology
  • Peptide Synthases / genetics
  • Polyketide Synthases / genetics
  • Ralstonia solanacearum / chemistry
  • Ralstonia solanacearum / genetics*
  • Solanum lycopersicum / microbiology


  • Bacterial Proteins
  • Lipopeptides
  • Polyketide Synthases
  • Peptide Synthases
  • non-ribosomal peptide synthase