Genomics-Driven Discovery of a Symbiont-Specific Cyclopeptide from Bacteria Residing in the Rice Seedling Blight Fungus

Chembiochem. 2018 Oct 18;19(20):2167-2172. doi: 10.1002/cbic.201800400. Epub 2018 Oct 2.


The rice seedling blight fungus Rhizopus microsporus harbors endosymbiotic bacteria (Burkholderia rhizoxinica) that produce the virulence factor rhizoxin and control host development. Genome mining indicated a massive inventory of cryptic nonribosomal peptide synthetase (NRPS) genes, which have not yet been linked to any natural products. The discovery and full characterization of a novel cyclopeptide from endofungal bacteria is reported. In silico analysis of an orphan, symbiont-specific NRPS predicted the structure of a nonribosomal peptide, which was targeted by LC-MS/MS profiling of wild-type and engineered null mutants. NMR spectroscopy and chemical derivatization elucidated the structure of the bacterial cyclopeptide. Phylogenetic analyses revealed the relationship of starter C domains for rare N-acetyl-capped peptides. Heptarhizin is produced under symbiotic conditions in geographically constrained strains from the Pacific clade; this indicates a potential ecological role of the peptide.

Keywords: cyclopeptides; enzymes; genomics; natural products; symbiotic bacteria.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Burkholderia / classification
  • Burkholderia / genetics
  • Burkholderia / metabolism*
  • Oryza / microbiology*
  • Peptide Synthases / metabolism
  • Peptides, Cyclic* / chemistry
  • Peptides, Cyclic* / genetics
  • Peptides, Cyclic* / metabolism
  • Plant Diseases / microbiology*
  • Rhizopus / metabolism*
  • Seedlings / microbiology*
  • Symbiosis


  • Peptides, Cyclic
  • Peptide Synthases
  • non-ribosomal peptide synthase