Chaxapeptin, a Lasso Peptide from Extremotolerant Streptomyces leeuwenhoekii Strain C58 from the Hyperarid Atacama Desert

J Org Chem. 2015 Oct 16;80(20):10252-60. doi: 10.1021/acs.joc.5b01878. Epub 2015 Sep 24.

Abstract

Lasso peptides are ribosomally synthesized and post-translationally modified peptides (RiPPs) that possess a unique "lariat knot" structural motif. Genome mining-targeted discovery of new natural products from microbes obtained from extreme environments has led to the identification of a gene cluster directing the biosynthesis of a new lasso peptide, designated as chaxapeptin 1, in the genome of Streptomyces leeuwenhoekii strain C58 isolated from the Atacama Desert. Subsequently, 1 was isolated and characterized using high-resolution electrospray ionization mass spectrometry and nuclear magnetic resonance methods. The lasso nature of 1 was confirmed by calculating its nuclear Overhauser effect restraint-based solution structure. Chaxapeptin 1 displayed a significant inhibitory activity in a cell invasion assay with human lung cancer cell line A549.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Biological Products / chemistry*
  • Cell Line / chemistry*
  • Humans
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / metabolism
  • Macrolides / chemistry*
  • Macrolides / pharmacology*
  • Magnetic Resonance Spectroscopy
  • Peptides / chemical synthesis*
  • Peptides / chemistry*
  • Peptides, Cyclic / chemical synthesis
  • Peptides, Cyclic / chemistry*
  • Peptides, Cyclic / pharmacology*
  • Ribosomes / chemistry*
  • Streptomyces / chemistry*

Substances

  • Biological Products
  • Macrolides
  • Peptides
  • Peptides, Cyclic
  • chaxalactin A
  • chaxapeptin