Structure, bioactivity, and resistance mechanism of streptomonomicin, an unusual lasso Peptide from an understudied halophilic actinomycete

Chem Biol. 2015 Feb 19;22(2):241-50. doi: 10.1016/j.chembiol.2014.11.017. Epub 2015 Jan 15.


Natural products are the most historically significant source of compounds for drug development. However, unacceptably high rates of compound rediscovery associated with large-scale screening of common microbial producers have resulted in the abandonment of many natural product drug discovery efforts, despite the increasing prevalence of clinically problematic antibiotic resistance. Screening of underexplored taxa represents one strategy to avoid rediscovery. Herein we report the discovery, isolation, and structural elucidation of streptomonomicin (STM), an antibiotic lasso peptide from Streptomonospora alba, and report the genome for its producing organism. STM-resistant clones of Bacillus anthracis harbor mutations to walR, the gene encoding a response regulator for the only known widely distributed and essential two-component signal transduction system in Firmicutes. To the best of our knowledge, Streptomonospora had been hitherto biosynthetically and genetically uncharacterized, with STM being the first reported compound from the genus. Our results demonstrate that understudied microbes remain fruitful reservoirs for the rapid discovery of novel, bioactive natural products.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actinobacteria / genetics
  • Actinobacteria / metabolism*
  • Anti-Bacterial Agents / biosynthesis
  • Anti-Bacterial Agents / chemistry*
  • Anti-Bacterial Agents / pharmacology
  • Bacterial Proteins / biosynthesis
  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / pharmacology
  • Genome, Bacterial
  • Gram-Negative Bacteria / drug effects
  • Gram-Positive Bacteria / drug effects
  • Magnetic Resonance Spectroscopy
  • Microbial Sensitivity Tests
  • Multigene Family
  • Peptides / chemistry*
  • Peptides / metabolism
  • Peptides / pharmacology
  • Peptides, Cyclic / biosynthesis
  • Peptides, Cyclic / chemistry*
  • Peptides, Cyclic / pharmacology
  • Protein Structure, Tertiary
  • Sequence Analysis, DNA
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization


  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Peptides
  • Peptides, Cyclic
  • streptomonomicin peptide, Streptomonospora alba