Molecular networking as a dereplication strategy

J Nat Prod. 2013 Sep 27;76(9):1686-99. doi: 10.1021/np400413s. Epub 2013 Sep 11.


A major goal in natural product discovery programs is to rapidly dereplicate known entities from complex biological extracts. We demonstrate here that molecular networking, an approach that organizes MS/MS data based on chemical similarity, is a powerful complement to traditional dereplication strategies. Successful dereplication with molecular networks requires MS/MS spectra of the natural product mixture along with MS/MS spectra of known standards, synthetic compounds, or well-characterized organisms, preferably organized into robust databases. This approach can accommodate different ionization platforms, enabling cross correlations of MS/MS data from ambient ionization, direct infusion, and LC-based methods. Molecular networking not only dereplicates known molecules from complex mixtures, it also captures related analogues, a challenge for many other dereplication strategies. To illustrate its utility as a dereplication tool, we apply mass spectrometry-based molecular networking to a diverse array of marine and terrestrial microbial samples, illustrating the dereplication of 58 molecules including analogues.

Publication types

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

MeSH terms

  • Bacillus subtilis / chemistry
  • Bacteria / chemistry*
  • Biological Products / chemistry*
  • Chromatography, High Pressure Liquid
  • Cyanobacteria / chemistry
  • Marine Biology
  • Molecular Structure
  • Molecular Weight
  • Nuclear Magnetic Resonance, Biomolecular
  • Plant Extracts / chemistry
  • Pseudomonas aeruginosa / chemistry
  • Serratia marcescens / chemistry
  • Tandem Mass Spectrometry


  • Biological Products
  • Plant Extracts