Mapping Molecular Space with Mass Spectrometry

Mass spectrometry has become an invaluable tool in the discovery and characterization of specialized metabolites and biotechnologically relevant molecules. One aspect of characterizing specialized metabolites involves connecting these molecules to their biosynthetic machineries. Here we employ several mass spectrometry methods and introduce the idea of connecting molecular families to their gene cluster families on a large scale that takes advantage of publicly accessible genomes. As proof of principle, we used molecular networking to analyze sixty bacteria, 42 bacilli and 18 pseudomonads, simultaneously and matched eight molecular families to their gene cluster families. To illustrate the effectiveness of this technique, we combined it with imaging mass spectrometry to examine two marine Pseudoalteromonas that both showed inhibition against Bacillus subtilis 3610. The signals showing bioactivity against B. subtilis were shown to be a family of molecules for which the biosynthetic gene cluster was discovered using a publiclyavailable genome sequence from Pseudoalteromonas piscicida JCM 20779T.