Structuring Microbial Metabolic Responses to Multiplexed Stimuli via Self-Organizing Metabolomics Maps.
Secondary metabolite biosynthesis in microorganisms responds to discrete chemical and biological stimuli; however, untargeted identification of these responses presents a significant challenge. Herein we apply multiplexed stimuli to Streptomyces coelicolor and collect the resulting response metabolomes via ion mobility-mass spectrometric analysis. Self-organizing map (SOM) analytics adapted for metabolomic data demonstrate efficient characterization of the subsets of primary and secondary metabolites that respond similarly across stimuli. Over 60% of all metabolic features inventoried from responses are either not observed under control conditions or produced at greater than 2-fold increase in abundance in response to at least one of the multiplexing conditions, reflecting how metabolites encode phenotypic changes in an organism responding to multiplexed challenges. Using abundance as an additional filter, each of 16 known S. coelicolor secondary metabolites is prioritized via SOM and observed at increased levels (1.2- to 22-fold compared with unperturbed) in response to one or more challenge conditions.
Department of Chemistry, Vanderbilt University, 7300 Stevenson Center, Nashville, TN 37235, USA; Vanderbilt Institute for Integrative Biosystems Research and Education, Vanderbilt University, 6301 Stevenson Center, Nashville, TN 37235, USA; Center for Innovative Technology, Vanderbilt University, 5401 Stevenson Center, Nashville, TN 37235, USA.
Cody R
CR
Goodwin
Department of Chemistry, Vanderbilt University, 7300 Stevenson Center, Nashville, TN 37235, USA.
Brett C
BC
Covington
Department of Chemistry, Vanderbilt University, 7300 Stevenson Center, Nashville, TN 37235, USA.
Dagmara K
DK
Derewacz
Department of Chemistry, Vanderbilt University, 7300 Stevenson Center, Nashville, TN 37235, USA.
C Ruth
CR
McNees
Vanderbilt Institute for Integrative Biosystems Research and Education, Vanderbilt University, 6301 Stevenson Center, Nashville, TN 37235, USA; Department of Biomedical Engineering, Department of Molecular Physiology and Biophysics, and Department of Physics and Astronomy, Vanderbilt University, 6301 Stevenson Center, Nashville, TN 37235, USA.
John P
JP
Wikswo
Department of Chemistry, Vanderbilt University, 7300 Stevenson Center, Nashville, TN 37235, USA; Vanderbilt Institute for Integrative Biosystems Research and Education, Vanderbilt University, 6301 Stevenson Center, Nashville, TN 37235, USA; Vanderbilt Institute of Chemical Biology, Vanderbilt University, 7300 Stevenson Center, Nashville, TN 37235, USA; Center for Innovative Technology, Vanderbilt University, 5401 Stevenson Center, Nashville, TN 37235, USA. Electronic address: john.a.mclean@vanderbilt.edu.
John A
JA
McLean
Department of Chemistry, Vanderbilt University, 7300 Stevenson Center, Nashville, TN 37235, USA; Vanderbilt Institute for Integrative Biosystems Research and Education, Vanderbilt University, 6301 Stevenson Center, Nashville, TN 37235, USA; Vanderbilt Institute of Chemical Biology, Vanderbilt University, 7300 Stevenson Center, Nashville, TN 37235, USA. Electronic address: brian.bachmann@vanderbilt.edu.
Brian O
BO
Bachmann
D002851:Chromatography, High Pressure Liquid; D024881:Drug Resistance, Bacterial; D013058:Mass Spectrometry; D055442:Metabolome; D055432:Metabolomics; D025341:Principal Component Analysis; D048372:Streptomyces coelicolor / Q000378:metabolism*