Improving the discovery of secondary metabolite natural products using ion mobility–mass spectrometry

Abstract

Secondary metabolite discovery requires an unbiased, comprehensive workflow to detect unknown unknowns for which little to no molecular knowledge exists. Untargeted mass spectrometry-based metabolomics is a powerful platform, particularly when coupled with ion mobility for high-throughput gas-phase separations to increase peak capacity and obtain gas-phase structural information. Ion mobility data are described by the amount of time an ion spends in the drift cell, which is directly related to an ion's collision cross section (CCS). The CCS parameter describes the size, shape, and charge of a molecule and can be used to characterize unknown metabolomic species. Here, we describe current and emerging applications of ion mobility-mass spectrometry for prioritization, discovery and structure elucidation, and spatial/temporal characterization.

Evaluating Separation Selectivity and Collision Cross Section Measurement Reproducibility in Helium, Nitrogen, Argon, and Carbon Dioxide Drift Gases for Drift Tube Ion Mobility–Mass Spectrometry

“…Ion mobility spectrometry (IM) is an important analytical technique for the rapid separation and identification of a wide variety of chemical compounds [1][2][3][4][5][6]. In a conventional drift tube, the separation of chemical species results from numerous, near-thermal collision between analyte ions and a chemically-inert drift gas.…”

Alkaloids of the Genus Datura: Review of a Rich Resource for Natural Product Discovery

“…Lesiak and Musah applied this method to D. stramonium, D. inoxia, and D. ferox seeds, which were sliced transversely and analyzed using soft-ionization positive-mode DART-MS [88]. Spectra of Datura seeds show characteristic tropane fragment ions (e.g., m/z 174, 158,142,124), and the different seed ions clustered on the basis of species by principal component analysis.…”

“…IMS can aid in separating isomers and revealing new compounds that may not be detected by conventional LC or LC-MS methods [ 157 ]. Additionally, IMS provides an additional “data point” in any compound’s given molecular signature, which is valuable in dereplication—two compounds may have identical masses, fragmentation patterns, and retention times, yet differ in their IMS drift times, and are therefore likely different compounds [ 158 ]. This method was applied to beta -carboline alkaloids from Peganum harmala, where more alkaloids were differentiated and identified using the 2D-combined LC-IMS method than by LC or IMS alone [ 157 ].…”

Synergizing the potential of bacterial genomics and metabolomics to find novel antibiotics

“…These latest developments shifted IMS-MS applications from a niche application for specialized applications to a technique that becomes more and more mainstream in natural products laboratories. 33 The key strength of IMS-MS lies in its ability to discern structural isomers that often occur in natural products mixtures, as most structure isomers have different CCS values due to their different geometry. A prominent example for such a case is the detection of streptorubin B from S. coelicolor .…”