Imaging mass spectrometry for natural products discovery: a review of ionization methods.

Covering: 2009-2019Over the last decade, methods in imaging mass spectrometry (IMS) have progressively improved and diversified toward a variety of applications in natural products research. Because IMS allows for the spatial mapping of the production and distribution of biologically active molecules in situ, it facilitates phenotype and organelle driven discovery efforts. As practitioners of IMS for natural products discovery, we find one of the most important aspects of these experiments is the sample preparation and compatibility with different ionization sources that are available to a given researcher. As such, we have focused this mini review to cover types of ionization sources that have been used in natural products discovery applications and provided concrete examples of use for natural products discovery while discussing the advantages and limitations of each method. We aim for this article to serve as a resource to guide the broader natural product community interested in IMS toward the application/method that would best serve their natural product discovery needs given the sample and analyte(s) of interest. This mini review has been limited to applications using natural products and thus is not exhaustive of all possible ionization methods which have only been applied to image other types of samples such as mammalian tissues. Additionally, we briefly review how IMS has been coupled with other imaging platforms, such as microscopy, to enhance information outputs as well as offer our future perspectives on the incorporation of IMS in natural products discovery.

[1]  Peter Williams.  Secondary Ion Mass Spectrometry , 1983 .

[2]  C. Allen,et al.  Structure of Ralsolamycin, the Interkingdom Morphogen from the Crop Plant Pathogen Ralstonia solanacearum. , 2017, Organic letters.

[3]  G. Stacey,et al.  Laser‐ablation electrospray ionization mass spectrometry with ion mobility separation reveals metabolites in the symbiotic interactions of soybean roots and rhizobia , 2017, The Plant journal : for cell and molecular biology.

[4]  Kellen DeLaney,et al.  Imaging with Mass Spectrometry of Bacteria on the Exoskeleton of Fungus-Growing Ants. , 2017, ACS chemical biology.

[5]  A. Svatoš,et al.  Linking metabolite production to taxonomic identity in environmental samples by (MA)LDI-FISH , 2015, The ISME Journal.

[6]  Marie-France Robbe,et al.  imzML--a common data format for the flexible exchange and processing of mass spectrometry imaging data. , 2012, Journal of proteomics.

[7]  C. Shih,et al.  Exploration of Fungal Metabolic Interactions Using Imaging Mass Spectrometry on Nanostructured Silicon. , 2018, Journal of natural products.

[8]  P. Dorrestein,et al.  Thiopeptide antibiotics stimulate biofilm formation in Bacillus subtilis , 2015, Proceedings of the National Academy of Sciences.

[9]  Nuno Bandeira,et al.  Mass spectral molecular networking of living microbial colonies , 2012, Proceedings of the National Academy of Sciences.

[10]  Per E Andrén,et al.  msIQuant--Quantitation Software for Mass Spectrometry Imaging Enabling Fast Access, Visualization, and Analysis of Large Data Sets. , 2016, Analytical chemistry.

[11]  P. Williams,et al.  Mass spectrometric detection of chlorophyll a and the tetrapyrrole secondary metabolite tolyporphin A in the filamentous cyanobacterium HT-58-2. Approaches to high-throughput screening of intact cyanobacteria , 2017 .

[12]  Nameera F. Baig,et al.  Quantitative SIMS Imaging of Agar-Based Microbial Communities. , 2018, Analytical chemistry.

[13]  B. Wolfe,et al.  Coproporphyrin III Produced by the Bacterium Glutamicibacter arilaitensis Binds Zinc and Is Upregulated by Fungi in Cheese Rinds , 2018, mSystems.

[14]  E. Gontier,et al.  A New Radio Frequency Plasma Oxygen Primary Ion Source on Nano Secondary Ion Mass Spectrometry for Improved Lateral Resolution and Detection of Electropositive Elements at Single Cell Level. , 2016, Analytical chemistry.

[15]  Sandra Schulz,et al.  Advanced MALDI mass spectrometry imaging in pharmaceutical research and drug development. , 2019, Current opinion in biotechnology.

[16]  Milad Nazari,et al.  MSiReader v1.0: Evolving Open-Source Mass Spectrometry Imaging Software for Targeted and Untargeted Analyses , 2017, Journal of The American Society for Mass Spectrometry.

[17]  M. Ford,et al.  Automation of a surface sampling probe/electrospray mass spectrometry system. , 2005, Analytical chemistry.

[18]  H. Rogniaux,et al.  Spatial mapping of lichen specialized metabolites using LDI-MSI: chemical ecology issues for Ophioparma ventosa , 2016, Scientific Reports.

[19]  V. Havlíček,et al.  Aspergillus infection monitored by multimodal imaging in a rat model , 2016, Proteomics.

[20]  A. Matusch,et al.  Bioimaging mass spectrometry of trace elements - recent advance and applications of LA-ICP-MS: A review. , 2014, Analytica chimica acta.

[21]  Eike E. Peters,et al.  Insights into the lifestyle of uncultured bacterial natural product factories associated with marine sponges , 2017, Proceedings of the National Academy of Sciences.

[22]  Katherine E. Zink,et al.  Imaging Mass Spectrometry Reveals Crosstalk between the Fallopian Tube and the Ovary that Drives Primary Metastasis of Ovarian Cancer , 2018, ACS central science.

[23]  J. Xu,et al.  Chemical and Topographical Single-Cell Imaging by Near-Field Desorption Mass Spectrometry. , 2019, Angewandte Chemie.

[24]  R. Hall,et al.  Spatially Resolved Plant Metabolomics: Some Potentials and Limitations of Laser-Ablation Electrospray Ionization Mass Spectrometry Metabolite Imaging1[OPEN] , 2015, Plant Physiology.

[25]  G. V. Van Berkel,et al.  Fully automated liquid extraction-based surface sampling and ionization using a chip-based robotic nanoelectrospray platform. , 2010, Journal of mass spectrometry : JMS.

[26]  D. Weston,et al.  Multimodal MSI in Conjunction with Broad Coverage Spatially Resolved MS2 Increases Confidence in Both Molecular Identification and Localization. , 2018, Analytical chemistry.

[27]  Marcy J. Balunas,et al.  Leisingera sp. JC1, a Bacterial Isolate from Hawaiian Bobtail Squid Eggs, Produces Indigoidine and Differentially Inhibits Vibrios , 2016, Front. Microbiol..

[28]  Lingjun Li,et al.  Mass Spectrometry Imaging: A Review of Emerging Advancements and Future Insights. , 2018, Analytical chemistry.

[29]  E. P. Stout,et al.  Desorption electrospray ionization mass spectrometry reveals surface-mediated antifungal chemical defense of a tropical seaweed , 2009, Proceedings of the National Academy of Sciences.

[30]  K. Ishida,et al.  A Pair of Bacterial Siderophores Releases and Traps an Intercellular Signal Molecule: An Unusual Case of Natural Nitrone Bioconjugation. , 2018, Angewandte Chemie.

[31]  M. Eberlin,et al.  Imprint Desorption Electrospray Ionization Mass Spectrometry Imaging for Monitoring Secondary Metabolites Production during Antagonistic Interaction of Fungi. , 2015, Analytical chemistry.

[32]  Forest Rohwer,et al.  Spatial Molecular Architecture of the Microbial Community of a Peltigera Lichen , 2016, mSystems.

[33]  Richard M. Caprioli,et al.  Fusion of mass spectrometry and microscopy: a multi-modality paradigm for molecular tissue mapping , 2015, Nature Methods.

[34]  Elizabeth K. Neumann,et al.  microMS: A Python Platform for Image-Guided Mass Spectrometry Profiling , 2017, Journal of The American Society for Mass Spectrometry.

[35]  R. Kostiainen,et al.  Simultaneous detection of nonpolar and polar compounds by heat-assisted laser ablation electrospray ionization mass spectrometry. , 2013, Analytical chemistry.

[36]  V. Havlíček,et al.  Batch-processing of imaging or liquid-chromatography mass spectrometry datasets and De Novo sequencing of polyketide siderophores. , 2017, Biochimica et biophysica acta. Proteins and proteomics.

[37]  Pieter C Dorrestein,et al.  Ralstonia solanacearum lipopeptide induces chlamydospore development in fungi and facilitates bacterial entry into fungal tissues , 2016, The ISME Journal.

[38]  J. Manni,et al.  IR-MALDESI Mass Spectrometry Imaging at 50 Micron Spatial Resolution , 2017, Journal of The American Society for Mass Spectrometry.

[39]  R. Musah,et al.  Development of "Laser Ablation Direct Analysis in Real Time Imaging" Mass Spectrometry: Application to Spatial Distribution Mapping of Metabolites Along the Biosynthetic Cascade Leading to Synthesis of Atropine and Scopolamine in Plant Tissue. , 2017, Analytical chemistry.

[40]  J. Carson,et al.  Towards High-Resolution Tissue Imaging Using Nanospray Desorption Electrospray Ionization Mass Spectrometry Coupled to Shear Force Microscopy , 2018, Journal of The American Society for Mass Spectrometry.

[41]  B. Lindberg Møller,et al.  Mass Spectrometry Based Imaging of Labile Glucosides in Plants , 2018, Front. Plant Sci..

[42]  Olga Vitek,et al.  Cardinal: an R package for statistical analysis of mass spectrometry-based imaging experiments , 2015, Bioinform..

[43]  Basil J. Nikolau,et al.  High spatial resolution mass spectrometry imaging reveals the genetically programmed, developmental modification of the distribution of thylakoid membrane lipids among individual cells of maize leaf , 2017, The Plant journal : for cell and molecular biology.

[44]  Yuta Murai,et al.  Ralstonins A and B, Lipopeptides with Chlamydospore-Inducing and Phytotoxic Activities from the Plant Pathogen Ralstonia solanacearum. , 2017, Organic letters.

[45]  Mass Spectrometry Imaging (MSI) for Plant Metabolomics. , 2018, Methods in molecular biology.

[46]  Andrew R. Korte,et al.  Spatial Mapping and Profiling of Metabolite Distributions during Germination1[OPEN] , 2017, Plant Physiology.

[47]  D. Muddiman,et al.  Quantitative mass spectrometry imaging of glutathione in healthy and cancerous hen ovarian tissue sections by infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI). , 2018, The Analyst.

[48]  Tingting Fu,et al.  Tandem Mass Spectrometry Imaging and in Situ Characterization of Bioactive Wood Metabolites in Amazonian Tree Species Sextonia rubra. , 2018, Analytical chemistry.

[49]  S. Johanningsmeier,et al.  Discovery and quantification of bioactive peptides in fermented cucumber by direct analysis IR-MALDESI mass spectrometry and LC-QQQ-MS. , 2019, Food chemistry.

[50]  P. Dorrestein,et al.  Homogeneous Matrix Deposition on Dried Agar for MALDI Imaging Mass Spectrometry of Microbial Cultures , 2015, Journal of The American Society for Mass Spectrometry.

[51]  Sage J. B. Dunham,et al.  A Versatile Strategy for Characterization and Imaging of Drip Flow Microbial Biofilms. , 2018, Analytical chemistry.

[52]  J. Frasor,et al.  Using Tumor Explants for Imaging Mass Spectrometry Visualization of Unlabeled Peptides and Small Molecules. , 2018, ACS medicinal chemistry letters.

[53]  Nanna Bjarnholt,et al.  Mass spectrometry imaging of plant metabolites--principles and possibilities. , 2014, Natural product reports.

[54]  G. Hurst,et al.  Atomic force microscope controlled topographical imaging and proximal probe thermal desorption/ionization mass spectrometry imaging. , 2014, Analytical chemistry.

[55]  K. Davis,et al.  A Genetics-Free Method for High-Throughput Discovery of Cryptic Microbial Metabolites , 2018, Nature Chemical Biology.

[56]  Riya C. Menezes,et al.  Monitoring metabolites from Schizophyllum commune interacting with Hypholoma fasciculare combining LESA–HR mass spectrometry and Raman microscopy , 2015, Analytical and Bioanalytical Chemistry.

[57]  Rachel V. Bennett,et al.  OmniSpect: An Open MATLAB-Based Tool for Visualization and Analysis of Matrix-Assisted Laser Desorption/Ionization and Desorption Electrospray Ionization Mass Spectrometry Images , 2013, Journal of The American Society for Mass Spectrometry.

[58]  L. Eberlin,et al.  Advances in mass spectrometry imaging coupled to ion mobility spectrometry for enhanced imaging of biological tissues. , 2018, Current opinion in chemical biology.

[59]  R. Cooks,et al.  Mass Spectrometry Sampling Under Ambient Conditions with Desorption Electrospray Ionization , 2004, Science.

[60]  Pieter C Dorrestein,et al.  Real-time metabolomics on living microorganisms using ambient electrospray ionization flow-probe. , 2013, Analytical chemistry.

[61]  Pieter C. Dorrestein,et al.  Primer on Agar-Based Microbial Imaging Mass Spectrometry , 2012, Journal of bacteriology.

[62]  J. Gross,et al.  Direct analysis in real time—a critical review on DART-MS , 2014, Analytical and Bioanalytical Chemistry.

[63]  A. Vertes,et al.  Molecular Imaging of Growth, Metabolism, and Antibiotic Inhibition in Bacterial Colonies by Laser Ablation Electrospray Ionization Mass Spectrometry. , 2016, Angewandte Chemie.

[64]  Malcolm R. Clench,et al.  Spatial Quantitation of Drugs in tissues using Liquid Extraction Surface Analysis Mass Spectrometry Imaging , 2016, Scientific Reports.

[65]  Nikola Tolić,et al.  Utilizing a Robotic Sprayer for High Lateral and Mass Resolution MALDI FT-ICR MSI of Microbial Cultures , 2016, Journal of The American Society for Mass Spectrometry.

[66]  Brandi S. Heath,et al.  Tissue imaging using nanospray desorption electrospray ionization mass spectrometry. , 2012, Analytical chemistry.

[67]  Bernhard Spengler,et al.  Atmospheric pressure MALDI mass spectrometry imaging of tissues and cells at 1.4-μm lateral resolution , 2016, Nature Methods.

[68]  S. Johanningsmeier,et al.  Direct Analysis of Triterpenes from High-Salt Fermented Cucumbers Using Infrared Matrix-Assisted Laser Desorption Electrospray Ionization (IR-MALDESI) , 2017, Journal of The American Society for Mass Spectrometry.