Native mass spectrometry-based metabolomics identifies metal-binding compounds

Allegra T Aron; Daniel Petras; Robin Schmid; Julia M Gauglitz; Isabell Büttel; Luis Antelo; Hui Zhi; Sean-Paul Nuccio; Christina C Saak; Kien P Malarney; Eckhard Thines; Rachel J Dutton; Lihini I Aluwihare; Manuela Raffatellu; Pieter C Dorrestein

doi:10.1038/s41557-021-00803-1

Native mass spectrometry-based metabolomics identifies metal-binding compounds

Nat Chem. 2022 Jan;14(1):100-109. doi: 10.1038/s41557-021-00803-1. Epub 2021 Nov 18.

Authors

Allegra T Aron^#^{1

2}, Daniel Petras^#^{1

2

3

4}, Robin Schmid^{1

5}, Julia M Gauglitz^{1

2

6}, Isabell Büttel⁷, Luis Antelo⁸, Hui Zhi⁹, Sean-Paul Nuccio⁹, Christina C Saak¹⁰, Kien P Malarney¹⁰, Eckhard Thines^{7

8}, Rachel J Dutton^{10

11}, Lihini I Aluwihare³, Manuela Raffatellu^{9

11

12}, Pieter C Dorrestein^{13

14

15}

Affiliations

¹ Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA, USA.
² Collaborative Mass Spectrometry Innovation Center, University of California, San Diego, La Jolla, CA, USA.
³ Scripps Institution of Oceanography, University of California, San Diego, La Jolla, CA, USA.
⁴ CMFI Cluster of Excellence, Interfaculty Institute of Microbiology and Medicine, University of Tübingen, Tübingen, Germany.
⁵ Institute of Inorganic and Analytical Chemistry, University of Münster, Münster, Germany.
⁶ Sapient Bioanalytics, La Jolla, CA, USA.
⁷ Institute of Molecular Physiology, Microbiology and Wine Research, Johannes Gutenberg University Mainz, Mainz, Germany.
⁸ Institute of Biotechnology and Drug Research (IBWF gGmbH), Johannes Gutenberg University Mainz, Mainz, Germany.
⁹ Division of Host-Microbe Systems & Therapeutics, Department of Pediatrics, University of California San Diego, La Jolla, CA, USA.
¹⁰ Division of Biological Sciences, University of California, San Diego, La Jolla, CA, USA.
¹¹ Center for Microbiome Innovation, University of California, San Diego, La Jolla, CA, USA.
¹² Chiba University-University of California San Diego Center for Mucosal Immunology, Allergy, and Vaccines (CU-UCSD cMAV), La Jolla, CA, USA.
¹³ Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA, USA. pdorrestein@health.ucsd.edu.
¹⁴ Scripps Institution of Oceanography, University of California, San Diego, La Jolla, CA, USA. pdorrestein@health.ucsd.edu.
¹⁵ Center for Microbiome Innovation, University of California, San Diego, La Jolla, CA, USA. pdorrestein@health.ucsd.edu.

^# Contributed equally.

Abstract

Although metals are essential for the molecular machineries of life, systematic methods for discovering metal-small molecule complexes from biological samples are limited. Here, we describe a two-step native electrospray ionization-mass spectrometry method, in which post-column pH adjustment and metal infusion are combined with ion identity molecular networking, a rule-based data analysis workflow. This method enabled the identification of metal-binding compounds in complex samples based on defined mass (m/z) offsets of ion species with the same chromatographic profiles. As this native electrospray metabolomics approach is suited to the use of any liquid chromatography-mass spectrometry system to explore the binding of any metal, this method has the potential to become an essential strategy for elucidating metal-binding molecules in biology.

Publication types

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

MeSH terms

Binding Sites
Chromatography, Liquid / methods
Mass Spectrometry / methods*
Metabolomics / methods*
Metals / metabolism*

Substances

Metals

Abstract

Publication types

MeSH terms

Substances

Grants and funding