Related Experiment Video

Updated: Jan 25, 2026

Using the Open-Source MALDI TOF-MS IDBac Pipeline for Analysis of Microbial Protein and Specialized Metabolite Data
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Using the Open-Source MALDI TOF-MS IDBac Pipeline for Analysis of Microbial Protein and Specialized Metabolite Data

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Chemical Derivatization Enables MALDI-TOF-Based High-Throughput Screening for Microbial Trimethylamine (TMA)-Lyase

Martin Winter1, Tom Bretschneider1, Sven Thamm1

  • 11 Drug Discovery Sciences, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riß, Germany.

SLAS Discovery : Advancing Life Sciences R & D
|May 7, 2019
PubMed

Insights

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) enables high-throughput screening for microbial trimethylamine (TMA) production inhibitors. This method advances drug discovery for cardiovascular and kidney diseases linked to TMA.

Area of Science:

  • Biochemistry
  • Analytical Chemistry
  • Microbiology

Background:

  • Microbial trimethylamine (TMA) production from dietary choline is linked to cardiovascular diseases (CVDs) and chronic kidney disease (CKD).
  • Inhibiting TMA-generating enzymes in gut bacteria offers a novel therapeutic strategy for these conditions.
  • Conventional mass spectrometry (MS) methods for tracking TMA-lyase activity lack the high-throughput screening (HTS) capacity needed for drug discovery.

Purpose of the Study:

  • To develop and validate a high-throughput screening (HTS) compatible assay for quantifying microbial TMA production.
  • To demonstrate the utility of matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) MS for tracking small molecule formation in complex biological samples.
  • To establish a method for screening microbial TMA-lyase inhibitors.

Main Methods:

  • Utilized matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) MS for high-throughput screening (HTS) of microbial TMA production.
  • Employed chemical derivatization of TMA to enable quantitative assessment within complex sample matrices.
  • Compared the developed MALDI-TOF MS assay against RapidFire-MS for primary screening and dose-response evaluations.

Main Results:

  • Successfully demonstrated the application of MALDI-TOF MS for tracking small molecule (TMA) formation in a complex microbial background.
  • Validated the assay's quantitative capabilities through chemical derivatization of TMA.
  • Showcased the assay's performance in side-by-side comparisons with RapidFire-MS, confirming its potential for inhibitor screening.

Conclusions:

  • MALDI-TOF MS is a versatile platform for HTS of microbial TMA production, applicable to small molecule targets.
  • The developed assay enables effective screening for microbial TMA-lyase inhibitors.
  • This work serves as a proof of concept for employing MALDI-TOF MS in demanding assay development beyond peptide-centric applications.
Keywords:
MALDI-TOFdrug discoveryhigh-throughput screeningmass spectrometry

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