Omics-Scale Capture of Electrophilic Metabolites
Abstract
The majority of metabolic pathways rely on the production of activated electrophilic intermediates, e.g., coenzyme-A esters, and their chemical structures and abundances are central to understanding enzyme function and biochemical mechanisms. However, most electrophilic metabolites are lost in traditional metabolomic analysis and thus remain poorly characterized. Here, we introduce a biochemical probe, O-(trimethylammoniobutyl)-hydroxylamine (TAMOHA), that enables comprehensive profiling of electrophilic species such as coenzyme-A esters, ketones, and aldehydes. TAMOHA incorporates a highly nucleophilic hydroxylamine that reacts quickly with electrophilic species upon tissue lysis, trapping them as stable derivatives that feature a tetraalkylammonium moiety whose constitutive charge and characteristic MS2 fragmentation fingerprint enable their highly sensitive detection. Using TAMOHA to survey the electrophilomes of E. coli, C. elegans, and mice revealed several thousand electrophilic metabolites, most of which have not been characterized. We then demonstrate trapping of electrophilic metabolites with TAMOHA in the context of specific biochemical pathways, confirming previously proposed functions of two fatty acid metabolism enzymes, detecting formaldehyde production in mice, and providing new insights into the biosynthesis of ascaroside pheromones in C. elegans. We anticipate that use of TAMOHA for the profiling of electrophilic species will help clarify enzyme function and uncover previously elusive biochemical mechanisms in a wide range of biological systems.
Related
- A Protocol for Lab-Scale Production of ¹³C-Labeled Yeast Extract as Internal Standard for Metabolomics and Quantification of Intracellular Metabolites.
- Benchmarking and optimisation of bait-capture metagenomics for sequencing of respiratory viruses at scale
- Alveolar Cytochrome P450 Mediates Butylated Hydroxytoluene-Induced Electrophilic Injury and Apoptosis
- Preclinical Validation of [211At]mABG, Synthesized via GMP-Friendly Electrophilic Astatodeboronylation Chemistry
- Cyanobacteria in sustainable agriculture: from bioactive metabolites toward mechanistically validated biostimulants
BibTeX
@article{schroeder2026omicsscale,
title = {{Omics-Scale Capture of Electrophilic Metabolites}},
author = {Allen F. Schroeder and Yan Yu and Ali Turk and Henry H. Le and Matthew LeClair and Marissa A. Fontaine and Nicholas W. Cheng and Saeideh Azad and Christopher N. Parkhurst and Jason Pan and David Artis and Meng Wang and Frank C. Schroeder},
journal = {ACS chemical biology},
year = {2026},
month = oct,
doi = {10.1021/acschembio.6c00711},
url = {https://doi.org/10.1021/acschembio.6c00711},
note = {CC BY},
}
RIS
TY - JOUR
TI - Omics-Scale Capture of Electrophilic Metabolites
AU - Allen F. Schroeder
AU - Yan Yu
AU - Ali Turk
AU - Henry H. Le
AU - Matthew LeClair
AU - Marissa A. Fontaine
AU - Nicholas W. Cheng
AU - Saeideh Azad
AU - Christopher N. Parkhurst
AU - Jason Pan
AU - David Artis
AU - Meng Wang
AU - Frank C. Schroeder
PY - 2026
DA - 2026/10/16
JO - ACS chemical biology
DO - 10.1021/acschembio.6c00711
UR - https://doi.org/10.1021/acschembio.6c00711
AB - The majority of metabolic pathways rely on the production of activated electrophilic intermediates, e.g., coenzyme-A esters, and their chemical structures and abundances are central to understanding enzyme function and biochemical mechanisms. However, most electrophilic metabolites are lost in traditional metabolomic analysis and thus remain poorly characterized. Here, we introduce a biochemical probe, O-(trimethylammoniobutyl)-hydroxylamine (TAMOHA), that enables comprehensive profiling of electrophilic species such as coenzyme-A esters, ketones, and aldehydes. TAMOHA incorporates a highly nucleophilic hydroxylamine that reacts quickly with electrophilic species upon tissue lysis, trapping them as stable derivatives that feature a tetraalkylammonium moiety whose constitutive charge and characteristic MS2 fragmentation fingerprint enable their highly sensitive detection. Using TAMOHA to survey the electrophilomes of E. coli, C. elegans, and mice revealed several thousand electrophilic metabolites, most of which have not been characterized. We then demonstrate trapping of electrophilic metabolites with TAMOHA in the context of specific biochemical pathways, confirming previously proposed functions of two fatty acid metabolism enzymes, detecting formaldehyde production in mice, and providing new insights into the biosynthesis of ascaroside pheromones in C. elegans. We anticipate that use of TAMOHA for the profiling of electrophilic species will help clarify enzyme function and uncover previously elusive biochemical mechanisms in a wide range of biological systems.
SN - 1554-8929
SN - 1554-8937
ER -