Biology subjects

Schroeder, A. F.

Publications and source records attributed to Schroeder, A. F..

3 recordsLinked to original sources

bioRxiv2026

Omics-scale capture of electrophilic metabolites

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 hydroxyl amine 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 mouse 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. Table of Contents artwork O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=106 SRC="FIGDIR/small/743530v1_ufig1.gif" ALT="Figure 1"> View larger version (47K): org.highwire.dtl.DTLVardef@79a416org.highwire.dtl.DTLVardef@3b937org.highwire.dtl.DTLVardef@74cae9org.highwire.dtl.DTLVardef@1b5a915_HPS_FORMAT_FIGEXP M_FIG C_FIG

biochemistry↗

bioRxiv2025

Nuclear receptor-neurotransmitter coupling links behavior to metabolic state

Animals must flexibly respond to environmental stimuli to survive, and optimal responses critically depend on the organisms current needs. Many organisms have evolved both cell-intrinsic and intertissue signaling pathways that integrate metabolic status. However, how this information is encoded in molecular signals is currently not well understood. Here we show that the nematode C. elegans employs lipidated neurohormones that combine the neurotransmitter octopamine and fat metabolism-derived building blocks to relay information about lipid metabolic status and drive inhibition of aversive olfactory responses during food removal. Using targeted metabolomics, we show that lipidated neurohormone synthesis requires the carboxylesterase CEST-2.1, which links octopamine-glucosides with endogenous methyl-branched or diet-derived cyclopropane fatty acids that act as agonists of the nuclear receptor and master regulator of fat metabolism, NHR-49/PPAR. Loss of cest-2.1, loss of bacterial cyclopropane fatty acid production, or loss of endogenous biosynthesis of the methyl-branched fatty acid substrates of CEST-2.1 mimics the behavioral responses of animals lacking octopamine, indicating that regulation of neurotransmitter-dependent behavior is linked to the coordination of fat metabolism via NHR-49/PPAR. Biosynthesis and subsequent neuromodulation via lipidated neurohormone relies on an intertissue trafficking pathway in which octopamine is shuttled first into the intestine where it is chemically modified, which is likely followed by neuronal import and intracellular hydrolysis to finally release free octopamine. We propose that esterase-dependent synthesis and subsequent hydrolysis of lipidated neurohormones represents a chemical encoding mechanism by which animals integrate information from neurotransmitter signaling and lipid homeostasis to direct appropriate behaviors.

neuroscience↗

bioRxiv2024

Catechol acetylglucose: A newly identified benzoxazinoid-regulated defensive metabolite in maize

An enormous diversity of specialized metabolites is produced in the plant kingdom, with each individual plant synthesizing thousands of these compounds. Previous research showed that benzoxazinoids, the most abundant class of specialized metabolites in maize, also function as signaling molecules by regulating the production callose as a defense response. In this study, we identified catechol acetylglucose (CAG) as a benzoxazinoid-regulated metabolite that is produced from salicylic acid via catechol and catechol-glucoside. Genome wide association studies of CAG abundance identified a gene encoding a predicted acetyltransferase. Knockout of this gene resulted in maize plants that lack CAG and over-accumulate catechol glucoside. Upon tissue disruption, maize plants accumulate catechol, which inhibits Spodoptera frugiperda (fall armyworm) growth. Analysis of caterpillar frass showed that S. frugiperda detoxifies catechol by glycosylation, and the efficiency of catechol glycosylation was correlated with S. frugiperda growth on a catechol-containing diet. Thus, the success of S. frugiperda as an agricultural pest may depend partly on its ability to detoxify catechol, which is produced as a defensive metabolite by maize plants.

plant biology↗