# Bacteria from foods and gut microbiota produce methylglyoxal and this metabolite leads to the formation of bioactive 1-acetyl-β-carboline alkaloids

## TL;DR

Bacteria in food and the gut produce a toxic compound, methylglyoxal, which reacts to form bioactive alkaloids.

## Contribution

The study identifies that bacteria with methylglyoxal synthase produce methylglyoxal, which spontaneously forms bioactive 1-acetyl-β-carboline alkaloids.

## Key findings

- Methylglyoxal is produced by bacteria like Escherichia coli and Lactilactobacillus sakei, leading to ACE-βCs formation.
- Methylglyoxal production depends on carbohydrate availability and environmental conditions like oxygen levels.
- The enzyme MgsA is essential for methylglyoxal production, confirmed by gene expression experiments.

## Abstract

Methylglyoxal (MGO) is a highly reactive and toxic compound whereas 1-acetyl-β-carbolines (ACE-βCs) are bioactive alkaloids. These compounds were studied in cultures of bacteria from foods and human gut microbiota. Two ACE-βCs were identified as 1-acetyl-β-carboline (AβC) and 1-acetyl-β-carboline-3-carboxylic acid (AβC-COOH). Cultures containing ACE-βCs also contained MGO that was produced during bacterial growth. MGO produced by bacteria reacted spontaneously with L-tryptophan (L-Trp) and afforded ACE-βCs. MGO and ACE-βCs appeared in cultures from Escherichia coli and Lactilactobacillus sakei but not in cultures from other lactobacilli (L. plantarum, L. rhamnosus, and L. paracasei). Those bacteria producing MGO contained the enzyme methylglyoxal synthase (MgsA). MgsA was needed for the production of MGO as demonstrated by expressing the mgsA gene from L. sakei DSM 15831 T into Lacticaseibacillus paracasei BL23, and the recombinant strain produced MGO. The factors involved in the bacterial production of MGO are highlighted. E. coli produced MGO only in presence of glucose and L. sakei on galactose. The bacterial production of MGO (and resultant ACE-βCs) increased with the concentration of carbohydrates (glucose or galactose). The production of MGO from glucose in E. coli highly increased when phosphate was added and higher levels were produced under anaerobic or oxygen-limited conditions than in aerobic conditions. The results suggest that E coli may produce MGO under gut conditions and MGO may result from the accumulation of phosphorylated intermediates in glycolysis. It is concluded that bacteria possessing MgsA present in foods and human gut microbiota produce MGO that leads to the formation of ACE-βCs alkaloids. Bacterial production of MGO is relevant owing to its reactive and toxic nature whereas ACE-βCs are bioactive substances investigated in different targets.

The online version contains supplementary material available at 10.1038/s41598-026-35162-9.