Scavenging nitrogen in the gut: the next step of Nε-carboxymethyllysine metabolism in Escherichia coli

Amino acids are modified through a plethora of enzymatic and non-enzymatic reactions. Glycation, or Maillard reaction, takes place at high temperatures between reducing sugars and free amino groups of proteins, producing compounds commonly found in processed foods (Maillard et al. 1912). One of the best-known glycated amino acids, Nε-carboxymethyllysine(CML), is consumed widely by humans reaching a daily intake of 24.6 mg( Mark et al. 2014). Most of it remains undigested, and the limited absorption in the gastrointestinal tract suggests a major role in its degradation by colonic bacteria (Lassak et al. 2023). E. coli produces novel metabolites when exposed to CML, mainly carboxymethylcadaverine, however no enzyme responsible for this degradation has been identified (Hellwig et al. 2019). We have unveiled an underground metabolism proceeding through promiscuous enzymes that accept CML and its downstream metabolites as substrates. Ornithine decarboxylase SpeC is the first enzyme that generates CM-Cad. Furthermore, E. coli can utilize CML as a sole nitrogen source, and based on the identified metabolites, we discovered that GABA transaminase GabT accepts CM-Cad and CML as substrates, with the formation of glutamate. Our findings suggest that the degradation route proceeds similarly to other biogenic amines like cadaverine or putrescine, likely involving other enzymes with broad substrate specificity. This study reveals a new metabolic route within E. coli, with the generation of unique compounds that may influence both gut microbiota dynamics and host physiology. The unknown effects of these metabolites on other gut bacteria and the human host warrant further exploration.