Underground metabolism in the gut: Degradation of Nε-carboxymethyllysine (CML) in Escherichia coli

Amino acids undergo numerous of enzymatic or non-enzymatic post-translational modifications. Nε-Carboxymethyllysine (CML) results from the condensation of a reducing sugar with the free amino group of lysine, in the so called Maillard reaction or glycation (Maillard et al., 1912). This non-enzymatic event is responsible for the flavour and colour of thermally processed foods. Up to 11.3 mg of CML per kg of protein are ingested daily by humans, but the limited absorption in the gastrointestinal tract suggests a major role in its degradation by colonic bacteria (Delgado-Andrade et al., 2012, Lassak et al., 2023). When exposing E. coli to CML the predominant degradation product is carboxymethylcadaverine (Hellwig et al., 2019). However, no enzyme in the CML metabolism is known to date. We have now unveiled an unexpected high promiscuity of the ornithine decarboxylase SpeC toward many lysine derivatives including CML. The enzyme is the first in an underground metabolism, enabling E. coli to utilize CML as sole nitrogen source. We further discovered that proton consumption in the CML decarboxylation reaction helps to counteract the mild acid pH in the colon. Investigating the molecular "players" of CML metabolism in E. coli will help understand how glycated amino acids influence the ability of gut bacteria to thrive and compete, and gain insight about the effect those compounds and their degradation products have on our health.