Deciphering underground decarboxylase activity towards N_ε-modified lysine derivatives in enterobacteria

Thermal food processing generates diverse compounds interacting with the gut microbiota. Despite their abundance, the microbial turnover of diet-borne N_ε-modified lysine derivatives remains largely unexplored. We demonstrate that the enterobacterial ornithine decarboxylase SpeC degrades the prevalent advanced glycation end product N_ε-carboxymethyllysine (CML) to carboxymethylcadaverine via an underground activity (∼4 molecules/enzyme/min). This promiscuity extends to additional N_ε-modified lysine derivatives - namely formylated (FmL), monomethylated (MML) and dimethylated (DML) lysine - yielding previously unknown biogenic amines (mono- and dimethylcadaverine, formylcadaverine). Functionally, SpeC enables Escherichia coli to utilize CML as a sole nitrogen source. In specific strains, this metabolism reinforces pH-stress responses, supporting survival under mild acidic conditions typical for the colon. Furthermore, SpeC orthologs are widespread across human gut genomes, correlating with geography, diet, and disease. Together, these findings suggest a potential diet-microbiome communication axis, linking the intake of modified dietary chemicals to microbial physiology and hypothesized host impacts.