Transcriptional regulation of the Nε‐fructoselysine metabolism in Escherichia coli by global and substrate‐specific cues

Thermally processed food is an important part of the human diet. Heat‐treatment, however, promotes the formation of so‐called Amadori rearrangement products, such as fructoselysine. The gut microbiota including Escherichia coli can utilize these compounds as a nutrient source. While the degradation route for fructoselysine is well described, regulation of the corresponding pathway genes frlABCD remained poorly understood. Here, we used bioinformatics combined with molecular and biochemical analyses and show that fructoselysine metabolism in E. coli is tightly controlled at the transcriptional level. The global regulator CRP (CAP) as well as the alternative sigma factor σ32 (RpoH) contribute to promoter activation at high cAMP‐levels and inside warm‐blooded hosts, respectively. In addition, we identified and characterized a transcriptional regulator FrlR, encoded adjacent to frlABCD, as fructoselysine‐6‐phosphate specific repressor. Our study provides profound evidence that the interplay of global and substrate‐specific regulation is a perfect adaptation strategy to efficiently utilize unusual substrates within the human gut environment. Thermal food processing promotes the formation of Amadori rearrangement products, such as fructoselysine. The gut microbiota including Escherichia coli can utilize these compounds as a nutrient source. We show that in E. coli, fructoselysine metabolism is tightly controlled at the transcriptional level by global and substrate‐specific regulators. Their interplay is a perfect adaptation strategy to efficiently utilize fructoselysine within the human gut environment.