Abstract
D-Tagatose is a promising low-calorie sugar-substituting sweetener in the food industry. Most ingested D-tagatose is fermented by intestinal microorganisms. Until now, Escherichia coli has been considered incapable of growing on D-tagatose. Here, we discovered a gene cluster involved in D-tagatose utilization in E. coli. The chromosome of the intestinal probiotic E. coli Nissle 1917 contains a six-gene cluster encoding the ABC transporter, D-tagatose kinase, D-tagatose-bisphosphate aldolase, and putative aldose 1-epimerase. The functionality of the gene cluster was experimentally validated. Based on single-gene deletions, D-tagatose dissimilation occurs via D-tagatose 6-phosphate to D-tagatose 1,6-bisphosphate to D-glyceraldehyde 3-phosphate plus dihydroxyacetone phosphate. Remarkably, this gene cluster was located in 93% of the completely sequenced genomes of the E. coli B2 phylogroup, which contains the majority of extraintestinal pathogenic and adherent-invasive E. coli strains prevalent in patients with inflammatory bowel disease. This highlights the importance of understanding the clinical significance of D-tagatose in microbiota alterations.