Unique Microbial Catabolic Pathway for the Human Core -Glycan Constituent Fucosyl-α-1,6--Acetylglucosamine-Asparagine.

The survival of commensal bacteria in the human gut partially depends on their ability to metabolize host-derived molecules. The use of the glycosidic moiety of -glycoproteins by bacteria has been reported, but the role of -glycopeptides or glycoamino acids as the substrates for bacterial growth has not been evaluated. We have identified in strain BL23 a gene cluster () involved in the catabolism of the glycoamino acid fucosyl-α-1,6--GlcNAc-Asn (6'FN-Asn), a constituent of the core-fucosylated structures of mammalian -glycoproteins. The cluster consists of the genes , encoding a major facilitator superfamily (MFS) permease and the α-l-fucosidase AlfC, and the divergently oriented (aspartate 4-decarboxylase), (transcriptional regulator), (peptidase), (glycosyl-asparaginase), and (sugar kinase) genes. Knockout mutants showed that , , , , and are necessary for efficient 6'FN-Asn utilization. The genes are induced by 6'FN-Asn, but not by its glycan moiety, via the AlfR2 regulator. The constitutive expression of genes in an strain allowed the metabolism of a variety of 6'-fucosyl-glycans. However, GlcNAc-Asn did not support growth in this mutant background, indicating that the presence of a 6'-fucose moiety is crucial for substrate transport via AlfH. Within bacteria, 6'FN-Asn is defucosylated by AlfC, generating GlcNAc-Asn. This glycoamino acid is processed by the glycosylasparaginase AsnA2. GlcNAc-Asn hydrolysis generates aspartate and GlcNAc, which is used as a fermentable source by These data establish the existence in a commensal bacterial species of an exclusive metabolic pathway likely to scavenge human milk and mucosal fucosylated -glycopeptides in the gastrointestinal tract. The gastrointestinal tract accommodates more than 10 microorganisms that have an enormous impact on human health. The mechanisms enabling commensal bacteria and administered probiotics to colonize the gut remain largely unknown. The ability to utilize host-derived carbon and energy resources available at the mucosal surfaces may provide these bacteria with a competitive advantage in the gut. Here, we have identified in the commensal species a novel metabolic pathway for the utilization of the glycoamino acid fucosyl-α-1,6--GlcNAc-Asn, which is present in the core-fucosylated -glycoproteins from mammalians. These results give insight into the molecular interactions between the host and commensal/probiotic bacteria and may help to devise new strategies to restore gut microbiota homeostasis in diseases associated with dysbiotic microbiota.