Exploring the dynamic role of L-fucose and α-L-fucosidases in the cross talk between gut bacteria and host

Abstract

As for all cells on earth, both human gut epithelial cells and our gut microbiota are covered by a dense coat of glycans, called the glycocalyx. The unique glycans in this glycocalyx are not encoded in the genome and the biosynthesis of their complex structures is not template-driven. The regular molecular biology tools to study and manipulate the biomolecules DNA and proteins at the molecular level can therefore not be easily applied to elucidate the functional role of glycans and their interacting proteins at this human-gut microbiota interface. The application of techniques from the field of chemical biology however has resulted in a successful strategy for this through the development of smart tailor-made probes – carbohydrate-based bioactive small molecular tools – that target a specific carbohydrate or interacting protein class in a cell or whole organism. In the past decades such glycan-based probes have increasingly been used to unravel glycan-related biological processes. The focus of the research reported in this thesis was on studying fucosylated glycans and their interacting enzymes at the human-gut microbiota interface. Fucosylated glycoproteins are abundant at the gut-microbiota interface and have been implicated in critical biological processes such as immune response, signal transduction, and adhesion of pathogens. Quantification and visualization of fucosidases, the enzymes involved in altering this fucosylation pattern, will help us unravel their biological importance. The research described in this thesis includes the development of two different fucosidase-targeting activity-based probes (ABPs). These new tools can in the future potentially be used in high throughput methods to study the relationship between fucosylation and the maintenance of homeostasis at the human-gut microbiota interface.