Bacterial carbohydrate-active enzymes and transporters (CAZymes and transporters)

Bacterial carbohydrate-active enzymes (CAZymes) and their associated transporters constitute the primary metabolic machinery used by the microbiota to degrade complex glycans (Wardman et al., 2022). These systems are often organized into Polysaccharide Utilization Loci (PULs), which coordinate the sensing, binding, and transport of specific carbohydrates across the bacterial membrane for subsequent enzymatic cleavage (Ndeh & Gilbert, 2018). In the human gut, these enzymes allow commensal bacteria to harvest energy from dietary fibers and host-derived mucins that are inaccessible to human digestive enzymes (Kaoutari et al., 2013). This metabolic activity is a key driver of microbiome composition and the production of bioactive metabolites, such as short-chain fatty acids, which influence host immunity and energy homeostasis. This target entry represents a broad functional class of proteins rather than a single molecular entity. Therapeutically, CAZymes and transporters are targeted to modulate the gut environment and treat metabolic diseases like obesity and type 2 diabetes. For example, alpha-glucosidase inhibitors like acarbose can affect both human and bacterial enzymes to slow carbohydrate absorption. Additionally, specific bacterial enzymes, such as beta-glucuronidases, are targeted with small-molecule inhibitors to prevent the reactivation of toxic drug metabolites (e.g., from irinotecan) in the gastrointestinal tract (Wallace et al., 2010). These enzymes also play critical roles in bacterial cell wall synthesis and pathogenesis, making them attractive targets for the development of narrow-spectrum antibiotics and anti-virulence agents.

Other names

CAZymesPolysaccharide Utilization LociPULsBacterial glycan metabolism machineryGlycoside hydrolasesGlycosyltransferasesPolysaccharide lyasesCarbohydrate esterasesCarbohydrate-binding modulesSusCD-like transport systems

Inhibition of bacterial carbohydrate degradation to reduce caloric harvest; inhibition of specific bacterial enzymes to prevent toxic metabolite reactivation; disruption of bacterial cell wall synthesis.