Carbohydrate chains, known as glycans, are essential components of biological systems, influencing various cellular processes such as communication, immune responses, and structural integrity. These complex sugar molecules are widely found in plants, animals, and microorganisms, playing significant roles in metabolism and digestion. Among the many types of glycans, galactosides are particularly important due to their presence in plant cell walls and dietary fibers. They are also key components of prebiotic oligosaccharides, which help promote the growth of beneficial gut bacteria and support overall digestive health.
Glycans containing galactose are commonly added to processed foods such as juice and powdered milk because of their potential health benefits. The study of enzymes responsible for breaking down these glycans is crucial for understanding their role in prebiotic activity and for optimizing their application in food science and health products. These enzymes, known as β-galactosidases, specialize in cleaving galactose from complex carbohydrate structures, making them essential for carbohydrate digestion and metabolism. However, different β-galactosidases target specific galactosides, and understanding their functions can lead to advancements in both biotechnology and medicine.
In mammals, including humans, β-galactosidases are found in the intestines, where they help break down complex carbohydrates. One of the most well-studied sources of these enzymes is the gut bacterium Bifidobacterium, which plays a key role in digesting plant-derived carbohydrates. Another gut bacterium, Bacteroides xylanisolvens, has been recognized for its ability to utilize a broad range of carbohydrates. However, little was known about the specific mechanisms and enzymatic capabilities of this bacterium until a recent scientific breakthrough provided new insights into its carbohydrate metabolism.
A research team led by Associate Professor Masahiro Nakajima from the Tokyo University of Science in Japan has discovered a novel β-galactosidase enzyme in Bacteroides xylanisolvens that specifically targets unique galactose-containing glycans. The study, which was published in Communications Biology on January 16, 2025, involved a collaboration with researchers from Niigata University and Kagawa University. Their findings reveal new aspects of glycan metabolism and could lead to the development of prebiotic products that enhance gut health.
The motivation behind this research stems from the fact that glycans have diverse and complex structures, many of which remain unexplored. Dr. Nakajima explains that since enzymes are essential for the synthesis and breakdown of glycans, the discovery of new enzymes is a crucial step toward unlocking their potential applications. This novel enzyme could be used to produce large quantities of unique glycans with prebiotic properties, which may be beneficial to human health by promoting the growth of beneficial gut bacteria.
Within Bacteroides xylanisolvens, multiple genes encode β-galactosidases, but the researchers identified one particular gene, Bxy_22780, that encodes a previously unknown enzyme. Initial experiments showed that this enzyme exhibited no activity toward natural β-galactosides, which was unexpected. However, further investigations using specialized reaction conditions revealed that when the enzyme was exposed to a nucleophile mutant, α-D-galactosyl fluoride as a donor substrate, and galactose or D-fucose as an acceptor substrate, reaction products were successfully detected. Nuclear magnetic resonance analysis confirmed that the reaction products included β-1,2-galactobiose, a specific type of disaccharide.
Further studies on the enzyme’s specificity demonstrated that it acts primarily on galactooligosaccharides, a mixture of oligosaccharides containing galactose in different linkages. The enzyme exhibited a unique preference for β-1,2-galactosidic linkages, distinguishing it from other β-galactosidases that typically target different glycan structures. Kinetic analysis revealed that this enzyme is particularly effective in breaking down β-1,2-galactobiose and β-1,2-galactotriose, suggesting a highly specialized function.
To better understand why the enzyme is so selective, the researchers performed structural analysis using X-ray diffraction. The findings showed that the enzyme binds specifically to a molecule called methyl β-galactopyranose at a key site known as subsite +1. The chemical group of this molecule is positioned in a way that makes it particularly well-suited for recognizing and breaking down β-1,2-galactooligosaccharides. This structural insight explains why the enzyme is highly specific for these rare glycan structures and helps differentiate it from other known β-galactosidases.
According to Dr. Nakajima, β-1,2-galactooligosaccharides and the enzymes that process them have rarely been studied, making this discovery a significant step toward understanding the functions of these unique glycans. Although there is currently no direct evidence that β-1,2-galactooligosaccharides have prebiotic properties, their potential for promoting beneficial gut bacteria remains an exciting area of future research. The ability to synthesize and modify these glycans using the newly discovered enzyme could lead to novel dietary supplements and functional foods designed to improve digestive health.
Beyond their potential prebiotic benefits, β-1,2-galactooligosaccharides may also have medical applications. Certain parasitic infections, such as Chagas disease, are caused by pathogens that produce glycans containing β-1,2-galactosidic linkages. Understanding and manipulating these structures could pave the way for the development of new therapeutic strategies to combat such diseases. The newly discovered enzyme could therefore serve not only as a tool for enhancing gut health but also as a potential target for future drug development.
The discovery of the Bxy_22780 enzyme marks a breakthrough in the study of carbohydrate metabolism and prebiotic research. By unlocking new possibilities for the production and application of β-1,2-galactooligosaccharides, this enzyme could contribute to advancements in both the food and pharmaceutical industries. As researchers continue to explore the biological functions and health benefits of these glycans, new opportunities may arise for improving human health through dietary interventions and medical treatments. The ability to harness the power of this novel enzyme could lead to significant innovations in biotechnology, making it a promising development in the field of carbohydrate science.
More information: Yutaka Nakazawa et al, Structure and function of a β-1,2-galactosidase from Bacteroides xylanisolvens, an intestinal bacterium, Communications Biology (2025). DOI: 10.1038/s42003-025-07494-1