Scientists discover enzymes that redefine glycan pathways

Carbohydrates are fundamental to life, playing a vital role in energy storage and structural support. Among them, β-1,2-glucans, found in bacteria, play key roles in processes like infection and environmental adaptation. However, their rare occurrence and complex structure have made them difficult to study – until now. 

A study published in Protein Science by researchers at Tokyo University of Science (TUS) has identified and characterised new glycoside hydrolase (GH) families that break down β-1,2-glucans. This allows for synthetic carbohydrate production and a deeper understanding of glycan metabolism.  

Discovery of novel enzyme families 

The study, led by Associate Professor Masahiro Nakajima, focused on unclassified glycoside hydrolase enzymes, including β-1,2-glucan-degrading families GH144 and GH162. 

Using sequence, biochemical, structural, and phylogenetic analyses, the team uncovered three new GH families that can degrade β-1,2-glucans. These enzymes exhibited only 16–20 percent amino acid similarity, yet shared key structural features like the (α/α)₆ barrel fold and a common anomer-inverting mechanism. These are both essential for cleaving β-1,2-glucan molecules. 

Defining the “SGL clan” 

This work led to the proposal of a new enzyme group: the “SGL clan.” It brings together unifies known β-1,2-glucanases (SGLs) from GH144 and GH162 with newly identified families GH192, GH193 and GH194. The clan also includes GH189, despite its anomer-retaining reaction mechanism, due to phylogenetic similarities. 

The study highlighted an irregular distribution of catalytic mechanisms within the clan, influenced by the positioning of catalytic residues. Even though these enzymes serve similar functions, they share only three conserved residues – E239, Y367 and F286. All of which are proposed as defining markers of the SGL clan. 

Implications for carbohydrate synthesis and beyond 

The findings underline a unique pathway of molecular evolution for these enzymes and show immense diversity within carbohydrate-active proteins. 

“Glycans serve numerous physiological functions, but due to their complexity and difficulty in synthesis, studying them is challenging in many cases,” said Dr Nakajima. “However, practical synthesis of glycans aids in exploring newer degrading enzymes, and these enzymes can potentially be used to synthesize glycans. This duo of synthesis and degradation helps in enriching the knowledge in the domain of carbohydrate-associated enzymes.” 

The work not only furthers our understanding of glycan metabolism but also presents the possibility of new applications in medicine, agriculture and biofuels where carbohydrate synthesis is increasingly valuable. 

Future potential in enzyme engineering 

Beyond natural degradation, the study hints at exciting possibilities for enzyme re-engineering.  

“The identification of this clan showcases the extensive diversity of carbohydrate-active enzymes,” says Nakajima. “If the reaction mechanism can be elucidated, it will be possible to use it to modify enzyme function, converting degradative enzymes into synthetic enzymes to synthesise new oligosaccharides.” 

With these discoveries, researchers are now better equipped to design and synthesise complex carbohydrates. This could potentially lead to innovations across synthetic biology and disease treatment.