How one sweet molecule makes all the difference

The hidden power of sugar molecules

When we think about sugars, we often think about them in the context of energy metabolism, whether our own or from our food sources. Will this soft drink give me a sugar dip after drinking it? How will the starch pasta affect the sauce? What will the alcohol percentage of the beer be if using this or that malt for brewing? All these questions are tied to how sugars are processed for energy, whether for immediate use (such as in a soft drink), or long-term energy storage (in wheat and in barley malt). But sugars have a huge role beyond energetics; a single sugar molecule can be the key to molecular function, structure and transport. Today we learn about the importance of glycosylation, in nature, medicine, and industry.

Glycosylation is the process in which a sugar molecule (the “donor”) is added to another molecule (the “acceptor”) to create a glycoconjugate. “Sugar” in this case is defined as a simple carbohydrate, such as the monomers glucose, fructose, etc. or dimers such as lactose and sucrose. When the donor is specifically glucose, the process is known as glucosylation. What kinds of molecules are gly/glucosylated? All kinds! From simple metabolites to large proteins, glycosylation plays an important role.

From protein folding to immune recognition

In proteins, glycosylation plays a key role in how a protein folds or is transported to where it is needed. Proteins are made up of a chain of amino acids that have been “translated” from the information in the DNA. These amino-acids all interact with each other in ways that lead to the protein to fold into its functional shape, at least initially. However, sometimes, post-translational modifications are needed to ensure the correct fold for the correct function, or once folded, to be transported to their workplace. Glycosylation can play a key role in that folding. By adding one or more sugars molecules in strategic places, the protein’s internal chemistry shifts to promote better folding. These sugars can also serve as directions, a tag that points the cell to where the proteins need to be to do their job.

These sugars tags are often used to convey information. In fact, the field of glycobiology often intersects with immunology and cancer research. Our immune system is attuned to detect antigens, or molecules associated with certain pathogens. These can often be certain sugar combinations on the surface of bacterial or cancerous cells. By studying these sugar signals, researchers can design new diagnostic tools as well as new targeted treatments based on these particular sugar signatures.

From nature’s chemistry to better ingredients

In other areas of nature, glycosylation is used by organisms to manage their repertoire of chemicals. Plants, for example, are amazing chemists, able to synthesize a range of compounds used to attract pollinators, to communicate with each other, or to defend themselves against herbivores.  By adding a sugar donor to these acceptor molecules, the compound changes some of its physical properties, by becoming more water soluble, less or more bioactive or by providing anchor points for further chemical modifications. Glycosylation is an in-built system that transports, aids in synthesis, or deploys these chemicals.

Inspired by nature, glycosylation can happen in the lab, whether by chemical synthesis or making use of nature’s repertoire of enzymes. Chemical glycosylation can sometimes be tricky in ensuring the sugar is added in the right place and in the right orientation, while glycosyltransferase enzymes can be overly inflexible or may require the use of expensive/rare “activated sugars”. A sweet medium are glucanotransferases, able to use glucose as a donor for a variety of molecules. While these enzymes usually use sugars to build larger polysaccharides, they are flexible enough to sometimes add a glucose molecule to different kinds of molecules.

At CarbExplore, we have used our expertise in carbohydrate active enzymes (CAZymes) to create new ingredients via glucosylation. For example, we have made a natural non-caloric sweetener even taste better! Using a sweet compound from the stevia plant and a CAZyme from lactic acid bacteria, we were able to glucosylate this compound, which has resulted in a more water-soluble, stable and less bitter tasting product! Inspired by this success story, we continue to search for novel glucosylations that result in improved ingredients to be used in the food and cosmetic industries.