Artificial production of breast milk’s ‘super-sugar’

A research group at DTU Chemical Engineering has successfully produced rare sugar structures found in breast milk and which are thought to possess beneficial health properties.

Breast milk contains large quantities of highly specialized carbohydrates unique to humans. Although their properties have not yet been fully identified, they are believed to play a key role in preventing disease and the cognitive development of infants. A research team at DTU Chemical Engineering has successfully produced 10 g of these carbohydrates, and both the industry and the scientific community have high hopes for their beneficial effects on health.

Among other things, breast milk helps build the child’s healthy intestinal flora, and the carbohydrates also help develop the immune system of newborns. The carbohydrates can also prevent pathogenic bacteria such as salmonella and campylobacter causing illness in children and it is believed that they can prevent the transfer of HIV from mother to child.

Breast milk contains a couple of hundred different molecular carbohydrate structures, but it is unknown whether a few, highly potent structures have the ability to prevent infection or whether the interaction between them all causes the preventive effect.

Companies and scientists the world over have joined the race to be the first to devise a method to produce the carbohydrate structures outside the human body with the aim of conducting research into the properties of the carbohydrates and exploiting them for formula production and other purposes.
Looking to the future, the aim is to exploit them in other contexts—e.g. in food production—so that more people reap the benefits of the carbohydrates’ health-promoting properties through functional foods.


Four years of intensive research

With the help of tailored enzymes, Professor Jørn Dalgaard Mikkelsen’s research group at DTU Chemical Engineering has successfully produced more than 10 g of the rare sugar structures—among them sialyllactose. It has taken four years of intensive research to design enzymes that function in the biocatalytic process.

“The sugar is extremely difficult to produce,” is the short reply from Jørn Dalgaard Mikkelsen as he describes his research into breast milk sugar structures.

The longer version sounds something like this:
“To produce sialyllactose, you need lactose (milk sugar, ed.), present in many substances, including cow’s milk. The lactose needs to be ‘laced’ with sialic acid, an extremely rare sugar building block. We have therefore searched for donor molecules—i.e. natural sources from which we could extract sialic acid,” explains the Professor.

The researchers found this natural source in whey—a by-product of cheese production. However, the two sugar structures—lactose and sialic acid—do not automatically combine when mixed.
“The substances must be activated before they combine into a single molecule. A catalyst must be present—and we have invented an enzyme whose molecular design causes biocatalysis occur. The enzyme can transport the sialic acid from the whey and combine it with lactose.”


Patented enzyme

The enzyme discovery resulted in a patent in mid-2013—and from a technical standpoint—the research group is now ready to upscale sialyllactose production. Production is still a costly undertaking, however, so focus is now on finding a financially sustainable process.

At the same time, the DTU Chemical Engineering research group is attempting to produce one of the other sugar structures in breast milk—namely fucosyllactose—which poses the same challenges as sialyllactose: The researchers must identify natural sources from which they can extract the building blocks in order to invent a method to combine them again into the much sought-after sugar.

Professor Jørn Dalgaard Mikkelsen’s research goes hand in hand with that of Professor Anne Meyer’s research group in the same department—namely identifying methods to produce molecular structures with health-promoting properties.