A Sweeter Pathway to Rare Sugar Production

Rare sugars are called rare for a reason—they're found in very small amounts in some fruits and a few other foods. Many rare sugars are niche products because of the challenges of producing them, yet once those hurdles have been overcome they have the potential to play a role in addressing the rising levels of diabetes and other diet-related diseases.

"Some plants can produce a trace amount, but not a lot," of rare sugars, explains Shota Atsumi, professor of chemistry at the University of California, Davis. "Some of them have the really important bioactivities and from some of them we can get a low-calorie sweetener."

One of those rare sugars, psicose (also called allulose), is a promising substitute for sugars and current popular sweeteners. Psicose is a monosaccharide, almost free of calories, and has about 70% of sucrose's sweetness. It also behaves like regular sugar; it browns, for example, so there should theoretically be plenty of opportunities to use it instead of sugar.

However, while some ingredient companies do offer psicose, current methods for making it are too expensive for it to extensively replace other types of sugars and they also create waste byproducts, Atsumi says. To put that into perspective, current bulk prices for allulose run around four times that of sucrose and fructose, which usually costs around $1 a pound.

Atsumi was part of a research team that wanted to find a more efficient and cost-effective method to produce psicose for both consumer food applications and also to make it more accessible to researchers like himself.

"Many people want to study psicose for its important bioactivity. If we cannot get enough psicose, we cannot do this research," Atsumi says.

Atsumi and his colleagues have found a surprising pathway to making psicose. They discovered that a strain of nonpathogenic bacteria Escherichia coli can make psicose from glucose naturally. "It means this microbe already has all the required components to produce psicose from glucose," he says.

Their method produced a 62% yield; the most commonly used current method gets about 50%, the researchers say. "I can say that our method has a good possibility to reduce the production cost dramatically, which means our method may reduce the price on the market," says Atsumi.

Channeling Psicose

The researchers were able to improve the amount of psicose generated by using CRISPR and CRISPR interference (CRISPRi), a type of gene-editing technology that blocks specific selected genes, a process known as gene knockdown. They used CRISPR on the E. coli to delete competing gene pathways, and CRISPRi to knock down those that couldn't be deleted. What that did was enable them to both increase the pathway of the natural carbon flux from the glucose to psicose and also to reduce the competing pathway, explains Atsumi.

It's a process akin to channeling a river, Atsumi says. "First, we increase water flow to the target location. Then sometimes if the water branches out, we can remove a competing river to increase the flux."

The researchers were surprised, according to Atsumi, that E. coli already possessed the pathway. They had originally wanted to see if they could create a completely new pathway to produce psicose but discovered they didn't need to. "Nature is really smart, and sometimes microbes are smarter than us," Atsumi notes.

Because the chemical reaction should work for other rare sugars, according to Atsumi, the researchers are confident that the method they've discovered will be applicable more broadly. "We want to expand this strategy to produce different types of rare sugars," he says.

The researchers have applied for a patent for their method, and they're also in the process of working with industry to explore scaling up their process for industrial production.

"If we can commercialize it, it will help maintain people's health, and people can still enjoy sweet food," Atsumi observes.ft