Researchers Develop Way to Make Healthier Sugar Substitute

Newswise — From saccharin in the 19th century to stevia and monk fruit in the 21st, researchers and the food industry have long sought a sweetener that delivers the taste of sugar without its drawbacks—excess calories, tooth decay, and heightened risk for obesity, insulin resistance, and diabetes. 

Now, in a study published in Cell Reports Physical Science, Tufts researchers have developed a way to biosynthetically produce an otherwise rare sugar called tagatose, which could very well provide the sweetness and natural taste of table sugar without its potential harms. It might even provide some health benefits.

Tagatose occurs naturally in only very small amounts compared to common sugars like glucose, fructose, or sucrose. It can be found in milk and other dairy products when lactose is broken down by heat or enzymes, such as might be found in the production of yogurt, cheese, and kefir. 

Some fruits like apples, pineapples, and oranges contain trace levels of tagatose as part of their natural carbohydrate spectrum. Since tagatose is typically less than 0.2% of sugars found in natural sources, it is usually manufactured, not extracted, for consumption.

“There are established processes to produce tagatose, but they are inefficient and expensive,” said Nik Nair, associate professor of chemical and biological engineering at Tufts. 

“We developed a way to produce tagatose by engineering the bacteria Escherichia coli to work as tiny factories, loaded with the right enzymes to process abundant amounts of glucose into tagatose. This is much more economically feasible than our previous approach, which used less abundant and expensive galactose to make tagatose.

Unlike sucrose, which fuels cavity-causing bacteria in the mouth, tagatose appears to reduce the growth of some of those bacteria, and evidence suggests it has probiotic effects to support healthy oral and gut bacteria. 

The bacteria are engineered to include a newly discovered enzyme from slime mold called galactose-1-phosphate-selective phosphatase (Gal1P), which can help make galactose directly from glucose. A second enzyme expressed by the bacteria called arabinose isomerase completes the conversion of galactose to tagatose. 

The yield of tagatose from glucose generated by the bacteria could reach up to 95%, significantly greater and more cheaply attained than conventional manufacturing in which yields only reach 40 to 77%.

Tagatose is 92% as sweet as sucrose—table sugar—and has about 60% fewer calories. Tagatose has been designated “generally recognized as safe” by the FDA, which means it can safely be used in consumer foods. To put that in perspective, that’s the same designation given to salt, vinegar, and baking soda. 

Its potential benefits for diabetics derive from the fact that it is only partially absorbed in the small intestine; much of it being fermented by gut bacteria in the colon. Because of this, its impact on blood glucose and insulin is much less than that of conventional sugar. Clinical studies show very low increases in plasma glucose or insulin after ingestion of tagatose.

Unlike sucrose, which fuels cavity-causing bacteria in the mouth, tagatose appears to reduce the growth of some of those bacteria, and evidence suggests it has probiotic effects to support healthy oral and gut bacteria. 

With low calories and low absorption, tagatose is an attractive “bulk sweetener,” which means it not only can replace sugar for sweetness, but can also provide a similar bulk texture in cooking that comes with adding the sugar in some quantity, something that high intensity sweetener substitutes can’t do. It even browns like table sugar during cooking. In taste testing compared to other sugars and sugar substitutes, it has the most similarity to table sugar.

“The key innovation in the biosynthesis of tagatose was in finding the slime mold Gal1P enzyme and splicing it into our production bacteria,” said Nair. “That allowed us to reverse a natural biological pathway that metabolizes galactose to glucose and instead generate galactose from glucose supplied as a feedstock. Tagatose and potentially other rare sugars can be synthesized from that point.”