For more than a century, scientists and food companies have been looking for ways to replicate the taste of sugar without its health drawbacks. From early sweeteners like saccharin in the 19th century to modern alternatives such as stevia and monk fruit, the goal has remained the same. The challenge has been finding something that delivers sugar's familiar flavor while avoiding excess calories, tooth decay, and increased risks of obesity, insulin resistance, and diabetes.

A new study published in Cell Reports Physical Science suggests that researchers may be closer to that goal. Scientists at Tufts University have developed a biosynthetic method to produce tagatose, a naturally occurring but extremely rare sugar. Tagatose closely mimics the taste of table sugar and could offer a way to enjoy sweetness with fewer negative health effects. Researchers say it may even provide added benefits.

Tagatose exists naturally, but only in very small quantities compared with common sugars such as glucose, fructose, and sucrose. It appears in milk and other dairy products when lactose breaks down under heat or enzymatic activity, including during the production of yogurt, cheese, and kefir.

Tiny amounts of tagatose are also present in fruits like apples, pineapples, and oranges. However, it typically makes up less than 0.2% of the sugars found in these natural sources. Because of this scarcity, tagatose is usually produced through manufacturing rather than extracted directly from foods.

"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.

To address this problem, the research team developed a new production strategy using genetically engineered bacteria. "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."

The bacteria were modified to include a newly identified enzyme from slime mold called galactose-1-phosphate-selective phosphatase (Gal1P). This enzyme enables the bacteria to generate galactose directly from glucose. Another enzyme produced by the bacteria, known as arabinose isomerase, then converts the galactose into tagatose.

Using this method, the engineered bacteria can convert glucose into tagatose with yields as high as 95%. This represents a major improvement over traditional manufacturing techniques, which typically achieve yields ranging from 40 to 77%. The higher efficiency also makes the process significantly more cost-effective.

Sweetness, Safety, and Fewer Calories

Tagatose delivers about 92% of the sweetness of sucrose -- table sugar -- while containing roughly 60% fewer calories. It has been classified by the FDA as "generally recognized as safe," meaning it can be used in consumer food products. This designation is shared by everyday ingredients such as salt, vinegar, and baking soda.

One reason tagatose may be beneficial for people with diabetes is how the body processes it. Only part of the sugar is absorbed in the small intestine, while much of it is fermented by gut bacteria in the colon. As a result, tagatose has a much smaller effect on blood glucose and insulin levels than conventional sugar. Clinical studies have shown only minimal increases in plasma glucose or insulin after consumption.

Tagatose may also support oral health. Unlike sucrose, which feeds bacteria that cause cavities, tagatose appears to limit the growth of some of those harmful microbes. Research also suggests it may have probiotic effects that promote healthier bacteria in both the mouth and the gut.

Because it is low in calories and poorly absorbed by the body, tagatose functions well as a "bulk sweetener." This means it can replace sugar not only for sweetness but also for the physical properties sugar provides in cooking and baking. High intensity sweeteners cannot replicate this effect. Tagatose browns like table sugar when heated, and taste tests show it closely matches the flavor and mouthfeel of conventional 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."

The researchers say this approach could open the door to producing other rare sugars more efficiently, potentially reshaping how sweeteners are made and used in the future.

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