The initial promise of artificial sweeteners was to enhance the health profile of sugary confections and beverages. However, contemporary scrutiny is now directed towards several prevalent zero-calorie alternatives, sparking novel apprehensions.
A burgeoning natural substitute, potentially manufacturable on a significantly expanded scale, is emerging, facilitated by the enzymatic capabilities of slime mold.
This naturally occurring saccharide is identified as tagatose. Not only does it exhibit a sweetness intensity approximating 92 percent of that of sucrose (commonly known as table sugar), but it also contributes merely about one-third of the caloric content.
What renders it particularly compelling is its distinct physiological effect: it does not precipitate a surge in insulin levels, unlike sucrose or potent artificial sweeteners. This characteristic positions it as a potentially advantageous choice for individuals managing diabetes or blood glucose fluctuations.
Academic investigators at Tufts University, in collaboration with the biotechnology enterprises Manus Bio (situated in the US) and Kcat Enzymatic (based in India), have spearheaded an initial study demonstrating the feasibility of producing tagatose in a sustainable and efficient manner. This very challenge has historically impeded the market’s growth.
Tagatose is an infrequently encountered natural sweetener, found in minimal quantities within select dairy products and fruits. It presents a more salutary alternative to sucrose, as well as to artificial sweeteners, both of which are capable of inducing significant insulin spikes.
A primary determinant of tagatose’s different metabolic impact is that a substantial portion undergoes fermentation within the large intestine. Its absorption into the systemic circulation via the small intestine is only partial.
Within the gastrointestinal tract, this rare sugar is processed similarly to fructose, the sugar found in fruits. Consequently, individuals with fructose intolerance should exercise caution. Nonetheless, tagatose is broadly recognized as safe for consumption by both the United States Food and Drug Administration (FDA) and the World Health Organization (WHO).
Furthermore, tagatose is regarded as ‘tooth-friendly’ and may even confer prebiotic benefits to the oral microbiota. In contrast to sucrose, which nourishes specific oral bacteria implicated in dental caries, preliminary investigations indicate that tagatose inhibits the proliferation of detrimental oral microorganisms.
An additional significant advantage is tagatose’s suitability for baking into food products, a capability not shared by many alternative high-intensity sweetener substitutes.
While its potential is evident, the tagatose market has hitherto been hindered by constrained production volumes.
“Established methodologies exist for tagatose production, yet they are characterized by inefficiency and substantial cost,” explains Nik Nair, a biological engineer at Tufts.
“Our team devised a novel production strategy by genetically modifying the bacterium Escherichia coli to function as miniature bio-factories. These engineered bacteria are equipped with the requisite enzymes to transform ample quantities of glucose into tagatose.”
Specifically, the researchers introduced a recently identified enzyme from slime mold, known as galactose-1-phosphate-selective phosphatase (Gal1P), into these bacteria. This enzyme facilitates the conversion of glucose to galactose, which is subsequently transformed into tagatose by a secondary enzyme.
Leveraging this innovative sequence, Nair and his collaborators have demonstrated production yields for tagatose reaching as high as 95 percent, a marked improvement over the approximately 40 to 77 percent currently attainable.
“The pivotal breakthrough in tagatose biosynthesis involved the discovery of the slime mold Gal1P enzyme and its integration into our production bacteria,” states Nair.
“This allowed us to invert a natural biochemical pathway that normally metabolizes galactose into glucose, enabling instead the generation of galactose from glucose supplied as a substrate. From this point, tagatose and potentially other rare sugars can be synthesized.”
The research group intends to further refine their tagatose production system, anticipating that their methodological approach will offer a valuable blueprint for the future synthesis of rare sugars.
According to certain projections, the tagatose market is anticipated to achieve a valuation of US$250 million by the year 2032.
The findings of this study have been published in Cell Reports Physical Science.
