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Sweet science: new approach to synthesize rare health-packed sugars

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A new study by ITQB NOVA researchers could change the way we synthetize rare sugars, making them more accessible for applications in the food, pharmaceutical and nutraceutical industries.

Rare sugars are naturally scarce, making their extraction from plants and other sources both challenging and expensive. Even so, they are gaining attention for their unique benefits and positive effects on health and have been used as food additives, nutritional supplements, and in pharmaceuticals.

ITQB NOVA researchers from the Microbial and Enzyme Technology and the Bioorganic Chemistry laboratories have developed a new method to synthesize these rare sugars more efficiently, using a combination of enzymatic and chemical methods.

In their new study, published in Green Chemistry, the research team describes a new eco-friendly method for producing D-allose, a rare sugar with numerous health benefits. It is a non-caloric sweetener that also offers anticancer, antioxidant, anti-inflammatory, anti-hypertensive and immunosuppressive properties. Despite these benefits, it has struggled to gain a foothold in the industrial market due to its laborious, time-consuming and complicated synthetic methods, as well as high production costs.

Their approach involved making a bacterial enzyme better at processing a common sugar, D-glucose, through a method called "directed evolution". This process mimics natural evolution in the lab, but speeds it up. To do this, the researchers introduced random changes to the enzyme’s genetic code, tested how well each version worked with the sugar, and kept the best ones. By repeating this process, making further changes and improvements over several rounds, they reached a version of the enzyme that performed as they desired. “Our approach involves a glucose derivative as the starting point, which allows the enzyme to work effectively. After the enzymatic reaction, two simple chemical steps finalize D-allose synthesis”, explains André Taborda, PhD student at ITQB NOVA and first author of the paper. “We were very pleased to achieve an overall yield of 81% and have submitted this strategy to a patent”, he adds.

“This work was only possible through our collaboration with Rita Ventura, head of the Bioorganic Chemistry lab at ITQB NOVA, that has a long-lasting experience in carbohydrate synthesis. This work opens up possibilities for synthesizing other rare sugars in an environmentally friendly and cost-effective manner”, explains Lígia Martins, leader of the Microbial and Enzyme Technology laboratory.

The study was featured in the backcover of the magazine.

ITQB NOVA researchers André Taborda, Lígia Martins and Rita Ventura 

This work was supported by the Fundação para a Ciência e Tecnologia (FCT), Portugal grant 2022.02027.PTDC, Project MOSTMICRO-aITQB (UIDB/04612/2020 and UIDP/04612/2020) and LS4FUTURE Associated laboratory (LA/P/0087/2020). The NMR data were acquired at CERMAX, ITQB‐NOVA, Oeiras, Portugal, with equipment funded by FCT, project AAC 01/SAICT/2016. AT acknowledges FCT for his PhD fellowship 2020.07928.

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