Abstract

Lactulose is a disaccharide produced industrially by chemical synthesis, having several applications in the pharmaceutical, food, and feed sectors. It has received much attention in recent years because of its therapeutic and health-promoting properties, being considered as one of the most valuable compounds derived from lactose. In the last decades, research has been mainly focused on its enzymatic synthesis allowing to overcome the limitations that are inherent to chemical processes. Initially the synthesis of lactulose by fructose transgalactosylation catalyzed by β-galactosidases was thoroughly studied. β-galactosidases are readily available low-priced commercial enzymes; many of them having a record of safe use in food and medicinal uses. However, lactulose yields are rather low and other transgalactosylated products, mainly galacto-oligosaccharides, are produced along. Later on, a promiscuous cellobiose 2-epimerase proved to be able to produce lactulose by straight lactose isomerization; but the enzyme is not commercially available the enzyme also epimerizes lactose to produce epilactose along with lactulose. Both β-galactosidases and cellobiose 2-epimerase can also produce other carbohydrates with prebiotic potential. In fact, the synthesis of other rare sugars, like lactosucrose and fructosyl-galacto-oligosaccharides with β-galactosidases and epilactose, talose, and mannose with cellobiose 2-epimerase has been reported. Most of these compounds display several health-promoting effects and also other functional properties of interest to the food and pharmaceutical industries. © 2026 Elsevier Inc. All rights reserved.