Biocatalytic Production of Rare Sugars

Rare sugars such as D-allulose, D-tagatose and D-psicose possess unique stereochemistry and valuable physiological properties yet occur only in minute natural quantities. Biocatalytic production harnesses enzymes to perform regioselective and stereoselective transformations under mild conditions, reducing energy consumption and waste compared with purely chemical routes. Core strategies include isomerisation of abundant hexoses via epimerases or isomerases, oxidoreductive cascades to drive conversions beyond thermodynamic equilibria, and chemo-enzymatic sequences coupling enzyme-catalysed oxidations with chemical reductions. Advances in enzyme engineering—through directed evolution, rational mutagenesis and biosensor-assisted screening—have yielded catalysts with enhanced activity, stability and substrate scope. Whole-cell systems further integrate enzyme expression, cofactor regeneration and membrane permeability optimisation, enabling streamlined, scalable processes. These innovations underpin more efficient, sustainable access to rare sugars for applications in functional foods, pharmaceuticals and fine chemicals.

Research from Nature Portfolio

Recent studies have addressed fundamental constraints of isomerase-based production by recasting the reaction network within living cells. One study engineered a yeast strain to perform intracellular oxidoreductive steps that convert lactose to D-tagatose, effectively bypassing the unfavourable equilibrium of conventional isomerases and achieving high product titres. A separate work encapsulated a galactose isomerase in permeabilised Lactobacillus plantarum cells, combining chemical permeabilisation with cell-wall engineering to operate at elevated temperatures and attain rapid galactose-to-tagatose conversion with improved yield and thermostability. These foundational approaches demonstrate how in vivo and cell-encapsulation strategies can overcome kinetic, thermodynamic and stability limitations in rare sugar biocatalysis.

Biocatalytic Production of Rare Sugars publication trend

The graph below shows the total number of articles in biocatalytic production of rare sugars across all publications each year (not limited to Nature Index journals).

Technical terms

Biocatalysis: Use of enzymes or whole cells to catalyse chemical reactions under mild, sustainable conditions.

Ketose 3-epimerase: Enzyme that inverts stereochemistry at the third carbon of a ketose sugar, e.g. converting D-fructose to D-allulose.

Isomerase: Enzyme that rearranges atoms within a molecule, such as interconverting aldose and ketose forms.

Oxidoreductive cascade: Sequential oxidation and reduction steps designed to shift reaction equilibrium and produce target stereoisomers.

Chemo-enzymatic synthesis: Integrated approach combining enzymatic and chemical transformations to achieve complex molecular conversions.

References

1. Growth‐Coupled Evolutionary Pressure Improving Epimerases for D‐Allulose Biosynthesis Using a Biosensor‐Assisted In Vivo Selection Platform. Advanced Science (2024).
2. A new chemo-enzymatic approach to synthesize rare sugars using an engineered glycoside-3-oxidase. Green Chemistry (2025).
3. Redesign of a novel d-allulose 3-epimerase from Staphylococcus aureus for thermostability and efficient biocatalytic production of d-allulose. Microbial Cell Factories (2019).
4. Overcoming the thermodynamic equilibrium of an isomerization reaction through oxidoreductive reactions for biotransformation. Nature Communications (2019).
5. Galactose to tagatose isomerization at moderate temperatures with high conversion and productivity. Nature Communications (2019).