Title : One hydroxyl flip: Biocatalytic isomerization unlocks high-value chemicals
Abstract:
Stereochemical inversion at a single hydroxyl group can profoundly alter the physicochemical properties, biological functions, and application value of carbohydrate molecules. D-Tagatose, a rare sugar with growing interest in food, health, and biomanufacturing, differs from D-fructose only in the configuration of the hydroxyl group at C4. This subtle structural change provides an attractive model for understanding how enzymes achieve precise stereochemical control and how such catalytic principles can be translated into practical manufacturing processes. In this work, we focus on C4 epimerization as a stereoselective biocatalytic process, integrating enzyme discovery, molecular engineering, catalytic mechanism analysis, and process intensification. Tagatose 4-epimerase (T4E)-mediated catalysis involves ring opening, proton abstraction, formation of a cis-enediol intermediate, stereoselective reprotonation at C4, and subsequent ring closure, highlighting the critical role of active-site architecture in controlling stereochemical outcome. Enzyme screening and engineering strategies were therefore employed to improve catalytic efficiency, stability, and substrate compatibility, followed by optimization of catalytic and bioprocess conditions toward efficient tagatose production. More broadly, this study illustrates how “flipping one hydroxyl” can be treated as a fundamental catalytic design problem rather than merely a sugar-conversion reaction. Understanding and engineering hydroxyl epimerization may provide a general framework for developing selective biocatalysts for rare sugars and other stereochemically complex molecules, bridging molecular catalysis with sustainable chemical manufacturing.
Keywords: biocatalysis; C4 epimerization; D-tagatose; rare sugars; stereoselectivity; enzyme engineering.
