2025-12-11 タフツ大学
<関連情報>
- https://now.tufts.edu/2025/12/11/researchers-develop-way-make-healthier-sugar-substitute
- https://www.cell.com/cell-reports-physical-science/fulltext/S2666-3864(25)00592-2
グルコースからガラクトースとタガトースの合成を促進するためのルロア経路の逆転 Reversal of the Leloir pathway to promote galactose and tagatose synthesis from glucose
Aaron M. Love ∙ Christopher G. Toomey ∙ Abhishek Kumar ∙ … ∙ Pravin Kumar R. ∙ Nikhil U. Nair ∙ Christine N.S. Santos
Cell Reports Physical Science Published:December 11, 2025
DOI:https://doi.org/10.1016/j.xcrp.2025.102993
Graphical abstract

Highlights
- Engineered E. coli to convert glucose directly into D-tagatose
- Reversed the Leloir pathway to enable galactose formation directly from glucose
- Identified a phosphatase specific to galactose-1-phosphate
- Computational analyses revealed basis of phosphatase substrate selectivity
Summary
D-Tagatose is a low-calorie rare sugar with health benefits as a low-glycemic sweetener. Current production methods are limited, often relying on galactose isomerization, and remain inefficient and costly. Here, we report a whole-cell process in Escherichia coli that converts glucose directly to tagatose by reversing the Leloir pathway. Central to this approach is a galactose-1-phosphate-specific phosphatase that drives equilibrium toward galactose. Computational analyses reveal hydrogen-bond networks that underlie stringent substrate selectivity. By co-expressing this phosphatase with an L-arabinose isomerase in a metabolically engineered strain, we demonstrate direct glucose-to-tagatose conversion. Cultures produced ∼10.5 g/L galactose from 30 g/L glucose (35% yield) and >1 g/L tagatose. While this is a proof-of-principle demonstration and further optimization is required to improve tagatose production, this strategy eliminates dependence on lactose-derived galactose and provides a framework for scalable, glucose-based biosynthesis of tagatose and other galactose-derived molecules, supporting sustainable rare-sugar production.


