Biosynthesis of a healthy natural sugar D-tagatose: advances and opportunities.

D-tagatose is a natural low-calorie rare sugar with nearly the same sweet taste as sucrose. It has nutritional and functional properties of great interest for health, such as anti-diabetes, anti-caries, anti-atherosclerosis, anti-hyperlipidemia, anti-aging, improvement of intestinal microflora, etc. The production of D-tagatose from D-galactose catalyzed by an alkali suffers from limited supplies of costly feedstock (i.e., lactose) and high manufacturing costs due to harsh reaction conditions, costly separation, as well as severe degradation and pollution. In this review, we briefly present the properties of D-tagatose and its physiological effects, review the recent advances in the biosynthesis of D-tagatose from inexpensive and abundant glucans (e.g., starch) and their derivatives (e.g., D-glucose and D-fructose) and from lactose, including both academic literature and industrial patents, as well as discuss its future challenges and opportunities. The biosynthesis of D-tagatose can be catalyzed by four types of biocatalysts: enzymes, whole-cells, microbial fermentation, and in vitro multi-enzyme molecular machines. The biomanufacturing of starchy D-tagatose catalyzed by multi-enzyme molecular machines could be the most promising approach because it not only makes D-tagatose from ample starch but also surpasses the equilibria of monosaccharide isomerization reactions (e.g., D-fructose-to-D-tagatose, D-galactose-to-D-tagatose). D-tagatose as a filler for a variety of food and drinks or a key component mixed with other sweeteners would become a predominant starch-derived sweetener and partially replace high-fructose corn sirup in the future.