Evolution in reverse: engineering a D-xylose-specific xylose reductase.

Xylitol (1) is a pentitol and is used not only as a sweetener but also as a platform chemical for the production of industrially important chemicals. As a sweetener, it has been shown to possess several favorable properties in comparison to other sugar substitutes, such as anticariogenicity, good gastrointestinal tolerance, low caloric content, and minimal insulin dependence for metabolism. As an alternative to direct chemical reduction with gaseous hydrogen over Raney nickel catalyst, safer and environmentally-friendly biosynthetic routes of producing xylitol by fermentation and enzymatic reduction of dxylose (2) into xylitol by using xylose reductases (XR) have also been studied extensively (Scheme 1). 4] However, the unspecif-