초록 |
Low calorie sweeteners have the health and financial impacts on treating obesity and diabetes. Rare ketohexose sugars, naturally occurring in small amounts, have attracted great interest in the food and drug industry because they are potent sugar substitutes as well as important building blocks for pharmaceutical active ingredients. To produce rare sugars biologically from abundant raw materials (e.g., starch, whey or hemicellulose), we focused on carbohydrate isomerases and epimerases derived from extremophiles. Detailed biochemical and biophysical inspection of thermophilic sugar enzymes indicates that despite the close overall structural similarity to their mesophilic counterparts, they have evolved distinct structural features that promote the promiscuity of substrate specificity as well as thermostability. Further, a structure-guided semi-rational strategy was employed to generate non-natural sugar enzymes to meet industrial demands, thereby providing a variety of repertoire of substrate specificity and delineating the evolutionary relationship between protein sequences and their functions. |