Glycobiotechnology: enzymes for the synthesis of nucleotide sugars

Complex carbohydrates, as constituting part of glycoconjugates such as glycoproteins, glycolipids, hormones, antibiotics and other secondary metabolites, play an active role in inter- and intracellular communication. The aim of "glycobiotechnology" as an upcoming interdisciplinary research field is to develop highly efficient synthesis strategies, including in vivo and in vitro approaches, in order to bring such complex molecules into analytical and therapeutic studies. The enzymatic synthesis of glycosidic bonds by Leloir-glycosyltransferases is an efficient strategy for obtaining saccharides with absolute stereo- and regioselectivity in high yields and under mild conditions. There are, however, two obstacles hindering the realization of this process on a biotechnological scale, namely the production of recombinant Leloir-glycosyltransferases and the availability of enzymes for the synthesis of nucleotide sugars (the glycosyltransferase donor substrates). The present review surveys some synthetic targets which have attracted the interest of glycobiologists as well as recombinant expression systems which give Leloir-glycosyltransferase activities in the mU and U range. The main part summarizes publications concerned with the complex pathways of primary and secondary nucleotide sugars and the availability and use of these enzymes for synthesis applications. In this context, a survey of our work will demonstrate how enzymes from different sources and pathways can be combined for the synthesis of nucleotide deoxysugars and oligosaccharides.