PSEUDOGLYCOSYLTRANSFERASES are a previously unknown group of glycosyltransferase homologues that are involved in natural product biosynthesis. Glycosyltransferases are among the most ubiquitous enzymes in nature and play a central role in structural and physiological aspects of living organisms. They catalyze the transfer of a sugar moiety from an activated donor sugar onto sugar or nonsugar acceptors, resulting in glycosylated products, such as glycoproteins, glycolipids, glycosylated natural products, oligo/polysaccharides, and many others. Our recent study revealed that some putative glycosyltransferases do not catalyze glycosylation reactions but rather catalyze a nonglycosidic C-N coupling in the biosynthesis of certain natural products (JACS 2011, 133, 12124-12135). These “pseudoglycosyltransferases” (pseudo-GTs) might have evolved from ancestral glycosyltransferases to the extent that they no longer recognize activated sugars as substrates. In collaboration with Prof. Yong-Hwan Lee’s group at Louisiana State University, the three-dimensional structures of VldE from Streptomyces hygroscopicus subsp. limoneus was determined in apo form, in complex with GDP, in complex with GDP and validoxylamine A 7´-phosphate, and in complex with with GDP and trehalose. The elucidation of the VldE structure in complex with the entirety of its products provides insight into the internal return mechanism by which catalysis occurs with a net retention of the stereochemical configuration of the donor moiety (PloS ONE 2012, 7, e44934).
