Crystal structure of SsfS6, the putative C-glycosyltransferase involved in SF2575 biosynthesis


Correspondence to: George N. Phillips, Jr., George R. Brown Hall, W200Q, 6100 Main Street, Rice University, Houston, TX 77005. E-mail: or Jon S. Thorson, University of Kentucky College of Pharmacy, 789 South Limestone Street, Lexington, KY 40536. E-mail:


The molecule known as SF2575 from Streptomyces sp. is a tetracycline polyketide natural product that displays antitumor activity against murine leukemia P388 in vivo. In the SF2575 biosynthetic pathway, SsfS6 has been implicated as the crucial C-glycosyltransferase (C-GT) that forms the C-C glycosidic bond between the sugar and the SF2575 tetracycline-like scaffold. Here, we report the crystal structure of SsfS6 in the free form and in complex with TDP, both at 2.4 Å resolution. The structures reveal SsfS6 to adopt a GT-B fold wherein the TDP and docked putative aglycon are consistent with the overall C-glycosylation reaction. As one of only a few existing structures for C-glycosyltransferases, the structures described herein may serve as a guide to better understand and engineer C-glycosylation. Proteins 2013; 81:1277–1282. © 2013 Wiley Periodicals, Inc.