Isoprenoid Phosphonophosphates as Glycosyltransferase Acceptor Substrates

ABSTRACT: Glycosyltransferases that act on polyprenol pyrophosphate substrates are challenging to study because their lipid-linked substrates are difficult to isolate from natural sources and arduous to synthesize. To facilitate access to glycosyl acceptors, we assembled phosphono-phosphate analogues and showed these are effective substrate surrogates for GlfT1, the essential product of mycobacterial gene Rv3782. Under chemically defined conditions, the galactofuranosyltransferase GlfT1 catalyzes the formation of a tetrasaccharide sequence en route to assembly of the mycobacterial galactan. L ipid-linked oligosaccharide pyrophosphates serve asacceptors for a large class of glycosyltransferases.1 Progress in understanding these enzymes is hindered by the difficulty of isolating these biosynthetic acceptors from natural sources and the challenge of their chemical synthesis.2,3 Although som