Inhibition of lipid-linked mannose and mannoprotein synthesis in yeast by diumycin in vitro.
Diumycin, a phosphoglycolipid antibiotic, inhibits different mannosyl transfer reactions in yeast. Using membrane preparations, the drug effectively inhibited the formation of dolichyl phosphate mannose (DolP-Man); 50% inhibition was observed at approximately 10 microgram/ml. To a lesser extent also mannosyl transfer from DolP-Man to protein decreased in presence of diumycin. Both mannosyl transfer to protein-serine/threonine acceptor sites as well as into positions within the asparagine-linked polymannose part of the yeast mannoprotein are inhibited to about 60% under conditions where DolP-Man formation is blocked. DolP-Man synthesis as well as mannosyl transfer from DolP-Man to protein are also inhibited by diumycin using solubilized enzymes and exogenous acceptor substrates. Glycosyltransfer reactions from GDP-mannose either to protein-serine/threonine-linked mannose (formation of short manno-oligosaccharides) or to dolichyl-diphosphate-linked chitobiose (formation of lipid-linked trisaccharide) are not inhibited by diumycin under conditions where DolP-Man synthesis is blocked by the antibiotic. The inhibitory action of diumycin on DolP-Man formation does not seem to be competitive with respect to dolichyl phosphate, since it cannot be overcome by higher concentrations of dolichyl phosphate.
D002462:Cell Membrane / Q000378:metabolism; D004287:Dolichol Monophosphate Mannose / Q000096:biosynthesis*; D006023:Glycoproteins / Q000096:biosynthesis*; D006155:Guanosine Diphosphate Mannose / Q000378:metabolism; D008562:Membrane Glycoproteins; D010743:Phospholipids / Q000494:pharmacology; D011105:Polyisoprenyl Phosphate Sugars / Q000096:biosynthesis*; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000378:metabolism*
D006023:Glycoproteins; D008562:Membrane Glycoproteins; D010743:Phospholipids; D011105:Polyisoprenyl Phosphate Sugars; C025363:mannoproteins; C026602:diumycin; D006155:Guanosine Diphosphate Mannose; D004287:Dolichol Monophosphate Mannose